Case Report: Efavirenz as a cause of ataxia in children

Acute ataxia in childhood is often caused by toxin ingestion. With the increasing number of paediatric patients on antiretroviral medication, we observe more side-effects of these drugs. Acute ataxia is defined as unsteadiness of walking or fine motor movement of <72 hours. The most common causes are postinfectious acute cerebellar ataxia, toxin ingestion and Guillain-Barré syndrome. However, the possibility of a mass lesion must always be excluded. Reported neurological abnormalities in HIV-positive children range from 10% to 68%. A South African study found the prevalence of neurological complications to be 59%, the most common of which were HIV encephalopathy and long-tract motor signs; however, no cases of cerebellar dysfunction were documented. Ataxia rarely ocurs in an HIV-positive person, the chronic sequelae being neurocognitive impairment and polyneuropathy. Ataxia in the setting of HIV is generally secondary to an infectious, vascular or neoplastic cerebellar lesion. However, most infections are opportunistic and unlikely to occur when CD4 levels are adequate. The vascular or mass lesions are readily excluded with neuro-imaging. We report two cases of efavirenz toxicity that caused ataxia. We treated two children who presented in a 1-month period, which highlighted an important differential to consider in HIV-positive paediatric patients presenting with ataxia

Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain’s inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the “genetic distance” statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus

Auditory cognition and perception of action video game players

A training method to improve speech hearing in noise has proven elusive, with most methods failing to transfer to untrained tasks. One common approach to identify potentially viable training paradigms is to make use of cross-sectional designs. For instance, the consistent finding that people who chose to avidly engage with action video games as part of their normal life also show enhanced performance on non-game visual tasks has been used as a foundation to test the causal impact of such game play via true experiments (e.g., in more translational designs). However, little work has examined the association between action video game play and untrained auditory tasks, which would speak to the possible utility of using such games to improve speech hearing in noise. To examine this possibility, 80 participants with mixed action video game experience were tested on a visual reaction time task that has reliably shown superior performance in action video game players (AVGPs) compared to non-players (≤ 5 h/week across game categories) and multi-genre video game players (> 5 h/week across game categories). Auditory cognition and perception were tested using auditory reaction time and two speech-in-noise tasks. Performance of AVGPs on the visual task replicated previous positive findings. However, no significant benefit of action video game play was found on the auditory tasks. We suggest that, while AVGPs interact meaningfully with a rich visual environment during play, they may not interact with the games’ auditory environment. These results suggest that far transfer learning during action video game play is modality-specific and that an acoustically relevant auditory environment may be needed to improve auditory probabilistic thinking

On the crossing relation in the presence of defects

The OPE of local operators in the presence of defect lines is considered both in the rational CFT and the $c>25$ Virasoro (Liouville) theory. The duality transformation of the 4-point function with inserted defect operators is explicitly computed. The two channels of the correlator reproduce the expectation values of the Wilson and 't Hooft operators, recently discussed in Liouville theory in relation to the AGT conjecture.Comment: TEX file with harvmac; v3: JHEP versio

A new species from Tasmania of the freshwater hoplonomertean, Potamonemertes

A new species of freshwater hoplonemertean, Potamonemertes gibsoni, is described from lakes In Tasmania and its relationship to the type species from New Zealand and to the terrestrial nemerteans of the region is discusse

Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance.

In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB

Boundary operators in minimal Liouville gravity and matrix models

We interpret the matrix boundaries of the one matrix model (1MM) recently constructed by two of the authors as an outcome of a relation among FZZT branes. In the double scaling limit, the 1MM is described by the (2,2p+1) minimal Liouville gravity. These matrix operators are shown to create a boundary with matter boundary conditions given by the Cardy states. We also demonstrate a recursion relation among the matrix disc correlator with two different boundaries. This construction is then extended to the two matrix model and the disc correlator with two boundaries is compared with the Liouville boundary two point functions. In addition, the realization within the matrix model of several symmetries among FZZT branes is discussed.Comment: 26 page

Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in vitro

Aims: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype. Isolevuglandins (IsoLG) are a family of acyclic γ-ketoaldehydes formed through oxidation of arachidonic acid or as by-products of the cyclooxygenase pathway. IsoLGs are highly reactive aldehydes which are efficient at forming protein adducts and cross-links at concentrations 100-fold lower than 4-hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG could induce activation of HSC. / Results: Primary human HSC were exposed to 15-E2-IsoLG for up to 48 hours. Exposure to 5 μM 15-E2-IsoLG in HSCs promoted cytotoxicity and apoptosis. At non-cytotoxic doses (50 pM-500 nM) 15-E2-IsoLG promoted HSC activation, indicated by increased expression of α-SMA, sustained activation of ERK and JNK signaling pathways, and increased mRNA and/or protein expression of cytokines and chemokines, which was blocked by inhibitors of JNK and NF-kB. In addition, IsoLG promoted formation of reactive oxygen species, and induced an early activation of ER stress, followed by autophagy. Inhibition of autophagy partially reduced the pro-inflammatory effects of IsoLG, suggesting that it might serve as a cytoprotective response. / Innovation: This study is the first to describe the biological effects of IsoLG in primary HSC, the main drivers of hepatic fibrosis. / Conclusions: IsoLGs represent a newly identified class of activators of HSC in vitro, which are biologically active at concentrations as low as 500 pM, and are particularly effective at promoting a pro-inflammatory response and autophagy

Fast Ensemble Smoothing

Smoothing is essential to many oceanographic, meteorological and hydrological applications. The interval smoothing problem updates all desired states within a time interval using all available observations. The fixed-lag smoothing problem updates only a fixed number of states prior to the observation at current time. The fixed-lag smoothing problem is, in general, thought to be computationally faster than a fixed-interval smoother, and can be an appropriate approximation for long interval-smoothing problems. In this paper, we use an ensemble-based approach to fixed-interval and fixed-lag smoothing, and synthesize two algorithms. The first algorithm produces a linear time solution to the interval smoothing problem with a fixed factor, and the second one produces a fixed-lag solution that is independent of the lag length. Identical-twin experiments conducted with the Lorenz-95 model show that for lag lengths approximately equal to the error doubling time, or for long intervals the proposed methods can provide significant computational savings. These results suggest that ensemble methods yield both fixed-interval and fixed-lag smoothing solutions that cost little additional effort over filtering and model propagation, in the sense that in practical ensemble application the additional increment is a small fraction of either filtering or model propagation costs. We also show that fixed-interval smoothing can perform as fast as fixed-lag smoothing and may be advantageous when memory is not an issue