Ernährung bei angeborenen Stoffwechselerkrankungen — ein Spagat zwischen Genuss und Therapie

For many inborn metabolic diseases, a lifelong diet is a crucial part of the therapy since pharmacological therapy is available for only a few conditions and patients. The implementation of a low natural protein diet with a reduced intake of natural protein and the complementary use of synthetic amino acid mixtures is described using the examples of phenylketonuria and urea cycle disorders focusing on children and adolescents. For phenylketonuria, the amino acid supplement is free of phenylalanine whereas for urea cycle disorders, it exclusively consists of essential amino acids. The dietary treatment aims to maintain metabolic stability and to prevent accumulation of toxic metabolites. At the same time, the nutritional requirements to ensure growth and development must be met. Therefore, patients need to follow strict rules regarding the choice of food products. This restrictive therapy interferes with the desire for autonomy and the joy of eating and often results in a reduced quality of life.Following the diet is crucial for a favorable outcome. To meet its requirements, patients and their families are provided with training. It is a~great challenge not only to support the patients and their families in all practical aspects of dietary management, but also to motivate them to lifelong adherence in order to ensure the best possible outcome.Bei vielen angeborenen Stoffwechselkrankheiten ist eine lebensbegleitende Diät von Geburt an fester Bestandteil der Therapie. Alternative medikamentöse Therapieansätze stehen erst für einige wenige Patienten zur Verfügung. Am Beispiel der Phenylketonurie und der Harnstoffzyklusstörungen wird das Prinzip der eiweißdefinierten Diät mit dem Schwerpunkt auf Kinder und Jugendliche erläutert. Die Herausforderungen, die sich bei dieser Ernährungstherapie ergeben, werden aufgezeigt. Bei der eiweißdefinierten Diät erfolgt eine verminderte Zufuhr von natürlichem Protein, ergänzt durch die Gabe spezieller Aminosäuremischungen. Diese enthalten bei der Phenylketonurie kein Phenylalanin, bei den Harnstoffzyklusdefekten ausschließlich essenzielle Aminosäuren. Mithilfe der Diät soll zum einen eine gute metabolische Einstellung erreicht und die Anhäufung toxischer Metabolite vermieden werden. Zum anderen muss eine bedarfsdeckende Energie- und Nährstoffversorgung für das adäquate Wachstum und die Entwicklung des Kindes gewährleistet sein. Für die Patienten bedeutet dies, sich an restriktive Vorgaben bei der Lebensmittelauswahl halten zu müssen. Diese konkurrieren oft mit dem Bedürfnis nach Freiheit/Spontaneität und dem Genuss bei der Nahrungsaufnahme. Viele Patienten empfinden ihre Diät daher als drastische Einschränkung der Lebensqualität. Eine konsequente Umsetzung der Diät ist entscheidend für die Prognose der Erkrankungen. Hierfür bringen die Patienten und ihre Familien oft unterschiedliche Voraussetzung und Fähigkeiten mit. Für Therapeuten stellt es eine große Herausforderung dar, die Patienten nicht nur bei der praktischen Umsetzung ihrer Diät in allen Lebensabschnitten zu unterstützen, sondern auch zu einer langfristigen Adhärenz zu motivieren, um ein bestmögliches Outcome zu erreichen

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Refinement of the GINGF3 locus for hereditary gingival fibromatosis

Hereditary gingival fibromatosis (HGF) is a rare, clinically variable disorder characterized by slowly progressive fibrous overgrowth of the gingiva. Four gene loci have been mapped for autosomal dominant non-syndromic HGF (adHGF). The molecular basis of adHGF remains largely unknown, with only a single SOS1 gene mutation identified so far at the gingival fibromatosis 1 (GINGF1) locus in one family. We identified an adHGF family with ten affected individuals in whom onset of gingival fibromatosis concurred with the eruption of the primary teeth. In order to identify the molecular basis in this family, we tested for linkage of the disease to known adHGF loci. A maximal multipoint logarithm of the odds score of 3.91 was obtained with marker D2S390 (θ = 0) at the GINGF3 locus on chromosome 2p23.3–p22.3, and linkage to other known loci was excluded. Sequencing two candidate genes, ALK and C2orf18, and a single nucleotide polymorphisms array analysis did not reveal a mutation or copy number variation in a patient from the family. We refined the GINGF3 locus to a 6.56-cM, 8.27-Mb region containing 112 known and hypothetical genes, and our data and a search of the literature suggest that GINGF3 is a major adHGF locus

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%–80%) were revised and re-introduced in Phase 3, and statements with low agreement (80%) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at \u3e 80 %, and five multiple-choice questions. Statements with moderate agreement (70 % – 80 %) were revised and re-introduced in Phase 3, and statements with low agreement ( \u3c 70 %) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. Results: Topic experts from Australia (n = 62, 92.5 %) and New Zealand (n = 5, 7.5 %) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7 %) were women, 38 (56.7 %) were health professionals and 27 (40.3 % ) were researchers/academics. In Phase 2, 15 of 18 (83.3 %) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100 %) and offering tailored resistance training to people with sarcopenia (92.5 %). Forty-seven experts participated in Phase 3; 5/6 (83.3 %) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9 %) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement ( \u3e 80 %) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia

The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) sarcopenia diagnosis and management task force: Findings from the consumer expert Delphi process

Objectives: To develop guidelines, informed by health-care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand. Methods: A three-phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adults with lived experience of sarcopenia or health-care utilisation. Phase 1 involved a structured meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force and consumer representatives from which the Phase 2 survey was developed. In Phase 2, consumers from Australia and New Zealand were surveyed online with opinions sought on sarcopenia outcome priorities, consultation preferences and interventions. Findings were confirmed and disseminated in Phase 3. Descriptive statistical analyses were performed. Results: Twenty-four consumers (mean ± standard deviation age 67.5 ± 12.8 years, 18 women) participated in Phase 2. Ten (42%) identified as being interested in sarcopenia, 7 (29%) were health-care consumers and 6 (25%) self-reported having/believing they have sarcopenia. Consumers identified physical performance, living circumstances, morale, quality of life and social connectedness as the most important outcomes related to sarcopenia. Consumers either had no preference (46%) or preferred their doctor (40%) to diagnose sarcopenia and preferred to undergo assessments at least yearly (54%). For prevention and treatment, 46% of consumers preferred resistance exercise, 2–3 times per week (54%). Conclusions: Consumer preferences reported in this study can inform the implementation of sarcopenia guidelines into clinical practice at local, state and national levels across Australia and New Zealand

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum