Increased Frequency of Self-Reported Obsessive-Compulsive Symptoms in Patients with Functional Movement Disorders.

Background: Functional movement disorders (FMD) are associated with a high prevalence of psychiatric comorbidities. Objective: To assess the frequency of obsessive-compulsive symptoms (OCS) in FMD. Methods: A total of 167 consecutive patients with clinically definite FMD (mean age = 44.4 years, standard deviation [SD] = 12.0, 119 females) and 145 healthy controls (mean age = 43.2 years, SD = 11.8, 103 females) completed the Obsessive-Compulsive Inventory-Revised (OCI-R), which is a widely used tool for assessing OCS. The cutoff score ≥21 is indicative of clinically significant obsessive-compulsive disorder (OCD). Motor symptom severity was assessed using the Simplified FMD Rating Scale (S-FMDRS). All subjects completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints, health-related quality of life, and childhood trauma. Personality traits were assessed using the Big Five questionnaire. Results: FMD patients had higher mean OCI-R score and higher proportion of individuals with OCI-R ≥ 21 42%, 95% confidence interval (CI) = (30.2, 54.6) versus 16%, 95% CI = (8.2, 28.2) in controls, P < 0.001. Patients had higher scores in three domains: checking, ordering, and obsessing (P < 0.001). FMD patients with OCI-R score ≥21 had higher depression, anxiety, cognitive complaints, and lower quality of life compared to those with score <21 (P < 0.001). No correlation between OCI-R and S-FMDRS scores was found. Conclusions: FMD patients reported higher rates of OCS compared to controls, along with higher rates of non-motor symptoms and lower quality of life. This finding may have clinical implications and raises the possibility of shared risk factors and common pathophysiological mechanisms in FMD and OCD.

Emotional arousal in patients with functional movement disorders: A pupillometry study.

OBJECTIVE: Pathophysiology explanations for functional movement disorders often assume a role for emotional hyperarousal. Pupillometry is a validated method for evaluation of emotional arousal by detecting changes in pupil size in response to emotional stimuli. In a case-control study design, we aimed to study objective and subjective emotional arousal using pupillometry and affective ratings. To assess attentional engagement by affective stimuli, we used videooculographic tracking of eye movement patterns (scanpath). METHODS: Twenty-five female patients with functional movement disorders (mean age: 40.9 [SD 12.7] years) and 23 age matched healthy female controls participated in the study. Using infrared high-resolution eye-tracker, both pupil size and eye movement pattern in response to emotionally charged erotic, adventure, threat, victim, and neutral pictures were recorded along with subjective ratings of emotional valence and arousal of the presented pictures. RESULTS: A between-group comparison showed significantly smaller pupil dilation to adventure stimuli compared to neutral stimuli in patients compared to controls (P < 0.004, bootstrap, uncorr., adj. η2 = 0.00). No significant difference in pupillary response to other stimuli and scanpath parameters was found between the groups. Patients rated significantly lower emotional arousal to erotic pictures than controls (P < 0.001, bootstrap, uncorr., adj. η2 = 0.09). CONCLUSION: This study did not find evidence of autonomous or subjective emotional hyperarousal. The mismatch between objective autonomic measures and subjective arousal ratings in patients is of pathophysiological interest and in line with recent findings of impaired interoception in functional movement disorders.

Validity of the Aktibipo Self-rating Questionnaire for the Digital Self-assessment of Mood and Relapse Detection in Patients With Bipolar Disorder: Instrument Validation Study.

