Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease.

PURPOSE: To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. METHODS: Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. RESULTS: In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The 'alcoholic beverages' PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. CONCLUSION: In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD.

N-terminal heterogeneity of parenchymal and vascular amyloid-ß deposits in Alzheimer's disease.

AIMS: The deposition of amyloid-ß (Aß) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aß starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aß peptides have been identified by mass spectrometry in autopsy samples from individuals with AD. METHODS: Selectivity of several antibodies detecting full-length, total or N-terminally truncated Aß species has been characterized with capillary isoelectric focusing assays using a set of synthetic Aß peptides comprising different N-termini. We further assessed the N-terminal heterogeneity of extracellular and vascular Aß peptide deposits in the human brain by performing immunohistochemical analyses using sporadic AD cases with antibodies targeting different N-terminal residues, including the biosimilar antibodies Bapineuzumab and Crenezumab. RESULTS: While antibodies selectively recognizing Aß1-x showed a much weaker staining of extracellular plaques and tended to accentuate cerebrovascular amyloid deposits, antibodies detecting Aß starting with phenylalanine at position 4 of the Aß sequence showed abundant amyloid plaque immunoreactivity in the brain parenchyma. The biosimilar antibody Bapineuzumab recognized Aß starting at Asp-1 and demonstrated abundant immunoreactivity in AD brains. DISCUSSION: In contrast to other studied Aß1-x -specific antibodies, Bapineuzumab displayed stronger immunoreactivity on fixed tissue samples than with sodium dodecyl sulfate-denatured samples on Western blots. This suggests conformational preferences of this antibody. The diverse composition of plaques and vascular deposits stresses the importance of understanding the roles of various Aß variants during disease development and progression in order to generate appropriate target-developed therapies.

A conceptual framework for an oral cancer awareness campaign in Northern Germany - Challenges in campaign development and assessment.

Initial impetus for action: Oral cancer is still an underestimated disease in terms of incidence as well as mortality rates; it requires urgent prevention and early detection. At present, there is no best-practice systematic approach to raising awareness and informing the public about about this type of cancer in Germany. This article describes a framework that covers the significant stages of conceptual development and campaign design to promote oral cancer awareness in Germany. Solution: The challenges of the development, as well as evaluation of an oral cancer awareness campaign are shared in this article. Four key stages of the campaign are defined: (1) mass media, (2) target groups, (3) health care professionals, and (4) epidemiology. For each section, the following levels of assessment are proposed: (a) campaign development (formative assessment), (b) controlling and optimising campaign implementation (process assessment) and (c) measuring outcomes (summative assessment). Outcome: A process-oriented assessment concept for each of the four campaign sections was developed and merged to form a matrix, which includes each of the above sections regarding the prevention and early detection of oral cancer, as well as the three stages of campaign assessment. Future implications and learning points: The conceptual framework demonstrated that systematic planning and evaluation of different components helped to describe and evaluate an oral cancer campaign: For future campaigns, the use of a matrix covering different campaign targets as well as the entire campaign process, is recommended as a basis for campaign design and evaluation.

[Quality of life and depression in hearing-impairment : A German survey]. / Lebensqualität und Depression bei Hörminderung : Eine deutsche Bedarfsanalyse.

