who is missed and why?

Background Public health monitoring depends on valid health and disability estimates in the population 65+ years. This is hampered by high non- participation rates in this age group. There is limited insight into size and direction of potential baseline selection bias. Methods We analyzed baseline non-participation in a register-based random sample of 1481 inner-city residents 65+ years, invited to a health examination survey according to demographics available for the entire sample, self-report information as available and reasons for non-participation. One year after recruitment, non- responders were revisited to assess their reasons. Results Five groups defined by participation status were differentiated: participants (N = 299), persons who had died or moved (N = 173), those who declined participation, but answered a short questionnaire (N = 384), those who declined participation and the short questionnaire (N = 324), and non-responders (N = 301). The results confirm substantial baseline selection bias with significant underrepresentation of persons 85+ years, persons in residential care or from disadvantaged neighborhoods, with lower education, foreign citizenship, or lower health-related quality of life. Finally, reasons for non-participation could be identified for 78 % of all non-participants, including 183 non- responders. Conclusion A diversity in health problems and barriers to participation exists among non-participants. Innovative study designs are needed for public health monitoring in aging populations

Brain-Derived Neurotrophic Factor (Val66Met) and Serotonin Transporter (5-HTTLPR) Polymorphisms Modulate Plasticity in Inhibitory Control Performance Over Time but Independent of Inhibitory Control Training

Several studies reported training-induced improvements in executive function tasks and also observed transfer to untrained tasks. However, the results are mixed and there is large interindividual variability within and across studies. Given that training-related performance changes would require modification, growth or differentiation at the cellular and synaptic level in the brain, research on critical moderators of brain plasticity potentially explaining such changes is needed. In the present study, a pre-post-follow-up design (N=122) and a three-weeks training of two response inhibition tasks (Go/NoGo and Stop-Signal) was employed and genetic variation (Val66Met) in the brain-derived neurotrophic factor (BDNF) promoting differentiation and activity-dependent synaptic plasticity was examined. Because Serotonin (5-HT) signaling and the interplay of BDNF and 5-HT are known to critically mediate brain plasticity, genetic variation in the 5-HT transporter (5-HTTLPR) was also addressed. The overall results show that the kind of training (i.e., adaptive vs. non-adaptive) did not evoke genotype-dependent differences. However, in the Go/NoGo task, better inhibition performance (lower commission errors) were observed for BDNF Val/Val genotype carriers compared to Met-allele ones supporting similar findings from other cognitive tasks. Additionally, a gene-gene interaction suggests a more impulsive response pattern (faster responses accompanied by higher commission error rates) in homozygous l-allele carriers relative to those with the s-allele of 5-HTTLPR. This, however, is true only in the presence of the Met-allele of BDNF, while the Val/Val genotype seems to compensate for such non-adaptive responding. Intriguingly, similar results were obtained for the Stop-Signal task. Here, differences emerged at post-testing, while no differences were observed at T1. In sum, although no genotype-dependent differences between the relevant training groups emerged suggesting no changes in the trained inhibition function, the observed genotype-dependent performance changes from pre- to post measurement may reflect rapid learning or memory effects linked to BDNF and 5-HTTLPR. In line with ample evidence on BDNF and BDNF-5-HT system interactions to induce (rapid) plasticity especially in hippocampal regions and in response to environmental demands, the findings may reflect genotype-dependent differences in the acquisition and consolidation of task-relevant information, thereby facilitating a more adaptive responding to task-specific requirements

Tidal volumes during delivery room stabilization of (near) term infants

BACKGROUND We sought to assess tidal volumes in (near) term infants during delivery room stabilization. METHODS Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH$_{2}$O and positive end-expiratory airway pressure of 5 cmH$_{2}$O. Expired tidal volumes (V$_{t}$) were measured with a respiratory function monitor. Target range for V$_{t}$ was defined to be 4 - 8 ml/kg. RESULTS Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 - 39.0) weeks received 1828 inflations with a median V$_{t}$ of 4.6 (3.3 - 6.2) ml/kg. Median V$_{t}$ was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25-27) % of the inflations were in the target rage over the duration of PPV while 42 (25 - 65) % and 10 (3 - 33) % were above and below target range. CONCLUSIONS Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. TRIAL REGISTRATION This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493)

