[Implementation of an Open Door Policy on Two Acute Care Units]. / Implementierung eines Konzepts der offenen Türen auf zwei psychiatrischen Akutstationen an zwei Kliniken.

BACKGROUND: Since the amendments to the Baden-Württemberg Psychiatric Assistance Act, psychiatric patients who are treated involuntarily can be admitted to open wards. As a result, a comprehensive research project was carried out to implement an open-door policy. This work evaluates the attitudes of patients and therapeutic teams. METHODS: Over the course of a year, 8 focus groups with 6 to 11 participants were conducted with patients and staff before and at the end of the intervention phase and analyzed qualitatively. RESULTS: The concept of open doors was received positively. The staff raised safety concerns whereas on the patient side the door status seemed to be of limited relevance regarding the experience of autonomy or stigmatization. DISCUSSION: The elaboration of conflict issues allows a further development of specific concepts towards the implementation of open doors on psychiatric acute wards.

Prevalence of prehospital pain and pain assessment difference between patients and paramedics: a prospective cross-sectional observational study.

Adequate analgesia is one of the most important interventions in emergency medicine. However, studies suggest that many patients are undertreated for pain. There can be many reasons why patients assess their pain differently to the paramedics. This study aimed to assess the differences in pain ratings between patients and paramedics and factors influencing them in prehospital emergencies. This prospective cross-sectional observational study included patients treated and transported by paramedics or paramedics and emergency physicians of the German Red Cross in Reutlingen, Germany. This study included 6,365 patients. The prevalence of pain was 49.7%. Among patients with a self-reported numerical rating scale (NRS) > 0, the mean patient pain rating was NRS 4.2 ± 2.7, while the mean paramedic pain rating was NRS 3.6 ± 2.4 (p < 0.001). Approximately 11.8% (n = 751) of patients reported subjectively unbearable pain. Patients reported a mean NRS of 7.7 ± 1.8 for unbearable pain, but a mean NRS of 3.3 ± 2.0 for bearable pain (p < 0.001). The difference in pain ratings between patients and paramedics increased with pain severity. Univariate analysis showed that there were no gender differences, but the difference in pain rating was influenced by patient age (p < 0.001) and paramedic age (p = 0.042). The differences in pain ratings were particularly pronounced for abdominal diseases (p < 0.001) and trauma (p < 0.001). There is a difference in pain ratings between patients and paramedics, which increases with pain severity and appears to be associated with the patient's age and the paramedic's age. To determine the desire and need for analgesics, the question about unbearable pain is a good addition to the NRS.

Performance Differences of a Touch-Based Serial Reaction Time Task in Healthy Older Participants and Older Participants With Cognitive Impairment on a Tablet: Experimental Study.

BACKGROUND: Digital neuropsychological tools for diagnosing neurodegenerative diseases in the older population are becoming more relevant and widely adopted because of their diagnostic capabilities. In this context, explicit memory is mainly examined. The assessment of implicit memory occurs to a lesser extent. A common measure for this assessment is the serial reaction time task (SRTT). OBJECTIVE: This study aims to develop and empirically test a digital tablet-based SRTT in older participants with cognitive impairment (CoI) and healthy control (HC) participants. On the basis of the parameters of response accuracy, reaction time, and learning curve, we measure implicit learning and compare the HC and CoI groups. METHODS: A total of 45 individuals (n=27, 60% HCs and n=18, 40% participants with CoI-diagnosed by an interdisciplinary team) completed a tablet-based SRTT. They were presented with 4 blocks of stimuli in sequence and a fifth block that consisted of stimuli appearing in random order. Statistical and machine learning modeling approaches were used to investigate how healthy individuals and individuals with CoI differed in their task performance and implicit learning. RESULTS: Linear mixed-effects models showed that individuals with CoI had significantly higher error rates (b=-3.64, SE 0.86; z=-4.25; P<.001); higher reaction times (F1,41=22.32; P<.001); and lower implicit learning, measured via the response increase between sequence blocks and the random block (ß=-0.34; SE 0.12; t=-2.81; P=.007). Furthermore, machine learning models based on these findings were able to reliably and accurately predict whether an individual was in the HC or CoI group, with an average prediction accuracy of 77.13% (95% CI 74.67%-81.33%). CONCLUSIONS: Our results showed that the HC and CoI groups differed substantially in their performance in the SRTT. This highlights the promising potential of implicit learning paradigms in the detection of CoI. The short testing paradigm based on these results is easy to use in clinical practice.

