Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

Comparison of health information exchange data with self-report in measuring cancer screening.

BACKGROUND: Efficient measurement of the receipt of cancer screening has been attempted with electronic health records (EHRs), but EHRs are commonly implemented within a single health care setting. However, health information exchange (HIE) includes EHR data from multiple health care systems and settings, thereby providing a more population-based measurement approach. In this study, we set out to understand the value of statewide HIE data in comparison to survey self-report (SR) to measure population-based cancer screening. METHODS: A statewide survey was conducted among residents in Indiana who had been seen at an ambulatory or inpatient clinical setting in the past year. Measured cancer screening tests included colonoscopy and fecal immunochemical test (FIT) for colorectal cancer, human papilloma virus (HPV) and Pap tests for cervical cancer, and mammogram for breast cancer. For each screening test, the self-reported response for receipt of the screening (yes/no) and 'time since last screening' were compared with the corresponding information from patient HIE to evaluate the concordance between the two measures. RESULTS: Gwet's AC for HIE and self-report of screening receipt ranged from 0.24-0.73, indicating a fair to substantial concordance. For the time since receipt of last screening test, the Gwet's AC ranged from 0.21-0.90, indicating fair to almost perfect concordance. In comparison with SR data, HIE data provided relatively more additional information about laboratory-based tests: FIT (19% HIE alone vs. 4% SR alone) and HPV tests (27% HIE alone vs. 12% SR alone) and less additional information about procedures: colonoscopy (8% HIE alone vs. 23% SR alone), Pap test (13% HIE alone vs. 19% SR alone), or mammography (9% HIE alone vs. 10% SR alone). CONCLUSION: Studies that use a single data source should consider the type of cancer screening test to choose the optimal data collection method. HIE and self-report both provided unique information in measuring cancer screening, and the most robust measurement approach involves collecting screening information from both HIE and patient self-report.

Incorrect analysis in "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study" has resulted in incorrect conclusions of demonstrated effects where no such effects have been demonstrated.

In their 2023 Nutrition and Health paper "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study", Giacomello et al. investigated the effects of an educational intervention based on the Dietary Guidelines for the Brazilian Population among obese women. The authors concluded that the intervention significantly improved weight loss, quality of life, components of metabolic syndrome, and pain. However, we believe the statistical analysis employed in the study was flawed. The authors used within-group changes to draw conclusions, which is known as a difference in nominal significance error. This error has the potential to inflate Type I error rates substantially. To address this issue, we re-analyzed the data obtained from the authors. We focused on body mass and hip circumference and replicated the incorrectly chosen within-group analyses, which remained significant. However, to properly evaluate the intervention's effectiveness, it is essential to compare the differences between the groups directly. Therefore, we calculated change scores for each participant and used independent samples t-tests and linear mixed models to compare between-group differences. Both methods yielded similar non-significant p-values, indicating that there is no significant effect of treatment on body mass or hip circumference. The original paper's conclusions regarding the effectiveness of the intervention are not supported by the proper statistical analysis. The data should be re-analyzed using appropriate between-group comparisons, and the corrected results should be published, or the incorrect results and original paper should be retracted.

RELATIONSHIP BETWEEN REPRODUCTIVE AND BONE BIOMARKERS AND OSTEOARTHRITIS IN ZOO ASIAN (ELEPHAS MAXIMUS) AND AFRICAN (LOXODONTA AFRICANA) ELEPHANTS.

Osteoarthritis (OA) is common in zoo Asian (Elephas maximus) and African (Loxodonta africana) elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.22, P = 0.016; OR = 0.29, P = 0.020, respectively), however, not when adjusted for age (odds ratio [OR] = 0.31, P = 0.112; OR = 0.58, P = 0.369, respectively). In African elephants, none of the models between confirmed OA and cycling status were significant (P > 0.060), while the odds of having suspected OA decreased with cycling (OR = 0.12, P = 0.001), even after adjusting for age (OR = 0.15, P = 0.005). Progestagens (Asian elephants P > 0.096; African elephants P > 0.415), LH (Asian P > 0.129; African P > 0.359), and FSH (Asian P > 0.738; African P > 0.231) did not differ with confirmed or suspected OA status, unadjusted. CTX-I concentrations were not related to OA status (P > 0.655). This study concluded hormonal changes may not have a strong impact on OA, so additional investigation into other serologic biomarkers is warranted.