Effect of fingolimod on health-related quality of life in paediatric patients with multiple sclerosis: results from the phase 3 PARADIG MS Study

Background In the PARADIG MS Study, fingolimod demonstrated superior efficacy versus interferon (IFN) β-1a and comparable overall incidence of adverse events but slightly higher rate of serious adverse events in patients with paediatric-onset multiple sclerosis (PoMS). Here, we report the health-related quality of life (HRQoL) outcomes from PARADIG MS . Methods Patients with PoMS (N=215; aged 10–<18 years) were randomised to once-daily oral fingolimod (N=107) or once-weekly intramuscular IFN β-1a (N=108). HRQoL outcomes were assessed using the 23-item Pediatric Quality of Life (PedsQL) scale that comprises Physical and Psychosocial Health Summary Scores (including Emotional, Social and School Functioning). A post hoc inferential analysis evaluated changes in self-reported or parent-reported PedsQL scores from baseline up to 2 years between treatment groups using an analysis of covariance model. Results Treatment with fingolimod showed improvements versus IFN β-1a on the PedsQL scale in both the self-reported and parent-reported Total Scale Scores (4.66 vs −1.16, p≤0.001 and 2.71 vs −1.02, p≤0.05, respectively). The proportion of patients achieving a clinically meaningful improvement in the PedsQL Total Scale Score was two times higher with fingolimod versus IFN β-1a per the self-reported scores (47.5% vs 24.2%, p=0.001), and fingolimod was favoured versus IFN β-1a per the parent-reported scores (37.8% vs 24.7%, p=non-significant). Group differences in self-reported Total Scale Scores in favour of fingolimod were most pronounced among patients who had ≥2 relapses in the year prior to study entry or who showed improving or stable Expanded Disability Status Scale scores during the study. Conclusion Fingolimod improved HRQoL compared with IFN β-1a in patients with PoMS as evidenced by the self-reported and parent-reported PedsQL scores

Human β-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model

Asthma and allergies are complex, chronic inflammatory diseases in which genetic and environmental factors are crucial. Protection against asthma and allergy development in the context of farming environment is established by early animal contact, unpasteurized milk consumption and gut microbiota maturation. The human β-defensin 2 (hBD-2) is a host defense peptide present almost exclusively in epithelial tissues, with pronounced immunomodulatory properties, which has recently been shown to ameliorate asthma and IBD in animal models. We hypothesized that adequate hBD-2 secretion plays a role in the protection against asthma and allergy development and that genetic variations in the complex gene locus coding for hBD-2 may be a risk factor for developing these diseases, if as a consequence, hBD-2 is insufficiently produced. We used MALDI-TOF MS genotyping, sequencing and a RFLP assay to study the genetic variation including mutations, polymorphisms and copy number variations in the locus harboring both genes coding for hBD-2 (DEFB4A and DEFB4B). We administered hBD-2 orally in a mouse model of house dust mite (HDM)-asthma before allergy challenge to explore its prophylactic potential, thereby mimicking a protective farm effect. Despite the high complexity of the region harboring DEFB4A and DEFB4B we identified numerous genetic variants to be associated with asthma and allergy in the GABRIELA Ulm population of 1,238 children living in rural areas, including rare mutations, polymorphisms and a lack of the DEFB4A. Furthermore, we found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in our HDM mouse model. These data indicate that inadequate genetic capacity for hBD-2 is associated with increased asthma and allergy risk while adequate and early hBD-2 administration (in a mouse model) prevents atopic asthma. This suggests that hBD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development

Operationalizing multimorbidity and autonomy for health services research in aging populations - the OMAHA study

