Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice.

OBJECTIVE: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity. METHODS: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups. RESULTS: Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group. CONCLUSIONS: WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater "relative" fat in male mice.

Plasma metabolites and physical function in patients undergoing hemodialysis.

Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.e., 4 m walk, handgrip strength). Physical function measures were categorized as above/ below median, with grip utilizing sex-based medians. To develop composite scores, metabolites were identified via Wilcoxon uncorrected p < 0.05 and effect size > 0.40. Receiver operating characteristic analyses tested whether scores differentiated between above/below function groups. Participants were 54% male, 77% Black and 53 ± 14 y with dialysis vintage of 101 ± 50 days. Median (IQR) grip strength was 35.5 (11.1) kg (males) and 20 (8.4) kg (females); median gait speed was 0.82 (0.34) m/s. Of 246 measured metabolites, composite scores were composed of 22 and 12 metabolites for grip strength and gait speed, respectively. Area under the curve for metabolite composite was 0.88 (gait) and 0.911 (grip). Composite scores of physical function performed better than clinical parameters alone in patients on dialysis. These results provide potential pathways for interventions and needed validation in an independent cohort.

Advanced practice nurse pharmacogenomics capacity and utilization.

BACKGROUND: Guided by Clinical Pharmacogenomic Implementation Consortium (CPIC) guidelines for >140 medications, pharmacogenomic tests inform medication selection and dosing to optimize efficacy while minimizing toxicities. PURPOSE: This study assessed pharmacogenomic self-reported curricular content, knowledge, skills, attitudes, and usage in advanced practice registered nurses (APRNs) with prescriptive privileges. METHODOLOGY: An online survey was administered assessing pharmacogenomic curricular content, knowledge, skills, attitudes, and usage. RESULTS: Data from 266 APRNs were analyzed. Most graduated with their highest nursing degree ∼10 years ago and reported pharmacogenomic curricular content (n = 124, 48%). Pharmacogenomic curricular content was associated with pharmacogenomic familiarity (p = .045) but not with knowledge confidence (p = .615). Pharmacogenomic usage, defined as ordering a pharmacogenomic test within the past year, was low (n = 76, 29%) and most (n = 210, 84%) reported never using CPIC Guidelines. Advanced practice registered nurses (n = 162) who did not anticipate ordering a pharmacogenomic test in the next year (n = 77, 48%) indicated that they did not know what test to order. CONCLUSIONS: Deficits were identified in APRN pharmacogenomic knowledge and skills despite academic training. Most reported not ordering pharmacogenomic tests, did not know what test to order, and did not use CPIC guidelines. IMPLICATIONS: Pharmacogenomics is a quality and safety issue. Academic training did not result in practice integration and most reported capacity deficits. Recommendation for overcoming academic deficits include: (1) assessment of pharmacogenomics curricular content and faculty teaching capacity; (2) training addressing identified deficiencies; and (3) Commission of Collegiate Nursing Education policies that include pharmacogenomics in advanced pharmacology. Practicing APRN plans include on-the-job training and/or mandatory training at the time of relicensure.

The Feasibility of Using the National PulsePoint Cardiopulmonary Resuscitation Responder Network to Facilitate Overdose Education and Naloxone Distribution: Protocol for a Randomized Controlled Trial.

BACKGROUND: The use of naloxone, an opioid antagonist, is a critical component of the US response to fatal opioid-involved overdoses. The importance and utility of naloxone in preventing fatal overdoses have been widely declaimed by medical associations and government officials and are supported by strong research evidence. Still, there are gaps in the current US national strategy because many opioid-involved overdose fatalities have no evidence of naloxone administration. Improving the likelihood that naloxone will be used to prevent fatal overdoses is predicated on facilitating an environment wherein naloxone is available near each overdose and can be accessed by someone who is willing and able to use it. How to accomplish this on a national scale has been unclear. However, there exists a national network of >1 million cardiopulmonary resuscitation (CPR) layperson responders and 4800 emergency responder agencies linked through a mobile phone app called PulsePoint Respond. PulsePoint responders certify that they are trained to administer CPR and are willing to respond to possible cardiac events in public. When such an event occurs near their mobile phone's location, they receive an alert to respond. These motivated citizens are ideally positioned to carry naloxone and reverse overdoses that occur in public. OBJECTIVE: This randomized controlled trial will examine the feasibility of recruiting first responder agencies and layperson CPR responders who already use PulsePoint to obtain overdose education and carry naloxone. METHODS: This will be a 3-arm parallel-group randomized controlled trial. We will randomly select 180 first responder agencies from the population of agencies contracting with the PulsePoint Foundation. The 3 study arms will include a standard recruitment arm, a misperception-correction recruitment arm, and a control arm (1:1:1 allocation, with random allocation stratified by zip code designation [rural or nonrural]). We will study agency recruitment and, among the agencies we successfully recruit, responder certification of receiving overdose and naloxone education, carrying naloxone, or both. Hypothesis 1 contrasts agency recruitment success between arms 1 and 2, and hypothesis 2 contrasts the ratios of layperson certification across all 3 arms. The primary analyses will be a logistic regression comparing the recruitment rates among the arms, adjusting for rural or nonrural zip code designation. RESULTS: This study was reviewed by the Indiana University Institutional Review Board (20218 and 20219). This project was funded beginning September 14, 2023, by the National Institute on Drug Abuse. CONCLUSIONS: The hypotheses in this study will test whether a specific type of messaging is particularly effective in recruiting agencies and layperson responders. Although we hypothesize that arm 2 will outperform the other arms, our intention is to use the best-performing approach in the next phase of this study if any of our approaches demonstrates feasibility. TRIAL REGISTRATION: OSF Registries osf.io/egn3z; https://osf.io/egn3z. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57280.

