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1.
2.
  • Zhang, C., et al. (författare)
  • The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alc33oholic fatty liver disease
  • 2020
  • Ingår i: Molecular Systems Biology. - 1744-4292. ; 16:4
  • 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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3.
  • Bjermo, Helena, 1981- (författare)
  • Dietary Fatty Acids and Inflammation Observational and Interventional Studies
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory <em>in vitro</em>.</p> <p>This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity.</p> <p>In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA.</p> <p>The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.</p>
4.
  • Löfgren, Magnus, 1979- (författare)
  • Behavioral effects of female sex steroid hormones <em></em> models of PMS and PMDD in Wistar rats<em></em>
  • 2009
  • Ingår i: Stress- och könshormoners verkningar på centrala nervsystemet. - Umaå : Department of Clinical Sciences, Division of Obstetrics and Gynecology. - 978-91-7264-796-1
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background </strong>Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABA<sub>A</sub> receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors.</p> <p><strong>Aims </strong>The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids.</p> <p><strong>Methods </strong>In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA).</p> <p><strong>Results </strong>In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior.</p> <p><strong>Conclusions </strong>It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.</p>
5.
  • Georgsson, Mattias, et al. (författare)
  • Employing a user-centered cognitive walkthrough to evaluate a mHealth diabetes self-management application : A case study and beginning method validation
  • 2019
  • Ingår i: Journal of Biomedical Informatics. - Academic Press Inc.. - 1532-0464 .- 1532-0480. ; 91
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Introduction: Self-management of chronic diseases using mobile health (mHealth) systems and applications is becoming common. Current evaluation methods such as formal usability testing can be very costly and time-consuming; others may be more efficient but lack a user focus. We propose an enhanced cognitive walkthrough (CW) method, the user-centered CW (UC-CW), to address identified deficiencies in the original technique and perform a beginning validation with think aloud protocol (TA) to assess its effectiveness, efficiency and user acceptance in a case study with diabetes patient users on a mHealth self-management application. Materials and methods: A total of 12 diabetes patients at University of Utah Health, USA, were divided into UC-CW and think aloud (TA) groups. The UC-CW method included: making the user the main evaluator for detecting usability problems, having a dual domain facilitator, and using three other improved processes: validated task development, higher level tasks and a streamlined evaluation process. Users interacted with the same mHealth application for both methods. Post-evaluation assessments included the NASA RTLX instrument and a set of brief interview questions. Results: Participants had similar demographic characteristics. A total of 26 usability problems were identified with the UC-CW and 20 with TA. Both methods produced similar ratings: severity across all views (UC-CW = 2.7 and TA = 2.6), numbers of problems in the same views (Main View [UC-CW = 11, TA = 10], Carbohydrate Entry View [UC-CW = 4, TA = 3] and List View [UC-CW = 3, TA = 3]) with similar heuristic violations (Match Between the System and Real World [UC-CW = 19, TA = 16], Consistency and Standards [UC-CW = 17, TA = 15], and Recognition Rather than Recall [UC-CW = 13, TA = 10]). Both methods converged on eight usability problems, but the UC-CW group detected five critical issues while the TA group identified two. The UC-CW group identified needed personalized features for patients’ disease needs not identified with TA. UC-CW was more efficient on average time per identified usability problem and on the total evaluation process with patients. NASA RTLX scores indicated that participants experienced the UC-CW half as cognitively demanding. Common themes from interviews indicated the UC-CW as enjoyable and easy to perform while TA was considered somewhat awkward and more cognitively challenging. Conclusions: UC-CW was effective for finding severe, recurring usability problems and it highlighted the need for personalized user features. The method was also efficient and had high user acceptance. These results indicate UC-CW's utility and user acceptance in evaluating a mHealth self-management application. It provides an additional usability evaluation technique for researchers. © 2019</p>
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6.
  • Herlitz, Anders, 1981-, et al. (författare)
  • The Counseling, Self-care, Adherence Approach to Person-centered Care and Shared Decision Making: Moral Psychology, Executive Autonomy, and Ethics in Multi-dimensional Care Decisions
  • 2016
  • Ingår i: Health Communication. - 1041-0236 .- 1532-7027. ; 31:8, s. 964-973
  • Tidskriftsartikel (refereegranskat)abstract
    • This article argues that standard models of person-centred care (PCC) and shared decision making (SDM) rely on simplistic, often unrealistic assumptions of patient capacities that entail that PCC/SDM might have detrimental effects in many applications. We suggest a complementary PCC/SDM approach to ensure that patients are able to execute rational decisions taken jointly with care professionals when performing self-care. Illustrated by concrete examples from a study of adolescent diabetes care, we suggest a combination of moral and psychological considerations to support the claim that standard PCC/SDM threatens to systematically undermine its own goals. This threat is due to a tension between the ethical requirements of SDM in ideal circumstances and more long-term needs actualized by the context of self-care handled by patients with limited capacities for taking responsibility and adhere to their own rational decisions. To improve this situation, we suggest a counseling, self-care, adherence approach to PCC/SDM, where more attention is given to how treatment goals are internalized by patients, how patients perceive choice situations, and what emotional feedback patients are given. This focus may involve less of a concentration on autonomous and rational clinical decision making otherwise stressed in standard PCC/SDM advocacy.
7.