Bifidobacteriumlongum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants.

OBJECTIVE: To assess the effects of Bifidobacteriumlongum subsp. infantis EVC001 (Binfantis EVC001) administration on the incidence of necrotizing enterocolitis (NEC) in preterm infants in a single level IV neonatal intensive care unit (NICU). STUDY DESIGN: Nonconcurrent retrospective analysis of 2 cohorts of very low birth weight (VLBW) infants not exposed and exposed to Binfantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020. Outcomes included NEC incidence and NEC-associated mortality, including subgroup analysis of extremely low birth weight (ELBW) infants. Log-binomial regression models were used to compare the incidence and risk of NEC-associated outcomes between the unexposed and exposed cohorts. RESULTS: The cumulative incidence of NEC diagnoses decreased from 11.0% (n = 301) in the no EVC001 (unexposed) cohort to 2.7% (n = 182) in the EVC001 (exposed) cohort (P < .01). The EVC001 cohort had a 73% risk reduction of NEC compared with the no EVC001 cohort (adjusted risk ratio, 0.27; 95% CI, 0.094-0.614; P < .01) resulting in an adjusted number needed to treat of 13 (95% CI, 10.0-23.5) for Binfantis EVC001. NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P = .03). There were similar reductions in NEC incidence and risk for ELBW infants (19.2% vs 5.3% [P < .01]; adjusted risk ratio, 0.28; 95% CI, 0.085-0.698 [P = .02]) and mortality (5.6% vs 0%; P < .05) in the 2 cohorts. CONCLUSIONS: In this observational study of 483 VLBW infants, Binfantis EVC001 administration was associated with significant reductions in the risk of NEC and NEC-related mortality. Binfantis EVC001 supplementation may be considered safe and effective for reducing morbidity and mortality in the NICU.

Stimulated Insulin Secretion Predicts Changes in Body Composition Following Weight Loss in Adults with High BMI.

BACKGROUND: The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. OBJECTIVES: The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. METHODS: Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12-18% weight loss in ∼14 wk or 10-14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post-weight loss. Associations were analyzed using general linear models with adjustment for covariates. RESULTS: In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 µIU/mL increment in baseline insulin-30; P = 0.005; -1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (-0.465 kg per 100 µIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (-3.37% per 100 µIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. CONCLUSIONS: Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885.

Re-Analysis and Additional Information Needed to Inform Conclusions. Comment on Halenova et al. Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats. Molecules 2020, 25, 23.

We were interested to read the report by Halenova et al. [...].

Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance.

Randomization is an important tool used to establish causal inferences in studies designed to further our understanding of questions related to obesity and nutrition. To take advantage of the inferences afforded by randomization, scientific standards must be upheld during the planning, execution, analysis, and reporting of such studies. We discuss ten errors in randomized experiments from real-world examples from the literature and outline best practices for their avoidance. These ten errors include: representing nonrandom allocation as random, failing to adequately conceal allocation, not accounting for changing allocation ratios, replacing subjects in nonrandom ways, failing to account for non-independence, drawing inferences by comparing statistical significance from within-group comparisons instead of between-groups, pooling data and breaking the randomized design, failing to account for missing data, failing to report sufficient information to understand study methods, and failing to frame the causal question as testing the randomized assignment per se. We hope that these examples will aid researchers, reviewers, journal editors, and other readers to endeavor to a high standard of scientific rigor in randomized experiments within obesity and nutrition research.

Financial hardship is associated with lower uptake of colorectal, breast, and cervical cancer screenings.