State of illness-dependent associations of neuro-cognition and psychopathological syndromes in a large transdiagnostic cohort.

BACKGROUND: There is a lack of knowledge regarding the relationship between dimensional psychopathological syndromes and neurocognitive functions, particularly across the major psychiatric disorders (i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Schizophrenia (SZ)). METHOD: SANS, SAPS, HAMA, HAM-D, and YMRS were assessed in 1064 patients meeting DSM-IV-TR criteria for MDD, BD, SZ or schizoaffective disorder (SZA). In addition, a comprehensive neuropsychological test battery was administered. Psychopathological syndromes derived from factor analysis and present state of illness were used to explore psychopathology-cognition relationships. Correlational analyses were corrected for age, sex, verbal IQ, years of education, and DSM-IV-TR diagnosis. Age of onset and total duration of hospitalizations as proxies for illness severity were tested as moderators on the cognition - psychopathology relationship. RESULTS: The negative syndrome, positive formal thought disorder as well as the paranoid-hallucinatory syndrome exhibited associations with neuro-cognition in an illness state-dependent manner, while the psychopathological factors depression and increased appetite only showed weak associations. Illness severity showed moderating effects on the neurocognitive-psychopathology relationship only for the negative syndrome and positive formal thought disorder. LIMITATIONS: No healthy control subjects were entered into the analyses because of lack of variance in psychopathological symptoms, which prevents from drawing conclusions regarding the relative level of potential cognitive impairments. CONCLUSIONS: This study suggests the relationship of neuro-cognition and psychopathology to be highly state of illness-dependent across affective and psychotic disorders. Results hint at the moderating effects of illness severity on psychopathological factors that might be more treatment resistant.

Walking parameters of older adults from a lower back inertial measurement unit, a 6-year longitudinal observational study.

Gait changes during aging and differs between sexes. Inertial measurement units (IMUs) enable accurate quantitative evaluations of gait in ambulatory environments and in large populations. This study aims to provide IMU-based gait parameters' values derived from a large longitudinal cohort study in older adults. We measured gait parameters, such as velocity, step length, time, variability, and asymmetry, from straight, self-paced 20-m walks in older adults (four visits: 715/1102/1017/957 participants) every second year over 6 years using an IMU at the lower back. Moreover, we calculated the associations of gait parameters with sex and age. Women showed lower gait speed, step length, step time, stride time, swing time, and stance time, compared to men. Longitudinal analyses suggest that these parameters are at least partly deteriorating within the assessment period of 2 years, especially in men and at an older age. Variability and asymmetry parameters show a less clear sex- and age-associated pattern. Altogether, our large longitudinal dataset provides the first sex-specific information on which parameters are particularly promising for the detection of age-related gait changes that can be extracted from an IMU on the lower back. This information may be helpful for future observational and treatment studies investigating sex and age-related effects on gait, as well as for studies investigating age-related diseases.

Properties of Titanium Zirconium Molybdenum Alloy after Exposure to Indium at Elevated Temperatures.

Titanium zirconium molybdenum (TZM) is a high strength at high temperature alloy with favorable properties for use in high temperature structural applications. Use of TZM in high pressure, gas-containing autoclave systems was recently demonstrated for the ammonothermal method. Use of indium (In) in the system is desired, though there is a general lack of literature and understanding on the corrosion and impact of In on the mechanical properties of TZM. This study reports for the first time the mechanical properties of TZM after exposure to metallic In at temperatures up to 1000 °C. Static corrosion testing of TZM in In were performed at 750 °C and 1000 °C for 14 days. A microstructure analysis was performed suggesting no visible alteration of the grain structure. Differential thermal analysis (DTA) was performed to investigate compound formation between In and the primary constituents of TZM yielding no measurable reactions and hence no noticeable compound formation. X-ray energy dispersive spectroscopy (EDS) line scans across the TZM-In interface revealed no measurable mass transport of In into the TZM matrix. These results were confirmed using X-ray diffraction (XRD). Given the apparent inertness of TZM to In, mechanical properties of TZM after exposure to In were measured at test temperatures ranging from 22 °C to 800 °C and compared to unexposed, reference TZM samples from the same material stock. Tensile properties, including ultimate tensile strength, yield strength and total elongation, were found to be comparable between In-exposed and unexposed TZM samples. Impact fracture toughness testing (Charpy) performed at temperatures ranging from -196 °C to 800 °C showed that TZM is unaffected upon exposure to In. Tensile testing indicated ductile behavior at room temperature (slow strain rate) whereas impact testing (high strain rate) suggested a ductile to brittle transition temperature between 100 °C and 400 °C. Given these results, TZM appears to be a promising candidate for use as a force bearing material when exposed to In at high temperature.

