Anatomically Constrained Video-CT Registration via the V-IMLOP Algorithm

Functional endoscopic sinus surgery (FESS) is a surgical procedure used to treat acute cases of sinusitis and other sinus diseases. FESS is fast becoming the preferred choice of treatment due to its minimally invasive nature. However, due to the limited field of view of the endoscope, surgeons rely on navigation systems to guide them within the nasal cavity. State of the art navigation systems report registration accuracy of over 1mm, which is large compared to the size of the nasal airways. We present an anatomically constrained video-CT registration algorithm that incorporates multiple video features. Our algorithm is robust in the presence of outliers. We also test our algorithm on simulated and in-vivo data, and test its accuracy against degrading initializations.Comment: 8 pages, 4 figures, MICCA

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

The Healthy Steps Study: A randomized controlled trial of a pedometer-based Green Prescription for older adults. Trial protocol

Background: Graded health benefits of physical activity have been demonstrated for the reduction of coronary heart disease, some cancers, and type-2 diabetes, and for injury reduction and improvements in mental health. Older adults are particularly at risk of physical inactivity, and would greatly benefit from successful targeted physical activity interventions. Methods/Design: The Healthy Steps study is a 12-month randomized controlled trial comparing the efficacy of a pedometer-based Green Prescription with the conventional time-based Green Prescription in increasing and maintaining physical activity levels in low-active adults over 65 years of age. The Green Prescription interventions involve a primary care physical activity prescription with 3 follow-up telephone counselling sessions delivered by trained physical activity counsellors over 3 months. Those in the pedometer group received a pedometer and counselling based around increasing steps that can be monitored on the pedometer, while those in the standard Green Prescription group received counselling using time-based goals. Baseline, 3 month (end of intervention), and 12 month measures were assessed in face-to-face home visits with outcomes measures being physical activity (Auckland Heart Study Physical Activity Questionnaire), quality of life (SF-36 and EQ-5D), depressive symptoms (Geriatric Depression Scale), blood pressure, weight status, functional status (gait speed, chair stands, and tandem balance test) and falls and adverse events (self-report). Utilisation of health services was assessed for the economic evaluation carried out alongside this trial. As well, a process evaluation of the interventions and an examination of barriers and motives for physical activity in the sample were conducted. The perceptions of primary care physicians in relation to delivering physical activity counselling were also assessed. Discussion: The findings from the Healthy Steps trial are due in late 2009. If successful in improving physical activity in older adults, the pedometer-based Green Prescription could assist in reducing utilisation of health services and improve cardiovascular health and reduction of risk for a range of non-communicable lifestyles diseases

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Heterogeneous natural selection on oxidative phosphorylation genes among fishes with extreme high and low aerobic performance

Background: Oxidative phosphorylation (OXPHOS) is the primary source of ATP in eukaryotes and serves as a mechanistic link between variation in genotypes and energetic phenotypes. While several physiological and anatomical factors may lead to increased aerobic capacity, variation in OXPHOS proteins may influence OXPHOS efficiency and facilitate adaptation in organisms with varied energy demands. Although there is evidence that natural selection acts on OXPHOS genes, the focus has been on detection of directional (positive) selection on specific phylogenetic branches where traits that increase energetic demands appear to have evolved. We examined patterns of selection in a broader evolutionary context, i.e., on multiple lineages of fishes with extreme high and low aerobic performance. Results: We found that patterns of natural selection on mitochondrial OXPHOS genes are complex among fishes with different swimming performance. Positive selection is not consistently associated with high performance taxa and appears to be strongest on lineages containing low performance taxa. In contrast, within high performance lineages, purifying (negative) selection appears to predominate. Conclusions: We provide evidence that selection on OXPHOS varies in both form and intensity within and among lineages through evolutionary time. These results provide evidence for fluctuating selection on OXPHOS associated with divergence in aerobic performance. However, in contrast to previous studies, positive selection was strongest on low performance taxa suggesting that adaptation of OXPHOS involves many factors beyond enhancing ATP production in high performance taxa. The broader pattern indicates a complex interplay between organismal adaptations, ATP demand, and OXPHOS function.This work was supported by NSF award DEB-0732988 (to REB).Ye

Allodynia in rats infected with varicella zoster virus--a small animal model for post-herpetic neuralgia.

The most common complication of herpes zoster is post-herpetic neuralgia (PHN), which has been defined as severe pain occurring 1 month after rash onset or persisting for greater than 3 months. PHN is classed as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful. The development of therapies to treat PHN has been hampered by the lack of animal models, which mimic the clinical situation. We have previously reported that varicella zoster virus (VZV) infection in the rat results in mechanical allodynia and thermal hyperalgesia. Here, we report that following VZV infection of the left footpad rats develop a chronic mechanical allodynia, which is present for longer than 60 days post-infection and which resolves by 100 days PI. The model is robust and reproducible with animals consistently developing allodynia by 3 days PI and continuing to present with symptoms for at least 30 days. The reproducible nature of the induction and course of the allodynia allows the use of this model to determine the effect of various compounds on, and to investigate the pathogenic mechanisms underlying the development of VZV-induced allodynia. Comparative studies using HSV-1 show that the induction of the chronic allodynia is VZV-specific and is not a result is of virus replication-induced tissue damage or accompanying inflammation. Therefore, we propose that the rat VZV infection model could prove useful in studying the mechanisms underlying post-herpetic neuralgia