Recording the tactile P300 with the cEEGrid for potential use in a brain-computer interface.

Brain-computer interfaces (BCIs) are scientifically well established, but they rarely arrive in the daily lives of potential end-users. This could be in part because electroencephalography (EEG), a prevalent method to acquire brain activity for BCI operation, is considered too impractical to be applied in daily life of end-users with physical impairment as an assistive device. Hence, miniaturized EEG systems such as the cEEGrid have been developed. While they promise to be a step toward bridging the gap between BCI development, lab demonstrations, and home use, they still require further validation. Encouragingly, the cEEGrid has already demonstrated its ability to record visually and auditorily evoked event-related potentials (ERP), which are important as input signal for many BCIs. With this study, we aimed at evaluating the cEEGrid in the context of a BCI based on tactually evoked ERPs. To compare the cEEGrid with a conventional scalp EEG, we recorded brain activity with both systems simultaneously. Forty healthy participants were recruited to perform a P300 oddball task based on vibrotactile stimulation at four different positions. This tactile paradigm has been shown to be feasible for BCI repeatedly but has never been tested with the cEEGrid. We found distinct P300 deflections in the cEEGrid data, particularly at vertical bipolar channels. With an average of 63%, the cEEGrid classification accuracy was significantly above the chance level (25%) but significantly lower than the 81% reached with the EEG cap. Likewise, the P300 amplitude was significantly lower (cEEGrid R2-R7: 1.87 µV, Cap Cz: 3.53 µV). These results indicate that a tactile BCI using the cEEGrid could potentially be operated, albeit with lower efficiency. Additionally, participants' somatosensory sensitivity was assessed, but no correlation to the accuracy of either EEG system was shown. Our research contributes to the growing amount of literature comparing the cEEGrid to conventional EEG systems and provides first evidence that the tactile P300 can be recorded behind the ear. A BCI based on a thus simplified EEG system might be more readily accepted by potential end-users, provided the accuracy can be substantially increased, e.g., by training and improved classification.

Identifying potential training factors in a vibrotactile P300-BCI.

Brain-computer interfaces (BCI) often rely on visual stimulation and feedback. Potential end-users with impaired vision, however, cannot use these BCIs efficiently and require a non-visual alternative. Both auditory and tactile paradigms have been developed but are often not sufficiently fast or accurate. Thus, it is particularly relevant to investigate if and how users can train and improve performance. We report data from 29 healthy participants who trained with a 4-choice tactile P300-BCI during five sessions. To identify potential training factors, we pre-post assessed the robustness of the BCI performance against increased workload in a dual task condition and determined the participants' somatosensory sensitivity thresholds with a forced-choice intensity discrimination task. Accuracy (M = 79.2% to 92.0%) and tactually evoked P300 amplitudes increased significantly, confirming successful training. Pre-post somatosensory sensitivity increased, and workload decreased significantly, but results of the dual task condition remained inconclusive. The present study confirmed the previously reported feasibility and trainability of our tactile BCI paradigm within a multi-session design. Importantly, we provide first evidence of improvement in the somatosensory system as a potential mediator for the observed training effects.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Cross-sectional computed tomography assessment of exophthalmos in comparison to clinical measurement via Hertel exophthalmometry.

To determine protrusion assessment via Hertel exophthalmometry in comparison to measurement on Computed Tomography (CT). Retrospective blinded comparison of exophthalmos measurements on axial CT with Hertel exophthalmometry measurements in 113 patients. Descriptive statistics, Pearson's correlation, Kruskal-Wallis and Mann-Whitney-U test were employed for analysis. Mean difference of proptosis between both eyes was 2.4 (SD ± 2.0) mm in CT and 2.2 (SD ± 2.0) mm in Hertel measurements. Proptosis of 0-2 mm was present in 69 (61.1%), and > 2 mm in 42 (38.9%) patients in Hertel measurements (CT 64 (56.6%), and 49 (43.4%) patients). Pearson's coefficient showed a correlation of 0.793 between both methods (p < 0.001). Accuracy of Hertel measurement depended significantly from the examiners' experience (< 5 (group 1), 5-15 (2) and > 25 (3) years, p = 0.042, Kruskal-Wallis analysis; p = 0.086 group 1 vs. 2, p = 0.014 group 1 vs. 3, p = 0.688 group 2 vs. 3, Mann-Whitney-U-test), reflected by levels of Pearson's coefficient (correlation of both methods 0.691 (group 1), 0.837 (2) and 0.831 (3), respectively, p = 0.01). Generally, Hertel exophthalmometry correlates well with CT measurements. Subgroup analysis confirmed a superior quality of Hertel measurements in favour of experienced examiners. Teaching of accurate Hertel exophthalmometry should be improved. Assessment of exophthalmos using standardized criteria should be implemented for imaging reports.

