Anatomic variations of neurovascular structures of the ankle in relation to arthroscopic portals: a cadaveric study of Chinese subjects.

PURPOSE: To investigate anatomic variations of neurovascular structures in the ankle and the safety margin for arthroscopic portals. METHODS: 11 left and 12 right ankles from 8 female and 15 male fresh cadavers of Chinese ethnicity aged 53 to 88 (mean, 68) years were used. The ankle was standardised in a plantigrade position, zero-degree inversion, and neutral rotation. Four ankle portals, namely anteromedial (AM), anterolateral (AL), posteromedial (PM) and posterolateral (PL), were identified using 23-gauge needles. Skin and subcutaneous fat were dissected from the underlying fascia to visualise neurovascular structures. Distances were measured from: (1) the AM portal to the saphenous vein and nerve and its branches, (2) the AL portal to branches of the superficial peroneal nerves, of which the lateral one was labelled as the intermediate dorsal cutaneous branch and the medial one as the medial dorsal cutaneous branch, (3) the PM portal to the posterior tibial neurovascular bundles, and (4) the PL portal to the sural nerve. RESULTS: The distances from (1) the AM portal to branches of the great saphenous vein and nerve, and (2) the AL portal to the intermediate dorsal cutaneous branch of the superficial peroneal nerve were short and may be an anatomic hazard. Variations were significant among the cadavers in terms of distances of the portals to the neurovascular structures. CONCLUSION: In Chinese cadavers, variations of neurovascular structures are significant. Care must be taken to avoid inadvertent injury during ankle arthroscopy.published_or_final_versio

α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco

<p>Abstract</p> <p>Background</p> <p>Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high.</p> <p>Methods</p> <p>Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse.</p> <p>Results</p> <p>291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1.10-4.77), positive sputum smear after 3 months of treatment (OR 7.14, 95% CI 4.04-13.2), and hospitalization (OR 2.09, 95% CI 1.01-4.34). Higher weight at treatment initiation was protective. Male sex, substance use, missed doses, and hospitalization appeared to be risk factors for default, but subgroup analyses were limited by small numbers.</p> <p>Conclusions</p> <p>Outcomes of retreatment with a Category II regimen are suboptimal and vary by subgroup. Default among patients receiving tuberculosis retreatment is unacceptably high in urban areas in Morocco, and patients who fail initial tuberculosis treatment are at especially high risk of retreatment failure. Strategies to address risk factors for initial treatment default and to identify patients at risk for failure (including expanded use of drug susceptibility testing) are important given suboptimal retreatment outcomes in these groups.</p

Combined Analysis of all Three Phases of Solar Neutrino Data from the Sudbury Neutrino Observatory

We report results from a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory. By exploiting particle identification information obtained from the proportional counters installed during the third phase, this analysis improved background rejection in that phase of the experiment. The combined analysis resulted in a total flux of active neutrino flavors from 8B decays in the Sun of (5.25 \pm 0.16(stat.)+0.11-0.13(syst.))\times10^6 cm^{-2}s^{-1}. A two-flavor neutrino oscillation analysis yielded \Deltam^2_{21} = (5.6^{+1.9}_{-1.4})\times10^{-5} eV^2 and tan^2{\theta}_{12}= 0.427^{+0.033}_{-0.029}. A three-flavor neutrino oscillation analysis combining this result with results of all other solar neutrino experiments and the KamLAND experiment yielded \Deltam^2_{21} = (7.41^{+0.21}_{-0.19})\times10^{-5} eV^2, tan^2{\theta}_{12} = 0.446^{+0.030}_{-0.029}, and sin^2{\theta}_{13} = (2.5^{+1.8}_{-1.5})\times10^{-2}. This implied an upper bound of sin^2{\theta}_{13} < 0.053 at the 95% confidence level (C.L.)

