Ultra-processed food consumption and mortality among patients with stages I-III colorectal cancer: a prospective cohort study.

Background: Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Methods: Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I-III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980-2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. Findings: The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median = 3.6 servings/d), patients in the highest quintile (median = 10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR = 1.65, 95% CI = 1.13-2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR = 1.96, 95% CI = 1.41-2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR = 1.86, 95% CI: 1.33-2.61). No statistically significant association was found between UPF subgroups and overall mortality. Interpretation: Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. Funding: US National Institutes of Health and the American Cancer Society.

Caregiver perceptions of a pediatric produce prescription program during the COVID-19 pandemic.

Introduction: Produce prescription programs are rapidly expanding as a type of Food is Medicine intervention with prospects for mitigating food insecurity and reducing diet-related health disparities. Gaining insight into participant perspectives on program logistics and perceived impacts is crucial to program success and improvements. Methods: Between May and June 2021, we conducted individual and small group interviews with 23 caregivers with children aged 1-5 years who participated in a produce prescription program from 2020 to 2021 in Texas, U.S. They were provided with a gift card to a major national grocery retailer to purchase fresh produce. The card was reloaded $60 monthly for 8 months with automatic roll-over of unused funds to the next month. Participants also received nutrition education in the form of two videos. A deductive analysis approach was employed, and NVivo qualitative data analysis software was used to perform coding and to assist with subsequent analyses. Results: All 23 participants were female, with an average age of 37.5 years, and the majority identified as Hispanic/Latino (83%). About 43% of the families had three or more children. Six themes were generated from interviews. Three of these themes were related to program logistics: (1) ease of program use; (2) participant satisfaction with the incentive; and (3) desire for additional store options. The remaining main themes pertained to program impact: (1) the enhanced ability to purchase produce; (2) the usefulness of the nutrition education; and (3) persistent challenges encountered when preparing the produce for picky eaters and young children. Conclusion: A pediatric produce prescription program was perceived as logistically easy and a helpful source of financial support for accessing fresh produce. Program features such as card-based incentive system and partnership with major grocery retailer were favored by participants. For future program design, it may be beneficial to consider collaborating with multiple grocery outlets and enhancing the intensity and targeting of nutrition education.

A Dietary Pattern with More Fruits and Vegetables in Children of Mothers who Immigrated to the U.S. from Latin America is Associated with Healthful Nutrient Intake and Weight Status.

BACKGROUND: Children from families who immigrated to the U.S. may consume a lower-quality diet compared to their U.S.-born peers. However, specific features of their dietary patterns, which could be a focus for improving diet quality, are not well-studied. OBJECTIVE: To examine dietary patterns that distinguish interpersonal variability in dietary intake and explore the association of dietary patterns with nutrient intake and weight status. DESIGN: This study was a cross-sectional analysis of baseline data from the Live Well randomized controlled trial collected between 2009 - 2010. PARTICIPANTS/SETTING: 313 children (3 - 12 years) whose mothers immigrated to the U.S. from Latin America and resided in Somerville, MA. MAIN OUTCOME MEASURES: dietary patterns (derived using principal component analysis); nutrient intake (derived from dietary data collected using the Block Food Screener); and weight status (categorized using BMI z-score based on measured height and weight) STATISTICAL ANALYSES PERFORMED: Nutrient intake levels were compared across quartiles for dietary patterns using ANCOVA. Multivariable logistic or linear regression models were used to determine the associations between dietary pattern scores and odds of overweight or obesity or BMI z-scores. RESULTS: Two dietary patterns emerged: "fruits and vegetables" (FV) and "meat and sweets" (MS). Highest adherence to the FV pattern was associated with more healthful nutrient intake and lower odds of having overweight or obesity (OR = 0.37, 95%CI = 0.16, 0.98) but not BMI z-score (ß = -0.07, 95%CI = -0.51, 0.36) compared with the lowest adherence. Adherence to the MS pattern was associated with less healthful nutrient intake but not with the odds of experiencing overweight or obesity (OR = 0.48, 95%CI = 0.16, 1.46). CONCLUSIONS: A healthful dietary pattern in children of families who immigrated to the U.S. from Latin America may include a variety of fruits and vegetables. Longitudinal studies should be conducted to further assess the role of dietary intake patterns on health of these children.

Chronic pain exacerbates memory impairment and pathology of Aß and tau by upregulating IL-1ß and p-65 signaling in a mouse model of Alzheimer's disease.