Stimulus modality influences session-to-session transfer of training effects in auditory and tactile streaming-based P300 brain-computer interfaces.

Despite recent successes, patients suffering from locked-in syndrome (LIS) still struggle to communicate using vision-independent brain-computer interfaces (BCIs). In this study, we compared auditory and tactile BCIs, regarding training effects and cross-stimulus-modality transfer effects, when switching between stimulus modalities. We utilized a streaming-based P300 BCI, which was developed as a low workload approach to prevent potential BCI-inefficiency. We randomly assigned 20 healthy participants to two groups. The participants received three sessions of training either using an auditory BCI or using a tactile BCI. In an additional fourth session, BCI versions were switched to explore possible cross-stimulus-modality transfer effects. Both BCI versions could be operated successfully in the first session by the majority of the participants, with the tactile BCI being experienced as more intuitive. Significant training effects were found mostly in the auditory BCI group and strong evidence for a cross-stimulus-modality transfer occurred for the auditory training group that switched to the tactile version but not vice versa. All participants were able to control at least one BCI version, suggesting that the investigated paradigms are generally feasible and merit further research into their applicability with LIS end-users. Individual preferences regarding stimulus modality should be considered.

Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

Week-long visuomotor coordination and relaxation trainings do not increase sensorimotor rhythms (SMR) based brain-computer interface performance.

Brain-computer interfaces (BCI) translate brain activity into control signals or commands for a device. Motor imagery of the limbs allows for modulating the sensorimotor rhythms (SMR), but there are up to 30% of the participants for whom electroencephalography (EEG) based SMR-BCI cannot detect any imagery-related changes. Individual variables, such as ability to concentrate on a task and error duration in a two-hand visuomotor coordination (VMC) task have been previously found to predict accuracy in an SMR-BCI. A first study attempted to substantiate those predictors by introducing a 30 min relaxation or VMC training period prior to an SMR-BCI session, but performance did not increase when compared to a control group. As the predictor training may have been too short, we applied 4 such training sessions on consecutive days in the current study. In a pre-post design, SMR-BCI accuracy of n = 39 participants increased from session 1 before to session 2 after the predictor training. While the manipulation of the predictor variables was successful, there was no effect on SMR-BCI performance. BCI accuracy correlated positively with the neurophysiological SMR predictor identified by Blankertz et al. [3], consolidating its predictive value, and with the state mindfulness scale. No other psychological predictor could be identified or replicated. Further studies should therefore focus more on delineating (partially) replicated or potential predictors such as VMC or mindfulness to help refining a sound model to predict SMR-BCI accuracy.

A Prospective, Controlled, Multicenter Study to Evaluate the Clinical Outcome of Implant Treatment in Women with Osteoporosis/Osteopenia: 5-Year Results.

