Kawasaki disease and increased cardiovascular risk: Is there a link to circulating glycocalyx biomarkers?

AIMS: Kawasaki disease (KD) is an acute systemic vasculitis with possible long-term impact of general cardio-vascular health. An endothelial glycocalyx disorder during the disease's acute phase might predispose to long-term vascular anomalies leading to endothelial dysfunction and atherosclerosis. To investigate any association between increased cardiovascular risk and endothelial glycocalyx, we assessed circulating glycocalyx components in patients with a KD history, and analysed their association with acute-phase clinical features and more importantly, with patients' current cardiovascular risk factors. METHODS: This prospective observational cohort study included 51 subjects: 31 patients with a history of KD, and 20 healthy subjects matched for age and sex. We analysed serum syndecan-1 and hyaluronan via ELISA. We assessed features reported during the acute phase of KD such as blood counts, C-reactive protein (CRP) levels and coronary artery aneurysms (CAA), and their current blood pressure and lipid markers in relation to measured glycocalyx components. RESULTS: Our multivariate analysis revealed that hyaluronan and syndecan-1 levels were not associated with KD. However, the latter exhibited a significant association with acute-phase blood count alterations in patients with KD. Furthermore, significant interactions of hyaluronan and syndecan-1 with certain cardiovascular risk factors like blood lipids and blood pressure were only present in KD patients. CONCLUSION: Vasculitis during KD's acute phase might predispose to a long-term endothelial glycocalyx alteration, influenced by other factors having a vascular impact such as blood pressure and circulating lipids. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register on 25th February 2016, DRKS00010071 https://www.drks.de/drks_web/.

KD Diagnosis Does Not Increase Cardiovascular Risk in Children According to Dynamic Intima-Media Roughness Measurements.

BACKGROUND: Kawasaki Disease (KD) is a generalized vasculitis in childhood with possible long-term impact on cardiovascular health besides the presence of coronary artery lesions. Standard vascular parameters such as carotid intima-media thickness (cIMT) have not been established as reliable markers of vascular anomalies after KD. The carotid intima-media roughness (cIMR) representing carotid intimal surface structure is considered a promising surrogate marker for predicting cardiovascular risk even beyond cIMT. We therefore measured cIMR in patients with a history of KD in comparison to healthy controls to investigate whether KD itself and/or KD key clinical aspects are associated with cIMR alterations in the long-term. METHODS: We assessed cIMR in this case-control study (44 KD, mean age in years (SD); 13.4 (7.5); 36 controls, mean age 12.1 (5.3)) approximately matched by sex and age. Different clinical outcomes such as the coronary artery status and acute phase inflammation data were analyzed in association with cIMR values. RESULTS: When comparing all patients with KD to healthy controls, we detected no significant difference in cIMR. None of the clinical parameters indicating the disease severity, such as the persistence of coronary artery aneurysm, were significantly associated with our cIMR values. However, according to our marginally significant findings (p = 0.044), we postulate that the end-diastolic cIMR may be rougher than the end-systolic values in KD patients. CONCLUSIONS: We detected no significant differences in cIMR between KD patients and controls that could confirm any evidence that KD predisposes patients to a subsequent general arteriopathy. Our results, however, need to be interpreted in the light of the low number of study participants.

Stability of Attention Performance of Adults with ADHD over Time: Evidence from Repeated Neuropsychological Assessments in One-Month Intervals.

Neuropsychological assessments of attention are valuable sources of information in the clinical evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the attention performance of adults with ADHD is stable or fluctuates over time, which is of great importance in the interpretation of clinical assessments. This study aimed to explore the stability of attention performance of adults with ADHD in repeated assessments at one-month intervals. Twenty-one adults diagnosed with ADHD took part in this study by completing selective attention and vigilance tests three times, each one month apart. Test scores of participants were compared with and interpreted based on test norms. A considerable proportion of 'below average' performance scores were observed in most of the variables of selective attention and vigilance in all three assessments. Further, selective attention and vigilance performance scores did not differ significantly between the three repeated assessments. Finally, the majority of participants received consistent test score interpretations across the three repeated assessments. This study confirms previous research and highlights abnormal selective attention and vigilance performance in adults with ADHD. Further, this study preliminarily demonstrates relatively stable attention performance across repeated assessments, which has the potential to support clinical assessment, treatment planning, and evaluation.

