Dietary treatment in Dutch children with phenylketonuria:An inventory of associated social restrictions and eating problems

OBJECTIVES: Dietary treatment in phenylketonuria (PKU) is known to cause eating problems, but knowledge of both prevalence and magnitude, especially for social restrictions, is scarce. Our aim was to evaluate the social restrictions and eating problems that children with PKU and their caregivers experience with dietary treatment. METHODS: A web-based questionnaire, based on the Behavioral Pediatrics Feeding Assessment Scale with additional PKU-specific questions, was developed in close collaboration with and distributed by the Dutch PKU Association, which sent an e-mail to its members containing a link to the questionnaire. The questionnaire was completed by caregivers of children with PKU in the Netherlands and caregivers of age-matched children without PKU. Data were analyzed with the Kruskal-Wallis and Mann-Whitney U test using SPSS. RESULTS: Compared with caregivers of children in the control group (ages 1-16 y; n = 50), caregivers of children with PKU (ages 1-16 y; n = 57) reported more difficulty in offering food variety, experienced more stress when eating an evening meal outside the home and during vacation, and were stricter about (accidental) spilling of food during dinner by the child (P < 0.05). They also reported to being angrier, more frustrated, and more anxious when feeding their child, and they more often felt that their child's eating pattern had a negative influence on the child's general health (P < 0.05). CONCLUSION: This pilot study provides further evidence that restriction of social activities and eating problems associated with dietary restrictions is more common in children with PKU, and warrants awareness on this topic among professionals working with these children

Aspartame and Phe-Containing Degradation Products in Soft Drinks across Europe

Phenylketonuria and tyrosinemia type 1 are treated with dietary phenylalanine (Phe) restriction. Aspartame is a Phe-containing synthetic sweetener used in many products, including many 'regular' soft drinks. Its amount is (often) not declared; therefore, patients are advised not to consume aspartame-containing foods. This study aimed to determine the variation in aspartame concentrations and its Phe-containing degradation products in aspartame-containing soft drinks. For this, an LC-MS/MS method was developed for the analysis of aspartame, Phe, aspartylphenylalanine, and diketopiperazine in soft drinks. In total, 111 regularly used soft drinks from 10 European countries were analyzed. The method proved linear and had an inter-assay precision (CV%) below 5% for aspartame and higher CVs% of 4.4-49.6% for the degradation products, as many concentrations were at the limit of quantification. Aspartame and total Phe concentrations in the aspartame-containing soft drinks varied from 103 to 1790 µmol/L (30-527 mg/L) and from 119 to 2013 µmol/L (20-332 mg/L), respectively, and were highly variable among similar soft drinks bought in different countries. Since Phe concentrations between drinks and countries highly vary, we strongly advocate the declaration of the amount of aspartame on soft drink labels, as some drinks may be suitable for consumption by patients with Phe-restricted diets

A Balkán és az Oszmán Birodalom III. : Társadalmi és gazdasági átalakulások a 18. század végétől a 20. század közepéig : Szerbia, Macedónia, Bosznia

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study. The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment

BackgroundGlioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.MethodsHigh-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.ResultsGlioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.ConclusionHigh-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy

Design of an In-situ cell, for hard X-ray spectroscopy of surfaces used in high-pressure and high-temperature experiments : Design av en In-situ cell för intensiv röntgenspektroskopi i högtryck- högtemperaturexperiment