BACKGROUND: Chronic pain is linked to cognitive impairment; however, the underlying mechanisms remain unclear. In the present study, we examined these mechanisms in a well-established mouse model of Alzheimer's disease (AD). METHODS: Neuropathic pain was modeled in 5-month-old transgenic APPswe/PS1dE9 (APP/PS1) mice by partial ligation of the sciatic nerve on the left side, and chronic inflammatory pain was modeled in another group of APP/PS1 mice by injecting them with complete Freund's adjuvant on the plantar surface of the left hind paw. Six weeks after molding, the animals were tested to assess pain threshold (von Frey filament), learning, memory (novel object recognition, Morris water maze, Y-maze, and passive avoidance), and depression-like symptoms (sucrose preference, tail suspension, and forced swimming). After behavioral testing, mice were sacrificed and the levels of p65, amyloid-ß (residues 1-42) and phospho-tau in the hippocampus and cerebral cortex were assayed using western blotting, while interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assay. RESULTS: Animals subjected to either type of chronic pain showed lower pain thresholds, more severe deficits in learning and memory, and stronger depression-like symptoms than the corresponding control animals. Either type of chronic pain was associated with upregulation of p65, amyloid-ß (1-42), and IL-1ß in the hippocampus and cerebral cortex, as well as higher levels of phosphorylated tau. CONCLUSIONS: Chronic pain may exacerbate cognitive deficits and depression-like symptoms in APP/PS1 mice by worsening pathology related to amyloid-ß and tau and by upregulating signaling involving IL-1ß and p65.

How a Medically Tailored Meal Intervention with Intensive Nutrition Counseling Created Active Coping with Behavior Change for Vulnerable Patients with Lung Cancer.

Purpose: The purpose of this study was to assess participants' perceptions and experiences while participating in a Food is Medicine medically tailored meal plus nutrition counseling intervention to create a theoretical explanation about how the intervention worked. Methods: This interpretive qualitative study included the use of semi-structured interviews with active intervention participants. Purposeful sampling included vulnerable (uninsured, rural zip code residency, racial/ethnic minority, 65 years old, and/or low-income) individuals with lung cancer treated at four cancer centers across the United States. Interviews were recorded, transcribed verbatim, and analyzed using conventional content analysis with principles of grounded theory. Results: Twenty individuals participated. Data analysis resulted in a theoretical explanation of the intervention's mechanism of action. The explanatory process includes 3 linked and propositional categories leading to patient resilience: engaging in treatment, adjusting to diagnosis, and active coping. The medically tailored meals plus intensive nutrition counseling engaged participants throughout treatment, which helped participants adjust to their diagnosis, leading to active coping through intentional self-care, behavior change, and improved quality of life. Conclusions: These findings provide evidence that a food is medicine intervention may buffer some of the adversity related to the diagnosis of lung cancer and create a pathway for participants to experience post-traumatic growth, develop resilience, and change behaviors to actively cope with lung cancer. Medically tailored meals plus intensive nutrition counseling informed by motivational interviewing supported individuals' adjustment to their diagnosis and resulted in perceived positive behavior change.

Adoption and implementation of produce prescription programs for under-resourced populations: clinic staff perspectives.

Background: Produce prescription programs represent a promising intervention strategy in the healthcare setting to address disparities in diet quality and diet-related chronic disease. The objective of this study was to understand adoption and implementation factors related to these programs that are common across contexts and those that are context-specific. Methods: In this qualitative case comparison study, we conducted qualitative interviews with eight clinic staff from five primary care "safety net" clinics, identified by a partnering non-profit organization that operated the programs, in April-July 2021. Results: Across clinics, the ability to provide a tangible benefit to patients was a key factor in adoption. Flexibility in integrating into clinic workflows was a facilitator of implementation. Fit with usual operations varied across clinics. Common challenges were the need for changes to the workflow and extra staff time. Clinic staff were skeptical about the sustainability of both the benefits to patients and the ability to continue the program at their clinics. Discussion: This study adds to a growing body of knowledge on the adoption and implementation of produce prescription programs. Future research will further this understanding, providing the evidence necessary to guide adopting clinics and to make informed policy decisions to best promote the growth and financial sustainability of these programs.

Lipidomics reveals the lipid metabolism disorders in Fructus Psoraleae-induced hepatotoxicity in rats with kidney-yin deficiency syndrome.

Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.

Higher ultra-processed food intake was positively associated with odds of NAFLD in both US adolescents and adults: A national survey.