BACKGROUND: Hearing-impairment can lead to a reduced quality of life and thus represents a vulnerability factor for mental disorders. OBJECTIVE: This study represents the first psychiatric analysis of subjective quality of life and depression in people with hearing-impairment in Germany. MATERIALS AND METHODS: The patient group included 30 hearing-impaired participants (27 women, 3 men) with a current or previous mental disorder and/or psychiatric/psychotherapeutic treatment (age: mean, M = 49.67 years; standard deviation, SD = 13.54 years). The control group consisted of 22 hearing-impaired participants (16 women, 6 men) without mental disorders or treatment (age: M = 52.41 years, SD = 17.30 years). Besides sociodemographic variables, we registered onset/extent of the various hearing-impairments and hearing aid provision. Both groups underwent extensive diagnostic assessment comprising subjective functional impairment (Sheehan Disability Scale, SDS), health-related quality of life (SF-36 Health Survey), and depressive symptoms (Beck Depression Inventory, BDI-II). RESULTS: Groups did not differ significantly in terms of sociodemographic variables such as age, gender, or intelligence. Participants of the patient group had a significantly greater subjective impairment, a lower quality of life, and more pronounced symptoms of depression. The invasiveness of the hearing aid (i. e., cochlear implant) as well as the timepoint of hearing-impairment onset (postlingually) appear to serve as vulnerability factors for mental health problems in this group. CONCLUSION: Our results indicate that besides delivering high-quality acoustic care, practitioners should continuously check patients' requirements for psychosocial treatment due to a loss of quality of life. The development of a specific psychotherapeutic treatment for hearing-impaired clients requires additional research focused on protective and vulnerability factors which may influence the emergence of mental disorders in these patients.

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

Perception of emotional prosody in adults with attention deficit hyperactivity disorder.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is associated with social conflicts. The purpose of this study was to explore domains of social cognition in adult patients with ADHD. METHODS: The assessment of social cognition was based on established neuropsychological tests: the Tübinger Affect Battery (TAB) for prosody and the Cambridge Behaviour Scale (CBS) for empathy. The performance of adults with ADHD (N = 28) was compared with the performance of a control group (N = 29) matched according to basic demographic variables. RESULTS: Treatment-naïve adults with ADHD showed deficits in emotional prosody (P = 0.02) and in the ability to empathize (P < 0.02) independent of executive functioning. In particular, their ability to perceive angry feelings was found to be compromised (P = 0.04). When emotional prosody was considered in relation to facial expressions, patients and controls showed no impairments (P > 0.2). No gender differences concerning social cognitive skills were detected. CONCLUSIONS: ADHD is associated with social cognition impairments involving both emotional prosody and empathy.

[Electroconvulsive therapy in nonconsenting patients]. / Elektrokonvulsionstherapie gegen den natürlichen Patientenwillen.

BACKGROUND: Electroconvulsive therapy (ECT) is a potent and successful method for the treatment of severe psychiatric disorders. Severe depressive and psychotic disorders may lead to legal incapacity and inability to consent. In Germany, administration of ECT against the patient's will is feasible under certain constellations and is regulated under the terms of the guardianship law. OBJECTIVE: This article outlines the prevalence, effectiveness and tolerability of ECT when applied in nonconsenting patients. MATERIAL AND METHODS: Case report and literature review. RESULTS: The literature on ECT as a treatment in nonconsenting patients is relatively sparse. In 2008 the prevalence in Germany was less than 0.5 % of all patients receiving ECT. Case reports and case series suggest a good and equal level of effectiveness when compared to consenting patients. In the course of treatment the majority of patients consented to receive further ECT and retrospectively judged ECT as helpful. CONCLUSION: The use of ECT is a highly effective treatment in severe psychiatric disorders even when administered as treatment in nonconsenting patients. It can be lifesaving and lead to a rapid improvement of symptoms and relief from severe suffering also from the patients' perspective. Thus, it seems unethical not to consider ECT as a treatment against the nonautonomous will of legally incompetent patients in individual cases. Nevertheless, physicians should always seek to obtain the patients' consent as soon as possible for both legal and ethical reasons.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of behavioral and psychological symptoms of dementia : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung psychischer und Verhaltenssymptome bei Demenz : Normative Personalbedarfsermittlung.