This project analyzes how an in-situ cell can be developed to withstand high amounts of pressure and temperature of at least 100 bar and 500 °C. A theoretical prototype will be created as a product for Malmö University and other researchers to use or improve. To make this possible, the five step method was used to present a symmetric geometrical concept for the cell. That geometric concept was designed in PTC Creo (Version 6.0.2.0 &amp; 7.0) in 3D and drawings in 2D. The programs GRANTA EduPack (Version 2020 \&amp; Version 2019) along with Hephaestus was used to determine a material selection that will be able to tolerate temperature, pressure and be at least ten percent transparent, to be able for the X-ray to pass through the material and into the sample. The Finite Element Method (FEM) was used to ensure that the cell adheres to the set values of pressure and not cause a catastrophic failure. The result turn out to be a elliptical three part in-situ cell of boron carbide outer shell, a beryllium main dome and a stainless steel plate for the material sample to be on top. The Finite Element Method also showed that the designed in-situ cells meet the requirements and fulfills the goal and purpose. Further development of safety features and the equipment will be needed to minimise the risk of and dangers of beryllium dust.Detta projekt analyserar hur en in-situ cell kan utvecklas för att motstå höga mängder tryck och temperatur på minst 100 bar och 500 °C . En teoretisk prototyp kommer att skapas som en produkt för Malmö universitet och andra forskare att använda eller förbättra. För att göra detta möjligt användes femstegsmetoden för att presentera ett symmetriskt och geometriskt koncept för cellen. Det geometriska konceptet kommer att utformas 3-dimensionellt i PTC Creo (Version 6.0.2.0  7.0) och 2-dimensionella ritningar . GRANTA EduPack-programmen (Version 2020 \&amp; Version 2019) tillsammans med Hephaestus användes för att bestämma ett materialval som kommer att kunna tolerera temperatur, tryck och vara minst tio procent transparent för att röntgenstrålningen ska kunna passera genom materialet och in i provet. Finite Element Method (FEM) kommer att användas för att säkerställa att cellen följer de inställda tryckvärdena och inte orsakar katastrofala fel. Resultatet visar sig vara en elliptisk tredelad in-situ cell av borkarbid som ett yttre skal, beryllium som huvudkupol och en rostfri stålplatta som underlag för materialprovet. Finite Element Method visade också att den designade in-situ-cellen uppfyller kraven och därför uppfyller målet och syftet. Detta innebär att vidareutveckling av säkerhetsfunktioner och utrustning kommer att behövas för att minimera risken för berusning från berylliumdammet

Design of an In-situ cell, for hard X-ray spectroscopy of surfaces used in high-pressure and high-temperature experiments : Design av en In-situ cell för intensiv röntgenspektroskopi i högtryck- högtemperaturexperiment

This project analyzes how an in-situ cell can be developed to withstand high amounts of pressure and temperature of at least 100 bar and 500 °C. A theoretical prototype will be created as a product for Malmö University and other researchers to use or improve. To make this possible, the five step method was used to present a symmetric geometrical concept for the cell. That geometric concept was designed in PTC Creo (Version 6.0.2.0 &amp; 7.0) in 3D and drawings in 2D. The programs GRANTA EduPack (Version 2020 \&amp; Version 2019) along with Hephaestus was used to determine a material selection that will be able to tolerate temperature, pressure and be at least ten percent transparent, to be able for the X-ray to pass through the material and into the sample. The Finite Element Method (FEM) was used to ensure that the cell adheres to the set values of pressure and not cause a catastrophic failure. The result turn out to be a elliptical three part in-situ cell of boron carbide outer shell, a beryllium main dome and a stainless steel plate for the material sample to be on top. The Finite Element Method also showed that the designed in-situ cells meet the requirements and fulfills the goal and purpose. Further development of safety features and the equipment will be needed to minimise the risk of and dangers of beryllium dust.Detta projekt analyserar hur en in-situ cell kan utvecklas för att motstå höga mängder tryck och temperatur på minst 100 bar och 500 °C . En teoretisk prototyp kommer att skapas som en produkt för Malmö universitet och andra forskare att använda eller förbättra. För att göra detta möjligt användes femstegsmetoden för att presentera ett symmetriskt och geometriskt koncept för cellen. Det geometriska konceptet kommer att utformas 3-dimensionellt i PTC Creo (Version 6.0.2.0  7.0) och 2-dimensionella ritningar . GRANTA EduPack-programmen (Version 2020 \&amp; Version 2019) tillsammans med Hephaestus användes för att bestämma ett materialval som kommer att kunna tolerera temperatur, tryck och vara minst tio procent transparent för att röntgenstrålningen ska kunna passera genom materialet och in i provet. Finite Element Method (FEM) kommer att användas för att säkerställa att cellen följer de inställda tryckvärdena och inte orsakar katastrofala fel. Resultatet visar sig vara en elliptisk tredelad in-situ cell av borkarbid som ett yttre skal, beryllium som huvudkupol och en rostfri stålplatta som underlag för materialprovet. Finite Element Method visade också att den designade in-situ-cellen uppfyller kraven och därför uppfyller målet och syftet. Detta innebär att vidareutveckling av säkerhetsfunktioner och utrustning kommer att behövas för att minimera risken för berusning från berylliumdammet

