Caregiver burden, and parents' perception of disease severity determine health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism.

Background Living with a non-acute (phenylketonuria) or acute (e.g. urea cycle disorders, organic acidurias) intoxication-type inborn error of metabolism (IT-IEM) can have a substantial impact on health-related quality of life (HrQoL) of paediatric patients and their families. Parents take primary responsibility for treatment monitoring and experience worry and fear about their child's health status. Quantitative evidence on parental psychological factors which may influence the HrQoL of patients with IT-IEM are sparse to non-existent. Methods In this multicenter survey study 50 parents of IT-IEM patients (ages 5-19) assessed the severity of their child's disease, reported on caregiver burden, and proxy-rated their child's HrQoL. Additionally, 35 patient self-reports on HrQoL were obtained (n = 16 female patients, n = 19 male patients). Multiple linear regressions were conducted to examine the predictive power of child age, sex, medical diagnosis type (acute / non-acute), parental perceived disease severity and caregiver burden on patients' HrQoL. Mediation analyses were used to investigate the relation of caregiver burden and parental ratings of disease severity with patients' HrQoL. Results Significant regression models for self-reported [F(5,34) = 10.752, p < .001, R 2 adj.. = 0.59] and parent proxy reported HrQoL [F(5,49) = 20.513, p < .001, R 2 adj.. = 0.67] emerged. High caregiver burden and perceived disease severity predicted significantly lower patient self- and proxy-reported HrQoL while type of diagnosis (acute versus non-acute) did not. Female sex predicted significantly lower self-reported HrQoL. High caregiver burden was the mediating factor between high perceived severity of the child's disease and lower proxy- by parent rated HrQoL. Conclusion Detecting elevated burden of care and providing support for parents seems crucial to prevent adverse consequences for their children's HrQoL. Intervention studies are needed, to assess which support programs are most efficient

Komplexumformung von Hybridstrukturen

Aktuell werden multifunktionale Baugruppen durch ein Multimaterialdesign lastoptimal ausgelegt. Gerade bei der Kombination faserverstärkter Kunststoffe (FVK) mit Metallen sind bei der Herstellung – aufgrund der heterogenen Werkstoffpartner – jedoch meist mehrere Prozessstufen notwendig. Im Projekt „Komplexumformung von Hybridstrukturen“ wird eine Technologie zum Umformen von FVK-Metall-Hybridbauteile neu entwickelt. Es wird angestrebt, die Verfahren Blechumformen, Fügen, FVK- Pressverfahren und Injektionsverfahren (z. B. Kunststoff-Spritzgießen) effizient miteinander zu kombinieren. Hauptziel des Projektes ist es, die FVK-Komponente technologisch gezielt in den Umformungsprozess der metallischen Komponente zu integrieren, um die Prozessstufentiefe von FVK-Hybridbauteilen zu verringern und den Integrationsgrad zu erhöhen. Die erzeugten partiellen Hinterschnitte ergeben einen formschlüssigen Verbund von Metall, Organoblech und Kunststoff

Hybridfügen durch Fließlochformen

Various processes with and without additional fasteners are currently used for the production of hy-brid material connections. This leads to different requirements and problems when joining. A cohesive hybrid composite joint of fiber reinforced plastics (FRP) and metal by gluing requires, for example, complex pretreatment of the joining partners. With mechanical joining concepts, the joining elements usually destroy the load-bearing fibers locally and require access to the metal and FKV semi-finished products from both sides. In addition, there is a lot of effort in positioning accuracy. The new process principle, which was developed jointly by the Fraunhofer Institute for Machine Tools and Forming Technology (IWU) and the Technical University of Braunschweig, represents an additional joining pro-cess for joining metal sheets with FRP, wood and plastic semi-finished products. The semi-finished products described are positioned in between at least two metal sheets. The metallic semi-finished products and the (fiber reinforced) plastic and wood semi-finished products can have the same or different dimensions. One of the metallic sheets or both metallic sheets can also be part of a sand-wich structure. Then the defined penetration of all semi-finished products takes place with a flow punch former. The metals are heated and deformed. This happens without material removal. The matrix of the FRP semi-finished product is melted and the reinforcing fibers are, if applicable, dis-placed by the flow punch former and not destroyed, so that a continuous fiber load path is guaran-teed. The deformed metal forms a kind of sleeve, which in turn can be used for shaping or for cutting or forming a thread. With a targeted choice of process parameters and material combination, a form closure and adhesive bond can be produced. The principle of the procedure for joining a metallic sheet with an FRP sheet and a metallic top layer of a metal foam sandwich has already been experi-mentally tested. The result is shown in Figure 1

