Cytokeratin positivity in paraffin-embedded malignant melanomas : comparative study of KL1, A4 and Lu5 antibodies

The unclear role of cytokeratin (CK) in the progression and diagnostics of malignant melanomas stimulated us to compare the reactivity of three antibodies directed to CK in 109 paraffin-embedded melanomas. By far the majority of melanomas did not express cytokeratin even at the<1% level, only vimentin. In about 6% of melanomas it was possible to find CK expression ranging between 3 and 40% of melanoma cells. There was a correlation between CK expression and pTstage. Cytokeratin-expressing tumours were found in the more advanced pT-stages. The independent prognostic values of none of the three CK antibodies investigated could be shown

Early Life Cognitive Abilities and Body Weight: Cross-Sectional Study of the Association of Inhibitory Control, Cognitive Flexibility, and Sustained Attention with BMI Percentiles in Primary School Children

The objective of this study was to investigate the association of different cognitive abilities with children’s body weight adjusted for further weight influencing sociodemographic, family, and lifestyle factors. Cross-sectional data of 498 primary school children (7.0 ± 0.6 years; 49.8% boys) participating in a health promotion programme in southwest Germany were used. Children performed a computer-based test battery (KiTAP) including an inhibitory control task (Go-Nogo paradigm), a cognitive flexibility task, and a sustained attention task. Height and weight were measured in a standardized manner and converted to BMI percentiles based on national standards. Sociodemographic features (migration background and parental education), family characteristics (parental body weight), and children’s lifestyle (TV consumption, physical activity, consumption of sugar-sweetened beverages and breakfast habits) were assessed via parental questionnaire. A hierarchical regression analysis revealed inhibitory control and cognitive flexibility to be significant cognitive predictors for children’s body weight. There was no association concerning sustained attention. The findings suggest that especially cognitive abilities known as executive functions (inhibitory control and cognitive flexibility) are associated with children’s body weight. Future longitudinal and intervention studies are necessary to investigate the directionality of the association and the potential of integrating cognitive training in obesity prevention strategies. This trial is registered with ClinicalTrials.gov DRKS00000494

Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase

Objective To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers. Methods The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA. Results CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05). Conclusion Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome

Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Objective: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. Methods: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), b-amyloid (Ab(1)-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. Results: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Ab1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. Conclusions: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Early Life Cognitive Abilities and Body Weight: Cross-Sectional Study of the Association of Inhibitory Control, Cognitive Flexibility, and Sustained Attention with BMI Percentiles in Primary School Children

The objective of this study was to investigate the association of different cognitive abilities with children&apos;s body weight adjusted for further weight influencing sociodemographic, family, and lifestyle factors. Cross-sectional data of 498 primary school children (7.0 ± 0.6 years; 49.8% boys) participating in a health promotion programme in southwest Germany were used. Children performed a computer-based test battery (KiTAP) including an inhibitory control task (Go-Nogo paradigm), a cognitive flexibility task, and a sustained attention task. Height and weight were measured in a standardized manner and converted to BMI percentiles based on national standards. Sociodemographic features (migration background and parental education), family characteristics (parental body weight), and children&apos;s lifestyle (TV consumption, physical activity, consumption of sugar-sweetened beverages and breakfast habits) were assessed via parental questionnaire. A hierarchical regression analysis revealed inhibitory control and cognitive flexibility to be significant cognitive predictors for children&apos;s body weight. There was no association concerning sustained attention. The findings suggest that especially cognitive abilities known as executive functions (inhibitory control and cognitive flexibility) are associated with children&apos;s body weight. Future longitudinal and intervention studies are necessary to investigate the directionality of the association and the potential of integrating cognitive training in obesity prevention strategies. This trial is registered with ClinicalTrials.gov DRKS00000494

Illness and determinants of health-related quality of life in a cross-sectional sample of schoolchildren in different weight categories

[english] Aim: To study associations between health-related quality of life (HRQoL), frequency of illness, and weight in primary school children in southern Germany. Methods: Data from baseline measurements of the outcome evaluation of a teacher based health promotion programme (“Join the Healthy Boat”) were analysed. Parents provided information about their children’s HRQoL (KINDL, EQ5D-Y Visual Analogue Scale). The number of visits to a physician, children’s days of absence because of sickness, and parental days of absence from work due to their children’s illness during the last year of school/kindergarten were queried. Children’s weight status was determined by body mass index (BMI), central obesity by waist to height ratio (WHtR ≥0.5). Results: From 1,888 children (7.1±0.6 years), 7.8% were underweight, 82% had normal weight, 5.7% were overweight and 4.4% obese. 8.4% of all children were centrally obese. Bivariate analysis showed no significant differences for parental absence and visits to a physician in weight groups classified by BMI, but obese children had more sick days than non-obese. Centrally obese children differed significantly from the rest in the number of sick days and visits to a physician, but not in the frequency of parental absence. In regression analyses, central obesity correlated significantly with EQ5D-Y VAS, KINDL total score and the subscales of “psyche”, “family” and “friends”. BMI weight groups showed no significant associations. Conclusions: Central obesity but not BMI derived overweight and obesity is associated with HRQoL and visits to a physician in primary school children. Future studies should include WHtR. Preventive measures for children should focus on a reduction of or slowed increase in waist circumference