Acute effects of a single dose of 2 mA of anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex on executive functions in patients with schizophrenia-A randomized controlled trial.

OBJECTIVE: Cognitive impairments are a frequent and difficult to treat symptom in patients with schizophrenia and the strongest predictor for a successful reintegration in occupational and everyday life. Recent research suggests transcranial direct current stimulation (tDCS) to enhance cognition in this patient group. However, the question regarding its acute effectiveness on executive functions remains largely unanswered. Here, we examined in a randomized, double blind, sham-controlled repeated-measures design the impact of tDCS on performance in several executive functions in patients with schizophrenia, schizoaffective disorder or acute transient psychotic disorder. METHODS: Patients (N = 48) were tested twice using standardized, well-constructed and clinically validated neuropsychological tests assessing verbal working memory, response inhibition, mental flexibility and problem solving. In session 1 they solely underwent the neuropsychological assessment, whereas in session 2 they additionally received 2 mA of anodal tDCS stimulation over the left dorsolateral prefrontal cortex (DLPFC), cathode right supraorbital ridge, or sham stimulation for 20 minutes. RESULTS: Patients of both groups were not able to correctly discriminate the type of stimulation received confirming the success of the blinding procedure. However, analyzing the whole sample the change in performance from session 1 to session 2 was the same in the verum as in the sham condition (all p >.5). Moreover, a subsequent exploratory analysis showed that performance in the response inhibition task was worse for patients that engaged in the task within 20 minutes after the end of the verum stimulation. CONCLUSION: Hence, 2 mA of anodal tDCS applied over the left DLPFC did not acutely enhance executive functions in patients with schizophrenia or related disorders but impaired performance in the response inhibition task shortly after. Future studies should continue to seek for effective stimulation configurations for this patient group. CLINICAL TRIAL REGISTRATION: The study is registered in the "Deutsches Register Klinischer Studien DRKS", German Clinical Trial Register and has been allocated the following number: DRKS00022126.

Working capacity of patients with Parkinson's disease - A systematic review.

INTRODUCTION: Parkinson's disease (PD) is characterized by motor and non-motor symptoms and has a median age-of-onset around 55 years. Many PD patients are thus diagnosed before reaching retirement age and it is likely that they are confronted with a reduced working capacity or loss of employment. This systematic literature review gives an overview of the research conducted on work capacity in PD. METHODS: A systematic literature search was performed in PsycINFO and PubMed (Keywords: "Parkinson" or "Parkinson's disease" combined with "employment", "work", "working", "retire" or "retirement"). RESULTS: Thirteen studies were identified and showed that PD patients retired 4-7 years earlier than the general population. Furthermore, 23%-75% of patients report that they retired early because of PD and slowness and fatigue were reported as the most debilitating symptoms in relation to working capacity. Early retirement of PD patients is associated with high societal costs and a high loss of individual lifetime earnings. Although many employed PD patients asked for adjustments at their workplace, their employers did not always support these. CONCLUSIONS: PD has a detrimental effect on working capacity and is associated with high costs. Employed PD patients do not, however, always receive the support they need. It is therefore very relevant that employers and patients are informed about strategies and techniques developed for counteracting symptoms of PD which might support patients to stay in the workforce for a longer period of time.

Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study.

PURPOSE: Artesunate (ART) has been used for a long time in the treatment of Plasmodium falciparum malaria and has been considered safe. The present phase I study aimed to determine the daily dose of ART that is well tolerated as add-on therapy in patients with breast cancer for 4 weeks of therapy. Ototoxicity could be a potential safety concern in settings different from malaria. Therefore, comprehensive audiological assessment was essential. METHODS: The ARTIC M33/2 study was a prospective, open, uncontrolled, monocentric phase I dose-escalation study to evaluate the safety and tolerability of ART in patients with advanced breast cancer. Patients received either 100, 150 or 200 mg oral ART daily for a test phase of 4 weeks as add-on therapy to their ongoing oncological treatment. For the investigation of the safety of ART for hearing, an audiological assessment was performed with each patient before the intake of ART and after 4 weeks of therapy. RESULTS: Twenty-three female patients were included in the study. During the test phase, four patients had adverse events (AEs) of the auditory system possibly related to the intake of ART. However, none of these AEs was classified as severe AE (SAE) and did not require treatment interruption. Four patients had AEs concerning the vestibular system (vertigo) during the test phase, one of which was classified as SAE. However, the SAE was fully reversible after discontinuation of ART. CONCLUSION: None of the audiological results after 4 weeks of therapy with ART showed any dose-limiting auditory toxicity. However, audiological monitoring in further clinical studies with prolonged use of oral ART in doses up to 200 mg daily is warranted. The ARTIC M33/2 study is registered at eudract.ema.europa.eu with the Number 2007-004432-23 and at clinicaltrials.gov with the Number NCT00764036.

