Genetic Characterization of Foot-and-Mouth Disease Viruses, Ethiopia, 1981�C2007

Foot-and-mouth disease (FMD) is endemic to sub-Saharan Africa. To further understand its complex epidemiology, which involves multiple virus serotypes and host species, we characterized the viruses recovered from FMD outbreaks in Ethiopia during 1981–2007. We detected 5 of the 7 FMDV serotypes (O, A, C, Southern African Territories [SAT] 1, and SAT 2). Serotype O predominated, followed by serotype A; type C was not recognized after 1983. Phylogenetic analysis of virus protein 1 sequences indicated emergence of a new topotype within serotype O, East Africa 4. In 2007, serotype SAT 1 was detected in Ethiopia and formed a new distinct topotype (IX), and serotype SAT 2 reappeared after an apparent gap of 16 years. The diversity of viruses highlights the role of this region as a reservoir for FMD virus, and their continuing emergence in Ethiopia will greatly affect spread and consequent control strategy of the disease on this continent.     

Spectrotemporal analysis of evoked and induced electroencephalographic responses in primary auditory cortex (A1) of the awake monkey

Electroencephalography is increasingly being used to probe the functional organization of auditory cortex. Modulation of the electroencephalographic (EEG) signal by tones was examined in primary auditory cortex (A1) of awake monkeys. EEG data were measured at 4 laminar depths defined by current source density profiles evoked by best frequency (BF) tones. Midlaminar multiunit activity was used to define the tuning characteristics of A1 sites. Presentation of BF tones increased EEG power across the range of frequencies examined (4-290 Hz), with maximal effects evident within the first 100 ms after stimulus onset. The largest relative increases in EEG power generally occurred at very high gamma frequency bands (130-210 Hz). Increases in EEG power for frequencies less than 70 Hz primarily represented changes in phase-locked activity, whereas increases at higher frequencies primarily represented changes in non-phase-locked activity. Power increases in higher gamma bands were better correlated with the A1 tonotopic organization than power increases in lower frequency bands. Results were similar across the 4 laminar depths examined. These findings highlight the value of examining high-frequency EEG components in exploring the functional organization of auditory cortex and may enhance interpretation of related studies in humans.     

Targeting Cancer-initiating Cells With Oncolytic Viruses

Recent studies in a variety of leukemias and solid tumors indicate that there is significant heterogeneity with respect to tumor-forming ability within a given population of tumor cells, suggesting that only a subpopulation of cells is responsible for tumorigenesis. These cells have been commonly referred to as cancer stem cells (CSCs) or cancer-initiating cells (CICs). CICs have been shown to be relatively resistant to conventional anticancer therapies and are thus thought to be responsible for disease relapse. As such, they represent a potentially critical therapeutic target. Oncolytic viruses are in clinical trials for cancer and kill cells through mechanisms different from conventional therapeutics. Because these viruses are not susceptible to the same pathways of drug or radiation resistance, it is important to learn whether CICs are susceptible to oncolytic virus infection. Here we review the available data regarding the ability of several different oncolytic virus types to target CICs for destruction.     

Electromyographic diagnosis of multifocal pyomyositis

Introduction: Multifocal pyomyositis is a rare inflammatory myopathy caused by bacterial infection and abscess formation in multiple skeletal muscles. To date, electromyography (EMG) of pyomyositis has not been reported. Methods: We describe the EMG findings of a patient with pathologically proven multifocal pyomyositis. Results and Conclusions: Muscles affected by pyomyositis demonstrate EMG features similar to those of other inflammatory myopathies. Other features such as acute entrapment neuropathy may exist concomitantly due to nerve compression from muscle abscess formation. Muscle Nerve 51 : 293–296, 2015     

Ophthalmic Presentation in the Emergency Department: A Case Report of a Girl With “Shimmering Eyes”

Background

Ophthalmic complaints are commonplace in the emergency department (ED) and are often initial presentations of a systemic illness. We present a 2-year-old girl presenting to the ED with ataxia and “shimmering” eyes.

Case Report

The patient was diagnosed with opsoclonus-myoclonus syndrome (OMS) involving involuntary, multi-vectorial (mostly horizontal), conjugate fast eye movements without intersaccadic intervals. The ophthalmic presentation led to a paraneoplastic work-up, which revealed an abdominal mass measuring 5.3 × 3.3 × 4.3 cm, suggestive of neuroblastoma. The patient's opsoclonus improved after a 5-day course of dexamethasone and intravenous immunoglobulin.

Why should an emergency physician be aware of this?

This case illustrates the importance of recognizing pathognomonic ophthalmic complaints in the ED. We present an overview of classic ophthalmic presentations associated with systemic illnesses.     

Pitch vs. spectral encoding of harmonic complex tones in primary auditory cortex of the awake monkey

Neuromagnetic studies in humans and single-unit studies in monkeys have provided conflicting views regarding the role of primary auditory cortex (A1) in pitch encoding. While the former support a topographic organization based on the pitch of complex tones, single-unit studies support the classical tonotopic organization of A1 defined by the spectral composition of the stimulus. It is unclear whether the incongruity of these findings is due to limitations of noninvasive recordings or whether the discrepancy genuinely reflects pitch representation based on population encoding. To bridge these experimental approaches, we examined neuronal ensemble responses in A1 of the awake monkey using auditory evoked potential (AEP), multiple-unit activity (MUA) and current source density (CSD) techniques. Macaque monkeys can perceive the missing fundamental of harmonic complex tones and therefore serve as suitable animal models for studying neural encoding of pitch. Pure tones and harmonic complex tones missing the fundamental frequency (f₀) were presented at 60 dB SPL to the ear contralateral to the hemisphere from which recordings were obtained. Laminar response profiles in A1 reflected the spectral content rather than the pitch (missing f₀) of the compound stimuli. These findings are consistent with single-unit data and indicate that the cochleotopic organization is preserved at the level of A1. Thus, it appears that pitch encoding of multi-component sounds is more complex than suggested by noninvasive studies, which are based on the assumption of a single dipole generator within the superior temporal gyrus. These results support a pattern recognition mechanism of pitch encoding based on a topographic representation of stimulus spectral composition at the level of A1.     

