| 1. |
- Bauzá-Thorbrügge, Marco, et al.
(author)
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NRF2 is essential for adaptative browning of white adipocytes.
- 2023
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In: Redox biology. - : Elsevier. - 2213-2317. ; 68
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Journal article (peer-reviewed)abstract
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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| 2. |
- Taddei, C, et al.
(author)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Journal article (peer-reviewed)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 3. |
- Walladbegi, Java, et al.
(author)
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Innovative intraoral cooling device better tolerated and equally effective as ice cooling.
- 2017
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 80:5, s. 965-972
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Journal article (peer-reviewed)abstract
- PURPOSE: Most of the patients who receive myeloablative therapy prior to stem cell transplantation develop oral mucositis (OM). This adverse reaction manifests as oral mucosal erythema and ulcerations and may require high doses of morphine for pain alleviation. OM may also interfere with food intake and result in weight loss, a need for parenteral nutrition, and impaired quality of life. To date, there have been very few studies of evidence-based interventions for the prevention of OM. Cryotherapy, using ice chips, has been shown to reduce in an efficient manner the severity and extent of OM, although clinical applications are still limited due to several shortcomings, such as adverse tooth sensations, problems with infectious organisms in the water, nausea, and uneven cooling of the oral mucosa. The present proof-of-concept study was conducted to compare the tolerability, temperature reduction, and cooling distribution profiles of an intra-oral cooling device and ice chips in healthy volunteers who did not receive myeloablative treatment, and therefore, did not experience the symptoms of OM.METHODS: Twenty healthy volunteers used the cooling device and ice chips for a maximum of 60 min each, using a cross-over design. The baseline and final temperatures were measured at eight intra-oral locations using an infra-red thermographic camera. The thermographic images were analysed using two digital software packages. A questionnaire was used to assess the tolerability levels of the two interventions.RESULTS: The intra-oral cooling device was significantly better tolerated than the ice-chips (p = 0.0118). The two interventions were equally effective regarding temperature reduction and cooling distribution.CONCLUSIONS: The intra-oral cooling device shows superior tolerability in healthy volunteers. Furthermore, this study shows that temperature reduction and cooling distribution are achieved equally well using either method.
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| 4. |
- Deland, Lily, et al.
(author)
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Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma.
- 2022
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In: Cancer genomics & proteomics. - : Anticancer Research USA Inc.. - 1109-6535 .- 1790-6245. ; 19:6, s. 711-726
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Journal article (peer-reviewed)abstract
- Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors.Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed.Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient.We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
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| 5. |
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| 6. |
- Guo, Annie, et al.
(author)
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Dietary intake and meal patterns among young adults with high caries activity : a cross-sectional study
- 2022
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In: BMC Oral Health. - : BioMed Central. - 1472-6831 .- 1472-6831. ; 22
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Journal article (peer-reviewed)abstract
- BackgroundDental caries is a multifactorial disease that is highly dependent on diet, where a lower consumption and intake frequency of sugar would be favorable. The aims were (i) to examine dietary intake and meal patterns, more specifically sugar intake and foods high in sugar, among young adults with high caries activity, and (ii) to investigate the association between dietary and meal patterns consumption, and level of caries activity.MethodsThis study presents baseline data from an ongoing randomized controlled trial. A total of 50 young adults (aged 23.0 ± 3.0 years) with ≥ 2 decayed tooth surfaces were included. Dietary intake was captured with a 59-item food frequency questionnaire (FFQ) and a three-day food diary. Adherence to dietary guidelines was analyzed by comparing the dietary intake to the Nordic Nutritional Recommendations (NNR) 2012 and by using the Healthy Dietary Adherence score (HDAS). Participants were categorized into two groups: (i) the Caries group with 2–4 decayed surfaces, and (ii) the High caries group with ≥ 5 decayed surfaces.ResultsThe High caries group reported a statistically significantly higher snack and total meal intake compared to the Caries group, as well as a sugar intake exceeding the Nordic nutritional recommendations. The majority of the participants reported a high intake frequency (> 2.5/day) of sweet foods and drinks and less than one intake of fruit and vegetables, respectively, per day. Similar results were found when analyzing adherence by using the HDAS, where the lowest adherence according to dietary guidelines was shown for the food groups of sugar, whole meal products, and fruit and vegetables.ConclusionThe results indicated a high intake of sugar and low intake of fruit, vegetables, and fiber in high caries-active individuals.
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| 7. |
- Timpka, Toomas, 1957-, et al.