BACKGROUND: The effect of ultra-processed foods (UPF) on NAFLD remains unclear. Related evidence for adult NAFLD is limited and no study has yet evaluated UPF's impact on NAFLD in adolescence. METHODS: We used data from the National Health and Nutrition Examination Survey (2017-2018) with 806 adolescents and 2734 adults. UPF intake was estimated using dietary data from two 24-hour dietary recalls. NAFLD was defined by transient elastography. Logistic regression was used to estimate the multivariable OR and 95% CI for associations between UPF and NAFLD with survey weight adjustments. RESULTS: The mean UPF intake was 812 g/d in adolescents and 823 g/d in adults. A total of 12.4% of the adolescents and 35.6% of the adults had NAFLD. Higher UPF intake was associated with higher odds of NAFLD in both adolescents (OR Quintile 5 vs. Quartile 1 = 2.34, 95% CI, 1.01, 5.41; ptrend = 0.15) and adults (OR Quintile 5 vs. Quintile 1 = 1.72, 95% CI, 1.01, 2.93; ptrend = 0.002). In adults, ~68% and 71% of the association between UPF intake and NAFLD was mediated by body mass index and waist circumference (all p-values < 0.001), respectively. The results were similar for adolescents but not statistically significant. A higher UPF intake was associated with lower levels of serum albumin and higher levels of C-reactive protein in adults. CONCLUSIONS: Higher UPF intake was linked to higher NAFLD odds in both adolescents and adults, mainly because of elevated body fatness. If confirmed, reducing UPF intake may help prevent NAFLD in both adolescents and adults.

Perspective: A Research Roadmap about Ultra-Processed Foods and Human Health for the United States Food System: Proceedings from an Interdisciplinary, Multi-Stakeholder Workshop.

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.

Impact of Produce Prescriptions on Diet, Food Security, and Cardiometabolic Health Outcomes: A Multisite Evaluation of 9 Produce Prescription Programs in the United States.

BACKGROUND: Produce prescriptions may improve cardiometabolic health by increasing fruit and vegetable (F&V) consumption and food insecurity yet impacts on clinical outcomes and health status have not been evaluated in large, multisite evaluations. METHODS: This multisite, pre- and post-evaluation used individual-level data from 22 produce prescription locations in 12 US states from 2014 to 2020. No programs were previously evaluated. The study included 3881 individuals (2064 adults aged 18+ years and 1817 children aged 2-17 years) with, or at risk for, poor cardiometabolic health recruited from clinics serving low-income neighborhoods. Programs provided financial incentives to purchase F&V at grocery stores or farmers markets (median, $63/months; duration, 4-10 months). Surveys assessed F&V intake, food security, and self-reported health; glycated hemoglobin, blood pressure, body mass index (BMI), and BMI z-score were measured at clinics. Adjusted, multilevel mixed models accounted for clustering by program. RESULTS: After a median participation of 6.0 months, F&V intake increased by 0.85 (95% CI, 0.68-1.02) and 0.26 (95% CI, 0.06-0.45) cups per day among adults and children, respectively. The odds of being food insecure dropped by one-third (odds ratio, 0.63 [0.52-0.76]) and odds of improving 1 level in self-reported health status increased for adults (odds ratio, 1.62 [1.30-2.02]) and children (odds ratio, 2.37 [1.70-3.31]). Among adults with glycated hemoglobin ≥6.5%, glycated hemoglobin declined by -0.29% age points (-0.42 to -0.16); among adults with hypertension, systolic and diastolic blood pressures declined by -8.38 mm Hg (-10.13 to -6.62) and -4.94 mm Hg (-5.96 to -3.92); and among adults with overweight or obesity, BMI decreased by -0.36 kg/m2 (-0.64 to -0.09). Child BMI z-score did not change -0.01 (-0.06 to 0.04). CONCLUSIONS: In this large, multisite evaluation, produce prescriptions were associated with significant improvements in F&V intake, food security, and health status for adults and children, and clinically relevant improvements in glycated hemoglobin, blood pressure, and BMI for adults with poor cardiometabolic health.

[Classification and Identification of Non-point Source Nitrogen Pollution in Surface Flow of the Shangwu River Watershed in the Qiandao Lake Region].