PURPOSE: Cancer screening uptake differs between groups in ways that cannot be explained by socioeconomic status alone. This study examined associations between material, psychosocial, and behavioral aspects of financial hardship and cancer screening behaviors. METHODS: Surveys were mailed to 7,979 people ages 18-75 who were seen in the statewide health system in Indiana. Participants reported SES, feelings about finances, and whether they had to forgo medical care due to cost. This was compared to uptake of mammogram, colonoscopy/sigmoidoscopy, and Pap testing in best-fit multivariable logistic regression analyses controlling for demographic and healthcare characteristics. RESULTS: A total of 970 surveys were returned; the majority of respondents were female (54%), non-Hispanic White (75%), and over 50 years old (76%). 15% reported forgoing medical care due to cost; this barrier was higher among Black than White participants (24% vs. 13%; p = 0.001). In a best fit regression model for colonoscopy/sigmoidoscopy, those who reported they had to forgo medical care due to cost had lower odds of screening (aOR 0.41; 95% CI 0.22-0.74). Forgoing medical care due to cost was not significantly associated with Pap testing in bivariate analyses. For mammogram, forgoing medical care due to cost was significant in bivariate analyses (OR 0.44; 95% CI 0.22-0.88), but was not significant in the multivariable model. CONCLUSION: Associations between financial hardship and cancer screening suggest the need to reduce barriers to cancer screening even among patients who have access to healthcare. Future research should explore barriers related to both healthcare and personal costs.

Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies.

BACKGROUND: The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk. OBJECTIVE: We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time. METHODS: The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk. RESULTS: The 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P < 0.001). Among 23 shorter trials, TEE was reduced on lower-carbohydrate diets (-50.0 kcal/d; 95% CI: -77.4, -22.6 kcal/d) with substantial heterogeneity (I2 = 69.8). Among 6 longer trials, TEE was increased on low-carbohydrate diets (135.4 kcal/d; 95% CI: 72.0, 198.7 kcal/d) with low heterogeneity (I2 = 26.4). Expressed per 10% decrease in carbohydrate as %EI, the TEE effects in shorter and longer trials were -14.5 kcal/d and 50.4 kcal/d, respectively. Findings were materially unchanged in sensitivity analyses. CONCLUSIONS: Lower-carbohydrate diets transiently reduce TEE, with a larger increase after ∼2.5 wk. These findings highlight the importance of longer trials to understand chronic macronutrient effects and suggest a mechanism whereby lower-carbohydrate diets may facilitate weight loss.

Adiposity, reproductive and metabolic health, and activity levels in zoo Asian elephant (Elephas maximus).

Many captive Asian elephant populations are not self-sustaining, possibly due in part to obesity-related health and reproductive issues. This study investigated relationships between estimated body composition and metabolic function, inflammatory markers, ovarian activity (females only) and physical activity levels in 44 Asian elephants (n=35 females, n=9 males). Deuterium dilution was used to measure total body water from which fat mass (FM) and fat-free mass (FFM) could be derived to estimate body composition. Serum was analyzed for progestagens and estradiol (females only), deuterium, glucose, insulin and amyloid A. Physical activity was assessed by an accelerometer placed on the elephant's front leg for at least 2 days. Relative fat mass (RFM) - the amount of fat relative to body mass - was calculated to take differences in body size between elephants into consideration. Body fat percentage ranged from 2.01% to 24.59%. Male elephants were heavier (P=0.043), with more FFM (P=0.049), but not FM (P>0.999), than females. For all elephants, estimated RFM (r=0.45, P=0.004) was positively correlated with insulin. Distance walked was negatively correlated with age (r=-0.46, P=0.007). When adjusted for FFM and age (P<0.001), non-cycling females had less fat compared with cycling females, such that for every 100 kg increase in FM, the odds of cycling were 3 times higher (P<0.001). More work is needed to determine what an unhealthy amount of fat is for elephants; however, our results suggest higher adiposity may contribute to metabolic perturbations.

Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

The dietary R-3-hydroxybutyrate- R-1,3-butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R, S-1,3-butanediol diacetoacetate (BD-AcAc2), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high-fat diet (HFD)-induced obesity. Thirty-five-week-old male C57BL/6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups ( n = 10 per group) for an additional 12 wk: 1) control (Con), continuous HFD, 2) pair-fed (PF) to ketone ester (KE); and 3) KE: HFD+30% energy from BD-AcAc2. Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs. 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs. 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs. 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat-mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein-1, deiodinase-2, and peroxisome proliferator-activated receptor γ coactivator-1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD-AcAc2 initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD-induced obesity.-Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

Data anomalies and apparent reporting errors in 'Randomized controlled trial testing weight loss and abdominal obesity outcomes of moxibustion'.

