Introduction: The quality of neonatal care is mainly determined by long-term neurodevelopmental outcome. The neurodevelopment of preterm infants is related to postnatal head growth and depends on medical interventions such as nutritional support. Head circumference (HC) is currently used as a two-dimensional measure of head growth. Since head deformities are frequently found in preterm infants, HC may not always adequately reflect head growth. Laser aided head shape digitizers offer semiautomatic acquisition of HC and cranial volume (CrV) and could thus be useful in describing head size more precisely. Aims: 1) To evaluate reproducibility of a 3D digital capture system in newborns. 2) To compare manual and digital HC measurements in a neonatal cohort. 3) To determine correlation of HC and CrV and predictive value of HC. Methods: Within a twelve-month period data of head scans with a laser shape digitizer were analysed. Repeated measures were used for method evaluation. Manually and digitally acquired HC was compared. Regression analysis of HC and CrV was performed. Results: Interobserver reliability was excellent for HC (bias-0.005%, 95% Limits of Agreement (LoA) −0.39–0.39%) and CrV (bias1.5%, 95%LoA-0.8–3.6%). Method comparison data was acquired from 282 infants. It revealed interchangeability of the methods (bias-0.45%; 95%LoA-4.55–3.65%) and no significant systematic or proportional differences. HC and CrV correlated (r2 = 0.859, p<0.001), performance of HC predicting CrV was poor (RSD ±24 ml). Correlation was worse in infants with lower postmenstrual age (r2 = 0.745) compared to older infants (r2 = 0.843). Discussion: The current practice of measuring HC for describing head growth in preterm infants could be misleading since it does not represent a 3D approach. CrV can vary substantially in infants of equal HC. The 3D laser scanner represents a new and promising method to provide reproducible data of CrV and HC. Since it does not provide data on cerebral structures, additional imaging is required.

Objective: Decrease of olfactory function in Parkinson's disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from “training” with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function. Methods: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the “Sniffin' Sticks” (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process. Results: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training. Conclusion: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.

Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75×10−6 and 8.3×10−7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of causal variants and their functional effects may unveil yet unknown players in the neurodevelopment and the pathogenesis of neuropsychiatric disorders.

In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

It has been repeatedly shown that functional magnetic resonance imaging (fMRI) triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA), as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID) in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults.

Disgust causes specific reaction patterns, observable in mimic responses and body reactions. Most research on disgust deals with visual stimuli. However, pictures may cause another disgust experience than sounds, odors, or tactile stimuli. Therefore, disgust experience evoked by four different sensory channels was compared. A total of 119 participants received 3 different disgusting and one control stimulus, each presented through the visual, auditory, tactile, and olfactory channel. Ratings of evoked disgust as well as responses of the autonomic nervous system (heart rate, skin conductance level, systolic blood pressure) were recorded and the effect of stimulus labeling and of repeated presentation was analyzed. Ratings suggested that disgust could be evoked through all senses; they were highest for visual stimuli. However, autonomic reaction toward disgusting stimuli differed according to the channel of presentation. In contrast to the other, olfactory disgust stimuli provoked a strong decrease of systolic blood pressure. Additionally, labeling enhanced disgust ratings and autonomic reaction for olfactory and tactile, but not for visual and auditory stimuli. Repeated presentation indicated that participant's disgust rating diminishes to all but olfactory disgust stimuli. Taken together we argue that the sensory channel through which a disgust reaction is evoked matters.

Background: Although the negative impact of sleep apnea on the clinical course of acute ischemic stroke (AIS) is well known, data regarding non-invasive ventilation in acute patients are scarce. Several studies have shown its tolerability and safety, yet no controlled randomized sequential phase studies exist that aim to establish the efficacy of early non-invasive ventilation in AIS patients. Methods/design: We decided to examine our hypothesis that early non-invasive ventilation with auto-titrating bilevel positive airway pressure (auto-BPAP) positively affects short-term clinical outcomes in AIS patients. We perform a multicenter, prospective, randomized, controlled, third rater- blinded, parallel-group trial. Patients with AIS with proximal arterial obstruction and clinically suspected sleep apnea will be randomized to standard stroke care alone or standard stroke care plus auto-BPAP. Auto-BPAP will be initiated within 24 hours of stroke onset and performed for a maximum of 48 hours during diurnal and nocturnal sleep. Patients will undergo unattended cardiorespiratory polygraphy between days three and five to assess sleep apnea. Our primary endpoint will be any early neurological improvement on the NIHSS at 72 hours from randomization. Safety, tolerability, short-term and three-months functional outcomes will be assessed as secondary endpoints by un-blinded and blinded observers respectively. Discussion: We expect that this study will advance our understanding of how early treatment with non-invasive ventilation can counterbalance, or possibly reverse, the deleterious effects of sleep apnea in the acute phase of ischemic stroke. The study will provide preliminary data to power a subsequent phase III study.

Background: Multimorbidity is defined as suffering from coexistent chronic conditions. Multimorbid patients demand highly complex patient-centered care which often includes polypharmacy, taking an average of six different drugs per day. Adverse drug reactions, adverse drug events and medication errors are all potential consequences of polypharmacy. Our study aims to detect the status quo of the health care situation in Saxony’s general practices for multimorbid patients receiving multiple medications. We will identify the most common clinical profiles as well as documented adverse drug events and reactions that occur during the treatment of patients receiving multiple medications. We will focus on exploring the motives of general practitioners for the prescription of selected drugs in individual cases where there is evidence of potential drug-drug-interactions and potentially inappropriate medications in elderly patients. Furthermore, the study will explore general practitioners’ opinions on delegation of skills to other health professions to support medical care and monitoring of patients receiving multiple medications. Methods/design: This is a retrospective cross sectional study using mixed methods. Socio-demographic data as well as diagnoses, medication regimens and clinically important events will be analyzed retrospectively using general practitioners documentation in patients’ records. Based on these data, short vignettes will be generated and discussed by general practitioners in qualitative telephone interviews. Discussion: To be able to improve outpatient health care management for patients receiving multiple medications, the current status quo of care, risk factors for deficient treatment and characteristics of concerned patients must be investigated. Furthermore, it is necessary to understand the physicians’ decision making process regarding treatment.

Background: Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods: A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings: The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions: The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Although most odorants we encounter in daily life are mixtures of several chemical substances, we still lack significant information on how we perceive and how the brain processes mixtures of odorants. We aimed to investigate the processing of odor mixtures using behavioral measures and functional magnetic resonance imaging (fMRI). The odor mixture contained a target odor (ambroxan) in a concentration at which it could be perceived by half of the subjects (sensitive group); the other half could not perceive the odor (insensitive group). In line with previous findings on multi-component odor mixtures, both groups of subjects were not able to distinguish a complex odor mixture containing or not containing the target odor. However, sensitive subjects had stronger activations than insensitive subjects in chemosensory processing areas such as the insula when exposed to the mixture containing the target odor. Furthermore, the sensitive group exhibited larger brain activations when presented with the odor mixture containing the target odor compared to the odor mixture without the target odor; this difference was smaller, though present for the insensitive group. In conclusion, we show that a target odor presented within a mixture of odors can influence brain activations although on a psychophysical level subjects are not able to distinguish the mixture with and without the target. On the practical side these results suggest that the addition of a certain compound to a mixture of odors may not be detected on a cognitive level; however, this additional odor may significantly change the cerebral processing of this mixture. In this context, FMRI offers unique possibilities to look at the subliminal effects of odors.