Piezoelectric titanium based microfluidic pump and valves for implantable medical applications

Medical devices often require precise movement of fluids. Automated implants with no need for manual handling improve patient care significantly. However, existing microfluidic devices do not fulfil the necessary specifications of size, safety, hermetic sealing, and artefact free medical imaging, as well as energy efficiency combined with adapted fluidic properties. In this work we designed, manufactured, and experimentally evaluated three piezoelectric microfluidic devices for implant automation: a diaphragm pump, a normally closed valve, and a normally open valve. All devices are made of titanium, minimizing the risk of artefacts in medical imaging. They have similar form factors and use the same actuation method. For the later, a specific mounting process of the piezo actuator enables outstanding fluidic performance during experimental evaluations. The titanium micropumps show a maximal flow of (14 ± 2.2) ml/min and pressure build-up of 75 kPa. The normally closed valve’s leakage rates are extremely low with less than 1 μL/min. Detailed investigations further include the actuator stroke, a lifetime study for normally open valves, and a numerical and experimental evaluation of the normally closed valve’s spring foil. The introduced titanium technology platform is ideally suited for system integration accounted for by the use of the same actuation principle and the similar form factor and a simple design. The development of small, smart, and energy efficient implants for improved treatment is possible based on the introduced platform

Food Intake, Diet Quality and Behavioral Problems in Children: Results from the GINI-plus/LISA-plus Studies

Background/Aims: To assess the association between food intake and diet quality and behavioral problems at the 10-year follow-up of the two population-based birth cohorts of the studies German Infant Nutritional Intervention and `Influences of lifestyle-related factors on the immune system and the development of allergies in childhood'. Methods: Cross-sectional data on food intake over the past year were collected by a parent-reported food frequency questionnaire. Diet quality was based on reference values of food amounts of the optimized mixed diet. Behavioral problems were assessed by a parent-reported Strengths and Difficulties Questionnaire. Relationships between food category intake, diet quality and behavior problems were examined using multivariable regression modeling adjusted for gender, sociodemographic characteristics, body mass index, physical exercise, television viewing/PC use and total energy intake. A total of 3,361 children with complete data were analyzed. Results: Children with increased intake of confectionery had increased odds of having emotional symptoms {[}adjusted odds ratio (ORadj) 1.19, 95% confidence interval (CI) 1.08-1.32] compared to children with low intake. A higher diet quality score was associated with lower likelihood of emotional symptoms (ORadj 0.89, 95% CI 0.80-0.98). The un-adjusted significant relationship between diet quality and hyperactivity/inattention was attenuated by adjusting for several confounders to an ORadj of 0.92 (95% CI 0.82-1.03). Conclusions: Increased consumption of high-sugar products and lower diet quality are associated with a higher likelihood of emotional symptoms in children. Copyright (C) 2012 S. Karger AG, Base

Work Disability in Soldiers with Posttraumatic Stress Disorder, Posttraumatic Embitterment Disorder and Not-Event-Related Common Mental Disorders

Objective: Posttraumatic mental disorders may occur with different affect qualities. Best known is posttraumatic stress disorder (PTSD), a conditioned anxiety reaction with intrusions. Another event-related mental disorder is posttraumatic embitterment (PTED), characterized by affect of embitterment and thoughts of revenge, occurring after an event deeply hurting basic believes. Knowing about associated disability is important for treatment and socio-medical decisions. This is the first study to explore work- disability in patients with PTSD, PTED and not-event-related common mental disorder (CMD). Methods: In this observational study 101 soldiers (85% men, 31 years, 50% experienced expedition abroad) with different mental disorders were investigated concerning common mental disorders (MINI) and accompanying work capacity impairment (Mini-ICF-APP). Interviews were conducted by a state-licensed psychotherapist with expertise in socio-medical description of (work) capacity impairment. Patients with PTSD, PTED, and other CMD were compared concerning their degrees and pattern of work capacity impairment. Results: PTSD patients (n = 23) were more strongly impaired in mobility as compared to patients with other CMD (n = 64) or PTED. Patients with PTED (n = 14) were more impaired in interactional capacities (contacts with others, group integration) as compared to patients with other CMD or PTSD. Conclusions: PTSD patients need support to improve mobility in (work-relevant) traffic situations. Apart from this, they are not specifically more or less impaired than patients with other CMD. PTED patients should get attention concerning their interactional problems as these may disturb esprit de corps which is an essential requirement for service in the armed forces

