| 1. |
- Björkman, Kristoffer, et al.
(författare)
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Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
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Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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| 2. |
- Brundin, Peik M. A., 1975-
(författare)
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Sex differences in immune response and sex hormone receptor expression in healthy individuals and during viral infection
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is sex-bias in morbidity and mortality from infectious diseases. Infections kill more men than women and several studies have pointed out differences in the immune system as a reason. The sex hormones estrogen, progesterone and testosterone all shape the effect of the immune response on multiple levels. Women at fertile age have been suggested to have higher proinflammatory responses from inflammatory stimuli compared to men and post-menopausal women, which has been ascribed to their higher estrogen levels. This could possibly lead to a more active pathogen response but may also result in a detrimental immunopathology to infections or development of autoimmune reaction.The overall aim of this thesis is to study the contribution of sex hormones and sex hormone receptors (SHR) to sex differences in immune response. We focus on peripheral blood mononuclear cells (PBMCs) to study such relationships in healthy individuals, as well as in individuals with asymptomatic Torque Teno Virus infection, and individuals with acute Puumala virus infection.In Paper I, we investigated expression of SHR and immune response genes in PBMC from healthy premenopausal (pre-MP) women during the menstrual cycle. The expression levels were estimated using a qPCR Array (Taqman low-density array, TLDA). SHR expression did not change significantly during the menstrual cycle, but several key immune regulatory genes were significantly more expressed during the ovulatory and mid luteal phase. Further, we separated PBMC into cell subsets (CD4+ T-cells, CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) and analyzed the expression through qPCR of estrogen receptors (ERs), ERα, ERβ1 (wildtype) and the isoform ERβ2. For the first time and unexpectedly, we demonstrate that the isoform ERβ2 was more abundant than wildtype ERβ1. The data from this paper provides new knowledge on the contribution of the menstrual cycle on immune response.In Paper II, we explored the use of Torque Teno Virus as a secondary functional immune marker in men and women. Expression of viral TTV DNA in PBMCs was estimated using a qPCR kit from Argene (R-gene) and analyzed in relation to serum sex hormone levels. The results showed that 50% of the men, 25% the post-MP women, and 18% of the pre-MP women were TTV+. Interestingly, all pre-MP women that were TTV+ had hormonal aberrances and were either anovulatory and/or hypothyroid. TTV+ pre-MP women also had significantly lower progesterone levels than TTV- pre-MP women. This paper indicates that the prevalence of TTV in PBMC differs between men, pre-MP and post-MP women. Furthermore, hormonal aberrances (at least in pre-MP women) will lead to increased prevalence of TTV.In Paper III we investigated the expression of ERα, ERβ1 and ERβ2 in PBMC from patients with Nephropathia epidemica, the viral zoonotic disease caused by Puumala virus, a Hanta virus known to affect more men than women. Expression of ERs in PBMCs and clinical laboratory results during the acute and convalescent phases were analyzed using a principal component analysis (PCA). The results show differences in ER expression and support previous findings that men and women have a different clinical pictureIn conclusion, the results in this thesis reveal distinct patterns of immune response related to sex hormone levels, SHR expression and the phases of the menstrual cycle supporting that there a link between sex hormone levels and immune responses. Further, we show that the ER isoform ERβ2 is more abundant in PBMCs than what was previously described. The data in this thesis adds to the knowledge to the sex differences in immune response and exemplifies the importance of taking these differences into account in the clinic.
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| 3. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Mejaddam, Ala, et al.