  • Pourhamidi, Kaveh, 1985-, et al. (författare)
  • Association between symptoms of neuropathy, nerve conduction and levels of heat shock protein 27 in type 2 diabetes
  • 2010
  • Konferensbidrag (refereegranskat)abstract
    • <p><strong>Background and aims:</strong> Increased levels of serum HSP27 (sHSP27) are associated with distal symmetric polyneuropathy (DSPN) in type 1 diabetic patients. However, the association between nerve function and sHSP27 has not been studied in subjects with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). Thus, our objectives were to investigate the association between nerve conduction in the legs, symptoms of distal polyneuropathy and sHSP27 levels. <strong>Methods:</strong> Subjects were consecutively recruited from the population-based Västerbotten Intervention Program; controls (n=39, m/f=19/20, mean age=61± 0.6 years), IGT (n=29, m/f=15/14, mean age=61± 0.8 years), T2D (n=51, m/f=30/21, mean age=61± 1.3 years). Nerve conduction studies were performed. Z-scores for motor conduction velocity (CV) of the peroneal nerve, and the sensory CV and amplitude of the sural nerve were measured and compiled into a composite Z-score of the right leg (Z-score leg). Neurological Disability Score (NDS), including examination of sensory perception, reflexes and muscle strength, were used to evaluate symptoms of neuropathy in the leg. NDS and Z-score leg were categorized into tertiles, respectively. sHSP27 levels were measured and divided into low and high levels.<strong> Results:</strong> Subjects in the highest NDS tertile had lower sHSP27 levels (328 ± 287 pg/mL) compared to subjects in the lowest NDS tertile (558 ± 404 pg/mL, p=0.04). Subjects in the lowest tertile of Z-score leg were in the lowest sHSP27 group (63%) compared to the subjects in the highest group (38%, p=0.034). The highest tertile of Z-score leg was associated with high levels of sHSP27 (OR 3.8, 95% CI 1.2; 11.5, p=0.02); adjusted for age and sex. However, this association was attenuated when adjusted for T2D status (OR 3.1, 95% CI 0.9; 9.9, p=0.06).<strong> Conclusion:</strong> In summary, increased sHSP27 levels were associated with an increasing Z-score of the leg; thus, a better nerve conduction, and fewer symptoms using the whole study population. The attenuation of the association when including diabetic status indicates an altered HSP27 production in T2D patients compared to controls and subjects with IGT.</p>
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8.
  • Boman, Åse, et al. (författare)
  • Health care to empower self-care in adolescents with type 1 diabetes mellitus and an immigrant minority background
  • 2017
  • Ingår i: Sage Open medicine. - 2050-3121 .- 2050-3121. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The pediatric diabetes team aims to support health, quality of life, and normal growth and development among adolescents with type 1 diabetes mellitus. Adolescents with an immigrant background have been found less successful in self-care. Previous research indicated that adolescents who had integrated the disease as a part of their self-image reasoned differently about their self-care to those who had not. Objective: The aim of this study was to identify elements in the patient–pediatrician consultations that might influence such integration of the disease among adolescents with type 1 diabetes mellitus. Methods: A total of 12 pediatrician–adolescent consultations were video-recorded and analyzed. The adolescents all had an immigrant background. Results: Integration of the disease appeared enabled when responsibility was shared; when hope, autonomy, and emotions were confirmed; and when the pediatrician asked probing questions. Letting objective data dominate the adolescent’s experiences, using risk as a motivator, neutralizing emotions in relation to having diabetes, and confirming forgetfulness, may instead inhibit disease integration. Conclusion: An extended person-centered approach with focus on the adolescent’s experiences of everyday life with a chronic disease and less attention on physical parameters in the pediatrician–adolescent consultations may increase integration of the disease.
9.
  • Herlitz, Anders, 1981-, et al. (författare)
  • Family-Centeredness as Resource and Complication in Outpatient Care with Weak Adherence, Using Adolescent Diabetes Care as a Case in Point
  • 2019
  • Ingår i: What about the family? : practices of responsibility in care / edited by Marian A. Verkerk, Hilde Lindemann, and Janice McLaughlin.. - Oxford : Oxford University Press. - 9780190624880 ; s. 137-146
  • Bokkapitel (refereegranskat)abstract
    • Care for adolescent patients with diabetes type 1 is a recognized challenge, with known adherence problems in a context where home-/self-care and continuous vital need of day-to-day life-style adjustment. The recommended care regimen often gives rise to conflicts with broader personal and social needs and desires, and in case of weak adherence negative spirals of undermined self-confidence and/or emotional denial further deteriorating the situation may result. The need to adjust care to the specific situation is accepted within the pediatric diabetes professional community, accepting a commitment to person centeredness involving alliance with the family as a critical part. Yet, families can be involved in different ways and the issue of how to involve families and what ethical tensions that may actualize is largely unexplored. Standard models of person- and family-centeredness tell us little about how to involve family members in care similar to that of diabetes. We have elsewhere proposed an alternative approach more attuned to such circumstances, aiming at empowering patients' long-term capacities to manage their condition domestically. This “counselling, self-care, adherence (CSA) approach” offers a look at the role that family can play to improve these types of care. We will illustrate how family members can assist in the care of teenagers with diabetes, but that there are also serious risks actualized by such involvement. In particular, we will highlight ethical complications that arise when the role of a family member is changed from “parent” to “care provider.”
10.
  • Lindqvist, A, et al. (författare)
  • Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients
  • 1997
  • Ingår i: Clinical Physiology. - Wiley Online Library. - 1365-2281. ; 17:2, s. 159-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.
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