Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton afferents. We recorded from CD and bouton afferents innervating the turtle posterior crista during electrical stimulation of vestibular efferents while applying several subtype-selective nAChR agonists and antagonists. The α9α10 nAChR antagonists, α-bungarotoxin and α-conotoxin RgIA, blocked efferent-mediated inhibition in bouton afferents while leaving efferent-mediated excitation in CD units largely intact. Conversely, 5-iodo-A-85380, sazetidine-A, varenicline, α-conotoxin MII, and bPiDDB (N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide) blocked efferent-mediated excitation in CD afferents without affecting efferent-mediated inhibition in bouton afferents. This pharmacological profile suggested that calyceal nAChRs contain α6 and β2, but not α9, nAChR subunits. Selective blockade of efferent-mediated excitation in CD afferents distinguished dimorphic from calyx afferents by revealing type II hair cell input. Dimorphic afferents differed in having higher mean discharge rates and a mean efferent-mediated excitation that was smaller in amplitude yet longer in duration. Molecular biological data demonstrated the expression of α9 in turtle hair cells and α4 and β2 in associated vestibular ganglia

Loss of α-Calcitonin Gene-Related Peptide (αCGRP) Reduces Otolith Activation Timing Dynamics and Impairs Balance

Calcitonin gene-related peptide (CGRP) is a neuroactive peptide that is thought to play a role at efferent synapses in hair cell organs including the cochlea, lateral line, and semicircular canal. The deletion of CGRP in transgenic mice is associated with a significant reduction in suprathreshold cochlear nerve activity and vestibulo–ocular reflex (VOR) gain efficacy when compared to littermate controls. Here we asked whether the loss of CGRP also influences otolithic end organ function and contributes to balance impairments. Immunostaining for CGRP was absent in the otolithic end organs of αCGRP null (-/-) mice while choline acetyltransferase (ChAT) immunolabeling appeared unchanged suggesting the overall gross development of efferent innervation in otolithic organs was unaltered. Otolithic function was assessed by quantifying the thresholds, suprathreshold amplitudes, and latencies of vestibular sensory-evoked potentials (VsEPs) while general balance function was assessed using a modified rotarod assay. The loss of αCGRP in null (-/-) mice was associated with: (1) shorter VsEP latencies without a concomitant change in amplitude or thresholds, and (2) deficits in the rotarod balance assay. Our findings show that CGRP loss results in faster otolith afferent activation timing, suggesting that the CGRP component of the efferent vestibular system (EVS) also plays a role in otolithic organ dynamics, which when coupled with reduced VOR gain efficacy, impairs balance

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

On-road and wind-tunnel measurement of motorcycle helmet noise

The noise source mechanisms involved in motorcycling include various aerodynamic sources and engine noise. The problem of noise source identification requires extensive data acquisition of a type and level that have not previously been applied. Data acquisition on track and on road are problematic due to rider safety constraints and the portability of appropriate instrumentation. One way to address this problem is the use of data from wind tunnel tests. The validity of these measurements for noise source identification must first be demonstrated. In order to achieve this extensive wind tunnel tests have been conducted and compared with the results from on-track measurements. Sound pressure levels as a function of speed were compared between on track and wind tunnel tests and were found to be comparable. Spectral conditioning techniques were applied to separate engine and wind tunnel noise from aerodynamic noise and showed that the aerodynamic components were equivalent in both cases. The spectral conditioning of on-track data showed that the contribution of engine noise to the overall noise is a function of speed and is more significant than had previously been thought. These procedures form a basis for accurate experimental measurements of motorcycle noise

Forecasting the burden of advanced knee osteoarthritis over a 10-year period in a cohort of 60–64 year-old US adults

To forecast the burden of symptomatic knee osteoarthritis (OA) in the elderly US population over a 10-year horizon

Evolutionary Dynamics of the Ty3/Gypsy LTR Retrotransposons in the Genome of Anopheles gambiae

