Hepatitis B virus e antigen loss during adefovir dipivoxil therapy is associated with enhanced virus-specific CD4+ T-cell reactivity

Weak T-cell reactivity to hepatitis B virus (HBV) is thought to be the dominant cause for chronic HBV infection. Treatment with adefovir dipivoxil (ADV) increases the rate of HBV e antigen (HBeAg) loss; however, the immune mechanisms associated with this treatment response are not understood. Serial analysis of HBV-specific CD4+ T-cell reactivity was performed during 48 weeks of therapy with ADV and correlated with treatment outcome for 19 HBeAg-positive patients receiving ADV (n = 13) or the placebo (n = 6). We tested T-cell reactivity to HBV at seven protocol time points by proliferation, cytokine production, and enzyme-linked immunospot assays. A panel of serum cytokines was quantitated by cytokine bead array. ADV-treated patients showed increased CD4+ T-cell responses to HBV and lower serum levels of cytokines compared to those of placebo-treated patients. Enhanced CD4+ T-cell reactivity to HBV, which peaked at treatment week 16, was confined to a subgroup of ADV-treated patients who achieved greater viral suppression (5.3 +/- 0.3 log(10) copies/ml [mean +/- standard error of the mean {SEM}] serum HBV DNA reduction from baseline) and HBeAg loss, but not to ADV-treated patients with moderate (3.4 +/- 0.2 log(10) copies/ml [mean +/- SEM]) viremia reduction who remained HBeAg positive or to patients receiving the placebo. In conclusion, T-cell reactivity to HBV increases in a proportion of ADV-treated patients and is associated with greater suppression of HBV replication and HBeAg loss.     

Sensorimotor cortical activation in patients with sleep bruxism

Sleep bruxism is assumed to be triggered by a dysfunctional subcortical and cortical network. This study investigates sensorimotor cortical activation in patients with sleep bruxism during clenching and chewing. Nine polysomnographically diagnosed patients and nine healthy control subjects underwent magnetoencephalography (MEG). During clenching and chewing, patients with bruxism revealed significantly larger event-related desynchronization in the somatomotor area (Brodmann area 4) than healthy subjects. Group differences in the muscle activity were ruled out by electromyography (EMG) assessments during MEG. This result might be regarded as a consequence of increased sensorimotor cortical representation of the tongue and chewing musculature due to an enhanced parafunctional muscle activity in bruxers potentially triggered by occlusal factors. Alternatively, a secondary activation of cortical structures during sleep bruxism in the context of an activated network of subcortical and cortical structures might lead to increased cortical representation of the chewing musculature via use dependent plasticity.     

Clonal expansions of CD8<Superscript>+</Superscript> T cells in latently HSV-1-infected human trigeminal ganglia

Herpes simplex virus type 1 latency in trigeminal ganglia (TG) is accompanied by a chronic immune cell infiltration. The aim of this study was to analyse the T-cell receptor β-chain repertoire in latently HSV-1 infected human TG. Using complementarity-determining region 3 spectratyping, 74 expanded β-chain sequences were identified in five TG. No clone appeared in more than one subject. Similar clones were present in the right and the left TG of two subjects. This indicates that these T cells are primed in the periphery and recognise the same antigen in the TG of both sides.     

Botulinum toxin type A and B for the reduction of hypersalivation in children with neurological disorders: a focus on effectiveness and therapy adherence

Botulinum toxin (BoNT) is an established treatment option to reduce hypersalivation in children with chronic neurological disorders. Objective of this study was (1) to discriminate differences in efficacy and safety of repeated interventions using BoNT with a focus on different preparations used and (2) to look for effectiveness and treatment adherence from a qualitative research perspective in this single-center cohort study. We prospectively assessed goal attainment scaling, drooling severity and frequency score and the number of towels/day before, and 4 to 8 weeks after intervention. A parent questionnaire assessed therapy-related effects on quality of life retrospectively. A total of 19 out of 34 patients received repeated injections of BoNT (106 total). Mean dose: 95 units onabotulinumtoxinA (Botox?), 2383 units rimabotulinumtoxinB (Neuro-/Myobloc?). Outcome parameters showed a distinct reduction in all treatment groups with a higher efficacy of riB. The child's need for care was reduced in 79% and social interaction improved in 84%. Main reason for discontinuation was "not enough effect" and "formation of antibodies." riB showed to be more effective in reducing hypersalivation, but antibody-formation seems to be clinically relevant. Despite clinical efficacy treatment adherence is influenced by personal and environmental factors of parents and caretakers balancing the short-term clinical benefit versus the burden of intervention.     

Dysphagia in patients with acute striatocapsular hemorrhage

Dysphagia is found in up to 80% of acute stroke patients. To date most studies have focused on ischemic stroke only. Little is known about the incidence and pattern of dysphagia in hemorrhagic stroke. Here we describe the characteristics of dysphagia in patients with striatocapsular hemorrhage. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) was carried out in 30 patients with acute striatocapsular hemorrhage. Dysphagia was classified according to the six-point Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) within 72 h after admission. Lesion volume, hemisphere and occurrence of ventricular rupture were determined from computer tomography scans. Data on initial NIH-SS, clinical symptoms, need for endotracheal intubation, diagnosis of pneumonia and feeding status on discharge were recorded. Swallowing impairment was observed in 76.7% of patients (n = 23). Mean FEDSS score was 3.1 ± 1.5. Main findings were penetration or aspiration of liquids as well as leakage to valleculae and piriform sinus. Incidence of pneumonia was 30.0% (n = 9). Age, NIH-SS and hematoma volume did not correlate with dysphagia severity. None of the clinical characteristics was predictive for dysphagia. On discharge after 12.9 ± 5.3 days, a two-point improvement on the FEDSS was seen in seven patients, (30.4%) and five patients (21.7%) had gained at least one point. In striatocapsular hemorrhage, dysphagia is a common and so far underrecognized symptom. FEES results indicate predominant impairment of oral motor control. Swallowing impairment is not related to other clinical deficits, stroke severity or lesion characteristics. Thus, detailed dysphagia assessment is indicated in all cases.     

Social fear conditioning: a novel and specific animal model to study social anxiety disorder

Social anxiety disorder (SAD) is a major health concern with high lifetime prevalence. The current medication is rather unspecific and, despite considerable efforts, its efficacy is still unsatisfactory. However, there are no appropriate and specific animal models available to study the underlying etiology of the disorder. Therefore, we aimed to establish a model of specific social fear in mice and use this social fear conditioning (SFC) model to assess the therapeutic efficacy of the benzodiazepine diazepam and of the antidepressant paroxetine; treatments currently used for SAD patients. We show that by administering electric foot shocks (2-5, 1?s, 0.7?mA) during the investigation of a con-specific, the investigation of unfamiliar con-specifics was reduced for both the short- and long-term, indicating lasting social fear. The induced fear was specific to social stimuli and did not lead to other behavioral alterations, such as fear of novelty, general anxiety, depression, and impaired locomotion. We show that social fear was dose-dependently reversed by acute diazepam, at doses that were not anxiolytic in a non-social context, such as the elevated plus maze. Finally, we show that chronic paroxetine treatment reversed social fear. All in all, we demonstrated robust social fear after exposure to SFC in mice, which was reversed with both acute benzodiazepine and chronic antidepressant treatment. We propose the SFC model as an appropriate animal model to identify the underlying etiology of SAD and possible novel treatment approaches.