Identification of candidate downstream genes for the homeodomain transcription factor Labial in Drosophila through oligonucleotide-array transcript imaging

BACKGROUND: Homeotic genes are key developmental regulators that are highly conserved throughout evolution. Their encoded homeoproteins function as transcription factors to control a wide range of developmental processes. Although much is known about homeodomain-DNA interactions, only a small number of genes acting downstream of homeoproteins have been identified. Here we use a functional genomic approach to identify candidate target genes of the Drosophila homeodomain transcription factor Labial. RESULTS: High-density oligonucleotide arrays with probe sets representing 1,513 identified and sequenced genes were used to analyze differential gene expression following labial overexpression in Drosophila embryos. We find significant expression level changes for 96 genes belonging to all functional classes represented on the array. In accordance with our experimental procedure, we expect that these genes are either direct or indirect targets of labial gene action. Among these genes, 48 were upregulated and 48 were downregulated following labial overexpression. This corresponds to 6.3% of the genes represented on the array. For a selection of these genes, we show that the data obtained with the oligonucleotide arrays are consistent with data obtained using quantitative RT-PCR. CONCLUSIONS: Our results identify a number of novel candidate downstream target genes for Labial, suggesting that this homeoprotein differentially regulates a limited and distinct set of embryonically expressed Drosophila genes

Associations between BMI and the FTO Gene Are Age Dependent: Results from the GINI and LISA Birth Cohort Studies up to Age 6 Years

Objective: The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity. Methods: This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-Generalized-Estimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status. Results: We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards. Conclusions: This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards

Epileptic Status in a PEDiatric cohort (ESPED) requiring intensive care treatment: A multicenter, national, two-year prospective surveillance study

The aim of this study was to provide seizure etiology, semiology, underlying conditions, and out-of- and in-hospital diagnostics, treatment, and outcome data on children with out-of- or in-hospital-onset status epilepticus (SE) according to the International League Against Epilepsy definition that required admission to the pediatric intensive care unit (PICU) for ≥4 hours.Dr Wolf Epilepsy, Grant/Award Number: N/

МИРГОРОДСЬКИЙ ПОЛК В РОСІЙСЬКО-ТУРЕЦЬКІЙ ВІЙНІ 1735-1739 РР.

Тема пропонованої шановному читачеві статті знаходиться на перетині воєнної історії та краєзнавства. Після тривалої неуваги, зараз воєнна історія, зокрема козаччини, розробляється досить динамічно. Варто згадати хоча б роботи І.Стороженка [1], В.Заруби [2], О.Сокирка [3], Г.Шпитальова [4]. Одночасно все ще не розроблена докладно воєнна історія полків, які складали Гетьманщину. Хоча спроби такого роду є [5], але вони зосереджені не стільки на воєнній історії, скільки на історії полку загалом і, на жаль, не представлені у вигляді монографічних досліджень та не викладені в Інтернеті, що суттєво ускладнює доступ до результатів таких досліджень. Сюжет, пов’язаний із участю Миргородського полку в російсько-турецькій війні 1735-1739 років, не знайшов висвітлення в історіографії, хоча деякі факти містять дослідження А.Байова [6], О.Апанович [7] та вже згадувана монографія Г.Шпитальова. Протягом війни Миргородський полк брав участь як у далеких виправах, так і в ближніх походах різного роду – фортифікаційних, тривожних, для планової охорони кордонів. Залучення козаків Миргородського полку до далеких походів розпочалося вже у червні 1735 р., коли всі полки (крім Стародубського та Чернігівського) вирушили до фортеці Святого Іоанна на Українській лінії, де мали збиратися для виправи на Крим. До прибуття на лінію генерального осавула Ф.Лисенка обов’язки командира цього з’єднання виконував миргородський полковник Павло Апостол [8]. Кількість козаків Миргородського полку, які вирушили в цей похід, точно невідома. Проте є дані щодо старшини, яка очолила виправу – полковник П.Апостол, суддя Ф.Остроградський, писар В.Тихонович, осавул А.Волевач, хорунжі Т.Калницький та К.Шкурка [9]. Згідно з планами Генеральної військової канцелярії (далі – ГВК) передбачалося для Кримської (1736) виправи мобілізувати 16001 гетьманця, в тому числі 1196 шабель Миргородського полку [10]. Виникли певні проблеми з залученням старшини. Наприклад, миргородський обозний С.Родзянка уперто відмовлявся від походу під приводом хвороби, в яку полковник абсолютно не вірив. Проте С.Родзянка апелював до ГВК, де знайшов підтримку. Врешті, полкова старшина миргородців у цій виправі була представлена тими ж постатями, що й 1735 р., лише осавула А.Волевача замінив його колега С.Ґалаґан [11]. За попередніми планами на 1737 р. Миргородський полк мав виставити 849 шабель у Кримський похід. Після рішення фельдмаршала Мініха залишити слобідських козаків для охорони кордону їм на заміну залучили ще 200 миргородців [12]. На цьому зміни не закінчилися. На вимогу фельдмаршала Мініха Миргородський полк перейшов у його підпорядкування і вирушив замість Кримського в Очаківський похід

