Frontloading Home Physical Therapy Visits for Patients With Heart Failure: A Multi-center Randomized Controlled Trial.

Frontloading home care visits has been found to be effective in the nursing profession but has not been investigated in physical therapy (PT) practice. This study aimed to examine the impact of frontloading home PT visits on function in persons with heart failure (HF). This was a prospective multi-center randomized controlled trial with blinded raters. A total of 82 ambulatory patients with a primary diagnosis of HF discharged from an acute care facility to home care participated in the study. Subjects were randomly allocated to an experimental frontloaded group (FLG) or control group (CG) for 4 weeks. FLG visit frequencies were five sessions per week for 2 weeks, and three sessions per week for 2 weeks. The CG received two sessions per week for 4 weeks. Functional measures including the 2-minute step test (2MST), 2-minute walk test (2MWT), gait speed (GS), Timed Up and Go (TUG), and 30-second chair rise test (30-CRT) were collected at the onset of care, at the end of 2 weeks and 4 weeks. The groups were statistically similar at baseline for all measures. All subjects significantly improved scores in all functional measures over time, within-subject main effect (p < .01). Significant between-subject effects were noted for 30-CRT (p = .04). Interaction effects were noted for GS (p = .03) and TUG test (p = .02). This is the first study to report meaningful improvements in function in individuals with HF. Significant treatment effect differences between the FLG and CG were found for GS, TUG, and 30-CRT. Future studies should examine the use of a standardized intervention to validate the effectiveness of frontloading home visits on quality of life and readmission rates.

Assessing attitudes towards pediatric research participation across diverse populations: Psychometric properties of a novel tool.

BACKGROUND: Clinical trials play a crucial role in advancing medical knowledge and improving health outcomes. However, there is a recognized need for greater representation of marginalized groups to ensure that research findings can be generalized and effectively applied to all individuals. While the Pediatric Research Participation Questionnaire (PRPQ) was developed to assist pediatric clinical trials research by identifying benefits and barriers to research participation among children with chronic medical conditions, there is still limited insight into the structure of the PRPQ when administered in diverse samples, including the general pediatric population. Therefore, the current study examined the factor structure of the PRPQ in a general pediatric population to investigate whether rural-urban differences exist in the PRPQ factor structure. METHODS: Caregivers (N = 600) of children under age 18 completed the PRPQ in a population-based survey in Mississippi. Sampling was stratified to ensure equal representation in rural (n = 300) and urban areas (n = 300). Exploratory and confirmatory factor analyses were conducted to determine the factor structure of the PRPQ. RESULTS: A five-factor structure was identified, compromising: social pressure, direct benefit, reasons for participation, mistrust in research/researchers, reasons against participation. While results were similar among urban participants, a three-factor structure emerged for rural participants. CONCLUSIONS: This study contributes to the broader understanding of research participation among underrepresented groups. The findings suggest that clinical researchers should consider tailoring recruitment strategies to increase clinical trial participation among children in rural areas. Understanding factors that influence pediatric research participation, particularly among marginalized communities, is crucial for developing effective recruitment and retention strategies.

Impact of COVID-19 on Families with Children: Examining Sociodemographic Differences.

OBJECTIVE: The COVID-19 pandemic has exacerbated differences related to employment and family psychological health. However, empirical evidence examining COVID-19-linked differences concerning children and families remains scant. This study addresses this gap by examining sociodemographic differences associated with COVID-19 on family access to resources and family psychological health. METHOD: A telephone survey of 600 caregivers living in Mississippi was conducted from August 2020 to April 2021. Caregivers answered questions about levels of worry regarding themselves or their child contracting COVID-19 and impact of the pandemic on household income, access to resources, and family psychological health. RESULTS: Multivariate models demonstrated that Black caregivers (n = 273; 45.5%) had increased odds of agreeing that they worry about contracting COVID-19 (odds ratio [OR] = 2.57). Furthermore, as caregiver reported household annual income decreased, caregivers had increased odds of agreeing that they worry about contracting COVID-19 (OR = 1.16), lost job-related income (OR = 1.14), and had a hard time obtaining resources (OR = 1.16) because of the pandemic. No significant differences related to rural or urban residence were observed. CONCLUSION: The findings highlight the need for pragmatic responses that are attuned to differences by providing more equitable access to resources for families. The findings suggest that strategies addressing family worry, obtaining job-related income support, and helping families obtain tangible resources may positively affect family psychological health. As population changes in vaccination rates and COVID variants emerge, reassessment of family and community impact seems indicated. Limitations and future research directions are discussed.