BACKGROUND: Self-reported mood is a valuable clinical data source regarding disease state and course in patients with mood disorders. However, validated, quick, and scalable digital self-report measures that can also detect relapse are still not available for clinical care. OBJECTIVE: In this study, we aim to validate the newly developed ASERT (Aktibipo Self-rating) questionnaire-a 10-item, mobile app-based, self-report mood questionnaire consisting of 4 depression, 4 mania, and 2 nonspecific symptom items, each with 5 possible answers. The validation data set is a subset of the ongoing observational longitudinal AKTIBIPO400 study for the long-term monitoring of mood and activity (via actigraphy) in patients with bipolar disorder (BD). Patients with confirmed BD are included and monitored with weekly ASERT questionnaires and monthly clinical scales (Montgomery-Åsberg Depression Rating Scale [MADRS] and Young Mania Rating Scale [YMRS]). METHODS: The content validity of the ASERT questionnaire was assessed using principal component analysis, and the Cronbach α was used to assess the internal consistency of each factor. The convergent validity of the depressive or manic items of the ASERT questionnaire with the MADRS and YMRS, respectively, was assessed using a linear mixed-effects model and linear correlation analyses. In addition, we investigated the capability of the ASERT questionnaire to distinguish relapse (YMRS≥15 and MADRS≥15) from a nonrelapse (interepisode) state (YMRS<15 and MADRS<15) using a logistic mixed-effects model. RESULTS: A total of 99 patients with BD were included in this study (follow-up: mean 754 days, SD 266) and completed an average of 78.1% (SD 18.3%) of the requested ASERT assessments (completion time for the 10 ASERT questions: median 24.0 seconds) across all patients in this study. The ASERT depression items were highly associated with MADRS total scores (P<.001; bootstrap). Similarly, ASERT mania items were highly associated with YMRS total scores (P<.001; bootstrap). Furthermore, the logistic mixed-effects regression model for scale-based relapse detection showed high detection accuracy in a repeated holdout validation for both depression (accuracy=85%; sensitivity=69.9%; specificity=88.4%; area under the receiver operating characteristic curve=0.880) and mania (accuracy=87.5%; sensitivity=64.9%; specificity=89.9%; area under the receiver operating characteristic curve=0.844). CONCLUSIONS: The ASERT questionnaire is a quick and acceptable mood monitoring tool that is administered via a smartphone app. The questionnaire has a good capability to detect the worsening of clinical symptoms in a long-term monitoring scenario.

No wink of sleep: Population sleep characteristics in response to the brexit poll and the 2016 U.S. presidential election.

INTRODUCTION: Personal well-being, including people's sleep characteristics, is affected by a variety of factors, one example of which is wide-ranging high-impact public events. In this study, we use a large sleep database obtained through a smartphone application for sleep tracking via anonymized time-sampled data to study the effect of two political events with a wide-ranging impact on people's sleep characteristics: the Brexit referendum in June 2016, and the presidential election of Donald Trump in November 2016 METHOD: Using Sleep as Android - an actigraphy-based sleep monitoring smartphone application - we collected 10.5 million geo-located sleep records from more than 69,000 users in Europe and North America. Population-based changes in sleep around each of these two events, in the United Kingdom and in the United States of America, were assessed using a non-parametric bootstrap test RESULTS: The analysis revealed a significant reduction by 16 min and 21 s in the mean sleep duration of British people in the night after the Brexit poll (p < 0.001). Similarly, the analysis of the US presidential election revealed a significant 12 min 49 s drop in the mean sleep duration during the night following the event, in comparison with the whole studied region (p < 0.001), and an increase by 5 min and 9 s in the subsequent night (p = 0.0328). Additional analysis comparing the election night to comparable days in preceding years revealed that the actual reduction in sleep length may have been even greater. There is also an increase in the proportion of subjects with very short sleep CONCLUSIONS: The results demonstrate a significant impact of two specific major political events on population sleep characteristics. Our results further underline the potential of mobile applications and informatics approaches in general to provide data that enable us to investigate fundamental physiological variables over time and location.

Relapse in schizophrenia: Definitively not a bolt from the blue.

Detailed study of the period before schizophrenic relapse when early warning signs (EWS) are present is crucial to effective pre-emptive strategies. To investigate the temporal properties of EWS self-reported weekly via a telemedicine system. EWS history was obtained for 61 relapses resulting in hospitalization involving 51 patients with schizophrenia. Up to 20 weeks of EWS history per case were evaluated using a non-parametric bootstrap test and generalized mixed-effects model to test the significance and homogeneity of the findings. A statistically significant increase in EWS sum score was detectable 5 weeks before hospitalization. However, analysis of EWS dynamics revealed a gradual, monotonic increase in EWS score across during the 8 weeks before a relapse. The findings-in contrast to earlier studies-suggest that relapse is preceded by a lengthy period during which pathophysiological processes unfold; these changes are reflected in subjective EWS.

Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration.

We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer.

Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity.

Obesity with related complications represents a widespread health problem. The etiopathogenesis of obesity is often studied using numerous rodent models. The mouse model of monosodium glutamate (MSG)-induced obesity was exploited as a model of obesity combined with insulin resistance. The aim of this work was to characterize the metabolic status of MSG mice by NMR-based metabolomics in combination with relevant biochemical and hormonal parameters. NMR analysis of urine at 2, 6, and 9 months revealed altered metabolism of nicotinamide and polyamines, attenuated excretion of major urinary proteins, increased levels of phenylacetylglycine and allantoin, and decreased concentrations of methylamine in urine of MSG-treated mice. Altered levels of creatine, citrate, succinate, and acetate were observed at 2 months of age and approached the values of control mice with aging. The development of obesity and insulin resistance in 6-month-old MSG mice was also accompanied by decreased mRNA expressions of adiponectin, lipogenetic and lipolytic enzymes and peroxisome proliferator-activated receptor-gamma in fat while mRNA expressions of lipogenetic enzymes in the liver were enhanced. At the age of 9 months, biochemical parameters of MSG mice were normalized to the values of the controls. This fact pointed to a limited predictive value of biochemical data up to age of 6 months as NMR metabolomics confirmed altered urine metabolic composition even at 9 months.

