An automated in vitro model for the evaluation of ultrasound modalities measuring myocardial deformation

<p>Abstract</p> <p>Background</p> <p>Echocardiography is the method of choice when one wishes to examine myocardial function. Qualitative assessment of the 2D grey scale images obtained is subjective, and objective methods are required. Speckle Tracking Ultrasound is an emerging technology, offering an objective mean of quantifying left ventricular wall motion. However, before a new ultrasound technology can be adopted in the clinic, accuracy and reproducibility needs to be investigated.</p> <p>Aim</p> <p>It was hypothesized that the collection of ultrasound sample data from an in vitro model could be automated. The aim was to optimize an in vitro model to allow for efficient collection of sample data.</p> <p>Material & Methods</p> <p>A tissue-mimicking phantom was made from water, gelatin powder, psyllium fibers and a preservative. Sonomicrometry crystals were molded into the phantom. The solid phantom was mounted in a stable stand and cyclically compressed. Peak strain was then measured by Speckle Tracking Ultrasound and sonomicrometry.</p> <p>Results</p> <p>We succeeded in automating the acquisition and analysis of sample data. Sample data was collected at a rate of 200 measurement pairs in 30 minutes. We found good agreement between Speckle Tracking Ultrasound and sonomicrometry in the in vitro model. Best agreement was 0.83 ± 0.70%. Worst agreement was -1.13 ± 6.46%.</p> <p>Conclusions</p> <p>It has been shown possible to automate a model that can be used for evaluating the in vitro accuracy and precision of ultrasound modalities measuring deformation. Sonomicrometry and Speckle Tracking Ultrasound had acceptable agreement.</p

Design and test of an automated version of the modified Jebsen test of hand function using Microsoft Kinect

Abstract Background The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor. Methods The MJT was administered twice to 11 chronic stroke subjects with varying degrees of hand function deficits. The test times of the MJT were evaluated manually by a therapist using a stopwatch, and automatically using the Microsoft Kinect sensor. The ground truth times were assessed based on inspection of the video-recordings. The agreement between the methods was evaluated along with the test-retest performance. Results The results from Bland-Altman analysis showed better agreement between the ground truth times and the automatic MJT time evaluations compared to the agreement between the ground truth times and the times estimated by the therapist. The results from the test-retest performance showed that the subjects significantly improved their performance in several subtests of the MJT, indicating a practice effect. Conclusions The results from the test showed that the Kinect can be used for automating the MJT

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex

The loss of dopamine (DA) in Parkinson’s is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1

Direction of the oblique medial malleolar osteotomy for exposure of the talus

A medial malleolar osteotomy is often indicated for operative exposure of posteromedial osteochondral defects and fractures of the talus. To obtain a congruent joint surface after refixation, the oblique osteotomy should be directed perpendicularly to the articular surface of the tibia at the intersection between the tibial plafond and medial malleolus. The purpose of this study was to determine this perpendicular direction in relation to the longitudinal tibial axis for use during surgery. Using anteroposterior mortise radiographs and coronal computed tomography (CT) scans of 46 ankles (45 patients) with an osteochondral lesion of the talus, two observers independently measured the intersection angle between the tibial plafond and medial malleolus. The bisector of this angle indicated the osteotomy perpendicular to the tibial articular surface. This osteotomy was measured relative to the longitudinal tibial axis on radiographs. Intraclass correlation coefficients (ICC) were calculated to assess reliability. The mean osteotomy was 57.2 ± 3.2° relative to the tibial plafond on radiographs and 56.5 ± 2.8 on CT scans. This osteotomy corresponded to 30.4 ± 3.7° relative to the longitudinal tibial axis. The intraobserver (ICC, 0.90-0.93) and interobserver (ICC, 0.65-0.91) reliability of these measurements were good to excellent. A medial malleolar osteotomy directed at a mean 30° relative to the tibial axis enters the joint perpendicularly to the tibial cartilage, and will likely result in a congruent joint surface after reductio

A Method to Quantify Mouse Coat-Color Proportions

Coat-color proportions and patterns in mice are used as assays for many processes such as transgene expression, chimerism, and epigenetics. In many studies, coat-color readouts are estimated from subjective scoring of individual mice. Here we show a method by which mouse coat color is quantified as the proportion of coat shown in one or more digital images. We use the yellow-agouti mouse model of epigenetic variegation to demonstrate this method. We apply this method to live mice using a conventional digital camera for data collection. We use a raster graphics editing program to convert agouti regions of the coat to a standard, uniform, brown color and the yellow regions of the coat to a standard, uniform, yellow color. We use a second program to quantify the proportions of these standard colors. This method provides quantification that relates directly to the visual appearance of the live animal. It also provides an objective analysis with a traceable record, and it should allow for precise comparisons of mouse coats and mouse cohorts within and between studies

Hippocampal state-dependent behavioral reflex to an identical sensory input in rats.

We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus) was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus) was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits

Cyclic and Sleep-Like Spontaneous Alternations of Brain State Under Urethane Anaesthesia

Background: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. Methodology/Principal Findings: Long-duration, multi-site forebrain field recordings were performed in urethaneanaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (,11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. Conclusions/Significance: Our results suggest that urethane promotes a condition of behavioural unconsciousness tha

Not All Are Lost: Interrupted Laboratory Monitoring, Early Death, and Loss to Follow-Up (LTFU) in a Large South African Treatment Program

Background: Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up. Methods: We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes. Results: In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39–0.62]. Conclusions: In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured