Nanodiamonds enable adaptive-optics enhanced, super-resolution, two-photon excitation microscopy

Particles of diamond in the 5–100 nm size range, known as nanodiamond (ND), have shown promise as robust fluorophores for optical imaging. We demonstrate here that, due to their photostability, they are not only suitable for two-photon imaging, but also allow significant resolution enhancement when combined with computational super-resolution techniques. We observe a resolution of 42.5 nm when processing two-photon images with the Super-Resolution Radial Fluctuations algorithm. We show manipulation of the point-spread function of the microscope using adaptive optics. This demonstrates how the photostability of ND can also be of use when characterizing adaptive optics technologies or testing the resilience of super-resolution or aberration correction algorithms

Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm

Abstract Background and purpose Acid has long been thought to play an important role in the pain process. Animal study showed that repeated acid stimulation induced central sensitization. The purpose of the study is to investigate muscle pain and hyperalgesia evoked byintramuscular infusion of saline at different pH levels, and to compare the effect of a single versus repeated acid infusions. Methods Twenty healthy subjects received infusions of buffered saline (pH 5.0, 6.0, and 7.4) into the brachioradialis muscle in a randomized order. Twelve of the subjects received repeated infusions. The subjects rated the pain intensity on visual analogue scale (VAS). Thermal pain sensitivity, and pressure pain threshold (PPT) were assessed in both arm before, during, immediately after, one hour after, and one day after the infusion. A McGill Pain Questionnaire and pain mapping were completed after each infusion. Results The pH 5 solution caused significantly higher pain and larger areas than pH 6.0 or 7.4. The local PPTs were significantly decreased (hyperalgesia) during and immediately after infusion of all three solutions. No significant differences were detected between the first and second infusion. Conclusions The intensity of acid-induced muscle pain is pH-dependent. All three solutions induced pressure hyperalgesia at the infusion site. Repeated infusions did not induce increased pain or prolonged hyperalgesia as compared with a single injection. Human intramuscular acidic saline infusion could not produce chronic pain model. Implications The acid-induced pain model may reflect the early stage responses to tissue injury of clinical conditions. Repeated intramuscular acidic saline injection model of prolonged hyperalgesia in rodents could not be translated into a human for modelling chronic musculoskeletal pain. </jats:sec

Analysis of lower limb internal kinetics and electromyography in elite race walking.

The aim of this study was to analyse lower limb joint moments, powers and electromyography patterns in elite race walking. Twenty international male and female race walkers performed at their competitive pace in a laboratory setting. The collection of ground reaction forces (1000 Hz) was synchronised with two-dimensional high-speed videography (100 Hz) and electromyography of seven lower limb muscles (1000 Hz). As well as measuring key performance variables such as speed and stride length, normalised joint moments and powers were calculated. The rule in race walking which requires the knee to be extended from initial contact to midstance effectively made the knee redundant during stance with regard to energy generation. Instead, the leg functioned as a rigid lever which affected the role of the hip and ankle joints. The main contributors to energy generation were the hip extensors during late swing and early stance, and the ankle plantarflexors during late stance. The restricted functioning of the knee during stance meant that the importance of the swing leg in contributing to forward momentum was increased. The knee flexors underwent a phase of great energy absorption during the swing phase and this could increase the risk of injury to the hamstring muscles

The structure of Herpesvirus Fusion Glycoprotein B-Bilayer Complex reveals the protein-membrane and lateral protein-protein interaction

Glycoprotein B (gB) is a key component of the complex herpesvirus fusion machinery. We studied membrane interaction of two gB ectodomain forms and present an electron cryotomography structure of the gB-bilayer complex. The two forms differed in presence or absence of the membrane proximal region (MPR) but showed an overall similar trimeric shape. The presence of the MPR impeded interaction with liposomes. In contrast, the MPR-lacking form interacted efficiently with liposomes. Lateral interaction resulted in coat formation on the membranes. The structure revealed that interaction of gB with membranes was mediated by the fusion loops and limited to the outer membrane leaflet. The observed intrinsic propensity of gB to cluster on membranes indicates an additional role of gB in driving the fusion process forward beyond the transient fusion pore opening and subsequently leading to fusion pore expansion

The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections.

BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. METHODS: Primigravidae and secundigravidae who participated in the ISTp arm of a noninferiority trial in 4 West African countries were screened with an HRP2/pLDH RDT on enrollment and, in Ghana, at subsequent antenatal clinic (ANC) visits. Blood samples were examined subsequently by microscopy and by a polymerase chain reaction (PCR) assay. RESULTS: The sensitivity of the RDT to detect peripheral blood infections confirmed by microscopy and/or PCR at enrollment ranged from 91% (95% confidence interval [CI], 88%, 94%) in Burkina Faso to 59% (95% CI, 48%, 70% in The Gambia. In Ghana, RDT sensitivity was 89% (95% CI, 85%, 92%), 83% (95% CI, 76%, 90%) and 77% (95% CI, 67%, 86%) at enrollment, second and third ANC visits respectively but only 49% (95% CI, 31%, 66%) at delivery. Screening at enrollment detected 56% of all infections detected throughout pregnancy. Seventy-five RDT negative PCR or microscopy positive infections were detected in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. CONCLUSIONS: The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative malaria infections were not associated with adverse birth outcomes but missed infections were uncommon