Sensitivity of a modified version of the ARCHITECT Anti-HCV test in detecting samples with immunoblot-confirmed, low-level antibody to hepatitis C virus.

BACKGROUND AND OBJECTIVES: Compliance with current regulations regarding the prevention of hepatitis C virus (HCV) transmission in the blood transfusion setting requires the use of sensitive assays for HCV antibody (anti-HCV) detection, which should, ideally, identify any donor having had prior contact with the virus. Therefore, low-level anti-HCV positive blood units should be detected by the screening assays, even those reflecting a past and resolved infection. To assess the sensitivity of two versions of an automated chemiluminescent microparticle immunoassay (CMIA) for anti-HCV screening (ARCHITECT Anti-HCV), 113 single serum samples containing low levels of anti-HCV, assessed by two immunoblot tests, were selected from 3686 samples received for confirmation of HCV infection by a reference laboratory over a 2-year period. MATERIALS AND METHODS: The panel included 17 samples with HCV RNA detected by the polymerase chain reaction (PCR) and 96 PCR negative samples with either positive or indeterminate (anti-Core and anti-NS3 alone) results by immunoblot. RESULTS: All but 13 specimens (100/113, 88.5%) were detected by the current version of the ARCHITECT Anti-HCV assay and 10 additional samples (110/113, 97.3%) tested positive in a modified version of the test. CONCLUSION: The results showed that the modification introduced in the ARCHITECT Anti-HCV assay achieves a significant sensitivity improvement including samples with low-level anti-HCV which are either PCR positive or negative.     

Neural modelling of the semantic predictability gain under challenging listening conditions

When speech intelligibility is reduced, listeners exploit constraints posed by semantic context to facilitate comprehension. The left angular gyrus (AG) has been argued to drive this semantic predictability gain. Taking a network perspective, we ask how the connectivity within language‐specific and domain‐general networks flexibly adapts to the predictability and intelligibility of speech. During continuous functional magnetic resonance imaging (fMRI), participants repeated sentences, which varied in semantic predictability of the final word and in acoustic intelligibility. At the neural level, highly predictable sentences led to stronger activation of left‐hemispheric semantic regions including subregions of the AG (PGa, PGp) and posterior middle temporal gyrus when speech became more intelligible. The behavioural predictability gain of single participants mapped onto the same regions but was complemented by increased activity in frontal and medial regions. Effective connectivity from PGa to PGp increased for more intelligible sentences. In contrast, inhibitory influence from pre‐supplementary motor area to left insula was strongest when predictability and intelligibility of sentences were either lowest or highest. This interactive effect was negatively correlated with the behavioural predictability gain. Together, these results suggest that successful comprehension in noisy listening conditions relies on an interplay of semantic regions and concurrent inhibition of cognitive control regions when semantic cues are available.     

Clostridium difficile toxins A and B directly stimulate human mast cells

Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects of C. difficile toxins on mast cells independently of the tissue context.     

Neural correlates of intonation and lexical tone in tonal and non‐tonal language speakers

Intonation, the modulation of pitch in speech, is a crucial aspect of language that is processed in right‐hemispheric regions, beyond the classical left‐hemispheric language system. Whether or not this notion generalises across languages remains, however, unclear. Particularly, tonal languages are an interesting test case because of the dual linguistic function of pitch that conveys lexical meaning in form of tone, in addition to intonation. To date, only few studies have explored how intonation is processed in tonal languages, how this compares to tone and between tonal and non‐tonal language speakers. The present fMRI study addressed these questions by testing Mandarin and German speakers with Mandarin material. Both groups categorised mono‐syllabic Mandarin words in terms of intonation, tone, and voice gender. Systematic comparisons of brain activity of the two groups between the three tasks showed large cross‐linguistic commonalities in the neural processing of intonation in left fronto‐parietal, right frontal, and bilateral cingulo‐opercular regions. These areas are associated with general phonological, specific prosodic, and controlled categorical decision‐making processes, respectively. Tone processing overlapped with intonation processing in left fronto‐parietal areas, in both groups, but evoked additional activity in bilateral temporo‐parietal semantic regions and subcortical areas in Mandarin speakers only. Together, these findings confirm cross‐linguistic commonalities in the neural implementation of intonation processing but dissociations for semantic processing of tone only in tonal language speakers.     

Measurement of intraocular pressure using the Tono-Pen in comparison with Goldmann applanation tonometry - a clinical study in 100 eyes

BACKGROUND: In clinical practice ophthalmologists often need a tonometer which is independent of a slit lamp. Such a hand-held device is the Tono-Pen. We compared the precision of two equal Tono-Pens with Goldmann applanation tonometry. MATERIAL AND METHODS: Measurement of intraocular pressure (IOP) was done in 100 eyes of 51 patients (mean age 63 +/- 15 years) suffering from ocular hypertension or glaucoma. According to a random table either the right or left eye was measured using Goldmann tonometer first and the Tono-Pen second. For the other eye the measurement was reversed. One of the two equal Tono-Pens (Solan/USA) was used according to a second random table. Three measurements were obtained with each instrument on both eyes within 15 minutes subsequently. Patients were placed in an upright position for all measurements. RESULTS: Even for well-trained ophthalmologists a learning curve of approximately 10 measurements was observed using the Tono-Pen. The Tono-Pen measured an average IOP of 16.9 mm Hg in all 100 eyes. The Goldmann tonometer measured an average IOP of 17.7 mm Hg. The difference was not statistically significant. The standard deviation for all measurements was better for the Tono-Pen (4.7 mm Hg vs 5.8 mm Hg for Goldmann tonometer). No reduction of the IOP after Tono-Pen measurement was observed (in contrast to the Goldmann tonometer). The reproducibility of the Tono-Pen on the same eye was inferior to the Goldmann tonometer by a factor of 2. There was an almost significant difference in reproducibility between two equal Tono-Pens. CONCLUSIONS: Measurement of IOP with the Tono-Pen is comparable to Goldmann applanation tonometry if an average of 3 measurements is used. The difference between two equal Tono-Pens indicates the need for improvement of the quality check during production.