Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus

BACKGROUND: The identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests. OBJECTIVE: We aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC). METHODS: Five wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement. RESULTS: Nine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s. CONCLUSION: There was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

ABSTRACT: INTRODUCTION: Anti-centromere antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20-40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA. METHODS: Sera collected from SSc patients (n=334) and various other diseases (n=619) and from healthy controls (n=175) were tested for anti-CENP-A antibodies by the novel CENP-A enzyme linked immunosorbent assay (ELISA). Furthermore, ACA were determined in the disease cohorts by IIF (ImmunoConcepts), CENP-B ELISA (Dr. Fooke), EliA(R) CENP (Phadia) and line-immunoassay (LIA, Mikrogen). Serological and clinical associations of anti-CENP-A with other autoantibodies were conducted in one participating centre. Inhibition experiments with either the CENP-A peptide or recombinant CENP-B were carried out to analyse the specificity of anti-CENP-A and -B antibodies. RESULTS: The CENP-A ELISA results were in good agreement with other ACA detection methods. According to the kappa method, the qualitative agreements were: 0.73 (vs. IIF), 0.81 (vs. LIA), 0.86 (vs. CENP-B ELISA) and 0.97 (vs. EliA(R) CENP). The quantitative comparison between CENP-A and CENP-B ELISA using 265 samples revealed a correlation value of rho=0.5 (by Spearman equation). The receiver operating characteristic analysis indicated that the discrimination between SSc patients (n=131) and various controls (n=134) was significantly better using the CENP-A as compared to CENP-B ELISA (p<0.0001). Modified Rodnan skin score was significantly lower in the CENP-A negative group compared to the positive patients (p=0.013). Inhibition experiments revealed no significant cross reactivity of anti-CENP-A and anti-CENP-B antibodies. Statistically relevant differences for gender ratio (p=0.0103), specific joint involvement (Jaccoud) (p=0.0006) and anti-phospholipid syndrome (p=0.0157) between ACA positive SLE patients and the entire SLE cohort were observed. CONCLUSION: Anti-CENP-A antibodies as determined by peptide ELISA represent a sensitive, specific and independent marker for the detection of ACA and are useful biomarkers for the diagnosis of SSc. Our data suggest that anti-CENP-A antibodies are a more specific biomarker for SSc than antibodies to CENP-B. Furthers studies are required to verify these findings.status: publishe

Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus

BackgroundThe identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests.ObjectiveWe aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC).MethodsFive wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement.ResultsNine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s.ConclusionThere was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern

Deep learning improves pancreatic cancer diagnosis using RNA-based variants

For optimal pancreatic cancer treatment, early and accurate diagnosis is vital. Blood-derived biomarkers and genetic predispositions can contribute to early diagnosis, but they often have limited accuracy or applicability. Here, we seek to exploit the synergy between them by combining the biomarker CA19-9 with RNA-based variants. We use deep sequencing and deep learning to improve differentiating pancreatic cancer and chronic pancreatitis. We obtained samples of nucleated cells found in peripheral blood from 268 patients suffering from resectable, non-resectable pancreatic cancer, and chronic pancreatitis. We sequenced RNA with high coverage and obtained millions of variants. The high-quality variants served as input together with CA19-9 values to deep learning models. Our model achieved an area under the curve (AUC) of 96% in differentiating resectable cancer from pancreatitis using a test cohort. Moreover, we identified variants to estimate survival in resectable cancer. We show that the blood transcriptome harbours variants, which can substantially improve noninvasive clinical diagnosis

Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug

AbstractAnti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Coaching und Mentoring als Reflexionsräume

Neben den universitären Begleitveranstaltungen während der Praxisphasen wurden für die Lehramtsstudierenden der Universität zu Köln zwei neue Formate entwickelt und implementiert, in denen die Möglichkeit besteht, schulpraktische Erfahrungen und berufsbiografische Themen mit professioneller Unterstützung individuell zu reflektieren: Coaching und Mentoring. Im folgenden Artikel wird zunächst das Konzept und die Realisierung der Lernbegleitung im Kölner Zentrum für LehrerInnenbildung (ZfL) beschrieben. Anschließend werden die quantitativen und qualitativen Evaluationsergebnisse der Begleitformate Coaching und Mentoring skizziert. (DIPF/Orig.

Synthesis of New Anthihelmintic Analogs of Marine Natural Products

The synthesis of new anthelmintic compounds derived from 2-amine-4-hydroxy-δ-valerolactams and 2,4-dialkylthiazoles is described. The synthetic procedures and biological activity data for these compounds will be presented

Ventral pallidum GABA neurons bidirectionally control opioid relapse across rat behavioral models.

Opioid addiction is a chronic, relapsing disorder. Whether addicted individuals are forced to abstain or they decide themselves to quit using drugs, relapse rates are high-especially upon encountering contexts and stimuli associated with prior opioid use. Rodents similarly show context- and cue-induced reinstatement of drug seeking following abstinence, and intriguingly, the neural circuits underlying these relapse-like behaviors differ when abstinence is involuntarily imposed, responding is extinguished, or animals decide themselves to cease taking drug. Here, we employ two complementary rat behavioral models of relapse-like behavior for the highly reinforcing opioid drug remifentanil, and asked whether GABAergic neurons in the ventral pallidum (VPGABA) control opioid seeking under these behavioral conditions. Specifically, we asked how chemogenetically stimulating VPGABA neurons with clozapine-N-oxide (CNO) influences the ability of contextual or discrete remifentanil-paired cues to reinstate drug seeking following either voluntary abstinence (punishment-induced; GroupPunish), or extinction training (GroupExt). In GroupPunish rats, we also chemogenetically inhibited VPGABA neurons, and examined spontaneous VP activity (Fos) during cued reinstatement. In both GroupPunish and GroupExt rats, stimulating Gq-signaling in VPGABA neurons augmented remifentanil reinstatement in a cue- and context-dependent manner. Conversely, engaging inhibitory Gi-signaling in VPGABA neurons in GroupPunish suppressed cue-induced reinstatement, and cue-triggered seeking was correlated with Fos expression in rostral, but not caudal VP. Neither stimulating nor inhibiting VPGABA neurons influenced unpunished remifentanil self-administration. We conclude that VPGABA neurons bidirectionally control opioid seeking regardless of the specific relapse model employed, highlighting their fundamental role in opioid relapse-like behavior across behavioral models, and potentially across species