State-Level Trends in Lifespan Variability in the United States, 1960-2019: A Research Note.

State-level disparities in life expectancy are wide, persistent, and potentially growing in the United States. However, the extent to which differences in lifespan variability by state have changed over time is unclear. This research note describes trends in lifespan variability for the United States overall and by state from 1960 to 2019 using period life table data from the United States Mortality Database. Lifespan disparity at birth (e0†) decreased over time in the United States overall from 14.0 years in 1960-1964 to 12.2 in 2015-2019. Lifespan variability decreased in all states, but states differed in the level and pace with which these changes occurred. Southern states and the District of Columbia exhibited consistently higher (i.e., less equitable) levels of lifespan variability than the nation overall. Conversely, lifespan variability was lower among several states in the Northeast (e.g., Connecticut and Massachusetts), Upper Midwest (e.g., Iowa, Minnesota, and Wisconsin), and West (e.g., California, Oregon, Utah, and Washington). We observe a particularly worrisome trend of increasing lifespan variability for the United States overall and for most states from 2010-2014 to 2015-2019. Monitoring state-level trends in lifespan variability has the potential to inform policies designed to ameliorate population health disparities.

Trends in lifespan variation across the spectrum of rural and urban places in the United States, 1990-2017.

Mortality disparities between urban and rural areas in the United States widened in recent decades as mortality improvements in rural areas slowed. Although the existence of a rural mortality penalty is well-documented, previous research in this area has focused almost exclusively on differences in average levels of mortality between rural and urban areas rather than differences in levels of lifespan variation within rural and urban areas. This oversight is important because monitoring trends in lifespan variation provides unique insights into levels of inequality in the age-at-death distribution within a population. Does the rural mortality penalty in life expectancy extend to lifespan variation? We used U.S. Multiple Cause of Death data files to measure life disparity at birth ( e 0 † ) from 1990 to 2017. We found that the rural mortality penalty extends to lifespan variation as large metropolitan areas had greater improvements in life disparity than nonmetropolitan areas. Beginning around 2011, all areas began to show increased life disparity with the largest increases occurring in nonmetropolitan areas. Age decomposition results showed that the nonmetropolitan increases were due to rising working-age mortality. Greater variability in the age-at-death distribution represents an additional dimension of inequality for Americans living in rural places.

Childhood adversity associated with poorer health: Evidence from the U.S. National Survey of Children's Health.

BACKGROUND: The association between adverse childhood experiences (ACEs) and increased risk of health problems is well established. However, many studies have relied on unrepresentative or high-risk samples and have focused on a narrow range of health problems. Prior research assessing potential age differences in the ACE-health connection is also sparse. OBJECTIVE: To comprehensively examine the extent to which ACEs are associated with physical, mental, and neurodevelopmental health outcomes in childhood and assess whether these associations differ between age groups. PARTICIPANTS & SETTING: Pooled cross-sectional data from the 2016-2019 National Survey of Children's Health (N = 98,732). METHODS: We estimated age-stratified binary logistic regression models examining associations between the number of ACEs and physical, mental, and neurodevelopmental health problems net of sociodemographic and socioeconomic controls. Separate models were estimated for the total population (ages 3-17), early childhood (ages 3-5), middle childhood (ages 6-11), and adolescence (ages 12-17). RESULTS: We observed a dose-response relationship between ACE exposure and childhood physical, mental, and neurodevelopmental health problems in all age groups. The largest disparities exist between children with no ACEs and three or more ACEs. Compared to children without ACEs, children with three or more ACEs had significantly higher adjusted odds of externalizing disorders (OR = 4.40), internalizing disorders (OR = 5.13), neurodevelopmental disorders (OR = 2.40), and physical health problems (OR = 2.08). CONCLUSIONS: Our results add to evidence linking ACEs to childhood health disparities. Further, findings indicate that ACEs have persistent negative effects across age groups and that clinicians should monitor ACEs when assessing children's physical, mental, and neurodevelopmental health at any age.

Target-directed evolution of novel modulators of the dopamine transporter in Lobelia cardinalis hairy root cultures.

The dopamine transporter (DAT) is targeted in substance use disorders (SUDs), and "non-classical"" DAT inhibitors with low abuse potential are therapeutic candidates. Lobinaline, from Lobelia cardinalis, is an atypical DAT inhibitor lead. Chemical synthesis of lobinaline is challenging; thus, "target-directed evolution" was used for lead optimization. A target protein is expressed in plant cells, and a mutant cell population is selected under conditions where target protein functional inhibition confers a survival advantage. Surviving mutants are "mined" for the targeted activity. Applied to a mutant L. cardinalis cell population expressing the human DAT, we identified 20 mutants overproducing DAT inhibitors. Microanalysis prioritized novel lobinaline derivatives, and we first investigated the more water-soluble lobinaline N-oxide. It inhibited rat synaptosomal [3H]DA uptake with an IC50 similar to lobinaline. Against repeated DA microinjections into the rat striatum, lobinaline produced transient DA clearance reductions. In contrast, lobinaline N-oxide prolongingly increased DA peak amplitudes, particularly in the ventral striatum. Lobinaline N-oxide also produced complex changes in post-peak DA clearance inconsistent with simple DAT inhibition. This unusual DAT interaction may prove therapeutically useful for treating SUDs. This study demonstrates the value of target-directed evolution of plant cells for optimizing lead compounds difficult to synthesize chemically.

Quantification of the Hemodynamic Changes of Cirrhosis with Free-Breathing Self-Navigated MRI.

BACKGROUND: Non-invasive assessment of the hemodynamic changes of cirrhosis might help guide management of patients with liver disease but are currently limited. PURPOSE: To determine whether free-breathing 4D flow MRI can be used to quantify the hemodynamic effects of cirrhosis and introduce hydraulic circuit indexes of severity. STUDY TYPE: Retrospective. POPULATION: Forty-seven patients including 26 with cirrhosis. FIELD STRENGTH/SEQUENCE: 3 T/free-breathing 4D flow MRI with soft gating and golden-angle view ordering. ASSESSMENT: Measurements of the supra-celiac abdominal aorta, supra-renal abdominal aorta (SRA), celiac trunk (CeT), superior mesenteric artery (SMA), splenic artery (SpA), common hepatic artery (CHA), portal vein (PV), and supra-renal inferior vena cava (IVC) were made by two radiologists. Measures of hepatic vascular resistance (hepatic arterial relative resistance [HARR]; portal resistive index [PRI]) were proposed and calculated. STATISTICAL ANALYSIS: Bland-Altman, Pearson's correlation, Tukey's multiple comparison, and Cohen's kappa. P < 0.05 was considered significant. RESULTS: Forty-four of 47 studies yielded adequate image quality for flow quantification (94%). Arterial structures showed high inter-reader concordance (range; ρ = 0.948-0.987) and the IVC (ρ = 0.972), with moderate concordance in the PV (ρ = 0.866). Conservation of mass analysis showed concordance between large vessels (SRA vs. IVC; ρ = 0.806), small vessels (celiac vs. CHA + SpA; ρ = 0.939), and across capillary beds (CeT + SMA vs. PV; ρ = 0.862). Splanchnic flow was increased in patients with portosystemic shunting (PSS) relative to control patients and patients with cirrhosis without PSS (P < 0.05, difference range 0.11-0.68 liter/m). HARR was elevated and PRI was decreased in patients with PSS (3.55 and 1.49, respectively) compared to both the control (2.11/3.18) and non-PSS (2.11/2.35) cohorts. DATA CONCLUSION: 4D flow MRI with self-navigation was technically feasible, showing promise in quantifying the hemodynamic effects of cirrhosis. Proposed quantitative metrics of hepatic vascular resistance correlated with PSS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Defining the role of exposure to ACEs in ADHD: Examination in a national sample of US children.

BACKGROUND: Clinical presentations of ADHD vary according to biological and environmental developmental influences. An emerging field of research has demonstrated relationships between exposure to adverse childhood experiences (ACEs) and ADHD prevalence, particularly in high-risk samples. However, research examining the combined role of traditional risk factors of ADHD and ACEs is limited, and reliance on high-risk samples introduces sampling bias. OBJECTIVE: To examine the influence of ACEs on ADHD diagnosis using a large, nationally representative sample of US children. PARTICIPANTS AND SETTING: Nationally representative samples (2017 and 2018) of 40,075 parents from the National Survey of Children's Health (NSCH). METHODS: We conducted logistic regression models to examine the association of ACEs and ADHD diagnosis, controlling for child and parent demographic variables and other risk factors. RESULTS: Exposure to ACEs was significantly associated with parent-reported ADHD diagnosis, controlling for known parental and child-risk factors of ADHD. The association followed a gradient pattern of increased ADHD prevalence with additional exposures. Compared to children with no ACEs, the odds of an ADHD diagnosis were 1.39, 1.92, and 2.72 times higher among children with one, two and three or more ACEs. The ACE most strongly associated with the odds of ADHD was having lived with someone with mental illness closely followed by parent/guardian incarceration. CONCLUSIONS: Results further strengthen the evidence that ACEs exposure is associated with increased ADHD prevalence. Clinicians should assess ACEs in the diagnosis of ADHD. Furthermore, results of the study lend support to the efforts of agencies (both institutional and state-level) promoting routine screening of ACEs in children.

Seroprevalence of Brucella canis in dogs rescued from South Dakota Indian reservations, 2015-2019.

Canine brucellosis, caused by Brucella canis, is an infectious disease with implications for canine as well as human health. The identification of infected dogs originating from and around two South Dakota Indian reservations prompted an examination of the seroprevalence of B. canis in stray or owner-surrendered dogs from these communities. Using results from in-clinic screening tests of 3898 dogs over more than 4 years, we determined an overall apparent B. canis seroprevalence of 6.8% (adjusted estimated true prevalence of 29.4%), with rates declining over time. The apparent rate was similar to other surveys of stray dog populations in the US. Older dogs were significantly more likely to be B. canis-positive than younger dogs, as were reproductively intact dogs versus altered dogs (although this difference was not statistically significant). There were geographic differences in seropositive rates as well, with higher rates found in dogs originating from one reservation compared to other locations. Current diagnostic tests lack sensitivity to effectively identify all B. canis-infected dogs, but results from this study are valuable for investigating differences among risk factors for infection. Because of the potential for B. canis to infect other dogs and people, stray dog populations should be screened for B. canis before those animals are placed in adoptive homes.

Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells.

Metformin (MET) is increasingly implicated in reducing the incidence of multiple cancer types in patients with diabetes. However, similar effects of MET in non-diabetic women with endometrial cancer (EC) remain unknown. In a pilot study, obese non-diabetic women diagnosed with type 1, grade 1/2 EC, and consenting to participate were randomly assigned to receive MET or no MET (control (CON)) during the pre-surgical window between diagnosis and hysterectomy. Endometrial tumors obtained at surgery (MET, n = 4; CON, n = 4) were analyzed for proliferation (Ki67), apoptosis (TUNEL), and nuclear expression of ERα, PGR, PTEN, and KLF9 proteins in tumor glandular epithelial (GE) and stromal (ST) cells. The percentages of immunopositive cells for PGR and for KLF9 in GE and for PTEN in ST were higher while those for ERα in GE but not ST were lower, in tumors of MET vs. CON patients. The numbers of Ki67- and TUNEL-positive cells in tumor GE and ST did not differ between groups. In human Ishikawa endometrial cancer cells, MET treatment (60 µM) decreased cell numbers and elicited distinct temporal changes in ESR1, KLF9, PGR, PGR-B, KLF4, DKK1, and other tumor biomarker mRNA levels. In the context of reduced KLF9 expression (by siRNA targeting), MET rapidly amplified PGR, PGR-B, and KLF4 transcript levels. Our findings suggest that MET acts directly in EC cells to modify steroid receptor expression and signaling network and may constitute a preventative strategy against EC in high-risk non-diabetic women.

Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa.

Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureusin vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner.IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus.

Type 1 diabetes mellitus and endometriosis separately affect millions of women worldwide. Reproductive-age women diagnosed with type 1 diabetes may also suffer from endometriosis, but the asymptomatic pre-clinical period of highly variable duration for each condition can lead to challenges in the timely recognition of co-morbid disease onset and misdiagnosis. While knowledge of the pathogenesis of each condition has grown substantially, co-morbid endometriosis and type 1 diabetes has not been widely considered and much less addressed. This review discusses the molecular rationale for the likelihood of their co-existence, and prospects for improvements in therapeutic strategies and reduced complications, if this paradigm is included as a significant variable in disease management.

Comparability of Mortality Estimates from Social Surveys and Vital Statistics Data in the United States.

Social surveys prospectively linked with death records provide invaluable opportunities for the study of the relationship between social and economic circumstances and mortality. Although survey-linked mortality files play a prominent role in U.S. health disparities research, it is unclear how well mortality estimates from these datasets align with one another and whether they are comparable with U.S. vital statistics data. We conduct the first study that systematically compares mortality estimates from several widely-used survey-linked mortality files and U.S. vital statistics data. Our results show that mortality rates and life expectancies from the National Health Interview Survey Linked Mortality Files, Health and Retirement Study, Americans' Changing Lives study, and U.S. vital statistics data are similar. Mortality rates are slightly lower and life expectancies are slightly higher in these linked datasets relative to vital statistics data. Compared with vital statistics and other survey-linked datasets, General Social Survey-National Death Index life expectancy estimates are much lower at younger adult ages and much higher at older adult ages. Cox proportional hazard models regressing all-cause mortality risk on age, gender, race, educational attainment, and marital status conceal the issues with the General Social Survey-National Death Index that are observed in our comparison of absolute measures of mortality risk. We provide recommendations for researchers who use survey-linked mortality files.

Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice.

Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with ApcMin/+ mice to obtain male ApcMin/+/ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male ApcMin/+/ME1-Tg than ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria. Small intestines of male ApcMin/+/ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/ß-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro, but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.

Notch-1 Signaling Activation and Progesterone Receptor Expression in Ectopic Lesions of Women With Endometriosis.

CONTEXT: Progesterone (P) resistance is a hallmark of endometriosis, but the underlying mechanism(s) for loss of P sensitivity leading to lesion establishment remains poorly understood. OBJECTIVE: To evaluate the association between Notch-1 signaling activation and P resistance in the progression of endometriosis. DESIGN: Case control study; archived formalin-fixed, paraffin-embedded tissues. SETTING: University hospitals (United States, Taiwan). PATIENTS: Women with endometriosis; human endometrial stromal cell line (HESC). INTERVENTION: Eutopic endometria (EU) and ectopic lesions (ECs) were collected from surgically diagnosed patients. Archived tissue sections of EU and ECs were identified. HESCs were treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and valproic acid (VPA) to, respectively, suppress and induce Notch-1 activation. OUTCOME MEASURES: Tissues were analyzed for Notch Intra-Cellular Domain 1 (NICD1) and progesterone receptor (PGR) protein expression by immunohistochemistry and for transcript levels of NICD1 target genes HES1, PGR, and PGR-B by quantitative reverse transcription polymerase chain reaction. DAPT- or VPA-treated HESCs with and without P cotreatment were evaluated for cell numbers and for PGR, HES1, and PGR target gene DKK1 transcript levels. RESULTS: Nuclear-localized stromal NICD1 protein levels were inversely associated with those of total PGR in EU and ECs. Stromal ECs displayed higher HES1 and lower total PGR and PGR-B transcript levels than EU. In HESCs, DAPT reduction of NICD1 decreased cell numbers and increased PGR transcript and nuclear PGR protein levels and, with P cotreatment, maintained P sensitivity. Conversely, VPA induction of NICD1 decreased PGR transcript levels and, with P cotreatment, abrogated P-induced DKK1 and maintained HES1 transcript levels. CONCLUSIONS: Aberrant Notch-1 activation is associated with decreased PGR that contributes to P resistance in endometriosis.

Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

Rice bran (RB) consumption has been shown to reduce colorectal cancer (CRC) growth in mice and modify the human stool microbiome. Changes in host and microbial metabolism induced by RB consumption was hypothesised to modulate the stool metabolite profile in favour of promoting gut health and inhibiting CRC growth. The objective was to integrate gut microbial metabolite profiles and identify metabolic pathway networks for CRC chemoprevention using non-targeted metabolomics. In all, nineteen CRC survivors participated in a parallel randomised controlled dietary intervention trial that included daily consumption of study-provided foods with heat-stabilised RB (30 g/d) or no additional ingredient (control). Stool samples were collected at baseline and 4 weeks and analysed using GC-MS and ultra-performance liquid chromatography-MS. Stool metabolomics revealed 93 significantly different metabolites in individuals consuming RB. A 264-fold increase in ß-hydroxyisovaleroylcarnitine and 18-fold increase in ß-hydroxyisovalerate exemplified changes in leucine, isoleucine and valine metabolism in the RB group. A total of thirty-nine stool metabolites were significantly different between RB and control groups, including increased hesperidin (28-fold) and narirutin (14-fold). Metabolic pathways impacted in the RB group over time included advanced glycation end products, steroids and bile acids. Fatty acid, leucine/valine and vitamin B6 metabolic pathways were increased in RB compared with control. There were 453 metabolites identified in the RB food metabolome, thirty-nine of which were identified in stool from RB consumers. RB consumption favourably modulated the stool metabolome of CRC survivors and these findings suggest the need for continued dietary CRC chemoprevention efforts.

Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties.

BACKGROUND: Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. RESULTS: This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. CONCLUSION: Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this metabolite network may occur via additive and synergistic effects between compounds in the food matrix.

A Pilot Randomized Controlled Clinical Trial to Assess Tolerance and Efficacy of Navy Bean and Rice Bran Supplementation for Lowering Cholesterol in Children.

Background: Navy beans and rice bran demonstrate efficacy to regulate serum cholesterol in hypercholesterolemic adults; however, the cardiovascular disease (CVD) protective properties of these foods in children are unknown and merit investigation. Objective: The objectives were to determine whether cooked navy bean powder (NBP) and/or heat-stabilized rice bran (RB) supplementation is tolerable, improves dietary fiber intake in children, and modulates lipid profiles. Methods: Children aged 8 to 13 years at risk for CVD due to abnormal lipids were recruited. Elevated cholesterol levels were defined as total cholesterol ≥180 mg/dL and high-density lipoprotein (HDL) <60 mg/dL; low-density lipoprotein (LDL) ≥100 mg/dL and HDL <60 mg/dL; or non-HDL >100 mg/dL and HDL <60 mg/dL. Participants completed a pilot 4-week, randomized controlled, 4-arm dietary intervention. They consumed study-provided muffins or a smoothie daily that included 0 g NBP or RB (control), 17.5 g NBP, 15 g RB, or a combination 9 g NBP + 8 g RB. Fasting blood was collected at baseline and week 4. Participants also completed 3-day food logs and gastrointestinal health questionnaires. RESULTS: Thirty-eight children completed the trial (n = 9 control, n = 10 NBP, n = 9 RB, and n = 10 NBP + RB groups). Only 3 participants withdrew due to noncompliance of required food consumption. Participants in the intervention groups significantly increased intake of NBP and RB at week 4 (p≤.01). The NBP and NBP + RB groups increased total fiber intake from baseline to week 4 (p=.02 and p=<.01, respectively). HDL-cholesterol was higher in NBP-group participants compared to control at week 4 (P = .02). Conclusion: Increasing NBP and/or RB intake is tolerable for children, and our findings suggest higher daily intakes are needed for a longer duration to induce favorable changes across multiple serum lipid parameters.

Disability Rises Gradually for a Cohort of Older Americans.

OBJECTIVES: We study changes in average disability over nearly two decades for a large epidemiological cohort of older Americans. As some people exit by mortality, do average disability levels for the living cohort rise rapidly, rise gradually, stay steady, or decline? METHOD: Data are from the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD) cohort for 1993-2010. Cohort members are aged 70+ in 1993 (mean = 77.5 years), and the survivors are aged 87+ in 2010 (mean = 90.2 years). Personal care disability (activities of daily living), household management disability (instrumental activities of daily living), and physical limitations are studied. We study average disability for the living cohort over time and the disability histories for decedent and survivor groups. RESULTS: Average disability rises gradually over time for the living cohort. Earlier decedent groups have higher average disability than later ones. Near death, disability rises sharply for all decedent groups. Longer surviving groups have less average disability, and slower disability increases, than shorter surviving groups. All results are repeated for younger cohort members (baseline age = 70-79 years), older ones (baseline age = 80+ years), women, and men. DISCUSSION: As a cohort ages, average disability among living members increases gradually, signaling behavioral, psychological, and biological fitness in very old persons.