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The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
The Lancet. Healthy Longevity Jul 2024Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated...
BACKGROUND
Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases.
METHODS
In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021. To test reproducibility of the findings (replication analysis), we used data from people aged 40 years or older included in the Finnish Public Sector study and the Finnish Health and Social Support study who responded to the study surveys, had data on BMI, and were successfully linked to electronic health records from national registers up to Dec 31, 2016. Obesity and clinical characteristics were assessed at baseline. Via linkage to national health records, participants were followed up for 83 diseases related to nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). Outcomes were the first instance of hallmark-related disease, in addition to co-occurrence of three or more hallmark-related diseases and mortality.
FINDINGS
496 530 adults (mean age 57·0 years [SD 8·1]) from the UK Biobank were included in the primary analysis, and 83 249 (mean age 48·2 years [6·4]) adults from the Finnish cohorts were included in the replication analysis. Median follow-up was 12·7 years (IQR 12·0-13·4) in the UK Biobank and 14·0 years (8·0-15·0) in the Finnish cohorts. After adjusting for demographic characteristics, lifestyle factors, and depression, UK Biobank participants with obesity (BMI ≥30·0 kg/m) had a 1·40 (95% CI 1·38-1·41) times higher hazard ratio for the first hallmark-related disease than those with a healthy weight (BMI 18·5-24·9 kg/m). The corresponding hazard ratios for three co-occurring diseases were 2·92 (95% CI 2·64-3·22) for deregulated nutrient sensing, 2·73 (2·46-3·02) for telomere attrition, 2·33 (2·10-2·60) for epigenetic alterations, 2·30 (2·14-2·48) for mitochondrial dysfunction, 2·23 (2·04-2·45) for stem cell exhaustion, 2·02 (1·89-2·16) for altered intercellular communication, 2·01 (1·89-2·15) for cellular senescence, 1·83 (1·67-2·00) for loss of proteostasis, and 1·39 (1·27-1·52) for genomic instability. These findings were replicated in the Finnish cohorts. In both studies, the associations between other risk factors (low education, unhealthy dietary factors [available only in the UK Biobank], smoking, high alcohol consumption, physical inactivity, and depression) and hallmark-related diseases were weaker than those with obesity. 45-60% of the excess mortality in people with obesity was attributable to hallmark-related diseases.
INTERPRETATION
Obesity might have an important role in the development of diseases associated with cellular ageing. Tackling ageing mechanisms could potentially help to reduce the disease and mortality burden resulting from the obesity epidemic.
FUNDING
Wellcome Trust, UK Medical Research Council, US National Institute on Aging, Academy of Finland, and Finnish Foundation for Cardiovascular Research.
TRANSLATIONS
For the German and Finnish translations of the abstract see Supplementary Materials section.
Topics: Humans; Obesity; Middle Aged; Male; Female; Aged; Adult; Cellular Senescence; Finland; Cohort Studies; Risk Factors; Aging; United Kingdom; Body Mass Index
PubMed: 38945128
DOI: 10.1016/S2666-7568(24)00087-4 -
Endocrinology, Diabetes & Metabolism Jul 2024Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine... (Observational Study)
Observational Study Comparative Study
INTRODUCTION
Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance.
METHODOLOGY
A cross-sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist-to-hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-β).
RESULTS
Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA-IR than controls (p < 0.05, respectively). Results showed a significant relationship between circulating CC levels versus HOMA-β (r = -0.40, p = 0.001), CS (r = -0.70, p = 0.001) and AC (r = -0.72, p = 0.001) levels in patients with T2DM. The adjusted odds increased in the T2DM patients for VLDL (OR = 6.66, p = 0.002), HbA1c (OR = 6.50, p = 0.001), FPG (OR = 3.17, p = 0.001), TG (OR = 2.36, p = 0.010), being female (OR = 2.09, p = 0.020) and CC (OR = 1.14, p = 0.016).
CONCLUSION
Overall, alterations in mitochondrial biomarkers, measured by AC, CC and CS, were observed in people with T2DM and showed a direct relationship with insulin resistance. These findings are potentially significant in Africa, although additional confirmation from a larger cohort is necessary.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Cross-Sectional Studies; Male; Female; Biomarkers; Middle Aged; Mitochondria; Adult; Carnitine; Cytochromes c; Citrate (si)-Synthase; Glycated Hemoglobin; Blood Glucose; Aged; Body Mass Index
PubMed: 38943337
DOI: 10.1002/edm2.507 -
Nigerian Journal of Clinical Practice Jun 2024Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase...
BACKGROUND
Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase exercise capacity.
AIMS
In this study, the effect of metformin administered in combination with exercise on osteocalcin (OCN), insulin, and interleukin-6 (IL-6) levels in rats was investigated.
METHODS
Forty-two male Wistar rats were used in this study. The animals were randomly divided into six groups: control (CONT), only exercise (EXE), metformin_100 mg/kg (Met100), metformin_200 mg/kg (Met200), metformin_100 mg/kg+exercise (Met100+EXE), and metformin_200 mg/kg+exercise (Met200+EXE). A 10-week intervention was conducted, excluding exercise training. During the experiment, the groups receiving metformin application (100 or 200 mg/kg) were administered with metformin. At the end of the study, serum samples were collected from the rats to determine the levels of osteocalcin, insulin, and IL-6 using the enzyme-linked immunosorbent assay method. In addition, glucose levels and body weights were evaluated. GraphPad Prism was used for the analyses.
RESULTS
The OCN and insulin levels of the Met100+EXE and Met200+EXE groups were found to be higher compared to the CONT, Met100, and Met200 groups (P < 0.05). The IL-6 level of the EXE group was determined to be higher than that of the CONT, Met100, and Met200 groups (P < 0.01). It was observed that both exercise and the individual or combined application of metformin resulted in lower blood glucose levels compared to the CONT group. The mean body weight of the EXE group was higher than that of the other groups.
CONCLUSION
The combined application of metformin and exercise has increased osteocalcin and insulin levels compared to metformin application alone.
Topics: Animals; Metformin; Interleukin-6; Osteocalcin; Rats, Wistar; Male; Rats; Physical Conditioning, Animal; Insulin; Hypoglycemic Agents; Blood Glucose; Body Weight
PubMed: 38943302
DOI: 10.4103/njcp.njcp_884_23 -
Trials Jun 2024Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a...
BACKGROUND
Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear.
METHODS
Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability.
DISCUSSION
Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.
Topics: Humans; Infant, Newborn; Gestational Age; Dietary Supplements; Randomized Controlled Trials as Topic; Vitamin D; Birth Weight; Enteral Nutrition; Vitamin D Deficiency; Treatment Outcome; Infant, Extremely Premature; Time Factors; Female; Vitamins; Calcifediol; Male
PubMed: 38943179
DOI: 10.1186/s13063-024-08274-8 -
International Breastfeeding Journal Jun 2024Despite global public health organizations endorsing breastfeeding or human milk (HM) as the optimal source of nutrition for infants, detailed knowledge of how HM...
BACKGROUND
Despite global public health organizations endorsing breastfeeding or human milk (HM) as the optimal source of nutrition for infants, detailed knowledge of how HM composition influences infant growth is lacking. In this commentary we summarize and interpret the key findings of a large systematic review on HM components and child growth (N = 141 articles included). We highlight the most consistent associations, discuss study quality issues, explore socio-economic and time trends in this body of research, and identify gaps and future research directions.
KEY FINDINGS OF SYSTEMATIC REVIEW
We grouped HM components into three categories: micronutrients (28 articles), macronutrients (57 articles), and bioactives (75 articles). Overall, we struggled to find consistent associations between HM components and infant growth. The majority of studies (85%) were of moderate or low-quality, with inconsistent HM collection and analysis strategies being identified as the most substantial quality concerns. Additional quality issues included failing to account for potential confounding by factors such as breastfeeding exclusivity and maternal body mass index.
CONSIDERATIONS FOR FUTURE HUMAN MILK RESEARCH
Many opportunities exist for the future of HM research. Using untargeted metabolomics will expand our understanding of HM components beyond previously defined and well-understood components. Machine learning will allow researchers to investigate HM as an integrated system, rather than a collection of individual components. Future research on HM composition should incorporate evidence-based HM sampling strategies to encompass circadian variation as well as infant consumption. Additionally, researchers need to focus on developing high quality growth data using consistent growth metrics and definitions. Building multidisciplinary research teams will help to ensure that outcomes are meaningful and clinically relevant.
CONCLUSION
Despite a large body of literature, there is limited quality evidence on the relationship between HM composition and infant growth. Future research should engage in more accurate collection of breastfeeding data, use standardized HM collection strategies and employ assays that are validated for HM. By systematically evaluating the existing literature and identifying gaps in existing research methods and practice, we hope to inspire standardized methods and reporting guidelines to support robust strategies for examining relationships between HM composition and child growth.
Topics: Humans; Milk, Human; Infant; Breast Feeding; Infant, Newborn; Infant Nutritional Physiological Phenomena; Anthropometry; Female; Child Development
PubMed: 38943170
DOI: 10.1186/s13006-024-00652-x -
Medicine Jun 2024Hypertension has long been a worldwide health concern. Our aim was to investigate the prevalence, awareness, treatment, and control rates of hypertension and analyze the...
Hypertension has long been a worldwide health concern. Our aim was to investigate the prevalence, awareness, treatment, and control rates of hypertension and analyze the factors related to hypertension among adult residents of the coastal areas of Tianjin, China. This was a cross-sectional study. Adults aged 35 to 75 years were selected for the study using cluster random sampling methods. Detailed information was collected via face-to-face surveys and medical checkups. We assessed the rates of hypertension in the total population and sub-populations and used multivariable logistic regression to identify the factors associated with the prevalence and the control of hypertension. In total, 6305 participants aged 55.22 ± 10.37 years were included in this study. Approximately 49.8% (95% confidence interval [CI]: 48.5%-51.1%) of the population had hypertension; the prevalence increased with age and body mass index (all P < .001). Multivariable logistic regression showed that the odds ratio of hypertension was 5.93 times more in participants aged 65 to 75 years than in those aged 35 to 44 (95% CI: 4.85-7.26, P < .001). The odds ratio of hypertension was 3.63 times more in obese participants than in those of normal weight (95% CI: 3.08-4.28, P < .001). Additionally, the awareness, treatment, control, and control under-treatment rates of hypertension were 89.7%, 83.6%, 54.4%, and 60.5%, respectively. Factors associated with having controlled hypertension included sex, body mass index, and dyslipidemia (all P < .01). Our study identified that in the coastal area of Tianjin, China, about half have hypertension, also the region has high rates of hypertension awareness, treatment and control, and more than half of hypertension patients receiving treatment have controlled hypertension.
Topics: Humans; Hypertension; Middle Aged; Male; China; Female; Cross-Sectional Studies; Prevalence; Adult; Aged; Health Knowledge, Attitudes, Practice; Body Mass Index; Risk Factors; Age Factors; Logistic Models
PubMed: 38941429
DOI: 10.1097/MD.0000000000038676 -
Medicine Jun 2024Healthy eating and weight control are recommended for cancer survivors; however, dietary interventions are not routinely offered to them. This study aimed to assess the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Healthy eating and weight control are recommended for cancer survivors; however, dietary interventions are not routinely offered to them. This study aimed to assess the effects of dietary interventions on survival, nutritional status, morbidity, dietary changes, health-related quality of life (QOL), and clinical measures in cancer survivors.
METHODS
Searches were conducted from October 1, 2018 to November 21, 2011 in the Medline, EMBASE, CENTRAL, Emcare, and DARE electronic databases. We included randomized controlled trials (RCTs) that involved individuals diagnosed with cancer, excluding conference abstracts, case studies, other reviews, and meta-analyses, and screened the articles.
RESULTS
Eight studies were included in this meta-analysis. We observed significant improvements in QOL and clinical data in 3 of 6 studies and in one study, respectively, significant weight loss on anthropometry in 2 of 5 studies, and dietary improvement in 4 of 5 studies of adult cancer survivors. However, we did not observe any benefits of dietary intervention for cancer survivors with undernutrition.
DISCUSSION
Dietary interventions for adult cancer survivors might contribute to improving their nutritional status; however, further clarification requires a study that standardizes the intervention method. Furthermore, RCTs are required to determine the effects on cancer survivors with undernutrition.