Effects of aging on functional connectivity in a neurodegenerative risk cohort: resting state versus task measurement using near-infrared spectroscopy.

Changes in functional brain organization are considered to be particularly sensitive to age-related effects and may precede structural cognitive decline. Recent research focuses on aging processes determined by resting state (RS) functional connectivity (FC), but little is known about differences in FC during RS and cognitive task conditions in elderly participants. The purpose of this study is to compare FC within and between the cognitive control (CCN) and dorsal attention network (DAN) at RS and during a cognitive task using functional near-infrared spectroscopy (fNIRS). In a matched, neurodegenerative high-risk cohort comprising early (n = 98; 50-65 y) and late (n = 98; 65-85 y) elder subjects, FC was measured at RS and during performance of the Trail Making Test (TMT) via fNIRS. Both, under RS and task conditions our results revealed a main effect for age, characterized by reduced FC for late elder subjects within the left inferior frontal gyrus. During performance of the TMT, negative correlations of age and FC were confirmed in various regions of the CCN and DAN. For the whole sample, FC of within-region connections was elevated, while FC between regions was decreased at RS. The results confirm a reorganization of functional brain connectivity with increasing age and cognitive demands.

Open Doors by Fair Means: a quasi-experimental controlled study on the effects of an open-door policy on acute psychiatric wards.

BACKGROUND: Psychiatric wards treating involuntarily admitted patients are traditionally locked to prevent absconding. However, on the basis of observational evidence, the necessity for locked units in psychiatric hospitals has increasingly been questioned. Updated Mental Health Laws in several Federal States of Germany legitimate involuntary commitment without generally locked doors. METHODS: We examined the effects of an open-door policy in a quasi-experimental, prospective design. For the first time, at each of two locations, two identical wards serving as control and intervention could be compared. After a baseline period of three months, one ward at each location started the 12 month intervention period with the implementation of an open-door policy, while the respective control ward, as before, used open doors only facultatively. Primary outcomes were average opening times of the four wards between 8 a.m. and 8 p.m., and the number of involuntary treatment days with the doors open. Secondary outcomes were adverse events including aggressive incidents, absconding, suicide attempts and coercive measures. RESULTS: Overall, door-opening times increased significantly at both sites´ intervention wards. The number of adverse events did not increase during intervention period. Frequencies of coercive measures decreased in Friedrichshafen and remained unchanged in Tuebingen. In case of the intervention ward in Friedrichshafen, doors were open in up to 91% of all involuntary treatment days, whereas in the control ward, this was only the case in 67% of all involuntary treatment days (p < .001). In case of the intervention ward in Tuebingen, 45% of involuntary treatment days had open doors, compared to 30% in the control ward (p < .001). CONCLUSIONS: It is possible to manage psychiatric wards with open doors without taking inappropriate risks. The extent to which open-door policies are achievable is be dependent on staffing and patient characteristics. Further research is necessary to explore the role of staff attitudes. TRIAL REGISTRATION: Our trial "Open Doors by Fair Means" is retrospectively registered with DRKS ( DRKS00015154 ) on Sept. 10th 2018 and displayed on the public web site. It is searchable via its meta-registry ( http://apps.who.int/trialsearch/ ).

[Telemedicine in mobile geriatric rehabilitation : Results of the VITAAL study]. / Telemedizin in der mobilen geriatrischen Rehabilitation : Ergebnisse der VITAAL-Studie.