Differences in urinary proteins related to surgical margin status after radical prostatectomy.

Presented exploratory pilot study was aimed at evaluation of proteins present in urinary specimens collected from prostate cancer suffering subjects after radical prostatectomy, divided into two experimental cohorts: positive (n=15) and negative (n=15) surgical margins (PSM/NSM). The presence of PSM suggests inadequate cancer clearance and the possible need for additional treatment. Proper identification of these risk-patients is therefore of a paramount importance. Total protein profiles were firstly identified by using SDS-PAGE and compared by using partial least square discrimination analysis (PLS-DA), which revealed differences in molecular weights of 80-99 and 150-235 kDa between the experimental groups. For further identification of proteins, comparative proteomic technologies were employed. Two-dimensional gel electrophoresis with subsequent identification of protein spots by using MALDI-TOF mass fingerprinting revealed differential expression of proteins between NSM/PSM cohorts. Moreover, in PSM group, three uniquely identified proteins (cyclin-dependent kinase 6, galectin-3-binding protein and L-lactate dehydrogenase C chain) were found, which show tight connection with prostate cancer and presence of all of them was previously linked to certain aspects of prostate cancer. These proteins may be associated with the molecular mechanisms of prostate cancer development; hence, their identification may be helpful for the assessment of disease progression risk after radical prostatectomy, but also for possible early diagnosis.

Strategy for NMR metabolomic analysis of urine in mouse models of obesity--from sample collection to interpretation of acquired data.

The mouse model of monosodium glutamate induced obesity was used to examine and consequently optimize the strategy for analysis of urine samples by NMR spectroscopy. A set of nineteen easily detectable metabolites typical in obesity-related studies was selected. The impact of urine collection protocol, choice of (1)H NMR pulse sequence, and finally the impact of the normalization method on the detected concentration of selected metabolites were investigated. We demonstrated the crucial effect of food intake and diurnal rhythms resulting in the choice of a 24-hour fasting collection protocol as the most convenient for tracking obesity-induced increased sensitivity to fasting. It was shown that the Carr-Purcell-Meiboom-Gill (CPMG) experiment is a better alternative to one-dimensional nuclear Overhauser enhancement spectroscopy (1D-NOESY) for NMR analysis of mouse urine due to its ability to filter undesirable signals of proteins naturally present in rodent urine. Normalization to total spectral area provided comparable outcomes as did normalization to creatinine or probabilistic quotient normalization in the CPMG-based model. The optimized approach was found to be beneficial mainly for low abundant metabolites rarely monitored due to their overlap by strong protein signals.

Perioperative Tight Glucose Control Reduces Postoperative Adverse Events in Nondiabetic Cardiac Surgery Patients.

CONTEXT: Tight glucose control (TGC) reduces morbidity and mortality in patients undergoing elective cardiac surgery, but only limited data about its optimal timing are available to date. OBJECTIVE: The purpose of this article was to compare the effects of perioperative vs postoperative initiation of TGC on postoperative adverse events in cardiac surgery patients. DESIGN: This was a single center, single-blind, parallel-group, randomized controlled trial. SETTINGS: The setting was an academic tertiary hospital. PARTICIPANTS: Participants were 2383 hemodynamically stable patients undergoing major cardiac surgery with expected postoperative intensive care unit treatment for at least 2 consecutive days. INTERVENTION: Intensive insulin therapy was initiated perioperatively or postoperatively with a target glucose range of 4.4 to 6.1 mmol/L. MAIN OUTCOME MEASURES: Adverse events from any cause during postoperative hospital stay were compared. RESULTS: In the whole cohort, perioperatively initiated TGC markedly reduced the number of postoperative complications (23.2% vs 34.1%, 95% confidence interval [CI], 0.60-0.78) despite only minimal improvement in glucose control (blood glucose, 6.6 ± 0.7 vs 6.7 ± 0.8 mmol/L, P < .001; time in target range, 39.3% ± 13.7% vs 37.3% ± 13.8%, P < .001). The positive effects of TGC on postoperative complications were driven by nondiabetic subjects (21.3% vs 33.7%, 95% CI, 0.54-0.74; blood glucose 6.5 ± 0.6 vs 6.6 ± 0.8 mmol/L, not significant; time in target range, 40.8% ± 13.6% vs 39.7% ± 13.8%, not significant), whereas no significant effect was seen in diabetic patients (29.4% vs 35.1%, 95% CI, 0.66-1.06) despite significantly better glucose control in the perioperative group (blood glucose, 6.9 ± 1.0 vs 7.1 ± 0.8 mmol/L, P < .001; time in target range, 34.3% ± 12.7% vs 30.8% ± 11.5%, P < .001). CONCLUSIONS: Perioperative initiation of intensive insulin therapy during cardiac surgery reduces postoperative morbidity in nondiabetic patients while having a minimal effect in diabetic subjects.