BACKGROUND: Dementia is of increasing medical and societal relevance. Hospitalization of dementia patients is mostly due to behavioral and psychological symptoms of dementia (BPSD). There is a need for sufficient qualified personnel in hospitals in order to be able to effectively treat these symptoms. OBJECTIVES: This study aims at identifying the personnel requirements for guideline-conform, evidence-based inpatient treatment concepts for patients with BPSD and to compare these with the resources defined by the German psychiatric personnel regulations (Psych-PV). Furthermore, it was the aim to identify how often patients with dementia received non-pharmacological therapy during inpatient treatment. METHODS: Based on the current scientific evidence for treatment of BPSD, a schedule for a multimodal non-pharmacological treatment was defined and based on this the corresponding personnel requirements were calculated. Using the treatment indicators in psychiatry and psychosomatics (VIPP) database as a reference, it was calculated on what proportion of treatment days patients were classified into G1 according to the German Psych-PV and at least once received more than two treatment units per week. RESULTS: For the implementation of a guideline-oriented and evidence-based treatment plan, a higher need for personnel resources than that provided by the Psych-PV was detected in all areas. Currently patients with dementia who received at least more than two treatment units per week during inpatient hospitalization, were classified into G1 according to German Psych-PV on 17.9 % of treatment days. CONCLUSION: Despite evidence for the efficacy of non-pharmacological treatment measures on BPSD, these forms of treatment cannot be sufficiently provided under the current conditions. The realization of a new quality controlled therapeutic concept is necessary to enable optimized treatment of patients with BPSD.

Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a 'European ADNI study'.

BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

[Biomarkers for dementia and other neurodegenerative diseases : Current developments]. / Biomarker bei Demenzen und anderen neurodegenerativen Erkrankungen : Aktuelle Entwicklungen.

Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines ( www.DGPPN.de ). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (Aß 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other). Generally, CSF-NDD should be combined with blood-based routine diagnostics and should be part of routine CSF diagnostics, e. g. cell count and cell differentiation (if applicable), intrathecal antibody synthesis and blood-CSF barrier analysis. The CSF-NDD are most valuable for the improved differentiation between reversible dementia syndromes and irreversible neurodegenerative dementia, e. g. cognitive deficits due to late onset depression (pseudodementia due to depression) or AD. Combined with extended psychometric neuropsychological evaluation and neuroimaging methods, such as magnetic resonance imaging (MRI), dopamine transporter scanning (DaTscan) by single photon emission computed tomography (SPECT), 18F-fluorodeoxyglucose positron emission tomography (glucose-PET) and amyloid-PET, CSF-NDD also significantly improve the differential diagnostics within the heterogeneous group of primary neurodegenerative dementias. Meanwhile, several independent studies have indicated that the Aß 1-42:Aß 1-40 ratio is superior to the determination of Aß 1-42 alone. Currently, several international research initiatives have been launched to further harmonize and optimize preanalytical procedures and CSF-NDD biomarker assays.

[Psychiatric interventions for the unemployed]. / Psychiatrische Interventionen für Arbeitslose.

Unemployment is related to a higher risk for psychological distress and mental disorders, which cause individual suffering and socioeconomic costs for society in general. This selective review surveys the relationship between unemployment and psychological well-being and mental disorders. The most important programs for the improvement of the mental health of the unemployed are summarized: 1. Interventions for the unemployed with the aim of improving coping strategies reduce the risk of developing depressive symptoms. 2. The SUPPORT liaison outpatient unit collaborates closely with the unemployment agency and offers a low-threshold screening for mental disorders for unemployed subjects as well as counseling for those in need of treatment. 3. A group training based on cognitive behavioral therapy improves the psychological well-being of unemployed participants. 4. Supported employment is an effective means of placing severely mentally ill patients in a work-place accompanied by an extensive professional support.

[Novel methods for dementia diagnostics]. / Neue diagnostische Methoden bei Demenzen.