The silent chain – noise reduction in conveying systems

Um die in einem Kunststoffkettenfördersystem auftretenden Geräusche zu reduzieren, wurde ein spezielles Bauteil der Kette im Zweikomponenten-Spritzguss aus einem thermoplastischen Elastomer (TPE) und kettentypischen Kunststoffen gefertigt. Im Rahmen der Entwicklung wurden u. a. Voruntersuchungen zur Haftung zwischen den Werkstoffen durchgeführt. Die neu geschaffene Kette bewirkt eine Verringerung des Schalldruckpegels um 3 4 dB[A] gegenüber herkömmlichen Kunststoffketten im Fördersystem. Das ermöglicht eine Steigerung der Fördergeschwindigkeit um bis zu 30% ohne zusätzliche Lärmbelastung.Conveying systems with plastic sliding chains can be noisy. Because of this, a conveyor chain has been modified using a hybrid part made of thermoplastic elastomer (TPE) and application-typical plastics. The new chain causes a noise reduction of 3-4 dB[A] compared to the state of the art. This allows an increase of the conveyor speed up to 30% without extra noise emission

Congenital Central Hypothyroidism due to a Homozygous Mutation in the TSHβ Subunit Gene

Congenital central hypothyroidism (CCH) is a rare condition occurring in 1 : 20000 to 1 : 50000 newborns. As TSH plasma levels are low, CCH is usually not detected by TSH-based neonatal screening for hypothyroidism, and, as a result, diagnosis is often delayed putting affected children at risk for developmental delay and growth failure. We report on a girl with isolated central hypothyroidism due to a homozygous one-base pair deletion (T313del) in exon 3 of the TSHβ subunit gene. The molecular genetic and typical radiologic findings are discussed, and a systematic diagnostic workup for congenital central hypothyroidism is proposed. Physicians need to be aware of this rare condition to avoid diagnostic delay and to install prompt replacement therapy

Defective lysosomal storage in Fabry Disease modifies mitochondrial structure, metabolism and turnover in renal epithelial cells

Fabry disease (FD) is an X‐linked lysosomal storage disorder. Deficiency of the lysosomal enzyme alpha‐galactosidase (GLA) leads to accumulation of potentially toxic globotriaosylceramide (Gb3) on a multisystem level. Cardiac and cerebrovascular abnormalities as well as progressive renal failure are severe, life‐threatening long‐term complications. The complete pathophysiology of chronic kidney disease (CKD) in FD and the role of tubular involvement for its progression are unclear. We established human renal tubular epithelial cell lines from the urine of male FD patients and male controls. The renal tubular system is rich in mitochondria and involved in transport processes at high energy costs. Our studies revealed fragmented mitochondria with disrupted cristae structure in FD patient cells. Oxidative stress levels were elevated and oxidative phosphorylation was up‐regulated in FD pointing at enhanced energetic needs. Mitochondrial homeostasis and energy metabolism revealed major changes as evidenced by differences in mitochondrial number, energy production and fuel consumption. The changes were accompanied by activation of the autophagy machinery in FD. Sirtuin1, an important sensor of (renal) metabolic stress and modifier of different defense pathways, was highly expressed in FD. Our data show that lysosomal FD impairs mitochondrial function and results in severe disturbance of mitochondrial energy metabolism in renal cells. This insight on a tissue‐specific level points to new therapeutic targets which might enhance treatment efficacy

Caregiver burden, and parents' perception of disease severity determine health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism

Background Living with a non-acute (phenylketonuria) or acute (e.g. urea cycle disorders, organic acidurias) intoxication-type inborn error of metabolism (IT-IEM) can have a substantial impact on health-related quality of life (HrQoL) of paediatric patients and their families. Parents take primary responsibility for treatment monitoring and experience worry and fear about their child's health status. Quantitative evidence on parental psychological factors which may influence the HrQoL of patients with IT-IEM are sparse to non-existent. Methods In this multicenter survey study 50 parents of IT-IEM patients (ages 5–19) assessed the severity of their child's disease, reported on caregiver burden, and proxy-rated their child's HrQoL. Additionally, 35 patient self-reports on HrQoL were obtained (n = 16 female patients, n = 19 male patients). Multiple linear regressions were conducted to examine the predictive power of child age, sex, medical diagnosis type (acute / non-acute), parental perceived disease severity and caregiver burden on patients' HrQoL. Mediation analyses were used to investigate the relation of caregiver burden and parental ratings of disease severity with patients' HrQoL. Results Significant regression models for self-reported [F(5,34) = 10.752, p < .001, R2 adj.. = 0.59] and parent proxy reported HrQoL [F(5,49) = 20.513, p < .001, R2 adj.. = 0.67] emerged. High caregiver burden and perceived disease severity predicted significantly lower patient self- and proxy-reported HrQoL while type of diagnosis (acute versus non-acute) did not. Female sex predicted significantly lower self-reported HrQoL. High caregiver burden was the mediating factor between high perceived severity of the child's disease and lower proxy- by parent rated HrQoL. Conclusion Detecting elevated burden of care and providing support for parents seems crucial to prevent adverse consequences for their children's HrQoL. Intervention studies are needed, to assess which support programs are most efficient