Long-term seizure outcome after stereotactic amygdalohippocampectomy.

BACKGROUND: The aim of the study was to evaluate the long-term seizure outcome and complications after stereotactic radiofrequency amygdalohippocampectomy (SAHE) performed for mesial temporal lobe epilepsy (MTLE). METHODS: The article describes the cases of 61 patients who were treated at our institution during the period 2004-2010. Mean post-operative follow-up was 5.3 years. RESULTS: At the last postsurgical visit, 43 (70.5 %) patients were Engel Class I, six (9.8 %) Class II, nine (14.8 %) Class III and three (4.9 %) Class IV. The surgery was complicated by four intracranial haematomas. One of them caused acute hydrocephalus and was treated by shunting and resolved without sequelae. After SAHE, we performed open epilepsy surgery and re-thermo lesions in three and two patients, respectively (8.2 %). There were two cases of meningitis which required antibiotic treatment. In six patients psychiatric disorders developed and one of these committed suicide due to postoperative depression. CONCLUSIONS: Our results provide preliminary evidence for good long-term seizure outcomes after SAHE. SAHE could be an alternative therapy for MTLE.

Use of brightness wavelet transformation for automated analysis of serum metallothioneins- and zinc-containing proteins by Western blots to subclassify childhood solid tumours.

In this study, we determined serum levels of metallothioneins (MTs) and zinc in children with solid tumours (neuroblastoma, Hodgkin lymphoma, medulloblastoma, osteosarcoma, Ewing sarcoma and nephroblastoma) by differential pulse voltammetry Brdicka reaction and ELISA. Zn(II) level in patients sera was 40% compared to controls, contrariwise, MT level was 4.2 × higher in patients. No significant differences among single diagnoses were found both for Zn(II) and MT. When determined Zn(II)/MT ratio, in controls its value was 24.6, but it was 2.6 in patients. After Western-blotting with anti-MT and anti-Zn chicken antibodies, variable intensities of the bands within the samples were observed. The brightness curve obtained for each sample both for MT- and Zn blots was further analysed to produce a list of band positions together with some complementary information related to the intensity of the observed bands by the optimised algorithm. We constructed from those profiles decision trees that enable to distinguish different groups of tumours. The blood samples were heat-treated, in which we supposed mainly MT, but samples contained other thermostable Zn-containing proteins that were helpful for identification of embryonal tumours with 88% accuracy and for identification of sarcomas with 78% accuracy. In MT blots the accuracies were 53 and 45%, respectively. Simultaneous analysis of MT and Zn blots did not increased accuracy of identification neither in embryonal tumours (80%) nor in sarcomas. Those results are promising not only from diagnostic point of view but particularly in the area of studying of individual MT isoforms and their aggregates in malignant tumours.

Tissue specific electrochemical fingerprinting.

BACKGROUND: Proteomics and metalloproteomics are rapidly developing interdisciplinary fields providing enormous amounts of data to be classified, evaluated and interpreted. Approaches offered by bioinformatics and also by biostatistical data analysis and treatment are therefore of extreme interest. Numerous methods are now available as commercial or open source tools for data processing and modelling ready to support the analysis of various datasets. The analysis of scientific data remains a big challenge, because each new task sets its specific requirements and constraints that call for the design of a targeted data pre-processing approach. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a mathematical approach for evaluating and classifying datasets obtained by electrochemical analysis of metallothionein in rat 9 tissues (brain, heart, kidney, eye, spleen, gonad, blood, liver and femoral muscle). Tissue extracts were heated and then analysed using the differential pulse voltammetry Brdicka reaction. The voltammograms were subsequently processed. Classification models were designed making separate use of two groups of attributes, namely attributes describing local extremes, and derived attributes resulting from the level=5 wavelet transform. CONCLUSIONS/SIGNIFICANCE: On the basis of our results, we were able to construct a decision tree that makes it possible to distinguish among electrochemical analysis data resulting from measurements of all the considered tissues. In other words, we found a way to classify an unknown rat tissue based on electrochemical analysis of the metallothionein in this tissue.