Novel diagnostic methods, such as cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) and [18F] amyloid positron emission tomography (PET) are meanwhile recommended for specific indications by international guidelines for the improved early and differential diagnostics of multigenic (sporadic) Alzheimer's dementia (AD). In the case of CSF-NDD the German neuropsychiatric guidelines have already been validated on the S3 level of evidence (http://www.DGPPN.de) and the additional consideration of [18F] amyloid-PET in the current update of the guidelines is to be expected. By means of CSF-NDD and/or [18F] amyloid-PET a predictive diagnosis of incipient (preclinical) AD is also possible for patients at high risk for AD who are in prodromal stages, such as mild cognitive impairment (MCI). As accompanying (secondary) preventive therapy of AD cannot be offered a predictive molecular dementia diagnostics is not recommended by the German neuropsychiatric dementia guidelines (http://www.DGPPN.de). However, novel diagnostic approaches, which offer molecular positive diagnostics of AD have already gained high relevance in therapy research as they allow promising preventive treatment avenues to be validated directly in the clinical trial. Moreover, future blood-based dementia diagnostics by means of multiplex assays is becoming increasingly more feasible; however, so far corresponding proteomic or epigenetic assays could not be consistently validated in independent studies.

[Electroconvulsive therapy for the treatment of major depression]. / Elektrokonvulsionstherapie zur Behandlung unipolar depressiver Störungen.

BACKGROUND: Depressive disorders are common and lead to both individual suffering and high socioeconomic costs. Despite the fact that several effective therapies are available, remission is often not achieved. Electroconvulsive therapy (ECT) can be a therapeutic option in these cases. OBJECTIVES: This review outlines the current evidence for the efficacy, safety and tolerability of ECT for depressive disorders. MATERIAL AND METHODS: A selective literature search was carried out with particular consideration of meta-analyses, systematic reviews, and recommendations of national and international therapy guidelines. RESULTS: For the majority of patients ECT is an effective, safe and well-tolerated therapy for the treatment of depressive disorders. There are relatively high remission rates even in patients with pharmacoresistant depression. There is evidence for a particularly high responsiveness in specific populations. In contrast to the proven effectiveness in the acute treatment of depressive disorders, there is a relative lack of data concerning maintenance therapy. Side effects including cognitive deficits are mostly transient. Modifications in the ECT technique have an impact on effectiveness and tolerability. CONCLUSION: When administered correctly ECT is a highly effective therapy for the treatment of depressive disorders. In the light of the abundance of depressive disorders and lack of remission despite adequate pharmacological treatment, a broader availability and application of ECT would be desirable. The same is true for a more intensive research into the mechanisms of action and response predictors of ECT.

In vitro comparison of different carrier materials with rat bone marrow MSCs.

OBJECTIVES: Injectable or implantable scaffolds seeded with autologous chondrogenic cells may represent a promising option for treatment of cartilage defects in the future. Current problems with the autologous chondrocyte implantation including dedifferentiation and the development of fibrocartilage suggest the use of alternative chondrogenic cell sources such as mesenchymal stromal cells (MSCs). The aim of this study was to compare the early effects of different scaffolds on the proliferation and metabolic activity of chondrogenic MSCs in vitro. MATERIALS AND METHODS: Multipotent stromal cells were isolated from rat bone marrow, phenotyped by flow cytometry, and differentiated into distinct lineages proved by lineage-specific staining and gene expression (RT-PCR) pattern. Cell proliferation on Tutodent® Membrane, Bio-Gide®, TissuFleece E, and Belotero® Soft was quantified by the MTT and WST-1 assay and direct determination of total cell numbers. Potential cytotoxic effects of eluates obtained from the materials were quantified by lactate dehydrogenase (LDH) and 5-bromo-2-deoxyuridine (BrdU) assay. RESULTS: TissuFleece E displayed the best results regarding cell proliferation on the biomaterials and metabolic activity (MTT, WST-1) (p < 0.001). Yet, the eluates of TissuFleece E caused an increased LDH release and lower values in the BrdU test. Cell proliferations on Bio-Gide®, Tutodent® Membrane, and Belotero® Soft were similar to the control. The eluates of Belotero® Soft exhibited the highest LDH release and lowest values in the BrdU assay (p < 0.05). CONCLUSIONS: Our results support the use of Tissufleece E as scaffold for chondrogenic rat MSCs. However, it should be prewashed with culture medium before seeding of the cells. CLINICAL RELEVANCE: Tissufleece E may serve as a promising carrier material for chondrogenic MSCs for cartilage tissue engineering attempts.