Randomized Controlled Trials (RCTs) are the best method to determine causal effects for treatments if they are well done and well reported. Good evidence about proposed treatments for obesity is needed, and Hsieh et al. (Biomed Eng Online 17:149, 2018) are to be commended for putting moxibustion to the test. However, careful evaluation of the paper reveals inconsistencies and apparent reporting errors, which raise doubts about conclusions from the study.

Exceptional Reported Effects and Data Anomalies Merit Explanation from "A randomized controlled trial of coordination exercise on cognitive function in obese adolescents" by.

We read the recent article in Psychology of Sport and Exercise by Liu et al. ("A randomized controlled trial of coordination exercise on cognitive function in obese adolescents") with great interest. Our interest in the article stemmed from the extraordinary differences in obesity-related outcomes reported in response to a rope-jumping intervention. We requested the raw data from the authors to confirm the results and, after the journal editors reinforced our request, the authors graciously provided us with their data. We share our evaluation of the original data herein, which includes concerns that weight and BMI loss by the intervention appears extraordinary in both magnitude and aspects of the distributions. We request that the authors address our findings by providing explanations of the extraordinary data or correcting any errors that may have occurred in the original report, as appropriate.

Fat mass compared to four body condition scoring systems in the Asian elephant (Elephas maximus).

Captive elephant populations are not self-sustaining due to health concerns possibly related to obesity. Categorizing obesity relies on qualitative analyses like body condition scores (BCS). However, elephant indices have not been validated against measured body composition. The objective was to compare BCS systems to body composition determined by deuterium dilution in 28 zoo-kept Asian elephants. Elephants were weighed and given deuterated water orally (0.05 ml/kg). Blood was collected at ~0, 24, 120, 240, 360, and 480 hr after dosing. Photographs were taken to score the elephant based on four BCS systems (BCSWemmer [0 to 11 scoring], BCSMorfeld [1 to 5 scoring], BCSFernando [0 to 10 scoring], BCSWijeyamohan [1 to 10 scoring]). Based on regression analysis, relative fat ranged from -305 kg to 515 kg, where negative values indicate less and positive values indicate more fat than expected for the elephant's mass in this population. BCSFernando was associated with relative fat (p = .020, R2 = 0.194). Relative fat, adjusted for sex and age in the statistical model, was associated with BCSWemmer (p = .027, R2 = 0.389), BCSFernando (p = .002, R2 = 0.502), and BCSWijeyamohan (p = .011, R2 = 0.426). Inclusion of zoo and familial relatedness resulted in all BCS systems associated with relative fat (p ≤ .015). Only BCSFernando predicted relative fat, unadjusted, suggesting it is the most capable system for practical use. Compared to absolute fat, relative fat may be more biologically relevant as greater fat relative to body mass is more likely to lead to health issues.

Understanding and Parenting Children's Noncompliant Behavior: The Efficacy of an Online Training Workshop for Resource Parents.

The current study examined the effectiveness of an online training program on parenting children's noncompliant behavior. Eighty-two resource parents (foster, adoptive, and kinship) were recruited through Foster Parent College-an online training website-and randomly assigned to a treatment or wait-list control group. Parents in the treatment group participated in an online interactive workshop on noncompliant child behavior. Online assessments occurred before and after a 1-week intervention, and again 3 months later. Group differences at posttest were significant for parents' reports of children's positive behavior and parent knowledge related to children's noncompliant behavior. Only parents in the treatment group showed significant improvement from pre- to posttest on several other outcome measures of parenting noncompliant behavior. Satisfaction with the online workshop at posttest was very high. Results at the 3-month follow-up assessment showed significant group differences only for parents' knowledge about children's noncompliant behavior. Feedback on the workshop remained positive, with treatment group parents indicating that they felt the workshop had beneficially impacted their parenting and their children's behavior.