An Academic-Community Collaboration to Deliver Medication Therapy Management (MTM) Services to Patients Living in Rural Counties of a Southwestern State in the United States

Background: Patients living in rural communities often experience pronounced health disparities, have a higher prevalence of diabetes and hypertension, and poorer access to care compared to urban areas. To address these unmet healthcare service needs, an established, academic-based MTM provider created a novel, collaborative program to provide comprehensive, telephonic services to patients living in rural Arizona counties. Objective: This study assessed the program effectiveness and described differences in health process and outcome measures (e.g., clinical outcomes, gaps in care for prescribed medications, medication-related problems) between individuals residing in different rural-urban commuting area (RUCA) groups (urban, micropolitan, and small town) in rural Arizona counties. Methods: Subjects eligible for inclusion were 18 years or older with diabetes and/or hypertension, living in rural Arizona counties. Data were collected on: demographic characteristics, medical conditions, clinical values, gaps in care, medication-related problems (MRPs), and health promotion guidance. Subjects were analyzed using 3 intra-county RUCA levels (i.e., urban, micropolitan, and small town). Results: A total of 384 patients were included from: urban (36.7%), micropolitan (19.3%) and small town (44.0%) areas. Positive trends were observed for clinical values, gaps in care, and MRPs between initial and follow-up consultations. Urban dwellers had significantly lower average SBP values at follow-up than those from small towns (p < 0.05). A total of 192 MRPs were identified; 75.0% were resolved immediately or referred to providers and 16.7% were accepted by prescribers. Conclusion: This academic-community partnership highlights the benefits of innovative collaborative programs, such as this, for individuals living in underserved, rural areas. © The Author(s) 2021.Centers for Disease Control and PreventionThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Cardiorespiratory Fitness and Cognitive Function are Positively Related Among Participants with Mild and Subjective Cognitive Impairment

Background: By 2030, about 74 million people will be diagnosed with dementia, and many more will experience subjective (SCI) or mild cognitive impairment (MCI). As physical inactivity has been identified to be a strong modifiable risk factor for dementia, exercise and physical activity (PA) may be important parameters to predict the progression from MCI to dementia, but might also represent disease trajectory modifying strategies for SCI and MCI. Objective: A better understanding of the relationship between activity, fitness, and cognitive function across the spectrum of MCI and SCI would provide an insight into the potential utility of PA and fitness as early markers, and treatment targets to prevent cognitive decline. Methods: 121 participants were stratified into three groups, late MCI (LMCI), early MCI (EMCI), and SCI based on the Montreal Cognitive Assessment (MoCA). Cognitive function assessments also included the Trail Making Test A+B, and a verbal fluency test. PA levels were evaluated with an interviewer-administered questionnaire (LAPAQ) and an activity monitor. An incremental exercise test was performed to estimate cardiorespiratory fitness and to determine exercise capacity relative to population normative data. Results: ANCOVA revealed that LMCI subjects had the lowest PA levels (LAPAQ, p = 0.018; activity monitor, p = 0.041), and the lowest exercise capacity in relation to normative values (p = 0.041). Moreover, a modest correlation between MoCA and cardiorespiratory fitness (r = 0.25; p < 0.05) was found. Conclusion: These findings suggest that during the earliest stages of cognitive impairment PA and exercise capacity might present a marker for the risk of further cognitive decline. This finding warrants further investigation using longitudinal cohort studies

Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data.</p

DataSheet_1_The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment.docx

BackgroundGlioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.MethodsHigh-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.ResultsGlioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.ConclusionHigh-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.</p