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19.

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. RESULTS: Before early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. CONCLUSION: Available data will inform future research, albeit with less statistical power than originally planned.

Breastfeeding and Once-Daily Small-Volume Formula Supplementation to Prevent Infant Growth Impairment.

BACKGROUND: Randomized controlled trials in Guinea-Bissau and Uganda have revealed that the intensive promotion of exclusive breastfeeding (EBF) impairs growth in early infancy. When newborn growth is impaired, small amounts of formula may be combined with breastfeeding to promote growth. METHODS: To determine if breastfeeding combined with once-daily formula supplementation improves growth among at-risk newborns, we conducted a pilot randomized controlled trial in Bissau, Guinea-Bissau and Kampala, Uganda. We randomly assigned 324 healthy breastfeeding newborns who weighed 2000 g to 2499 g at birth or <2600 g at 4 days old to once-daily formula feeding through 30 days as a supplement to frequent breastfeeding followed by EBF from 31 days through 6 months, or to EBF through 6 months. The primary outcome was weight-for-age z score (WAZ) at 30 days. Other outcomes included weight-for-length z score (WLZ), length-for-age z score (LAZ), breastfeeding cessation, adverse events, and serious adverse events through 180 days. RESULTS: Daily formula consumption in the intervention group was 31.9 ± 11.8 mL. The random assignment did not impact WAZ, WLZ, LAZ, breastfeeding cessation, adverse events, or serious adverse events through 180 days. In the intervention and control groups, 19 (12%) and 35 (21%) infants, respectively, reported nonformula supplementation in the first 30 days (P = .02). CONCLUSIONS: Once-daily formula supplementation for 30 days was well-tolerated, but the small volume consumed did not alter growth through 180 days of age. Further research would be required to determine if larger formula volumes, longer duration of treatment, or more frequent feeding are effective at increasing growth for this at-risk population.

Communication with physicians and family about breast Cancer recurrence.

Objective: Adequate physician-patient communication about cancer recurrence is vital to quality of life and to informed decision-making related to survivorship care. The current study was guided by a cognitive-affective framework to examine communication with family and physicians about breast cancer recurrence risk. Methods: A survey of recently-diagnosed, early-stage breast cancer patients in Appalachia investigated physician-patient and familial communication about breast cancer recurrence risk. Results: Over 30% of participants reported not talking to family or physicians about breast cancer recurrence risk. Younger patients reported more conversations, and speaking with physicians was associated with greater perception risk factors associated with recurrence risk. Greater worry about recurrence was associated with more communication with family and plans to talk to family, physicians, and friends about recurrence risk in the future. Conclusion: Additional supports for patients and physicians are needed to improve understanding of breast cancer recurrence risk and risk factors for recurrence. Innovation: Family communication about breast cancer recurrence risk is understudied. The combination of physician and family communication adds novelty to our analysis.

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.

A comparison between perceived rurality and established geographic rural status among Indiana residents.

The study assessed the association and concordance of the traditional geography-based Rural-Urban Commuting Area (RUCA) codes to individuals' self-reported rural status per a survey scale. The study included residents from rural and urban Indiana, seen at least once in a statewide health system in the past 12 months. Surveyed self-reported rural status of individuals obtained was measured using 6 items with a 7-point Likert scale. Cronbach's alpha was used to measure the internal consistency between the 6 survey response items, along with exploratory factor analysis to evaluate their construct validity. Perceived rurality was compared with RUCA categorization, which was mapped to residential zip codes. Association and concordance between the 2 measures were calculated using Spearman's rank correlation coefficient and Gwet's Agreement Coefficient (Gwet's AC), respectively. Primary self-reported data were obtained through a cross-sectional, statewide, mail-based survey, administered from January 2018 through February 2018, among a random sample of 7979 individuals aged 18 to 75, stratified by rural status and race. All 970 patients who completed the survey answered questions regarding their perceived rurality. Cronbach's alpha value of 0.907 was obtained indicating high internal consistency among the 6 self-perceived rurality items. Association of RUCA categorization and self-reported geographic status was moderate, ranging from 0.28 to 0.41. Gwet's AC ranged from -0.11 to 0.26, indicating poor to fair agreement between the 2 measures based on the benchmark scale of reliability. Geography-based and self-report methods are complementary in assessing rurality. Individuals living in areas of relatively high population density may still self-identify as rural, or individuals with long commutes may self-identify as urban.