[Clinically validated molecular biomarkers of neurodegenerative dementia]. / Klinisch-validierte molekulare Biomarker neurodegenerativer Demenzerkrankungen.

As cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) has now been validated at the S3 evidence level, the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the German Society for Neurology (DGN) recommend CSF-NDD in the recent joint dementia guidelines for improved early and differential diagnostics of multigenic (sporadic) Alzheimer's dementia (AD). The CSF-NDD also provides a predictive diagnosis of incipient AD for high-risk patients when they are still in the prodromal stage of mild cognitive impairment (MCI) but as no (secondary) preventive therapy of AD is currently available, the use of CSF-NDD for the predictive molecular diagnosis of AD is not recommended in the neuropsychiatry guidelines (http://www.DGPPN.de). However, molecular diagnostics of preclinical AD by CSF-NDD and/or [18F]-amyloid positron emission tomography (PET) has meanwhile gained high clinical relevance for therapeutic clinical research, as this novel clinical model allows systematic screening for promising (secondary) preventive therapy options. Moreover, it has now become apparent that blood-based neurochemical diagnostics of preclinical and early AD will be possible by means of various formats of multiplex assays. However, so far promising blood assays have not been consistently validated by independent research groups and in contrast to CSF-NDD a blood-based diagnosis of AD is not yet available.

Nasal levels of soluble IL-33R ST2 and IL-16 in allergic rhinitis: inverse correlation trends with disease severity.

BACKGROUND: Serum levels of IL-16, IL-33 and the decoy receptor of IL-33, soluble ST2, are elevated in allergic rhinitis. Recent studies show that IL-16, soluble ST2 or anti-IL-33 reduce type 2 cytokines (such as IL-5) and eosinophilia in murine models of allergic asthma or allergic rhinitis respectively. OBJECTIVE: In this study, we studied the release of IL-5, IL-16, IL-33 and soluble ST2 in allergic rhinitis patients after nasal allergen challenge and natural pollen exposure. METHODS: The nasal lavages of 15 allergic and 14 non-allergic volunteers were collected during the pollen allergy season. In addition, six allergic volunteers underwent unilateral nasal allergen and control challenge out of season and nasal secretions and sera were collected. IL-5, IL-16, IL-33 and soluble ST2 in nasal secretions and sera were measured by electrochemiluminescent assay or ELISA, respectively. RESULTS: Nasal IL-5, IL-16 and soluble ST2 levels were significantly increased in seasonally pollen exposed allergic volunteers compared to control subjects (P < 0.001, P = 0.018 and P = 0.002 respectively), whereas IL-33 remained undetectable. Nasal IL-16 showed a weak inverse correlation trend with nasal symptoms (r = -0.48, P = 0.07). Nasal soluble ST2 concentrations were inversely correlated with nasal symptoms (r = -0.61, P = 0.02) and positively correlated with IL-16 (r = 0.56, P = 0.03). Significant increases of nasal IL-5, IL-16 and ST2 but not IL-33 were observed after nasal allergen challenge. At 24 h after allergen challenge, local ST2 and IL-5 concentrations showed an inverse correlation trend (r = -0.83, P = 0.04). Serum levels of IL-5, IL-16 and soluble ST2 rose in at least five of six volunteers tested at 5 or 24 h post-challenge. CONCLUSIONS AND CLINICAL RELEVANCE: The observed upregulation of soluble ST2 and IL-16 after nasal allergen challenge and during peak pollination season suggests potential regulatory roles of these cytokines in the inflammatory reaction in allergic rhinitis.

Development of a capillary isoelectric focusing immunoassay to measure DJ-1 isoforms in biological samples.

