Beneficial Effects of Ketogenic Diet on Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII)

Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII.Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD.Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved.Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.Peer reviewe

Oocyte donation pregnancies-non-disclosure of oocyte recipient status to obstetric care providers and perinatal outcomes

Background: Oocyte donation pregnancies-non-disclosure of oocyte recipient (OR) status to obstetric care providers and perinatal outcomes. Many studies report a higher rate of pregnancy-induced hypertension (PIH) and severe pre-eclampsia (PET) in OR pregnancies. The objective is to determine the rates of non-disclosure of OR pregnancy to obstetric care providers and also the rates of perinatal complications. Method: This was a retrospective review of all oocyte recipient (OR) pregnancies, who subsequently delivered at Cork University Maternity Hospital, between 2007-2012 inclusive. Obstetric case notes were reviewed to investigate perinatal outcomes and whether OR status had been documented (unambiguously, in code or not at all). Results Less than one-third (30.2%; n=32/106) had unambiguous documentation, one-third (33%; n=35/106) had no documentation and the remainder (36.8%; n=39/106) had a code familiar only to their obstetrician. There was a high rate of gestational hypertensive disorders (28.3%; n= 30), most frequently occurring with multiple gestation. Conclusion There was a low rate of clear documentation of OR status. Gestational hypertensive disorders occurred with increased frequency

Control of VEGF-A transcriptional programs by pausing and genomic compartmentalization.

Vascular endothelial growth factor A (VEGF-A) is a master regulator of angiogenesis, vascular development and function. In this study we investigated the transcriptional regulation of VEGF-A-responsive genes in primary human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using genome-wide global run-on sequencing (GRO-Seq). We demonstrate that half of VEGF-A-regulated gene promoters are characterized by a transcriptionally competent paused RNA polymerase II (Pol II). We show that transition into productive elongation is a major mechanism of gene activation of virtually all VEGF-regulated genes, whereas only ∼40% of the genes are induced at the level of initiation. In addition, we report a comprehensive chromatin interaction map generated in HUVECs using tethered conformation capture (TCC) and characterize chromatin interactions in relation to transcriptional activity. We demonstrate that sites of active transcription are more likely to engage in chromatin looping and cell type-specific transcriptional activity reflects the boundaries of chromatin interactions. Furthermore, we identify large chromatin compartments with a tendency to be coordinately transcribed upon VEGF-A stimulation. We provide evidence that these compartments are enriched for clusters of regulatory regions such as super-enhancers and for disease-associated single nucleotide polymorphisms (SNPs). Collectively, these findings provide new insights into mechanisms behind VEGF-A-regulated transcriptional programs in endothelial cells

Postglacial peatland vegetation succession in Store Mosse bog, south-central Sweden : An exploration of factors driving species change

Boreal peatlands are facing significant changes in response to a warming climate. Sphagnum mosses are key species in these ecosystems and contribute substantially to carbon sequestration. Understanding the factors driving vegetation changes on longer time scales is therefore of high importance, yet challenging since species changes are typically affected by a range of internal and external processes acting simultaneously within the system. This study presents a high-resolution macrofossil analysis of a peat core from Store Mosse bog (south-central Sweden), dating back to nearly 10 000 cal. a BP. The aim is to identify factors driving species changes on multidecadal to millennial timescales considering internal autogenic, internal biotic and external allogenic processes. A set of independent proxy data was used as a comparison framework to estimate changes in the bog and regional effective humidity, nutrient input and cold periods. We found that Store Mosse largely follows the expected successional pathway for a boreal peatland (i.e. lake -> fen -> bog). However, the system has also been affected by other interlinked factors. Of interest, we note that external nutrient input (originating from dust deposition and climate processes) has had a negative effect on Sphagnum while favouring vascular plants, and increased fire activity (driven by allogenic and autogenic factors) typically caused post-fire, floristic wet shifts. These effects interactively caused a floristic reversal and near disappearance of a once-established Sphagnum community, during which climate acted as an indirect driver. Overall, this study highlights that the factors driving vegetation change within the peatland are multiple and complex. Consideration of the role of interlinked factors on Sphagnum is crucial for an improved understanding of the drivers of species change on short- and long-term scales.Peer reviewe

Mind the gap! Exploring teachers’ professional learning needs to cultivate critical data literacies