(author)
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Community-level football injury epidemiology : traumatic injuries treated at Swedish emergency medical facilities
- 2018
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In: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 28:1, s. 94-99
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Journal article (peer-reviewed)abstract
- Background: Despite the popularity of the sport, few studies have investigated community-level football injury patterns. This study examines football injuries treated at emergency medical facilities using data from three Swedish counties.Methods: An open-cohort design was used based on residents aged 0-59 years in three Swedish counties (pop. 645 520). Data were collected from emergency medical facilities in the study counties between 1 January 2007 and 31 December 2010. Injury frequencies and proportions for age groups stratified by sex were calculated with 95% confidence intervals (95% CIs) and displayed per diagnostic group and body location.Results: Each year, more than 1/200 person aged 0-59 years sustained at least one injury during football play that required emergency medical care. The highest injury incidence was observed among adolescent boys [2009 injuries per 100 000 population years (95% CI 1914-2108)] and adolescent girls [1413 injuries per 100 000 population years (95% CI 1333-1498)]. For female adolescents and adults, knee joint/ligament injury was the outstanding injury type (20% in ages 13-17 years and 34% in ages 18-29 years). For children aged 7-12 years, more than half of the treated injuries involved the upper extremity; fractures constituted about one-third of these injuries.Conclusions: One of every 200 residents aged 0-59 years in typical Swedish counties each year sustained a traumatic football injury that required treatment in emergency healthcare. Further research on community-level patterns of overuse syndromes sustained by participation in football play is warranted.
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| 8. |
- Arnoldussen, Ilse A. C., et al.
(author)
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Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study
- 2019
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In: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 93:9, s. e864-e878
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.
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| 9. |
- Gustafson, Deborah R.
(author)
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Adipose Tissue Complexities in Dyslipidemias
- 2019
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In: Dyslipidemia. - London : IntechOpen. - 9781839680045 - 9781839680038 - 9781839680052 ; , s. 1-22
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Book chapter (peer-reviewed)abstract
- Adipose tissue is the largest organ in the human body and, in excess, contributes to dyslipidemias and the dysregulation of other vascular and metabolic processes. Adipose tissue is heterogeneous, comprised of several cell types based on morphology, cellular age, and endocrine and paracrine function. Adipose tissue depots are also regional, primarily due to sex differences and genetic variation. Adipose tissue is also characterized as subcutaneous vs. visceral. In addition, fatty deposits exist outside of adipose tissue, such as those surrounding the heart, or as infiltration of skeletal muscle. This review focuses on adipose tissue and its contribution to dyslipidemias. Dyslipidemias are defined as circulating blood lipid levels that are too high or altered. Lipids include both traditional and nontraditional species. Leaving aside traditional definitions, adipose tissue contributes to dyslipidemias in a myriad of ways. To address a small portion of this topic, we reviewed (a) adipose tissue location and cell types, (b) body composition, (c) endocrine adipose, (d) the fat-brain axis, and (e) genetic susceptibility. The influence of these complex aspects of adipose tissue on dyslipidemias and human health, illustrating that, once again, that adipose tissue is a quintessential, multifunctional tissue of the human body, will be summarized.
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| 10. |
- Johansson, Linda, 1978-, et al.
(author)
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Using aggregated data from Swedish national quality registries as tools to describe health conditions of older adults with complex needs
- 2021
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In: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 33:5, s. 1297-1306
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Journal article (peer-reviewed)abstract
- Background: Combining National Quality Registries (NQRs) with existing National Health Registries (NHRs) might make it possible to get a wider picture of older adults health situation. The aim was to examine the feasibility of aggregating data across different NQRs and existing NHRs to explore the possibility to investigate trajectories and patterns of disease and care, specifically for the most ill older adults. Method: A Swedish twin population (N = 44,816) was linked to nine NQRs and four NHRs. A descriptive mixed-method study was performed. A manifest content analysis identified which health parameters were collected from each NQR. Factor analysis identified patterns in representation across NQRs. Two case studies illustrated individual trajectories of care by using NQRs and NHRs. Results: About 36% of the population was registered in one or more NQRs. NQRs included 1849 variables that were sorted into 13 categories with extensive overlap across the NQRs. Health and function variables were identified, but few social or cognitive variables. Even though most individuals demonstrated unique patterns of multi-morbidities, factor analysis identified three clusters of representation in the NQRs with sufficient sample sizes for future investigations. The two cases illustrated the possibility of following patterns of disease and trajectories of care. Conclusions: NQRs seem to be a significant source for collecting data about a population that may be underrepresented in most research on aging because of their age and poor health. However, NQRs are primarily disease related, and further development of the registries to maximize coverage and utility is needed.
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