We report on the development of a novel assay protocol for the separation and detection of charge isoforms of DJ-1 in biological samples by automated capillary isoelectric focusing followed by immunological detection. DJ-1 (PARK7) is considered as a biomarker candidate for Parkinson's disease and may potentially support the differentiation of clinical subtypes of the disease. The new method allows for separation and subsequent relative quantitative comparison of different isoforms of DJ-1 in biological samples. The assay was successfully applied to the analysis of DJ-1 isoform patterns in brains from mice subjected to normal or high-fat diet and revealed statistically significant group differences. Furthermore, in a pooled and concentrated sample of human cerebrospinal fluid that was depleted of albumin and immunoglobulin G, four different charge variants of DJ-1 could be detected. Taken together, the capillary isoelectric focusing immunoassay for DJ-1 represents a promising tool that may ultimately serve in clinical biomarker studies.

Prospective evaluation of malignant cell seeding after percutaneous endoscopic gastrostomy in patients with oropharyngeal/esophageal cancers.

BACKGROUND AND STUDY AIMS: Insertion of a percutaneous endoscopic gastrostomy (PEG) is standard care for many patients with oropharyngeal (ENT) and esophageal malignancies in order to ensure enteral feeding. The current pull-through insertion technique involves direct contact with the tumor and case reports have demonstrated the presence of metastases at insertion sites. The aim of the current study was to prospectively evaluate the risk of malignant cell seeding and the development of abdominal wall metastases after PEG placement. PATIENTS AND METHODS: A total of 50 consecutive patients with ENT/esophageal tumors were included. After PEG placement (40 pull-through technique, 10 direct insertion), brush cytology was taken from the PEG tubing and the transcutaneous incision site. A second cytological assessment was performed after a follow-up period of 3 - 6 months. RESULTS: In total, 26 patients with ENT cancer, 13 with esophageal cancer, and one with esophageal infiltration of lung cancer underwent pull-through PEG placement with no immediate complications. Cytology following brushing of tubing and incision sites demonstrated malignant cells in 9 /40 cases (22.5 %). Correlation analyses revealed a higher rate of malignant seeding in older patients and in those with higher tumor stages. At follow-up, cytology was undertaken in 32 /40 patients who had undergone pull-through PEG placement. Malignant cells were present in three on cytology, resulting in a metastatic seeding rate of 9.4 %. CONCLUSION: This study showed that malignant cells were present in 22.5 % of patients immediately after pull-through PEG placement; local metastases were verified at follow-up in 9.4 %, all of which were from esophageal squamous cell carcinoma. This risk is particularly high in the older age group and in patients with higher tumor stages. Therefore, pull-through PEG placement should be avoided in these patients and direct access PEG favored instead.

The impact of acute tryptophan depletion on attentional performance in adult patients with ADHD.

OBJECTIVE: To date, the impact of the neurotransmitter serotonin (5-HT) on different neuropsychological functions in adults with attention deficit hyperactivity disorder (ADHD) is underinvestigated. We aimed to examine the effects of acute tryptophan depletion (ATD) and the resulting reduction in central nervous 5-HT synthesis on target/non-target discrimination ability and sustained attention in adults with ADHD using an AX-Continuous Performance Test (AX-CPT). METHOD: Twenty male patients with ADHD (age: M = 30.25 SD = 9.37) and twenty male healthy controls (age: M = 27.90 SD = 6.01) received ATD on one day and a tryptophan-balanced control condition (BAL) on another day in a double-blind within-subject crossover design. A continuous performance test (AX-CPT) with three conditions (AX, AY, and BX) was administered on both days under depleted and sham-depleted conditions. RESULTS: In patients omissions increased after ATD when compared with BAL. Patient's reaction time decreased after ATD when compared with BAL, which was contrasted by opposite effects in controls. Patients showed fewer correct responses (AX condition) and showed a higher rate of errors (condition AXE ) independent of ATD or BAL intake. CONCLUSION: The present preliminary results are indicative of the contribution of serotonergic neurotransmission to attentional processes in adults with ADHD.