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- Balk, Lennart, et al.
(author)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
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| 2. |
- Chaplin, John, et al.
(author)
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Varför ska du använda PROMIS? : Nytt system för patientrapporterad utfallsmått
- 2018
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Conference paper (other academic/artistic)abstract
- PROMIS är ett itembanksystem för hälso- och sjukvården. Syftet är att erbjuda moderna, patientrapporterade mått som kan användas för flertalet patientgrupper till en mycket låg kostnad och med ett nationellt supportsystem.En itembankär en modern form av elektronisk enkät som kan innehålla ett stort antal enkätfrågor. Ett datorprogram väljer ut de mest lämpade frågorna till varje person utifrån dennes svar på föregående frågor, på så sätt enkäten individanpassas.
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| 3. |
- Helmfrid, Ingela, et al.
(author)
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Risk och nytta med fisk
- 2008
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Reports (other academic/artistic)abstract
- Inom ramen för den nationella hälsorelaterade miljöövervakningen (HÄMI) har exponeringför metylkvicksilver (MeHg), persistenta organiska föreningar (POP) och intag avfiskfettsyror i form av fettsyresammansättningen (Omega-3 index) kartlagts. Studieområdetbegränsades till kommuner i Gävleborgs län, kring Vänern, Vättern och i Småländskahöglandet. Totalt skickades 6 500 enkäter till ett slumpmässigt urval av flickor och kvinnor ibarnafödande ålder (15-45 år). Svarsfrekvensen var 30 %.Enligt enkätsvaren är det endast en femtedel av landets kvinnor (15-45 år) som följerLivsmedelsverkets råd att äta fisk 2-3 gånger i veckan, och ca 5 procent åt sällan eller aldrigfisk. En mindre andel av kvinnorna (1,5 %) konsumerade all sorts fisk minst 30 gånger permånad, vilket är minst en fiskmåltid varje dag. Konsumtion av riskfiskar var betydligtvanligare i den studerade gruppen än vad Livsmedelsverket råd anger (2-3 gånger per år).Enligt enkätsvaren åt 80 procent MeHg-fisk och ca 60 procent åt POP-fisk mer än tre gångerper år, men de flesta åt dessa fiskar högst en gång per månad.Baserat på de 1950 enkätsvaren, valdes två grupper av personer ut för förfrågan omprovtagning och kompletterande enkät, en grupp med hög konsumtion av fisk och en medingen eller låg konsumtion. Totalt deltog 75 kvinnor i högkonsumentgruppen och 55 kvinnor ilågkonsumentgruppen.Blodserumhalten av PCB 153 och HCB hos högkonsumenter av POP-fiskar var signifikanthögre än hos lågkonsumenter. Medianhalten i serum för PCB 153 var 36 ng/g fett (range 9-125 ng/g fett) bland högkonsumenter och 24 ng/g fett (range 4-74 ng/g fett) blandlågkonsumenter. Halterna bland högkonsumenterna var något högre än jämförbara halter ibröstmjölk från förstföderskor från Uppsala (median 31 (range 19-91) ng/g fett) år 2006, menlägre än tidigare mätningar (median 68 (range 24-186) ng/g fett) från år 1996-97. PCB 153-halten och även HCB och DDE bland förstföderskor har generellt minskat över tid i takt medatt POP-halterna i miljön har minskat. I vår studie ingick både gravida, förstföderskor,omföderskor och kvinnor som inte fått barn. Trots att exponeringen har minskat syns ettsamband mellan PCB-halt och konsumtion av fisk, framförallt för konsumtion av fet fisk sominnehåller låg/medelhög halt av POP och av POP-fisk.Det var ett starkt samband mellan kvicksilverhalten i hår och konsumtion av mager fisk(R=0,51), riskfiskar (R=0,47) och total fiskkonsumtion (R=0,54). MeHg-halten i hår varsignifikant högre bland högkonsumenter av fisk (MeHg-grupp: median 0,28 mg/kg (range0,07-2,1 mg/kg), POP/MeHg-grupp: median 0,4 mg/kg (range 0,17-1,6 mg/kg), POP-grupp:median 0,37 mg/kg (range 0,10-1,2 mg/kg) jämfört med lågkonsumenterna (median 0,07mg/kg (range 0,01-0,45 mg/kg). Jämfört med tidigare HÄMI-studier var hårhalterna av MeHglåga i alla grupper. I en tidigare studie av kvinnor (19-56 år) med högt fiskintag varmedianhalten i hår 1,9 mg/kg (range 0,30-14 mg/kg). I en HÄMI-studie av gravidaförstföderskor (20-40 år) från Uppsala var medianhalten i hår 0,35 mg/kg (range 0,07-1,5mg/kg; Berglund et al., 2001) och i en studie av gravida kvinnor i Västsverige varmedianhalten i hår 0,43 mg/kg (range 0,02-1,8 mg/kg; Rödström et al., 2004). Trots ett(självrapporterat) högt intag av fisk med potentiellt höga kvicksilverhalter var det ingen avkvinnorna som överskred WHO:s expertorgan JECFA tolerabla kvicksilverhalt i hår på 2,2mg/kg. Tre procent av kvinnorna överskred National Research Concil (NRC) tolerabla hårhaltpå 1,2 mg/kg.Fettsyresammansättningen i blod visade tydligt samband mellan Omega-3 index och totalfiskkonsumtion och konsumtion av olika sorters fisk. Likaså visades att intag av Omega-3kosttillskott har stor betydelse. De flesta personerna hade ett adekvat intag av Omega-3.Några (10 %) hade Omega 3-index under 4. Dessa personer tillhör främst lågkonsumentgruppen.De skulle behöva öka sitt intag av Omega 3, t ex genom ökad fiskkonsumtion. Ettgenerellt ökat fiskintag enligt Livsmedelsverkets rekommendationer kommer dock att leda tillen ökad exponering för miljögifter i fisk, eftersom även andra fisksorter än riskfiskar, bidrartill den totala exponeringen. Det är därför viktigt att även i fortsättningsvis övervakaexponeringen.
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| 6. |
- Ström, Marika
(author)
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Systems biology approaches to investigate mechanisms of obstructive lung diseases
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Both asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases with a large impact on global health, causing 400 000 and 3 million deaths respectively each year. The numbers may be underestimated, since COPD often contributes to death without being registered as the cause of death. There is currently no therapeutic cure for either of these diseases, only symptomatic relief. One problem is that the available therapeutics do not always work, since the diseases present a range of clinical phenotypes with possibly different endotypes, so-called umbrella diseases. The aim of this thesis was to study asthma, COPD caused by smoking, and obstructive lung disease related to preterm birth using systems biology approaches. This includes studying several analytical platforms in a range of compartments in order to subphenotype the patients into subgroups and elucidate the related mechanisms. Identifying these endotypes increases the possibility of finding effective therapeutics for all patient groups. Obstructive lung diseases are often studied by collecting bronchoalveolar lavage (BAL) and epithelial cells from the lungs during bronchoscopy. This procedure is invasive, and costly which is why the cohorts studied are often small. Subgrouping results in even smaller sample sizes, which decreases the power of statistical analysis. Using multivariate analysis is a means of increasing power by taking all variables into account. A workflow for performing the multivariate method orthogonal projections to latent structures discriminant analysis (OPLS-DA) to compare groups one by one in small sample sizes was developed using the programming language R, and was formatted into an R package entitled roplspvs. The roplspvs package performs OPLS modeling using the package ropls in R, including variable selection to extract the variables driving the separation the most. As OPLS models are prone to overfitting, the significance of the models was investigated thoroughly using permutations. Using roplspvs on small sample sizes, it was shown that permutations performed before variable selection (termed “sans v.s.”) and permutations including the variable selection step (termed “over v.s.”) are better suited to estimate the level of model statistics achieved by random than permutations post variable selection. An example of running the package was shown using a publicly available metabolomics dataset. The roplspvs packages, along with the commercially available software SIMCA and univariate statistics, were then applied to investigate alterations between groups in a range of projects, including three clinical cohorts of asthma, COPD and BPD, as well as a project investigating the degradation of proteins in the processing of blood samples prior to biobanking the evaluate protein stability. COPD in smokers and ex-smokers was studied by investigating the miRNA content of small extracellular vesicles (EVs) using OPLS modeling as well as univariate analysis, with the finding that COPD gave highly altered miRNA content of small EVs compared to healthy subjects. After stratifying the analysis by gender, potential alterations compared to smokers were identified in males with significant p[CV-ANOVA]=0.05 and p[permutations over variable selection]=0.12, but permutations sans variable selection were highly insignificant. The alterations were connected to potentially affected pathways through pathway analysis of genes regulated by the altered miRNA. Pathway affected by COPD and smoking were mainly connected to cell- growth and death with the p53-pathway mostly altered, while the less pronounced miRNA alterations related to COPD alone was connected to degradation through autophagy and proteolysis. Premature birth has been connected to lung obstruction in adults who developed bronchopulmonary disease (BPD) during the neonatal period. To characterize T-cells in adults with a history of BPD, FACS analysis was performed on BAL cells. Univariate analysis showed increased levels of CD8+ T-cells, and decreased levels of CD4+ T-cells in subjects with BPD. Applying OPLS and stratifying the analysis by gender, it was indicated that the alterations were mostly driven by females. Asthmatic subjects were subphenotyped into clusters using four platforms from blood and urine into phenotypic groups, which were studied using OPLS models to compare the groups. Clinical features were extracted that separated a large portion of the groups. Finally, the metabolome of urine was used to separate asthmatics into severe and mild asthma, stratifying the analysis by oral corticosteroids (OCS). It was found that carnitines, which were the strongest drivers for separating the groups, were not affected by OCS use. Using roplspvs, it was shown that the levels of carnitines were strongly affected by gender, with higher levels in males than in females. In conclusion, it was shown that OPLS models can be used to investigate cohorts consisting of small sample sizes, and that permutation procedures including variable selection efficiently test the significance of the models. Subgroups of COPD and asthmatic subjects were compared, showing alterations in miRNA levels, metabolome, and lymphocyte composition, as well as in clinical data connected to potential endotypes with separate disease mechanisms. Stratifications by gender supported earlier findings that gender has a strong effect on obstructive lung diseases. Together with further analysis on the cohorts in this study using other platforms, this is a step towards finding candidates for diagnostics and therapeutics.
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