Neural mechanisms of rhythmic masking release in monkey primary auditory cortex: implications for models of auditory scene analysis

The ability to detect and track relevant acoustic signals embedded in a background of other sounds is crucial for hearing in complex acoustic environments. This ability is exemplified by a perceptual phenomenon known as "rhythmic masking release" (RMR). To demonstrate RMR, a sequence of tones forming a target rhythm is intermingled with physically identical "Distracter" sounds that perceptually mask the rhythm. The rhythm can be "released from masking" by adding "Flanker" tones in adjacent frequency channels that are synchronous with the Distracters. RMR represents a special case of auditory stream segregation, whereby the target rhythm is perceptually segregated from the background of Distracters when they are accompanied by the synchronous Flankers. The neural basis of RMR is unknown. Previous studies suggest the involvement of primary auditory cortex (A1) in the perceptual organization of sound patterns. Here, we recorded neural responses to RMR sequences in A1 of awake monkeys in order to identify neural correlates and potential mechanisms of RMR. We also tested whether two current models of stream segregation, when applied to these responses, could account for the perceptual organization of RMR sequences. Results suggest a key role for suppression of Distracter-evoked responses by the simultaneous Flankers in the perceptual restoration of the target rhythm in RMR. Furthermore, predictions of stream segregation models paralleled the psychoacoustics of RMR in humans. These findings reinforce the view that preattentive or "primitive" aspects of auditory scene analysis may be explained by relatively basic neural mechanisms at the cortical level.     

Learning reward timing in cortex through reward dependent expression of synaptic plasticity

The ability to represent time is an essential component of cognition but its neural basis is unknown. Although extensively studied both behaviorally and electrophysiologically, a general theoretical framework describing the elementary neural mechanisms used by the brain to learn temporal representations is lacking. It is commonly believed that the underlying cellular mechanisms reside in high order cortical regions but recent studies show sustained neural activity in primary sensory cortices that can represent the timing of expected reward. Here, we show that local cortical networks can learn temporal representations through a simple framework predicated on reward dependent expression of synaptic plasticity. We assert that temporal representations are stored in the lateral synaptic connections between neurons and demonstrate that reward-modulated plasticity is sufficient to learn these representations. We implement our model numerically to explain reward-time learning in the primary visual cortex (V1), demonstrate experimental support, and suggest additional experimentally verifiable predictions.     

Prophylactic COX 2 inhibitor: an end to the Yom Kippur headache

INTRODUCTION: Religious fasting is associated with headache. This has been documented as "Yom Kippur Headache" and "First of Ramadan Headache." The Cox2 inhibitor, rofecoxib, has been reported effective in preventing perimenstrual migraine and in preventing recurrence of migraine. Given its 17 hour half-life, we undertook this study to see whether 50 mg rofecoxib taken just prior to the 25 hour Yom Kippur fast would be effective in preventing headache. METHODS: We performed a double-blind randomized prospective trial of rofecoxib 50 mg versus placebo, taken just prior to the onset of fasting, Yom Kippur 2004. Healthy adults aged 18 to 65 were enrolled from the community and from hospital staff. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast, headache intensity, general ease of fasting, and side effects. RESULTS: We sent out 170 forms of which 105 were completed and returned. Of those subjects receiving rofecoxib (n = 53), 10 or 18.9% versus 34 or 65.4% of the placebo group (n = 52) had headache at some point during the fast (P < .0001). Severity of headache in the treatment group was significantly less for the treatment group (3.45 vs 6.29 on a visual analog scale of 10 (P= .009)). None of those receiving rofecoxib reported a "more difficult than usual fast" whereas the distribution of difficult to easy fast among the placebo group was more even. CONCLUSION: Rofecoxib 50 mg taken prior to a 25-hour ritual fast prevents and attenuates fasting headache.     

Operant matching is a generic outcome of synaptic plasticity based on the covariance between reward and neural activity

The probability of choosing an alternative in a long sequence of repeated choices is proportional to the total reward derived from that alternative, a phenomenon known as Herrnstein's matching law. This behavior is remarkably conserved across species and experimental conditions, but its underlying neural mechanisms still are unknown. Here, we propose a neural explanation of this empirical law of behavior. We hypothesize that there are forms of synaptic plasticity driven by the covariance between reward and neural activity and prove mathematically that matching is a generic outcome of such plasticity. Two hypothetical types of synaptic plasticity, embedded in decision-making neural network models, are shown to yield matching behavior in numerical simulations, in accord with our general theorem. We show how this class of models can be tested experimentally by making reward not only contingent on the choices of the subject but also directly contingent on fluctuations in neural activity. Maximization is shown to be a generic outcome of synaptic plasticity driven by the sum of the covariances between reward and all past neural activities.