The impact of osteoporosis on implant treatment is still a matter of debate in the scientific community, as it may possibly lead to higher failure rates. As long-term controlled trials are missing, the aim of this study was to verify the long-term outcome of implants placed in patients with systemic osteoporosis. Postmenopausal women in need of implants underwent bone mineral density measurements in hip and spine, using dual X-ray absorptiometry scans. Based on T-scores, they were divided into 2 groups: group O (osteoporosis group) with a T-score ≤-2 or group C (control group) with a T-score of ≥-1. Implants were placed in a 2-stage manner and loaded 4 to 8 wk after abutment surgery. Six months after loading and thereafter yearly, clinical and radiographical parameters were assessed. In total, 148 implants were placed in 48 patients (mean age: 67 y [range, 59-83]). Sixty-three implants were placed in 20 patients (group O) and 85 implants in 28 patients (group C). After 5 y, 117 implants (38 in group O and 79 in the group C) in 37 patients were assessed. Cumulative survival rate on an implant level was 96.5% (group O: 91.5%; group C: 100.0% [ P < 0.05]) and 95.7% (group O: 89.2%; group C: 100.0% [ P > 0.05]) on a patient level. The overall marginal bone-level alterations, after 5 y of loading, were -0.09 ± 0.78 mm (group O: -0.15 ± 0.50 mm; group C: -0.06 ± 0.89 mm) on an implant level and -0.09 ± 0.54 mm (group O: -0.18 ± 0.43 mm; group C: 0.06 ± 0.58 mm) on a patient level ( P > 0.05). Oral implant therapy in osteoporotic patients is a reliable treatment option with comparable osseointegration rates, implant survival, and marginal bone-level alterations after 5 y of functional loading (ClinicalTrials.gov NCT00745121).

Short progressive muscle relaxation or motor coordination training does not increase performance in a brain-computer interface based on sensorimotor rhythms (SMR).

Brain computer interfaces (BCIs) allow for controlling devices through modulation of sensorimotor rhythms (SMR), yet a profound number of users is unable to achieve sufficient accuracy. Here, we investigated if visuo-motor coordination (VMC) training or Jacobsen's progressive muscle relaxation (PMR) prior to BCI use would increase later performance compared to a control group who performed a reading task (CG). Running the study in two different BCI-labs, we achieved a joint sample size of N=154 naïve participants. No significant effect of either intervention (VMC, PMR, control) was found on resulting BCI performance. Relaxation level and visuo-motor performance were associated with later BCI performance in one BCI-lab but not in the other. These mixed results do not indicate a strong potential of VMC or PMR for boosting performance. Yet further research with different training parameters or experimental designs is needed to complete the picture.

An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia.

Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE). In vitro, treatment with 293C3-SDIE significantly enhanced activation, degranulation and lysis of primary CD133-positive AML cells by allogeneic and autologous NK cells as compared with its wild-type counterpart. In line with the observed lower expression levels of CD133 on healthy cells compared with malignant hematopoietic cells, 293C3-SDIE caused no relevant toxicity towards committed hematopoietic progenitor cells. In a NOD.Cg-PrkdcscidIL2rgtmWjl/Sz xenotransplantation model, 293C3-SDIE facilitated elimination of patient AML cells by human NK cells. Thus, 293C3-SDIE constitutes an attractive immunotherapeutic compound, in particular for elimination of minimal residual disease in the context of allogeneic stem cell transplantation in AML.

Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC).

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common malignancy worldwide. The past decades have not led to substantial improvement in diagnosis and therapy. Analysis of miRNA-expression may help to determine the progression profiles and outcomes of many different diseases, including HNSCC. Therefore, in this investigation, 43 formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were micro-dissected, analysed for expression of 30 miRNAs and were compared with non-tumorous tissue. Furthermore, correlation analysis was performed, investigating possible correlations of miRNA-expression and patient or tumour-linked data, such as age, sex, tumour stage and size. miRNA extraction from FFPE samples functioned well for OSCC, and several miRNAs were differently expressed in tumours compared with non-tumorous tissue (i.e., miR-99*; miR-224; miR-205*), indicating their possible utility as biomarkers. Moreover, some miRNAs showed significant correlations with clinical and pathological data (e.g. tumour size: miR-3156, P = 0.033; T-stage: miR-212, P = 0.0009).

Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma.

MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-µm) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE-A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE­A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

OBJECTIVE: Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. METHODS: Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. RESULTS: Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. CONCLUSIONS: Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. SIGNIFICANCE: To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential.

The effect of multimodal and enriched feedback on SMR-BCI performance.

OBJECTIVE: This study investigated the effect of multimodal (visual and auditory) continuous feedback with information about the uncertainty of the input signal on motor imagery based BCI performance. A liquid floating through a visualization of a funnel (funnel feedback) provided enriched visual or enriched multimodal feedback. METHODS: In a between subject design 30 healthy SMR-BCI naive participants were provided with either conventional bar feedback (CB), or visual funnel feedback (UF), or multimodal (visual and auditory) funnel feedback (MF). Subjects were required to imagine left and right hand movement and were trained to control the SMR based BCI for five sessions on separate days. RESULTS: Feedback accuracy varied largely between participants. The MF feedback lead to a significantly better performance in session 1 as compared to the CB feedback and could significantly enhance motivation and minimize frustration in BCI use across the five training sessions. CONCLUSION: The present study demonstrates that the BCI funnel feedback allows participants to modulate sensorimotor EEG rhythms. Participants were able to control the BCI with the funnel feedback with better performance during the initial session and less frustration compared to the CB feedback. SIGNIFICANCE: The multimodal funnel feedback provides an alternative to the conventional cursorbar feedback for training subjects to modulate their sensorimotor rhythms.

Effects of training and motivation on auditory P300 brain-computer interface performance.

OBJECTIVES: Brain-computer interface (BCI) technology aims at helping end-users with severe motor paralysis to communicate with their environment without using the natural output pathways of the brain. For end-users in complete paralysis, loss of gaze control may necessitate non-visual BCI systems. The present study investigated the effect of training on performance with an auditory P300 multi-class speller paradigm. For half of the participants, spatial cues were added to the auditory stimuli to see whether performance can be further optimized. The influence of motivation, mood and workload on performance and P300 component was also examined. METHODS: In five sessions, 16 healthy participants were instructed to spell several words by attending to animal sounds representing the rows and columns of a 5 × 5 letter matrix. RESULTS: 81% of the participants achieved an average online accuracy of ⩾ 70%. From the first to the fifth session information transfer rates increased from 3.72 bits/min to 5.63 bits/min. Motivation significantly influenced P300 amplitude and online ITR. No significant facilitative effect of spatial cues on performance was observed. CONCLUSIONS: Training improves performance in an auditory BCI paradigm. Motivation influences performance and P300 amplitude. SIGNIFICANCE: The described auditory BCI system may help end-users to communicate independently of gaze control with their environment.

Performance of cone beam computed tomography in comparison to conventional imaging techniques for the detection of bone invasion in oral cancer.

Detecting bone invasion in oral cancer is crucial for therapy planning and the prognosis. The present study evaluated cone beam computed tomography (CBCT) for detecting bone invasion in comparison to standard imaging techniques. A total of 197 patients with diagnoses of oral cancer underwent CBCT as part of preoperative staging between January 2007 and April 2013. The sensitivity, specificity, and accuracy of CBCT were compared with panoramic radiography (PR), multi-slice computed tomography (CT) or magnetic resonance imaging (MRI), and bone scintigraphy (BS) using McNemar's test. Histopathology and clinical follow-up served as references for the presence of bone invasion. CBCT and BS (84.8% and 89.3%, respectively), as well as CBCT and CT/MRI (83.2%), showed comparable accuracy (P = 0.188 and P = 0.771). CBCT was significantly superior to PR, which was reconstructed based on a CBCT dataset (74.1%, P = 0.002). In detecting bone invasion, CBCT was significantly more accurate than PR and was comparable to BS and CT/MRI. However, each method has certain advantages, and the best combination of imaging methods must be evaluated in prospective clinic trials.

Psychophysiological correlates of coping and quality of life in patients with ALS.