Topics: Adult; Humans; Cancer Survivors; Neoplasms; Nutritional Status; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38941414
DOI: 10.1097/MD.0000000000038675 -
Medicine Jun 2024Observational studies report inverse associations between educational attainment and depression/anxiety risks, but confounding hinders causal inference. This study aimed...
Observational studies report inverse associations between educational attainment and depression/anxiety risks, but confounding hinders causal inference. This study aimed to assess potential causal relationships using Mendelian randomization (MR). Two-sample MR analysis was conducted using genetic instruments for education, smoking, body mass index, and physical activity from published genome-wide association studies. Depression and anxiety data came from the UK Biobank ([UKB] 117,782 individuals) and FinnGen (215,644 individuals) cohorts. Inverse variance weighted regression determined associations between exposures and mental health outcomes. Increased educational attainment was causally associated with reduced risks of depression (odds ratio [OR] = 0.99 per year, 95% confidence interval [CI]: 0.990-0.996, P < .001) and anxiety (OR = 0.99, CI: 0.98-0.991, P < .001) in both cohorts. Smoking initiation conferred higher risks of depression (UKB OR = 1.05, CI: 1.03-1.06, P < .001; FinnGen OR = 1.20, CI: 1.10-1.32, P < .001) and anxiety (FinnGen only, OR = 1.10, CI: 1.01-1.21, P < .05). Likewise, maternal smoking history associated with greater depression (UKB OR = 1.15, CI: 1.10-1.35, P = .027) and anxiety susceptibility (FinnGen OR = 3.02, CI: 1.67-5.46, P = .011). Higher body mass index elevated depression risk in both cohorts. Physical activity showed no clear associations. This MR study provides evidence that education may causally reduce mental health disorder risk. Smoking, obesity, and low activity appear detrimentally linked to depression and anxiety. Improving access to education could offer effective strategies for lowering population psychiatric burden.
Topics: Humans; Female; Male; Mendelian Randomization Analysis; Depression; Educational Status; Anxiety; Middle Aged; Body Mass Index; Smoking; Mental Health; United Kingdom; Adult; Aged; Cohort Studies; Exercise; Genome-Wide Association Study; Risk Factors; Causality
PubMed: 38941394
DOI: 10.1097/MD.0000000000038602 -
PloS One 2024Obesity is a high-morbidity chronic condition and risk factor for multiple diseases that necessitate imaging. This study assesses the relationship between BMI and...
OBJECTIVE
Obesity is a high-morbidity chronic condition and risk factor for multiple diseases that necessitate imaging. This study assesses the relationship between BMI and same-year utilization of CT and MR imaging in a large healthcare population.
METHODS
In this retrospective population-based study, all patients aged ≥18 years with a documented BMI in the multi-institutional Cosmos database were included. Cohorts were identified based on ≥1 documented BMI in 2021 within pre-defined ranges. For each cohort, we assessed the percentage of patients undergoing head, neck, chest, spine, or abdomen/pelvis CT and MR during the same year. Disease severity was quantified based on emergency department (ED) visits and mortality.
RESULTS
In our population of 49.6 million patients, same-year CT and MR utilization was 14.5 ±0.01% and 6.0±0.01%, respectively. The underweight cohort had the highest CT (25.8±0.1%) and MR (8.01 ± 0.05) imaging utilization. At high extremes of BMI (>50 kg/m2), CT utilization mildly increased (18.4±0.1%), but MR utilization decreased (5.3±0.04%). While morbidity differences may explain some BMI-utilization relationships, lower MR utilization in the BMI>50 cohort contrasts with higher age-adjusted mortality (1.8±0.03%) and ED utilization (32.4±0.1%) in this cohort relative to normal weight (1.5±0.01% and 25.7±0.02%, respectively).
CONCLUSION
Underweight patients had disproportionately high CT/MR utilization, and high extremes of BMI are associated with mildly higher CT and lower MR utilization than the normal weight cohort. The elevated mortality and ED utilization in severely obese patients contrasts with their lower MR imaging utilization. Our findings may assist public health efforts to accommodate obesity trends.
Topics: Humans; Body Mass Index; Magnetic Resonance Imaging; Male; Female; Tomography, X-Ray Computed; Middle Aged; Retrospective Studies; Adult; Obesity; Aged; Emergency Service, Hospital; Morbidity
PubMed: 38941332
DOI: 10.1371/journal.pone.0306087