(författare)
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Comorbidity and quality of life in obesity–a comparative study with the general population in Gothenburg, Sweden
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- Context Obesity is considered to have a detrimental impact on health-related quality of life (HRQoL). Objective To compare HRQoL in a well-defined group of people with obesity with a population-based control group from the general public. Design Observational cross-sectional cohort study with a reference population. Setting The Regional Obesity Center at the Department of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden. Participants People with obesity (n = 1122) eligible for surgical and non-surgical obesity treatment in routine care were included consecutively between 2015 and 2017 into the BASUN study. Men and women from the WHO-MONICA-GOT project were used as a reference population (n = 414). Main outcome measures HRQoL was measured with the RAND-36/Short Form-36 questionnaire (SF-36) and a Visual Analogue Scale (VAS) for self-related health (SRH). Prescription drugs for hypertension, diabetes mellitus, depression, and anxiety were taken as a proxy for these conditions. Results People with obesity rated their overall HRQoL lower than the reference population according to the SRH-VAS. Lower scores were reported on physical and social functioning, vitality, general and mental health after adjustment for age and use of prescription drugs (considered a proxy for burden of disease, or comorbidities) using the RAND-36/SF-36 questionnaire. Use of some psychopharmacological agents was more common in patients with obesity. Conclusion People with obesity seeking help with weight reduction are more likely to have lower physical and mental self-reported HRQoL than the general population.
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| 5. |
- Li, Peishun, 1988, et al.
(författare)
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Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri
- 2021
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 6. |
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| 7. |
- Melin, Eva O., et al.
(författare)
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Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes : a Swedish multicentre cross-sectional study
- 2022
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Ingår i: BMC Endocrine Disorders. - : BioMed Central (BMC). - 1472-6823. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data. Methods Multicentre, cross-sectional study. Inclusion criteria: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI >= 30 and >= 40 kg/m(2)), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed. Results In 1027 T2D patients, aged 18-94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI >= 30 kg/m(2) (OR 1.7), BMI >= 40 kg/m(2) (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p <= 0.013). Younger women (n = 113), <= 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI >= 30 kg/m(2) (73% vs 60%) and BMI >= 40 kg/m(2)) (18% vs 9%), and smoking (26% vs 16%) (all p <= 0.029). Older women (n = 297), >= 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI >= 30 kg/m(2) (55% vs 47%), BMI >= 40 kg/m(2) (7% vs 3%) (all p <= 0.048), but not of current depression (both 9%). Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use. Conclusions In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression.
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| 8. |
- Haenni, Arvo, et al.
(författare)
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Circulating magnesium status is associated with type 2 diabetes remission after Roux-en-Y gastric bypass surgery : a long-term cohort study
- 2021
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier. - 1550-7289 .- 1878-7533. ; 17:2, s. 299-307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low serum magnesium levels predict cardiovascular and all-cause mortality in patients with typ 2 diabetes.SETTING: Outpatient clinic of obesity and central hospital.OBJECTIVES: To assess long-term alterations in circulating magnesium status after Roux-en-Y gastric bypass (RYGB) surgery and associations with remission of type 2 diabetes (T2D).METHODS: Retrospective analysis of 5-year outcomes of plasma magnesium (p-Mg) and glucometabolic statuses in patients who underwent primary RYGB and who completed the annual follow-up program. Data were investigated from 84 patients without diabetes and 62 with T2D before RYGB, who showed either prolonged remission (n = 30), temporary remission (n = 16), or no remission (n = 16) after surgery.RESULTS: Body mass indexes before RYGB were similar in patients with and without T2D, irrespective of remission. The patients not achieving remission showed longer diabetes durations; higher circulating glucose levels; more intensive antidiabetic drug treatment, including insulin; and significantly lower p-Mg concentrations (.73 [±.08] mmol/L compared with .80-.82 [±.07] mmol/L, respectively; P < .01) than the groups showing remission or without diabetes before surgery. After RYGB, the p-Mg increased similarly, by 10-12% in the groups with T2D before surgery, irrespective of remission; however, the nonremission group did not reach the p-Mg levels registered in the other groups after follow-up. The nonremission group reached .82 (.09) mmol/L, compared with .87 (.06) and .88 (.08) mmol/L (P < .05), respectively, in patients with remission or without a history of diabetes.CONCLUSION: The p-Mg concentrations increased after RYGB, with similar increments irrespective of T2D remission; however, the nonremission group started from an inferior level and did not reach the p-Mg concentrations seen in the groups achieving remission or without a history of diabetes before surgery.
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| 9. |
- Brundin, Peik M.A., et al.
(författare)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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| 10. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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