We should not forget the foot: relations between signs and symptoms, damage, and function in rheumatoid arthritis

We studied rheumatoid arthritis (RA) patients with foot complaints to address the associations between clinical signs and symptoms, radiographic changes, and function in connection with disease duration. Secondly, we describe the contribution of several foot segments to the clinical presentation and function. In 30 RA patients with complaints of their feet, attributed to either signs of arthritis and/or radiographic damage, we compared radiographic, ultrasound, clinical, and functional parameters of the feet and ankle. Pain and swelling of the ankle were correlated weakly but statistically significantly with limitation and disability (0.273 to 0.293) as measured on the 5-Foot Function Index (FFI). The clinical signs of the forefoot joints did not influence any of the functional outcome measures. Radiographic scores for both forefeet (SvdH) and hindfeet (Larsen) were correlated with the total Health Assessment Questionnaire Disability Index (HAQ DI) and the 5-FFI limitation subscale. Pain and disease duration, more than radiographic damage, influence the total HAQ DI significantly. With the progression of time, structural damage and function of the rheumatic foot worsen in RA patients. Pain and swelling of the ankle contribute more to disability than radiographic damage of the foot and ankle

Simulating biosignatures from pre-oxygen photosynthesising life on TRAPPIST-1e

This is the author accepted manuscript. The final version is available on open access from Oxford University Press via the DOI in this recordData availability: The model output used for this study will be made available following this work’s acceptance for publicationIn order to assess observational evidence for potential atmospheric biosignatures on exoplanets, it will be essential to test whether spectral fingerprints from multiple gases can be explained by abiotic or biotic-only processes. Here, we develop and apply a coupled 1D atmosphere-ocean-ecosystem model to understand how primitive biospheres, which exploit abiotic sources of H2 , CO and O2 , could influence the atmospheric composition of rocky terrestrial exoplanets. We apply this to the Earth at 3.8 Ga and to TRAPPIST-1e. We focus on metabolisms that evolved before the evolution of oxygenic photosynthesis, which consume H2 and CO and produce potentially detectable levels of CH4 . O2 -consuming metabolisms are also considered for TRAPPIST-1e, as abiotic O2 production is predicted on M-dwarf orbiting planets. We show that these biospheres can lead to high levels of surface O2 (approximately 1–5 %) as a result of CO consumption, which could allow high O2 scenarios, by removing the main loss mechanisms of atomic oxygen. Increasing stratospheric temperatures, which increases atmospheric OH can reduce the likelihood of such a state forming. O2 -consuming metabolisms could also lower O2 levels to around 10 ppm and support a productive biosphere at low reductant inputs. Using predicted transmission spectral features from CH4 , CO, O2 /O3 and CO2 across the hypothesis space for tectonic reductant input, we show that biotically-produced CH4 may only be detectable at high reductant inputs. CO is also likely to be a dominant feature in transmission spectra for planets orbiting M-dwarfs, which could reduce the confidence in any potential biosignature observations linked to these biospheres.Science and Technology Facilities Council (STFC)UK Research and InnovationJohn Templeton FoundationLeverhulme TrustHill Family ScholarshipInstitute of Physic

Frequency of D222G and Q223R Hemagglutinin Mutants of Pandemic (H1N1) 2009 Influenza Virus in Japan between 2009 and 2010

BACKGROUND: In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid. METHODS/RESULTS: To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009. CONCLUSIONS: These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008

The long-term effect of being treated in a geriatric ward compared to an orthopaedic ward on six measures of free-living physical behavior 4 and 12 months after a hip fracture - a randomised controlled trial

Background This study is part of the Trondheim Hip Fracture Trial, where we compared free-living physical behavior in daily life 4 and 12 months following hip surgery for patients managed with comprehensive geriatric care (CGC) in a geriatric ward with those managed with orthopedic care (OC) in an orthopedic ward. Methods This is a single centre, prospective, randomized controlled trial. 397 hip fracture patients were randomized to CGC (n = 199) or OC (n = 198) in the Emergency Department with follow-up assessments performed four and 12 months post-surgery. Outcomes were mean upright time, number and length of upright events recorded continuously for four days at four and 12 months post-surgery by an accelerometer-based activity monitor. Missing data were handled by multiple imputation and group differences assessed by linear regression with adjustments for gender, age and fracture type. Results There were no group differences in participants’ pre-fracture characteristics. Estimated group difference in favor of CGC in upright time at 4 months was 34.6 min (17.4 %, CI 9.6 to 59.6, p = .007) and at 12 months, 27.7 min (13.9 %, CI 3.5 to 51.8, p = .025). Average and maximum length of upright events was longer in the CGC (p’s &lt; .042). No group difference was found for number of upright events (p’s &gt; .452). Conclusion Participants treated with CGC during the hospital stay improved free-living physical behavior more than those treated with OC both 4 and 12 months after surgery, with more time and longer periods spent in upright. Results support findings from the same study for functional outcomes, and demonstrate that CGC impacts daily life as long as one year after surgery