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.

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.

Evaluation of Unintended Consequences of COVID-19 Pandemic Restrictions and Obesity Prevalence Among Youths.

This cohort study examines the association between COVID-19 pandemic restrictions and obesity prevalence among youths aged 2 to 19 years in Monroe County, Indiana.

Comment on Qiu et al. Effect of Protein-Rich Breakfast on Subsequent Energy Intake and Subjective Appetite in Children and Adolescents: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2021, 13, 2840.

In reading Qiu et al. [...].

Factors associated with choice of behavioural weight loss program by adults with obesity.

We assessed the preference for two behavioural weight loss programs, Diabetes Prevention Program (DPP) and Healthy Weight for Living (HWL) in adults with obesity. A cross-sectional survey was fielded on the Amazon Mechanical Turk. Eligibility criteria included reporting BMI ≥30 and at least two chronic health conditions. Participants read about the programs, selected their preferred program, and answered follow-up questions. The estimated probability of choosing either program was not significantly different from .5 (N = 1005, 50.8% DPP and 49.2% HWL, p = .61). Participants' expectations about adherence, weight loss magnitude, and dropout likelihood were associated with their choice (p < .0001). Non-White participants (p = .040) and those with monthly income greater than $4999 (p = .002) were less likely to choose DPP. Participants who had postgraduate education (p = .007), did not report high serum cholesterol (p = .028), and reported not having tried losing weight before (p = .025) were more likely to choose DPP. Those who chose HWL were marginally more likely to report that being offered two different programs rather than one would likely affect their decision to enrol in one of the two (p = .052). The enrolment into DPP and HWL was balanced, but race, educational attainment, income, previous attempt to lose weight, and serum cholesterol levels had significant associations with the choice of weight loss program.

Effectiveness of lactation cookies on human milk production rates: a randomized controlled trial.

BACKGROUND: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown. OBJECTIVES: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy. METHODS: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking galactagogues. The primary outcome was baseline-to-1-mo changes in human milk production rate (HMPR), measured with a validated milk expression protocol. Secondary outcomes included changes in perceived insufficient milk (PIM) and lactation self-efficacy scores. RESULTS: Among 176 randomly assigned participants (age: 31.3 ± 5.8 y; 71.0% self-identified as White, 15.3% Hispanic/Latin, 6.3% Black, and 4.0% Asian), 90 participants (51.1%) completed endline HMPR measures and 129 (73.3%) completed secondary outcomes. Imputed models showed a mean increase in HMPR of 5.8 ± 15.7 mL/h in control participants and 5.5 ± 17.6 mL/h in the LC participants after 1 mo of daily intake of the cookie. No significant differences were observed with adjusted linear mixed models on the multiply imputed data comparing baseline-to-endline changes in HMPR, PIM, or breastfeeding self-efficacy: mean (SE) difference-in-differences for HMPR, -0.33 (4.97), P = 0.948; PIM scores (range: 5-50), -0.52 (1.83), P = 0.775; and self-efficacy scores (range: 14-70), 0.31 (2.23), P = 0.888, respectively. CONCLUSIONS: This study found no evidence for the effect of consuming LCs on HMPR, PIM, or breastfeeding self-efficacy in exclusively breastfeeding parents with an overall adequate perceived milk supply. Recommendations to consume LCs for increasing objective or subjective milk supply may deliver false hope and unnecessary financial costs at a vulnerable time. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT04805008.

RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due to impaired disease tolerance. Using this aged host-virus model, we conducted longitudinal, single-fly respirometry studies to determine if metabolism impacts infection outcomes. Analysis using linear mixed models on Oxygen Consumption Rate (OCR) following the first 72-hours post-infection showed that FHV modulates respiration, but age has no significant effect on OCR. However, the longitudinal assessment revealed that OCR in young flies progressively and significantly decreases, while OCR in aged flies remains constant throughout the three days of the experiment. Furthermore, we found that the OCR signature at 24-hours varied in response to both experimental treatment and survival status. FHV-injected flies that died prior to 48- or 72-hours measurements had a lower OCR compared to survivors at 48-hours. Our findings suggest the host's metabolic profile could influence the outcome of viral infections.