Development of a species-specific coproantigen ELISA for human taenia solium taeniasis

Taenia solium causes human neurocysticercosis and is endemic in underdeveloped countries where backyard pig keeping is common. Microscopic fecal diagnostic methods for human T. solium taeniasis are not very sensitive, and Taenia saginata and Taenia solium eggs are indistinguishable under the light microscope. Coproantigen (CoAg) ELISA methods are very sensitive, but currently only genus (Taenia) specific. This paper describes the development of a highly species-specific coproantigen ELISA test to detect T. solium intestinal taeniasis. Sensitivity was maintained using a capture antibody of rabbit IgG against T. solium adult whole worm somatic extract, whereas species specificity was achieved by utilization of an enzyme-conjugated rabbit IgG against T. solium adult excretory-secretory (ES) antigen. A known panel of positive and negative human fecal samples was tested with this hybrid sandwich ELISA. The ELISA test gave 100% specificity and 96.4% sensitivity for T. solium tapeworm carriers (N = 28), with a J index of 0.96. This simple ELISA incorporating anti-adult somatic and anti-adult ES antibodies provides the first potentially species-specific coproantigen test for human T. solium taeniasis

Spectropolarimetry of Supernovae

Overwhelming evidence has accumulated in recent years that supernova explosions are intrinsically 3-dimensional phenomena with significant departures from spherical symmetry. We review the evidence derived from spectropolarimetry that has established several key results: virtually all supernovae are significantly aspherical near maximum light; core-collapse supernovae behave differently than thermonuclear (Type Ia) supernovae; the asphericity of core-collapse supernovae is stronger in the inner layers showing that the explosion process itself is strongly aspherical; core-collapse supernovae tend to establish a preferred direction of asymmetry; the asphericity is stronger in the outer layers of thermonuclear supernovae providing constraints on the burning process. We emphasize the utility of the Q/U plane as a diagnostic tool and revisit SN 1987A and SN 1993J in a contemporary context. An axially-symmetric geometry can explain many basic features of core-collapse supernovae, but significant departures from axial symmetry are needed to explain most events. We introduce a spectropolarimetry type to classify the range of behavior observed in polarized supernovae. Understanding asymmetries in supernovae is important for phenomena as diverse as the origins of gamma-ray bursts and the cosmological applications of Type Ia supernovae in studies of the dark energy content of the universe.Comment: Draft of Annual Review article prior to final copy editing; 85 pages, 13 figures, 1 tabl

Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice

BACKGROUND AND PURPOSE: Oxaliplatin is a platinum‐based chemotherapeutic drug used as a first‐line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side‐effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility. EXPERIMENTAL APPROACH: Oxaliplatin (3 mg·kg(−1) per day) was administered in vivo to Balb/c mice intraperitoneally three times a week. The distal colon was collected at day 14 of treatment. Immunohistochemistry was performed in wholemount preparations of submucosal and myenteric ganglia. Neuromuscular transmission was studied by intracellular electrophysiology. Circular muscle tone was studied by force transducers. Colon propulsive activity studied in organ bath experiments and faeces were collected to measure water content. KEY RESULTS: Chronic in vivo oxaliplatin treatment resulted in increased formation of reactive oxygen species (O(2)ˉ), nitration of proteins, mitochondrial membrane depolarisation resulting in the release of cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment enhanced NO‐mediated inhibitory junction potentials and altered the response of circular muscles to the NO donor, sodium nitroprusside. It also reduced the frequency of colonic migrating motor complexes and decreased circular muscle tone, effects reversed by the NO synthase inhibitor, Nω‐Nitro‐L‐arginine. CONCLUSION AND IMPLICATIONS: Our study is the first to provide evidence that oxidative stress is a key player in enteric neuropathy and colonic dysmotility leading to symptoms of chronic constipation observed in oxaliplatin‐treated mice

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.We thank Daniel Abebe for mouse colony maintenance and Kurt Auville for additional assistance with confocal imaging. We thank UNC Vector Core and Ed Boyden, MIT, Cambridge, MA, USA for generously providing AAV9-syn-Chrimson-TdTomato and AAV9-syn-Chronos-GFP. This work was supported by an intramural award to C.J.M. from the Eunice Kennedy–Shriver National Institute of Child Health and Human Development and a Competitive Fellowship Award to J.C.W. from the National Institute of Neurological Disorders and Strok

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

A survey of assistive technologies and applications for blind users on mobile platforms: a review and foundation for research

This paper summarizes recent developments in audio and tactile feedback based assistive technologies targeting the blind community. Current technology allows applications to be efficiently distributed and run on mobile and handheld devices, even in cases where computational requirements are significant. As a result, electronic travel aids, navigational assistance modules, text-to-speech applications, as well as virtual audio displays which combine audio with haptic channels are becoming integrated into standard mobile devices. This trend, combined with the appearance of increasingly user- friendly interfaces and modes of interaction has opened a variety of new perspectives for the rehabilitation and training of users with visual impairments. The goal of this paper is to provide an overview of these developments based on recent advances in basic research and application development. Using this overview as a foundation, an agenda is outlined for future research in mobile interaction design with respect to users with special needs, as well as ultimately in relation to sensor-bridging applications in genera

The episodic random utility model unifies time trade-off and discrete choice approaches in health state valuation

ABSTRACT: BACKGROUND: To present an episodic random utility model that unifies time trade-off and discrete choice approaches in health state valuation. METHODS: First, we introduce two alternative random utility models (RUMs) for health preferences: the episodic RUM and the more common instant RUM. For the interpretation of time trade-off (TTO) responses, we show that the episodic model implies a coefficient estimator, and the instant model implies a mean slope estimator. Secondly, we demonstrate these estimators and the differences between the estimates for 42 health states using TTO responses from the seminal Measurement and Valuation in Health (MVH) study conducted in the United Kingdom. Mean slopes are estimates with and without Dolan's transformation of worse-than-death (WTD) responses. Finally, we demonstrate an exploded probit estimator, an extension of the coefficient estimator for discrete choice data that accommodates both TTO and rank responses. RESULTS: By construction, mean slopes are less than or equal to coefficients, because slopes are fractions and, therefore, magnify downward errors in WTD responses. The Dolan transformation of WTD responses causes mean slopes to increase in similarity to coefficient estimates, yet they are not equivalent (i.e., absolute mean difference = 0.179). Unlike mean slopes, coefficient estimates demonstrate strong concordance with rank-based predictions (Lin's rho = 0.91). Combining TTO and rank responses under the exploded probit model improves the identification of health state values, decreasing the average width of confidence intervals from 0.057 to 0.041 compared to TTO only results. CONCLUSION: The episodic RUM expands upon the theo

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state