Efficacy of massage therapy in chronic pain: a pragmatic randomized trial.

BACKGROUND: Although classic massage is used widely in Germany and elsewhere for treating chronic pain conditions, there are no randomized controlled trials (RCT). DESIGN: Pragmatic RCT of classic massage compared to standard medical care (SMC) in chronic pain conditions of back, neck, shoulders, head and limbs. OUTCOME MEASURE: Pain rating (nine-point Likert-scale; predefined main outcome criterion) at pretreatment, post-treatment, and 3 month follow-up, as well as pain adjective list, depression, anxiety, mood, and body concept. RESULTS: Because of political and organizational problems, only 29 patients were randomized, 19 to receive massage, 10 to SMC. Pain improved significantly in both groups, but only in the massage group was it still significantly improved at follow-up. Depression and anxiety were improved significantly by both treatments, yet only in the massage group maintained at follow-up. CONCLUSION: Despite its limitation resulting from problems with numbers and randomization this study shows that massage can be at least as effective as SMC in chronic pain syndromes. Relative changes are equal, but tend to last longer and to generalize more into psychologic domains. Because this is a pilot study, the results need replication, but our experiences might be useful for other researchers.

A new piece of an old jigsaw: glucose kinase is activated posttranslationally in a glucose transport-dependent manner in streptomyces coelicolor A3(2).

Members of the soil-dwelling prokaryotic genus Streptomyces are indispensable for the recycling of complex polysaccharides, and produce a wide range of natural products. Nutrient limitation is likely to be a major signal for the onset of their development, resulting in spore formation by specialized aerial hyphae. Streptomycetes grow on numerous carbon sources, which they utilize in a preferential manner. The main signaling pathway underlying this phenomenon is carbon catabolite repression, which in streptomycetes is totally dependent on the glycolytic enzyme glucose kinase (Glk). How Glk exerts this fascinating dual role (metabolic and regulatory) is still largely a mystery. We show here that while Glk is made constitutively throughout the growth of Streptomyces coelicolor A3(2), its catalytic activity is modulated in a carbon source-dependent manner: while cultures growing exponentially on glucose exhibit high Glk activity, mannitol- grown cultures show negligible activity. Glk activity was directly proportional to the amount of two Glk isoforms observed by Western blot analysis. The activity profile of GlcP, the major glucose permease, correlated very well with that of Glk. Our data are consistent with a direct interaction between Glk and GlcP, suggesting that a Glk-GlcP permease complex is required for efficient glucose transport by metabolic trapping. This is supported by the strongly reduced accumulation of glucose in glucose kinase mutants. A model to explain our data is presented.

GlcP constitutes the major glucose uptake system of Streptomyces coelicolor A3(2).

We provide a functional and regulatory analysis of glcP, encoding the major glucose transporter of Streptomyces coelicolor A3(2). GlcP, a member of the Major Facilitator Superfamily (MFS) of bacterial and eucaryotic sugar permeases, was found to be encoded twice at two distinct loci, glcP1 and glcP2, located in the central core and in the variable right arm of the chromosome respectively. Heterologous expression of GlcP in Escherichia coli led to the full restoration of glucose fermentation to mutants lacking glucose transport activity. Biochemical analysis revealed an affinity constant in the low-micromolar range and substrate specificity for glucose and 2-deoxyglucose. Deletion of glcP1 but not glcP2 led to a drastic reduction in growth on glucose reflected by the loss of glucose uptake. This correlated with transcriptional analyses, which showed that glcP1 transcription was strongly inducible by glucose, while glcP2 transcripts were barely detectable. In conclusion, GlcP, which is the first glucose permease from high G+C Gram-positive bacteria characterized at the molecular level, represents the major glucose uptake system in S. coelicolor A3(2) that is indispensable for the high growth rate on glucose. It is anticipated that the activity of GlcP is linked to other glucose-mediated phenomena such as carbon catabolite repression, morphogenesis and antibiotic production.