Ty3/gypsy elements represent one of the most abundant and diverse LTR-retrotransposon (LTRr) groups in the Anopheles gambiae genome, but their evolutionary dynamics have not been explored in detail. Here, we conduct an in silico analysis of the distribution and abundance of the full complement of 1045 copies in the updated AgamP3 assembly. Chromosomal distribution of Ty3/gypsy elements is inversely related to arm length, with densities being greatest on the X, and greater on the short versus long arms of both autosomes. Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length. Additionally, the breakpoint regions of chromosomal inversion 2La appears to be a haven for LTRrs. These elements are underrepresented more than 7-fold in euchromatin, where 33% of the Ty3/gypsy copies are associated with genes. The euchromatin on chromosome 3R shows a faster turnover rate of Ty3/gypsy elements, characterized by a deficit of proviral sequences and the lowest average sequence divergence of any autosomal region analyzed in this study. This probably reflects a principal role of purifying selection against insertion for the preservation of longer conserved syntenyc blocks with adaptive importance located in 3R. Although some Ty3/gypsy LTRrs show evidence of recent activity, an important fraction are inactive remnants of relatively ancient insertions apparently subject to genetic drift. Consistent with these computational predictions, an analysis of the occupancy rate of putatively older insertions in natural populations suggested that the degenerate copies have been fixed across the species range in this mosquito, and also are shared with the sibling species Anopheles arabiensis

New Magnetic Anomaly Map of the Antarctic

The second generation Antarctic magnetic anomaly compilation for the region south of 60 degrees S includes some 3.5 million line-km of aeromagnetic and marine magnetic data that more than doubles the initial map's near-surface database. For the new compilation, the magnetic data sets were corrected for the International Geomagnetic Reference Field, diurnal effects, and high-frequency errors and leveled, gridded, and stitched together. The new magnetic data further constrain the crustal architecture and geological evolution of the Antarctic Peninsula and the West Antarctic Rift System in West Antarctica, as well as Dronning Maud Land, the Gamburtsev Subglacial Mountains, the Prince Charles Mountains, Princess Elizabeth Land, and Wilkes Land in East Antarctica and the circumjacent oceanic margins. Overall, the magnetic anomaly compilation helps unify disparate regional geologic and geophysical studies by providing new constraints on major tectonic and magmatic processes that affected the Antarctic from Precambrian to Cenozoic times.Korea Polar Research Institute (KOPRI) programs, PM15040 and PE17050Germany's AWI/Helmholtz Center for Polar and Marine ResearchFederal Institute for Geosciences and Natural ResourcesBritish Antarctic Survey/Natural Environmental Research CouncilItalian Antarctic Research ProgrammeRussian Ministry of Natural ResourcesU.S. National Science Foundation and National Space and Aeronautics AdministrationAustralian Antarctic Division and Antarctic Climate & Ecosystem Cooperative Research CentreFrench Polar InstituteGlobal geomagnetic observatories network (INTERMAGNET

Impact of Obesity and Knee Osteoarthritis on Morbidity and Mortality in Older Americans

Obesity and knee osteoarthritis are among the most frequent chronic conditions affecting Americans aged 50 to 84 years

Assessing the Association Between Asthma and Air Quality in the Presence of Wildfires

Asthma hospital/emergency room (patient) data are used as the foundation for creating a health outcome indicator of human response to environmental air quality. Daily U.S. Environmental Protection Agency (EPA) Air Quality System (AQS) fine particulates (PM2.5) ground data and the U.S. National Aeronautical Space Administration (NASA) MODIS aerosol optical depth (AOD) data were acquired and processed for years of 2007 and 2008. Figure 1 shows the PM2.5 annual mean composite of all the 2007 B-spline daily surfaces. Initial models for predicting the number of weekly asthma cases within a Florida county has focused on environmental variables. Weekly maximums of PM2.5, relative humidity, and the proportions of the county with smoke and fire were the environmental variables included in the model. Cosine and sine functions of time were used to account for seasonality in asthma cases. Counties were considered to be random effects, thereby adjusting for differences in socio ]demographics and other factors. The 2007 predictions for Miami ]Dade county when using B ]splines PM2.5 are displayed in Figures 2