<p>Abstract</p> <p>Background</p> <p>As part of a Berlin-based research consortium on health in old age, the OMAHA (Operationalizing Multimorbidity and Autonomy for Health Services Research in Aging Populations) study aims to develop a conceptual framework and a set of standardized instruments and indicators for continuous monitoring of multimorbidity and associated health care needs in the population 65 years and older.</p> <p>Methods/Design</p> <p>OMAHA is a longitudinal epidemiological study including a comprehensive assessment at baseline and at 12-month follow-up as well as brief intermediate telephone interviews at 6 and 18 months. In order to evaluate different sampling procedures and modes of data collection, the study is conducted in two different population-based samples of men and women aged 65 years and older. A geographically defined sample was recruited from an age and sex stratified random sample from the register of residents in Berlin-Mitte (Berlin OMAHA study cohort, n = 299) for assessment by face-to-face interview and examination. A larger nationwide sample (German OMAHA study cohort, n = 730) was recruited for assessment by telephone interview among participants in previous German Telephone Health Surveys. In both cohorts, we successfully applied a multi-dimensional set of instruments to assess multimorbidity, functional disability in daily life, autonomy, quality of life (QoL), health care services utilization, personal and social resources as well as socio-demographic and biographical context variables. Response rates considerably varied between the Berlin and German OMAHA study cohorts (22.8% vs. 59.7%), whereas completeness of follow-up at month 12 was comparably high in both cohorts (82.9% vs. 81.2%).</p> <p>Discussion</p> <p>The OMAHA study offers a wide spectrum of data concerning health, functioning, social involvement, psychological well-being, and cognitive capacity in community-dwelling older people in Germany. Results from the study will add to methodological and content-specific discourses on human resources for maintaining quality of life and autonomy throughout old age, even in the face of multiple health complaints.</p

Imaging of nanoparticle-labeled stem cells using magnetomotive optical coherence tomography, laser speckle reflectometry, and light microscopy

Cell transplantation and stem cell therapy are promising approaches for regenerative medicine and are of interest to researchers and clinicians worldwide. However, currently, no imaging technique that allows three-dimensional in vivo inspection of therapeutically administered cells in host tissues is available. Therefore, we investigate magnetomotive optical coherence tomography (MM-OCT) of cells labeled with magnetic particles as a potential noninvasive cell tracking method. We develop magnetomotive imaging of mesenchymal stem cells for future cell therapy monitoring. Cells were labeled with fluorescent iron oxide nanoparticles, embedded in tissue-mimicking agar scaffolds, and imaged using a microscope setup with an integrated MM-OCT probe. Magnetic particle-induced motion in response to a pulsed magnetic field of 0.2 T was successfully detected by OCT speckle variance analysis, and cross-sectional and volumetric OCT scans with highlighted labeled cells were obtained. In parallel, fluorescence microscopy and laser speckle reflectometry were applied as two-dimensional reference modalities to image particle distribution and magnetically induced motion inside the sample, respectively. All three optical imaging modalities were in good agreement with each other. Thus, magnetomotive imaging using iron oxide nanoparticles as cellular contrast agents is a potential technique for enhanced visualization of selected cells in OCT

High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation

Cardiomyopathies might lead to end-stage heart disease with the requirement of drastic treatments like bridging up to transplant or heart transplantation. A not precisely known proportion of these diseases are genetically determined. We genotyped 43 index-patients (30 DCM, 10 ARVC, 3 RCM) with advanced or end stage cardiomyopathy using a gene panel which covered 46 known cardiomyopathy disease genes. Fifty-three variants with possible impact on disease in 33 patients were identified. Of these 27 (51%) were classified as likely pathogenic or pathogenic in the MYH7, MYL2, MYL3, NEXN, TNNC1, TNNI3, DES, LMNA, PKP2, PLN, RBM20, TTN, and CRYAB genes. Fifty-six percent (n = 24) of index-patients carried a likely pathogenic or pathogenic mutation. Of these 75% (n = 18) were familial and 25% (n = 6) sporadic cases. However, severe cardiomyopathy seemed to be not characterized by a specific mutation profile. Remarkably, we identified a novel homozygous PKP2-missense variant in a large consanguineous family with sudden death in early childhood and several members with heart transplantation in adolescent age