BACKGROUND: In order to implement the principle of rehabilitation before care, adaptive concepts for geriatric patients are required. Patients with visual impairments, impaired communication skills, mental illnesses or cognitive deficits are often not or only insufficiently treatable in a rehabilitation clinic. Mobile geriatric rehabilitation (MoGeRe) closes this gap in the care system, but its scope is limited. With the 22 locations in Germany, it is not possible to make a comprehensive MoGeRe possible so far. Telemedicine offers solutions here. OBJECTIVE: Telemedicine supplements to MoGeRe in the form of video visits and video recording were examined with respect to their feasibility and acceptance in a very old target group. METHOD: A total of 101 video visits and 26 diagnostic video recordings were carried out with 25 patients. Interviews with patients and team members were evaluated with the help of a qualitative content analysis. RESULTS AND DISCUSSION: In particular, the acceptance of the video visit was high among all those involved. Its potential lies in the adaptation of the individual treatment, motivation, medical guidance and supervision of the team. The video recording can offer the opportunity to enrich the interdisciplinary exchange and to evaluate and adapt the therapeutic procedure. Specific strategies such as accompanying relatives, explaining the procedure and good timing are necessary for cognitively impaired patients. Our results prove that older people should also be taken into account as users of digital media.

Arm swing responsiveness to dopaminergic medication in Parkinson's disease depends on task complexity.

The evidence of the responsiveness of dopaminergic medication on gait in patients with Parkinson's disease is contradicting. This could be due to differences in complexity of the context gait was in performed. This study analysed the effect of dopaminergic medication on arm swing, an important movement during walking, in different contexts. Forty-five patients with Parkinson's disease were measured when walking at preferred speed, fast speed, and dual-tasking conditions in both OFF and ON medication states. At preferred, and even more at fast speed, arm swing improved with medication. However, during dual-tasking, there were only small or even negative effects of medication on arm swing. Assuming that dual-task walking most closely reflects real-life situations, the results suggest that the effect of dopaminergic medication on mobility-relevant movements, such as arm swing, might be small in everyday conditions. This should motivate further studies to look at medication effects on mobility in Parkinson's disease, as it could have highly relevant implications for Parkinson's disease treatment and counselling.

Abnormally reduced frontal cortex activity during Trail-Making-Test in prodromal parkinson's disease-a fNIRS study.

Parkinson's Disease (PD) is a neurodegenerative disorder leading to typical motor as well as a range of non-motor symptoms, including cognitive decline mainly characterized by executive deficits. The latter are known to appear years before the typical motor signs, thus representing the prodromal phase of PD. However, appropriate methods for measuring executive dysfunction in this context are not well established yet. Traditionally, executive performance is associated with frontal structures. Here, we investigated prodromal, early PD patients and healthy controls regarding their executive functioning on the behavioral and neural level, measured by the Trail-Making-Test (TMT) combined with functional near-infrared spectroscopy. We observed significantly reduced neural activity in the right dorsolateral prefrontal cortex within PD patients compared to controls completing the TMT-A and -B in contrast to the TMT-C, but no differences on a behavioral level. These promising results need to be confirmed and checked for reliability in future studies to extend the spectrum of markers applied in prodromal PD.

Impaired Executive Function and Depression as Independent Risk Factors for Reported Delirium Symptoms: An Observational Cohort Study Over 8 Years.

BACKGROUND: Acute medical illnesses, surgical interventions, or admissions to hospital in older individuals are frequently associated with a delirium. In this cohort study, we investigated the impact of specific cognitive domains and depression before the occurrence of delirium symptoms in an 8-year observation of older non-hospitalized individuals. METHODS: In total, we included 807 participants (48-83 years). Deficits in specific cognitive domains were measured using the CERAD test battery, and depressive symptoms were measured using Beck Depression Inventory and the Geriatric Depression Scale (GDS) before the onset of a delirium. Delirium symptoms were retrospectively assessed by a questionnaire based on the established Nursing Delirium Screening Scale. RESULTS: Fifty-eight of eight hundred seven participants (7.2%) reported delirium symptoms over the 8-year course of the study. Sixty-nine percent (n = 40) of reported delirium symptoms were related to surgeries. In multivariate regression analysis, impaired executive function was an independent risk factor (p = 0.034) for the occurrence of delirium symptoms. Furthermore, age (p = 0.014), comorbidities [captured by the Charlson Comorbidity Index (CCI)] (p < 0.001), and depression (p = 0.012) were significantly associated with reported delirium symptoms. CONCLUSION: Especially prior to elective surgery or medical interventions, screening for impaired executive function and depression could be helpful to identify patients who are at risk to develop delirium symptoms.

