| 1. |
- Migueles, Jairo H., et al.
(författare)
-
Effects of an Exercise Program on Cardiometabolic and Mental Health in Children With Overweight or Obesity A Secondary Analysis of a Randomized Clinical Trial
- 2023
-
Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health. Objective To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity. Design, Setting, and Participants This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context. Intervention The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines. Main Outcomes and Measures Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators. Results The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score byapproximately0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health.
|
|
| 2. |
- Henriksson, Hanna, et al.
(författare)
-
Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men
- 2020
-
Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:15, s. 1503-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, Little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with Later chronic disability due to specific causes of CVD disability (i.e. cerebrovascutar disease, ischaemic heart disease and heart failure). Methods and results This population-based cohort study included 1 078 685 male adolescents (16-19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05-0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak. Conclusions This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Michel, M., et al.
(författare)
-
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
-
Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
-
Tidskriftsartikel (refereegranskat)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
|
|
| 6. |
|
|
| 7. |
- Teixeira, G. Q., et al.
(författare)
-
Terminal complement complex formation is associated with intervertebral disc degeneration
- 2021
-
Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 30, s. 217-226
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD). Methods Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 +/- 12) and adolescent idiopathic scoliosis (AIS,n = 10, age 17 +/- 4) and compared with discs from healthy Young (n = 11, age 7 +/- 7) and Elder (n = 10, age 65 +/- 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes. Results Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients. Conclusion TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.
|
|
| 8. |
- Arias Tellez, Maria Jose, et al.
(författare)
-
Association of Neck Circumference with Anthropometric Indicators and Body Composition Measured by DXA in Young Spanish Adults
- 2020
-
Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Due to a clinical and public health interest of neck circumference (NC), a better understanding of this simple anthropometric measurement, as a valid marker of body composition is necessary. Methods: A total of 119 young healthy adults participated in this study. NC was measured over the thyroid cartilage and perpendicular to the longitudinal axis of the neck. Body weight, height, waist circumference (WC), and hip circumference were measured. A Dual X-ray absorptiometry (DXA) scan was used to determine fat mass, lean mass, and visceral adipose tissue (VAT). Additionally, body mass index (BMI) and triponderal mass index (TMI), the waist to hip and waist to height ratios, and the fat mass and lean mass indexes (FMI and LMI, respectively) were calculated. Results: NC was positively associated in women (W) and men (M), with BMI (rW = 0.70 and rM = 0.84, respectively), TMI (rW = 0.63 and rM = 0.80, respectively), WC (rW = 0.75 and rM = 0.86, respectively), VAT (rW = 0.74 and rM = 0.82, respectively), Waist/hip (rW = 0.51 and rM = 0.67, respectively), Waist/height (rW = 0.68 and rM = 0.83, respectively) and FMI (rW = 0.61 and rM = 0.81, respectively). The association between NC and indicators of body composition was however weaker than that observed by BMI, TMI, WC and Waist/height in both women and men. It is of note that in women, NC was associated with FMI, VAT and LMI independently of BMI. In men, adding NC to anthropometric variables did not improve the prediction of body composition, while slight improvements were observed in women. Conclusions: Taken together, the present study provides no indication for NC as a useful proxy of body composition parameters in young adults, yet future studies should explore its usefulness as a measure to use in combination with BMI, especially in women.
|
|
| 9. |
- Blasiak, Robert, et al.
(författare)
-
Evolving Perspectives of Stewardship in the Seafood Industry
- 2021
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Humanity has never benefited more from the ocean as a source of food, livelihoods, and well-being, yet on a global scale this has been accompanied by trajectories of degradation and persistent inequity. Awareness of this has spurred policymakers to develop an expanding network of ocean governance instruments, catalyzed civil society pressure on the public and private sector, and motivated engagement by the general public as consumers and constituents. Among local communities, diverse examples of stewardship have rested on the foundation of care, knowledge and agency. But does an analog for stewardship exist in the context of globally active multinational corporations? Here, we consider the seafood industry and its efforts to navigate this new reality through private governance. We examine paradigmatic events in the history of the sustainable seafood movement, from seafood boycotts in the 1970s through to the emergence of certification measures, benchmarks, and diverse voluntary environmental programs. We note four dimensions of stewardship in which efforts by actors within the seafood industry have aligned with theoretical concepts of stewardship, which we describe as (1) moving beyond compliance, (2) taking a systems perspective, (3) living with uncertainty, and (4) understanding humans as embedded elements of the biosphere. In conclusion, we identify emerging stewardship challenges for the seafood industry and suggest the urgent need to embrace a broader notion of ocean stewardship that extends beyond seafood.
|
|
| 10. |
- Bonagas, Nadilly, et al.
(författare)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
|
|