OBJECTIVE: Self-regulation models of coping suggest that patients with chronic diseases reporting low quality of life (QoL), an indicator of failed coping efforts, should show facilitated access to disease related words. Here we investigated whether a reduced N400 amplitude within an incongruent, i.e. unpredictable disease-related context would be a correlate of this facilitated access. METHODS: ERPs were recorded in N=18 patients with amyotrophic lateral sclerosis (ALS) and N=20 age-matched healthy controls during reading of sentences, ending either with congruent or incongruent words. Incongruent and congruent words were disease related or disease unrelated. Mean N400 amplitudes were analyzed with mixed models. RESULTS: Generally, incongruent words elicited a more negative N400 amplitude than congruent words in all groups and conditions, i.e. an N400 effect. In patients with high QoL this N400 effect did not differ between disease related and unrelated words. In patients with low QoL, however, the N400 effect was significantly smaller for disease related than for disease unrelated words. In healthy controls N400 amplitudes showed no such interaction between congruence, disease relatedness and QoL. Results remained stable when controlling for disease severity, duration and depression. CONCLUSION: The N400 indicates increased accessibility to disease related information in ALS patients with low QoL. The increased access may imply a constantly activated disease related context which is linked to low QoL. SIGNIFICANCE: N400 modulation by disease related information may serve as a psychophysiological correlate of coping and the patient's QoL.

Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells.

OBJECTIVES: The present study examined the relationship between MAGE-A tumor antigens and the efficacy of diamindichloridoplatin (DDP), 5-fluorouracil (5-FU), docetaxel, and paclitaxel for in vitro treatment of head and neck cancer. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with DDP (25-400 µM), 5-FU (0.75-12 mM), docetaxel (1.56-25 nM), and paclitaxel (1.56-25 nM) for a period of 24 or 48 h. The efficacy of the agents was observed dynamically using real-time cell analysis. Subsequently, the expression levels of MAGE-A1, MAGE-A5, MAGE-A8, MAGE-A9, MAGE-A11, and MAGE-A12 were determined by quantitative real-time polymerase chain reaction. Chemosensitivity and MAGE-A-expression were correlated by linear regression. RESULTS: The tumor cell lines showed a highly differentiated response to the chemotherapeutic agents. Expression of MAGE-A11 was significantly associated with a poorer response to treatment with DDP, 5-FU, docetaxel, and paclitaxel. Two cell lines, one of which was MAGE-A11-positive, showed a significant and concentration-dependent cisplatin-induced growth spurt during the first 24 h after treatment. MAGE-A5 was connected to a positive effect on treatment with paclitaxel within the first 24 h after application. In association with docetaxel treatment, MAGE-A8 was connected to a poorer susceptibility. CONCLUSIONS: The results describe, for the first time, a correlation between these MAGE-A tumor antigens and the susceptibility of head and neck cancer cells to DDP, 5-FU, docetaxel, and paclitaxel. CLINICAL RELEVANCE: These findings could affect the antineoplastic treatment of patients with MAGE-A11-positive tumors.

Correlates of food addiction in obese individuals seeking bariatric surgery.

Recent evidence suggests that palatable, high-calorie foods may have an addictive potential. Accordingly, obesity and overconsumption of such foods have been associated with addiction-like eating behaviour. The present study investigated whether individuals with obesity can be classified as food-addicted and which factors would differentiate between food-addicted and non-addicted individuals. We administered the German version of the Yale Food Addiction Scale and other questionnaires to obese individuals seeking bariatric surgery (N = 96). Results showed that 40% of the sample could be diagnosed as food-addicted. Food-addicted individuals reported more frequent food cravings, higher eating disorder psychopathology and more depressive symptoms than the non-addicted group. Age, body mass and gender distribution did not differ between groups. The food addiction group had higher attentional but similar motor and non-planning impulsivity, and had lower scores on the Alcohol Use Disorders Identification Test (AUDIT) compared with the non-addicted group. Scores on the AUDIT were associated with impulsivity in the non-addicted group only. We conclude that the prevalence of food addiction is higher in candidates for bariatric surgery compared with the general population and obese individuals not seeking bariatric surgery. A diagnosis of food addiction is associated with higher eating pathology and depression. Moreover, only attentional impulsivity, but not other dimensions of impulsivity, is associated with addictive eating. Finally, food addiction and impulsivity interactively predicted alcohol use, suggesting a crucial role of psychological variables and eating style in determining alcohol consumption in pre-bariatric patients, independent of body mass.