Age-related deterioration of performance and increase of cortex activity comparing time- versus item-controlled fNIRS measurement.

In our aging society, research into neurodegenerative processes is of great interest. Thereby, cortical activation under different neurocognitive conditions is considered to be a promising predictor. Against this background, the executive functions of a total of 250 healthy older adults (53-84 years) have been investigated using the Trail Making Test (TMT) and functional near-infrared spectroscopy in a block design. We investigated effects of age on the performance and cortical blood oxygenation during the TMT. Since it is assumed that older people may compensate for cognitive deficits by slowing their processing speed, we additionally analyzed the cortical blood oxygenation per solved item. Our results showed a significant decrease in processing speed in older participants compared to middle-aged individuals, however, also lower error rates during TMT part A. On a neurophysiological level, we observed increased cortical blood oxygenation in the older participants when completing the TMT. Finally, with respect to the combined measurement (O2Hb/item), no significantly higher hemodynamic cortical response per item was found within the older participants. The results confirm a deterioration of cognitive performance and an increase of cortical activity with increasing age. The findings are discussed in the light of current research.

Insulin sensitivity predicts cognitive decline in individuals with prediabetes.

INTRODUCTION: Epidemiological studies indicate an association between type 2 diabetes and cognitive dysfunction that appear to start already in the prediabetic state. Although cross-sectional studies have linked insulin resistance to impaired cognition, the potential predictive value of insulin resistance has not yet been sufficiently studied longitudinally without confounding by overt diabetes (and its pharmacological treatment). RESEARCH DESIGN AND METHODS: We investigated longitudinal data from participants of the 'Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration' Study. Subjects underwent a neurocognitive assessment battery (CERAD Plus battery; Consortium to Establish a Registry for Alzheimer's Disease) at baseline and followed every 2 years (median follow-up 4.0 Q1-3: 2.2-4.3 years). Subjects within a pre-diabetic glycated hemoglobin range of 5.6%-6.5% underwent 5-point 75 g oral glucose tolerance tests (OGTTs) with assessment of insulin sensitivity and insulin secretion (n=175). Subjects with newly diagnosed diabetes mellitus or with major depressivity (Beck Depression Inventory >20) were excluded (n=15). Data were analyzed by mixed models using sex, age and glycemic trait as fixed effects. Subject and time since first measurement were used as random effects. RESULTS: Insulin sensitivity was positively associated with the CERAD sum score (higher is better) in a time-dependent manner (p=0.0057). This result is mainly driven by a steeper decrease in the memory domain associated with lower insulin sensitivity (p=0.029). The interaction between age and insulin sensitivity was independent of glycemia (p=0.02). There was also no association between insulin secretion and cognition. CONCLUSIONS: Insulin resistance rather than sole elevation of blood glucose predicts cognitive decline, specifically in the memory domain, in persons with prediabetes. Treatments of diabetes that improve insulin sensitivity might therefore have the potential to postpone or even prevent cognitive decline in patients with diabetes.

Bottom-Up Design of Composite Supraparticles for Powder-Based Additive Manufacturing.

Additive manufacturing promises high flexibility and customized product design. Powder bed fusion processes use a laser to melt a polymer powder at predefined locations and iterate the scheme to build 3D objects. The design of flowable powders is a critical parameter for a successful fabrication process that currently limits the choice of available materials. Here, a bottom-up process is introduced to fabricate tailored polymer- and composite supraparticles for powder-based additive manufacturing processes by controlled aggregation of colloidal primary particles. These supraparticles exhibit a near-spherical shape and tailored composition, morphology, and surface roughness. These parameters can be precisely controlled by the mixing and size ratio of the primary particles. Polystyrene/silica composite particles are chosen as a model system to establish structure-property relations connecting shape, morphology, and surface roughness to the adhesion within the powder, which is accessed by tensile strength measurements. The adhesive properties are then connected to powder flowability and it is shown that the resulting powders allow the formation of dense powder films with uniform coverage. Finally, successful powder bed fusion is demonstrated by producing macroscopic single layer specimens with uniform distribution of nanoscale silica additives.