Incidence, disease onset and short-term outcome in urea cycle disorders – cross-border surveillance in Germany, Austria and Switzerland

Background: Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifestation and short-term outcome. Method: Cross-border surveillance of newly diagnosed patients with UCDs - below 16 years of age - was performed from July 2012 to June 2015 in Germany and Austria and from January 2012 to December 2015 in Switzerland. Inquiries were sent monthly to all Pediatric Departments in Germany and Switzerland, and quarterly to the Austrian Metabolic Group. In addition, data were collected via a second source (metabolic laboratories) in all three countries. Results: Between July 2012 and June 2015, fifty patients (Germany: 39, Austria: 7, Switzerland: 4) with newly diagnosed UCDs were reported and later confirmed resulting in an estimated cumulative incidence of 1 in 51,946 live births. At diagnosis, thirty-nine patients were symptomatic and 11 asymptomatic [10 identified by newborn screening (NBS), 1 by high-risk-family screening (HRF)]. The majority of symptomatic patients (30 of 39 patients) developed HE with (n = 25) or without coma (n = 5), 28 of them with neonatal onset. Despite emergency treatment 15 of 30 patients with HE already died during the newborn period. Noteworthy, 10 of 11 patients diagnosed by NBS or HRF remained asymptomatic. Comparison with the European registry and network for intoxication type metabolic diseases (E-IMD) demonstrated that cross-national surveillance identified a higher number of clinically severe UCD patients characterized by earlier onset of symptoms, higher peak ammonium concentrations in plasma and higher mortality. Conclusion: Cross-border surveillance is a powerful tool to identify patients with UCDs demonstrating that (1) the cumulative incidence of UCDs is lower than originally suggested, (2) the mortality rate is still high in patients with neonatal onset of symptoms, and (3) onset type and peak plasma ammonium concentration predict mortality

The selection and definition of indicators in public health monitoring for the 65+ age group in Germany

Selecting relevant indicators is an important step in the development of public health monitoring for older people. Indicators can be used to combine information comprehensively from various data sources and enable recurring, comparable findings to be made about the health of older people. Indicators were systematically compiled from existing international monitoring systems. An indicator set on health in old age was developed using a multistage, structured consensus-based process together with an interdisciplinary panel of experts. The resulting 18 indicators were assigned to three health areas: (1) environmental factors, (2) activities and participation, and (3) personal factors. Data sources that can be used for the indicators are the health surveys within the framework of the Robert Koch Institute’s (RKI) health monitoring system, as well as surveys from other research institutes and official statistics. In the future, the indicator set is to be developed further and integrated into an overall approach that is geared towards health reporting and the monitoring of chronic diseases in all phases of life