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American Journal of Physiology.... Sep 2017Normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active). HC has been... (Meta-Analysis)
Meta-Analysis Review
Normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active). HC has been previously used by healthy and athletic populations to enhance their physical capacity and improve performance in the lead up to competition. Recently, HC has also been applied acutely (single exposure) and chronically (repeated exposure over several weeks) to overweight and obese populations with the intention of managing and potentially increasing cardio-metabolic health and weight loss. At present, it is unclear what the cardio-metabolic health and weight loss responses of obese populations are in response to passive and active HC. Exploration of potential benefits of exposure to both passive and active HC may provide pivotal findings for improving health and well being in these individuals. A systematic literature search for articles published between 2000 and 2017 was carried out. Studies investigating the effects of normobaric HC as a novel therapeutic approach to elicit improvements in the cardio-metabolic health and weight loss of obese populations were included. Studies investigated passive ( = 7; 5 animals, 2 humans), active ( = 4; all humans) and a combination of passive and active ( = 4; 3 animals, 1 human) HC to an inspired oxygen fraction ([Formula: see text]) between 4.8 and 15.0%, ranging between a single session and daily sessions per week, lasting from 5 days up to 8 mo. Passive HC led to reduced insulin concentrations (-37 to -22%) in obese animals and increased energy expenditure (+12 to +16%) in obese humans, whereas active HC lead to reductions in body weight (-4 to -2%) in obese animals and humans, and blood pressure (-8 to -3%) in obese humans compared with a matched workload in normoxic conditions. Inconclusive findings, however, exist in determining the impact of acute and chronic HC on markers such as triglycerides, cholesterol levels, and fitness capacity. Importantly, most of the studies that included animal models involved exposure to severe levels of hypoxia ([Formula: see text] = 5.0%; simulated altitude >10,000 m) that are not suitable for human populations. Overall, normobaric HC demonstrated observable positive findings in relation to insulin and energy expenditure (passive), and body weight and blood pressure (active), which may improve the cardio-metabolic health and body weight management of obese populations. However, further evidence on responses of circulating biomarkers to both passive and active HC in humans is warranted.
Topics: Adult; Animals; Energy Metabolism; Female; Heart; Humans; Ischemic Preconditioning; Male; Mice; Obesity; Oxygen; Prevalence; Rats; Risk Factors; Treatment Outcome; Weight Loss
PubMed: 28679682
DOI: 10.1152/ajpregu.00160.2017 -
Therapeutic Drug Monitoring Feb 2020Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug...
Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Topics: Anti-Bacterial Agents; Bayes Theorem; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Half-Life; Humans; Linezolid; Liver Failure; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Pediatrics; Renal Insufficiency; Renal Replacement Therapy; Tuberculosis
PubMed: 31652190
DOI: 10.1097/FTD.0000000000000710 -
Clinical Epigenetics Mar 2023Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in... (Review)
Review
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in response to the individual exposure for the development and progression of CVD is still poorly understood and a synthesis of the evidence is lacking.
RESULTS
A systematic review of articles examining measurements of DNA cytosine methylation in CVD was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The search yielded 5,563 articles from PubMed and CENTRAL databases. From 99 studies with a total of 87,827 individuals eligible for analysis, a database was created combining all CpG-, gene- and study-related information. It contains 74,580 unique CpG sites, of which 1452 CpG sites were mentioned in ≥ 2, and 441 CpG sites in ≥ 3 publications. Two sites were referenced in ≥ 6 publications: cg01656216 (near ZNF438) related to vascular disease and epigenetic age, and cg03636183 (near F2RL3) related to coronary heart disease, myocardial infarction, smoking and air pollution. Of 19,127 mapped genes, 5,807 were reported in ≥ 2 studies. Most frequently reported were TEAD1 (TEA Domain Transcription Factor 1) and PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) in association with outcomes ranging from vascular to cardiac disease. Gene set enrichment analysis of 4,532 overlapping genes revealed enrichment for Gene Ontology molecular function "DNA-binding transcription activator activity" (q = 1.65 × 10) and biological processes "skeletal system development" (q = 1.89 × 10). Gene enrichment demonstrated that general CVD-related terms are shared, while "heart" and "vasculature" specific genes have more disease-specific terms as PR interval for "heart" or platelet distribution width for "vasculature." STRING analysis revealed significant protein-protein interactions between the products of the differentially methylated genes (p = 0.003) suggesting that dysregulation of the protein interaction network could contribute to CVD. Overlaps with curated gene sets from the Molecular Signatures Database showed enrichment of genes in hemostasis (p = 2.9 × 10) and atherosclerosis (p = 4.9 × 10).
CONCLUSION
This review highlights the current state of knowledge on significant relationship between DNA methylation and CVD in humans. An open-access database has been compiled of reported CpG methylation sites, genes and pathways that may play an important role in this relationship.
Topics: Humans; DNA Methylation; Cardiovascular Diseases; CpG Islands; Smoking; Air Pollution; Epigenesis, Genetic
PubMed: 36991458
DOI: 10.1186/s13148-023-01468-y -
Obesity (Silver Spring, Md.) Mar 2023Little is known about sex differences in response to lifestyle interventions among pediatric populations. The purpose of this analysis was to evaluate sex differences in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Little is known about sex differences in response to lifestyle interventions among pediatric populations. The purpose of this analysis was to evaluate sex differences in adiposity following lifestyle interventions among children and adolescents with overweight or obesity aged 6 to 18 years old.
METHODS
Searches were conducted in PubMed, Web of Science, and MEDLINE (from inception to March 2021), and references from included articles were examined. Eligibility criteria included children and adolescents aged 6 to 18 years with overweight or obesity, randomization to a lifestyle intervention versus a control group, and assessment of at least one adiposity measure. Corresponding authors were contacted to obtain summary statistics by sex (n = 14/49).
RESULTS
Of 89 full-text articles reviewed, 49 (55%) were included, of which 33 (67%) reported statistically significant intervention effects on adiposity. Only two studies (4%) evaluated sex differences in response to lifestyle intervention, reporting conflicting results. The results of the meta-regression models demonstrated no significant differences in the treatment effect between male and female youth for weight (beta = -0.05, SE = 0.18, z = -0.28, p = 0.8), BMI (beta = 0.03, SE = 0.14, z = 0.19, p = 0.85), BMI z score (beta = -0.04, SE = 0.18, z = -0.23, p = 0.82), percentage body fat (beta = -0.11, SE = 0.16, z = -0.67, p = 0.51), and waist circumference (beta = -0.30, SE = 0.25, z = -1.18, p = 0.24).
CONCLUSIONS
The meta-analysis revealed that youth with overweight or obesity do not demonstrate a differential response to lifestyle intervention in relation to adiposity-related outcomes.
Topics: Humans; Child; Adolescent; Female; Male; Overweight; Pediatric Obesity; Sex Characteristics; Life Style; Adiposity; Body Mass Index
PubMed: 36762579
DOI: 10.1002/oby.23663 -
Biomedicine & Pharmacotherapy =... Sep 2022Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary... (Review)
Review
Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.
Topics: Azetidines; Benzyl Compounds; Cytochrome P-450 CYP2C9; Genotype; Pharmacogenetics
PubMed: 36076616
DOI: 10.1016/j.biopha.2022.113536 -
Journal of Dairy Science Jan 2024To investigate the effects of supplemental monensin administration on the metabolic responses of dairy cows, a systematic review and dose-response meta-analysis were... (Meta-Analysis)
Meta-Analysis
Effects of monensin supplementation on rumen fermentation, methane emissions, nitrogen balance, and metabolic responses of dairy cows: A systematic review and dose-response meta-analysis.
To investigate the effects of supplemental monensin administration on the metabolic responses of dairy cows, a systematic review and dose-response meta-analysis were conducted. Initially, 604 studies were identified through comprehensive database searches, including Google Scholar, Scopus, Science Direct, and PubMed, using key words related to dairy cows, monensin, and metabolic outcomes. After a 2-stage screening process, 51 articles with a total of 60 experiments were selected for meta-analysis based on criteria such as study implementation date between 2001 and 2022, presence of a control group that did not receive monensin supplementation, reporting of at least 1 outcome variable, and presentation of means and corresponding errors. The meta-analysis used the 1-stage random-effects method, and sensitivity analyses were performed to assess the robustness of the results. The results showed that the administration of monensin at a dosage of 19 to 26 mg/kg was inversely related to methane emissions and that the administration of monensin at a dosage of 18 to 50 mg/kg resulted in a significant decrease in dry matter intake. Administration of monensin at doses of 13 to 28 and 15 to 24 mg/kg also resulted in a significant decrease in ruminal acetate proportion and an increase in propionate proportion, respectively, with no effects on ruminal butyrate, NH, or pH levels. We found no effects on blood parameters or nitrogen retention, but a significant negative correlation was observed between monensin supplementation and fecal nitrogen excretion. Based on the analysis of all variables evaluated, the optimal dose range of monensin was estimated to be 19 to 24 mg/kg.
Topics: Female; Cattle; Animals; Monensin; Milk; Fermentation; Methane; Rumen; Nitrogen; Dietary Supplements; Diet; Lactation
PubMed: 37709041
DOI: 10.3168/jds.2023-23441 -
Obesity Reviews : An Official Journal... Feb 2024Depending on the nature of their sports, athletes may be engaged in successive weight loss (WL) and regain, conducing to "weight cycling." The aims of this paper were to... (Meta-Analysis)
Meta-Analysis Review
Depending on the nature of their sports, athletes may be engaged in successive weight loss (WL) and regain, conducing to "weight cycling." The aims of this paper were to systematically (and meta-analytically when possible) analyze the post-WL recovery of (i) body weight and (ii) fat mass; fat-free mass; and performance and metabolic responses in weight cycling athletes (18-55 years old, body mass index < 30 kg.m ). MEDLINE, Embase, and SPORTDiscus databases were explored. The quality and risk of bias of the 74 included studies were assessed using the quality assessment tool for quantitative studies. Thirty-two studies were eligible for meta-analyses. Whatever the type of sports or methods used to lose weight, post-WL body weight does not seem affected compared with pre-WL. While similar results are observed for fat-free mass, strength sports athletes (also having longer WL and regain periods) do not seem to fully recover their initial fat mass (ES: -0.39, 95% CI: [-0.77; -0.00], p = 0.048, I = 0.0%). Although the methods used by athletes to achieve WL might prevent them from a potential post-WL fat overshooting, further studies are needed to better understand WL episodes consequences on athletes' performance as well as short- and long-term physical, metabolic, and mental health.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Weight Cycling; Body Composition; Weight Loss; Sports; Athletes; Body Weight
PubMed: 38096860
DOI: 10.1111/obr.13658 -
Obesity Reviews : An Official Journal... May 2024Almond consumption has an inverse relationship with obesity and factors related to metabolic syndrome. However, the results of available clinical trials are... (Meta-Analysis)
Meta-Analysis Review
Almond supplementation on appetite measures, body weight, and body composition in adults: A systematic review and dose-response meta-analysis of 37 randomized controlled trials.
BACKGROUND AND OBJECTIVE
Almond consumption has an inverse relationship with obesity and factors related to metabolic syndrome. However, the results of available clinical trials are inconsistent. Therefore, we analyzed the results of 37 randomized controlled trials (RCTs) and evaluated the association of almond consumption with subjective appetite scores and body compositions.
METHODS
Net changes in bodyweight, body mass index (BMI), waist circumference (WC), fat mass (FM), body fat percent, fat-free mass (FFM), waist-to-hip ratio (WHR), visceral adipose tissue (VAT), and subjective appetite scores were used to calculate the effect size, which was reported as a weighted mean differences (WMD) and 95% confidence interval (CI).
RESULTS
This meta-analysis was performed on 37 RCTs with 43 treatment arms. The certainty in the evidence was very low for appetite indices, body fat percent, FFM, VAT, and WHR, and moderate for other parameters as assessed by the GRADE evidence profiles. Pooled effect sizes indicated a significant reducing effect of almond consumption on body weight (WMD: -0.45 kg, 95% CI: -0.85, -0.05, p = 0.026), WC (WMD: -0.66 cm, 95% CI: -1.27, -0.04, p = 0.037), FM (WMD: -0.66 kg, 95% CI: -1.16, -0.17, p = 0.009), and hunger score (WMD: -1.15 mm, 95% CI: -1.98, -0.32, p = 0.006) compared with the control group. However, almond did not have a significant effect on BMI (WMD: -0.20 kg m, 95% CI: -0.46, 0.05, p = 0.122), body fat percent (WMD: -0.39%, 95% CI: -0.93, 0.14, p = 0.154), FFM (WMD: -0.06, 95% CI: -0.47, 0.34, p = 0.748), WHR (WMD: -0.04, 95% CI: -0.12, 0.02, p = 0.203), VAT (WMD: -0.33 cm, 95% CI: -0.99, 0.32), fullness (WMD: 0.46 mm, 95% CI: -0.95, 1.88), desire to eat (WMD: 0.98 mm, 95% CI: -4.13, 2.23), and prospective food consumption (WMD: 1.08 mm, 95% CI: -2.11, 4.28). Subgroup analyses indicated that consumption of ≥50 g almonds per day resulted in a significant and more favorable improvement in bodyweight, WC, FM, and hunger score. Body weight, WC, FM, body fat percent, and hunger scores were decreased significantly in the trials that lasted for ≥12 weeks and in the subjects with a BMI < 30 kg/m. Furthermore, a significant reduction in body weight and WC was observed in those trials that used a nut-free diet as a control group, but not in those using snacks and other nuts. The results of our analysis suggest that almond consumption may significantly improve body composition indices and hunger scores when consumed at a dose of ≥50 g/day for ≥12 weeks by individuals with a BMI < 30 kg/m.
CONCLUSION
However, further well-constructed randomized clinical trials are needed in order ascertain the outcome of our analysis.
Topics: Adult; Humans; Prunus dulcis; Appetite; Dietary Supplements; Randomized Controlled Trials as Topic; Body Weight; Body Mass Index; Body Composition
PubMed: 38351580
DOI: 10.1111/obr.13711 -
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203 -
Movement Disorders : Official Journal... Feb 2022Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive... (Review)
Review
BACKGROUND
Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.
OBJECTIVES
Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.
METHODS
734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.
RESULTS
Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.
CONCLUSIONS
Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Dystonia; Dystonic Disorders; Female; GTP Cyclohydrolase; Genotype; Humans; Male; Phenotype
PubMed: 34908184
DOI: 10.1002/mds.28874