Intraindividual Neurofilament Dynamics in Serum Mark the Conversion to Sporadic Parkinson's Disease.

BACKGROUND AND OBJECTIVES: With disease-modifying treatment strategies on the horizon, stratification of individual patients at the earliest stages of Parkinson's disease (PD) is key-ideally already at clinical disease onset. Blood levels of neurofilament light chain (NfL) provide an easily accessible fluid biomarker that might allow capturing the conversion from prodromal to manifest PD. METHODS: We assessed longitudinal serum NfL levels in subjects converting from prodromal to manifest sporadic PD (converters), at-risk subjects, and matched controls (72 participants with ≈4 visits), using single-molecule array (Simoa) technique. RESULTS: While NfL levels were not increased at the prodromal stage, subjects converting to the manifest motor stage showed a significant intraindividual acceleration of the age-dependent increase of NfL levels. CONCLUSIONS: The temporal dynamics of intraindividual NfL blood levels might mark the conversion to clinically manifest PD, providing a potential stratification biomarker for individual disease onset in the advent of precision medicine for PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients.

Importance: The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures. Objective: To investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants. Design, Setting, and Participants: This multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019. Main Outcomes and Measures: Sensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer. Results: A total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%). Conclusions and Relevance: The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

Cortical oxygenation during exposure therapy - in situ fNIRS measurements in arachnophobia.

Exposure therapy is a well-studied and highly efficacious treatment for phobic disorders. Although the neurobiological model of fear is well underpinned by various studies, the mechanisms of exposure therapy are still under discussion. Partly, this is due to the fact that most neurophysiological methods like fMRI are not able to be used in the natural therapeutic settings. The current study used in situ measurements of cortical blood oxygenation (O2Hb) during exposure therapy by means of functional near-infrared spectroscopy. 37 subjects (N = 30 completers) underwent exposure therapy during 5 adapted sessions in which subjects were exposed to Tegenaria Domestica (domestic house spider - experimental condition) and Dendrobaena Veneta/ Eisenaia hortensis (red earthworm - control condition). Compared to the control condition, patients showed higher O2Hb levels in the anticipation and exposure phase of spider exposure in areas of the cognitive control network (CCN). Further, significant decreases in O2Hb were observed during the session accompanied by reductions in fear related symptoms. However, while symptoms decreased in a linear quadratic manner, with higher reductions in the beginning of the session, CCN activity decreased linearly. Further, higher anxiety at the beginning of session one was associated with increased O2Hb in the CCN. This association decreased within the following sessions. The current study sheds light on the neuronal mechanisms of exposure therapy. The results are discussed in light of a phase model of exposure therapy that posits a role of cognitive control in the beginning and routine learning at the end of the therapy session.

Machine Learning to Detect Alzheimer's Disease from Circulating Non-coding RNAs.

Blood-borne small non-coding (sncRNAs) are among the prominent candidates for blood-based diagnostic tests. Often, high-throughput approaches are applied to discover biomarker signatures. These have to be validated in larger cohorts and evaluated by adequate statistical learning approaches. Previously, we published high-throughput sequencing based microRNA (miRNA) signatures in Alzheimer's disease (AD) patients in the United States (US) and Germany. Here, we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by RT-qPCR. We computed models to assess the relation between miRNA expression and phenotypes, gender, age, or disease severity (Mini-Mental State Examination; MMSE). Of the 21 miRNAs, expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts. 18 miRNAs were significantly correlated with neurodegeneration (Benjamini-Hochberg adjusted P < 0.05) with highest significance for miR-532-5p (Benjamini-Hochberg adjusted P = 4.8 × 10-30). Machine learning models reached an area under the curve (AUC) value of 87.6% in differentiating AD patients from controls. Further, ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted P = 0.0002). Interestingly, the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells, while those up-regulated in AD were enriched in serum, exosomes, cytotoxic t-cells, and B-cells. Our study represents the next important step in translational research for a miRNA-based AD test.