Peer reviewe

Liikuttavat oppimisympäristöt päiväkodissa:esiopetusikäisten kokemuksia

Tiivistelmä. Monipuolinen liikkuminen ja riittävä fyysinen aktiivisuus ovat välttämättömiä alle kouluikäisen lapsen kokonaisvaltaiselle kehitykselle. Fyysisessä aktiivisuudessa on merkittäviä eroja lasten välillä. Viidennes lapsista ei saavuta varhaiskasvatuksella tavoitteeksi asetettua kahden tunnin fyysisen aktiivisuuden määrää varhaiskasvatuspäivän aikana. Esiopetus on merkittävässä asemassa lasten päivittäisen liikunnan mahdollistajana ja liikunnallisen elämäntavan rakentajana. Varhaiskasvatuksen ja esiopetuksen liikuntaolosuhteilla on yhteys myös päiväkodissa olevien lasten motoristen taitojen kehitykseen. Tässä pro gradu -tutkielmassa selvitetään lasten kokemuksia esiopetuksen ja sitä täydentävän varhaiskasvatuksen liikuntaympäristöistä. Lasten kokemusten kuuleminen ja siitä saadun tiedon hyödyntäminen varhaiskasvatuksen ja esiopetuksen kehittämisessä on tärkeää. Tutkimuksen tavoitteena oli selvittää esikouluikäisten lasten kokemuksia esiopetuspäivän aikana tapahtuvasta liikunnasta sekä liikunnan mahdollistavista oppimisympäristöistä. Tutkimuksessa tarkastellaan, millaisia liikuntaleikkejä lapset esiopetuspäivän aikana leikkivät ja millaisissa fyysisissä ympäristöissä lapset liikkuvat. Tutkimuksella pyritään vahvistamaan liikuntaa tukevien oppimisympäristöjen kehittämistä varhaiskasvatuksessa, sekä kuulla lasten kokemuksia heitä koskevissa asioissa. Tutkimus toteutettiin laadullisena tutkimuksena ja siinä hyödynnettiin fenomenologista lähestymistapaa. Aineisto koostuu 11 esikouluikäisen lapsen parihaastattelusta ja yhdestä yksilöhaastattelusta. Haastateltavia esikoululaisia oli yhteensä 23. Haastattelut toteutettiin teemahaastattelun keinoin ja haastattelun tukena käytettiin kuvia. Haastatteluaineisto kerättiin syksyllä 2022 kahdessa erilaisessa ympäristössä sijaitsevassa päiväkodissa lasten esikoulupäivän aikana. Haastatteluaineiston analyysi tehtiin käyttäen teoriasidonnaista sisällönanalyysiä. Tutkimustulokset osoittivat, että lasten omiin kokemuksiin perustuen lapset liikkuvat esiopetuksessa monipuolisissa ympäristöissä. Liikunta on motoristen perustaitojen kehittymisen näkökulmasta monipuolisinta päiväkodin omassa liikuntasalissa. Myös aikuisen suunnittelema ja ohjaama liikunta painottuu liikuntasalissa tapahtuvaan liikuntaan. Tutkimuksen perusteella voidaan todeta, että lapset ovat fyysisesti aktiivisia päiväkodin omalla piha-alueella omaehtoisen leikin aikana. Liikuntaan innostavat telineet ja välineet lisäävät fyysistä aktiivisuutta. Esiopetuksessa lapsille tärkeitä oppimisympäristöjä ovat myös päiväkodin luonnonvaraiset ja rakennetut lähiympäristöt. Tutkimustulokset ovat linjassa aiempien tutkimustulosten kanssa

Quantitative proteomic analysis of bronchoalveolar lavage fluid in West Highland white terriers with canine idiopathic pulmonary fibrosis

Background Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, progressive, interstitial fibrosing lung disease, manifesting as cough, exercise intolerance and ultimately, dyspnea and respiratory failure. It mainly affects West Highland white terriers (WHWTs), lacks curable treatment and has a poor prognosis. Aspiration of gastroesophageal refluxate may play a role in the development of CIPF. In the first part of this study, we completed label-free quantitative proteomic analysis of bronchoalveolar lavage fluid (BALF) from CIPF and healthy WHWTs. In the second part, we evaluated potential protein markers of reflux aspiration from canine gastric juice and vomitus and whether these were present in BALF from the two groups. Results Across all BALF samples, 417 proteins were identified, and of these, 265 proteins were identified by two or more unique tryptic peptides. Using the 265 high confidence assignments, the quantitative proteome profiles were very similar in the two cohorts, but they could be readily resolved by principal component analysis on the basis of differential protein expression. Of the proteins that were differentially abundant in the two groups, several (including inflammatory and fibrotic markers) were elevated in CIPF, and a smaller, more diverse group of proteins were diminished in CIPF. No protein markers indicative of reflux aspiration were identified. Conclusions Label-free proteomics allowed discrimination between CIPF and healthy WHWTs, consistent with fibrotic process but did not provide clear evidence for gastrointestinal aspiration. The measurement of proteins may provide a proteomics signature of CIPF that could be used to evaluate treatment options.Peer reviewe

Development and evaluation of a rapid nucleic acid amplification method to detect influenza A and B viruses in human respiratory specimens

Isothermal nucleic acid amplification methods can potentially shorten the amount of time required to diagnose influenza. We developed and evaluated a novel isothermal nucleic acid amplification method, RT-SIBA to rapidly detect and differentiate between influenza A and B viruses in a single reaction tube. The performance of the RT-SIBA Influenza assay was compared with two established RT-PCR methods. The sensitivities of the RT-SIBA, RealStar RT-PCR, and CDC RT-PCR assays for the detection of influenza A and B viruses in the clinical specimens were 98.8%, 100%, and 89.3%, respectively. All three assays demonstrated a specificity of 100%. The average time to positive result was significantly shorter with the RT-SIBA Influenza assay (90 min). The method can be run using battery-operated, portable devices with a small footprint and therefore has potential applications in both laboratory and near-patient settings. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe