Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

Background: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.8061.00 mm; mean change695%CI). This change was inverted towards the inner four subfields (TRT inner = 21.8960.97 mm) with significant reduction of TRT in the fovea (TRT foveal = 26.6260.90 mm) at altitude. BCVA revealed no significant difference compared to baseline (0.0660.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = 21.1260.68 dB). At baseline recordings before and.2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance: During acute exposure to high altitude central retinal thickness is subject to minor, ye

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

The reliability of plantar pressure assessment during barefoot level walking in children aged 7-11 years

<p>Abstract</p> <p>Background</p> <p>Plantar pressure assessment can provide information pertaining to the dynamic loading of the foot, as well as information specific to each region in contact with the ground. There have been few studies which have considered the reliability of plantar pressure data and therefore the purpose of this study was to investigate the reliability of assessing plantar pressure variables in a group of typically developing children, during barefoot level walking.</p> <p>Methods</p> <p>Forty-five participants, aged 7 to 11 years, were recruited from local primary and secondary schools in East London. Data from three walking trials were collected at both an initial and re-test session, taken one week apart, to determine both the within- and between-session reliability of selected plantar pressure variables. The variables of peak pressure, peak force, pressure-time and force-time integrals were extracted for analysis in the following seven regions of the foot; lateral heel, medial heel, midfoot, 1st metatarsophalangeal joint, 2nd-5th metatarsophalangeal joint, hallux and the lesser toes. Reliability of the data were explored using Intra Class Correlation Coefficients (ICC 3,1 and 3,2) and variability with Coefficients of Variation (CoV's).</p> <p>Results</p> <p>The measurements demonstrated moderate to good levels of within-session reliability across all segments of the foot (0.69-0.93), except the lesser toes, which demonstrated poor reliability (0.17-0.50). CoV's across the three repeated trials ranged from 10.12-19.84% for each of the measured variables across all regions of the foot, except the lesser toes which demonstrated the greatest variability within trials (27.15-56.08%). The between-session results demonstrated good levels of reliability across all foot segments (0.79-0.99) except the lesser toes; with moderate levels of reliability reported at this region of the foot (0.58-0.68). The CoV's between-sessions demonstrated that the midfoot (16.41-36.23%) and lesser toe region (29.64-56.61) demonstrated the greatest levels of variability across all the measured variables.</p> <p>Conclusions</p> <p>These findings indicate that using the reported protocols, reliable plantar pressure data can be collected in children, aged 7 to 11 years in all regions of the foot except the lesser toes which consistently reported poor-to-moderate levels of reliability and increased variability.</p

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Variations on Fibrinogen-Erythrocyte Interactions during Cell Aging

Erythrocyte hyperaggregation, a cardiovascular risk factor, is considered to be caused by an increase in plasma adhesion proteins, particularly fibrinogen. We have recently reported a specific binding between fibrinogen and an erythrocyte integrin receptor with a β3 or β3-like subunit. In this study we evaluate the influence of erythrocyte aging on the fibrinogen binding. By atomic force microscopy-based force spectroscopy measurements we found that increasing erythrocyte age, there is a decrease of the binding to fibrinogen by decreasing the frequency of its occurrence but not its force. This observation is reinforced by zeta-potential and fluorescence spectroscopy measurements. We conclude that upon erythrocyte aging the number of fibrinogen molecules bound to each cell decreases significantly, due to the progressive impairment of the specific fibrinogen-erythrocyte receptor interaction. Knowing that younger erythrocytes bind more to fibrinogen, we could presume that this population is the main contributor to the cardiovascular diseases associated with increased fibrinogen content in blood, which could disturb the blood flow. Our data also show that the sialic acids exposed on the erythrocyte membrane contribute for the interaction with fibrinogen, possibly by facilitating its binding to the erythrocyte membrane receptor

Human papillomavirus 16 is an aetiological factor of scrotal cancer

Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry. Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16(INK4a)-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16(INK4a). Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers

Organizational culture, team climate and diabetes care in small office-based practices

Contains fulltext : 71456.pdf ( ) (Open Access)BACKGROUND: Redesigning care has been proposed as a lever for improving chronic illness care. Within primary care, diabetes care is the most widespread example of restructured integrated care. Our goal was to assess to what extent important aspects of restructured care such as multidisciplinary teamwork and different types of organizational culture are associated with high quality diabetes care in small office-based general practices. METHODS: We conducted cross-sectional analyses of data from 83 health care professionals involved in diabetes care from 30 primary care practices in the Netherlands, with a total of 752 diabetes mellitus type II patients participating in an improvement study. We used self-reported measures of team climate (Team Climate Inventory) and organizational culture (Competing Values Framework), and measures of quality of diabetes care and clinical patient characteristics from medical records and self-report. We conducted multivariate analyses of the relationship between culture, climate and HbA1c, total cholesterol, systolic blood pressure and a sum score on process indicators for the quality of diabetes care, adjusting for potential patient- and practice level confounders and practice-level clustering. RESULTS: A strong group culture was negatively associated to the quality of diabetes care provided to patients (beta = -0.04; p = 0.04), whereas a more 'balanced culture' was positively associated to diabetes care quality (beta = 5.97; p = 0.03). No associations were found between organizational culture, team climate and clinical patient outcomes. CONCLUSION: Although some significant associations were found between high quality diabetes care in general practice and different organizational cultures, relations were rather marginal. Variation in clinical patient outcomes could not be attributed to organizational culture or teamwork. This study therefore contributes to the discussion about the legitimacy of the widespread idea that aspects of redesigning care such as teamwork and culture can contribute to higher quality of care. Future research should preferably combine quantitative and qualitative methods, focus on possible mediating or moderating factors and explore the use of instruments more sensitive to measure such complex constructs in small office-based practices

Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

<p>Abstract</p> <p>Background</p> <p>Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the <it>BRAF </it>gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature.</p> <p>Case Presentation</p> <p>Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the <it>V600E </it>(<it>T1799A</it>) mutation was detected in exon 15 of the <it>BRAF </it>gene.</p> <p>Conclusion</p> <p>Since fistulae experience persistent inflammation, the fact that this melanoma harbours a <it>BRAF </it>mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of <it>BRAF </it>gene mutations.</p