Accurate quantification of non-point source pollution is an important step for non-point source pollution control and management at the watershed scale. Considering the non-point source pollution from baseflow, an improved export coefficient model (IECM) on a weekly scale was established based on the traditional export coefficient model (ECM), which was then used to estimate the surface flow non-point source total nitrogen (TN) loads contributed by different land use types of the Shangwu River watershed in the Qiandao Lake Region. The results showed that IECM performed well for the predictions of TN loads in the studied watershed, with the Nash-Sutcliffe efficiency coefficient (NSE) and R2values of 0.82 and 0.77 (P<0.01) for the calibration period and 0.87 and 0.84 (P<0.01) for the validation period, respectively. The IECM estimated TN exports through surface flow and baseflow were 5.74 kg·(hm2·a)-1and 9.85 kg·(hm2·a)-1 from the Shangwu River watershed in the period of Nov. 2020 to Oct. 2021, which accounted for 36.80% and 63.20% of the corresponding streamflow TN load, respectively. Without consideration of the baseflow non-point source TN pollution, the ECM-estimated surface flow TN loading was 54.21% higher than that estimated by IECM. Obviously, attributing baseflow non-point source pollution to surface flow directly would lead to a serious load overestimation of surface flow. According to IECM, the estimated TN export intensity through surface flow from paddy fields, grasslands, woodlands, rainfed croplands, and residential lands was 10.95, 5.42, 5.20, 12.34, and 2.77 kg·(hm2·a)-1, respectively, which accounted for 5.80%, 4.00%, 26.55%, 0.38%, and 0.03% of the corresponding total streamflow TN loads. Therefore, the future management of non-point source nitrogen pollution in the studied watershed should focus mainly on the prevention and management of groundwater non-point source pollution and control of load export from surface flow on cultivated land (paddy fields and rainfed croplands).

Health and Economic Impacts of Implementing Produce Prescription Programs for Diabetes in the United States: A Microsimulation Study.

Background Produce prescription programs, providing free or discounted produce and nutrition education to patients with diet-related conditions within health care systems, have been shown to improve dietary quality and cardiometabolic risk factors. The potential impact of implementing produce prescription programs for patients with diabetes on long-term health gains, costs, and cost-effectiveness in the United States has not been established. Methods and Results We used a validated state-transition microsimulation model (Diabetes, Obesity, Cardiovascular Disease Microsimulation model), populated with national data of eligible individuals from the National Health and Nutrition Examination Survey 2013 to 2018, further incorporating estimated intervention effects and diet-disease effects from meta-analyses, and policy- and health-related costs from published literature. The model estimated that over a lifetime (mean=25 years), implementing produce prescriptions in 6.5 million US adults with both diabetes and food insecurity (lifetime treatment) would prevent 292 000 (95% uncertainty interval, 143 000-440 000) cardiovascular disease events, generate 260 000 (110000-411 000) quality-adjusted life-years, cost $44.3 billion in implementation costs, and save $39.6 billion ($20.5-58.6 billion) in health care costs and $4.8 billion ($1.84-$7.70 billion) in productivity costs. The program was highly cost effective from a health care perspective (incremental cost-effectiveness ratio: $18 100/quality-adjusted life-years) and cost saving from a societal perspective (net savings: $-0.05 billion). The intervention remained cost effective at shorter time horizons of 5 and 10 years. Results were similar in population subgroups by age, race or ethnicity, education, and baseline insurance status. Conclusions Our model suggests that implementing produce prescriptions among US adults with diabetes and food insecurity would generate substantial health gains and be highly cost effective.

Food Processing, According to the Nova Classification System, and Dietary Intake of US Infants and Toddlers.

BACKGROUND: High intake of ultra-processed foods (UPFs) is associated with increased risk of chronic disease; thus, it is important to understand how UPFs influence diet quality early in life. OBJECTIVES: We describe complementary foods and beverages (CFBs) according to the Nova Classification System of Food Processing for infants and toddlers in the United States and estimate how Nova groups and subgroups contribute to energy and select nutrients and food groups. METHODS: We used day 1 24-h recall from infants and toddlers aged 6-23 mo from the cross-sectional, nationally representative 2013-18 National Health and Nutrition Examination Survey (n = 1140). We estimated contributions of Nova groups and subgroups to energy and select nutrients and food groups consumed as CFBs (excluding human milk and formula) using the population ratio with weighted survey commands in SAS. RESULTS: For infants and toddlers in the United States, 42 ± 0.9% (mean ± standard error of the mean) of energy intake from CFBs came from unprocessed/minimally processed foods (U/MPFs) and 45 ± 0.8% from UPFs. U/MPFs contributed most to nutrient intakes (except iron, zinc, and sodium); ≥20% of all selected nutrients was from UPFs. UPFs contributed most to iron (75 ± 1.0%) and zinc (48 ± 1.3%); breakfast cereals were the top source. Most fruit, vegetables, and dairy were from U/MPFs. More than 80% of total grains, whole grains, refined grains, and added sugars were UPFs. CONCLUSIONS: U/MPFs support healthy dietary intake of infants and toddlers in the United States, whereas UPFs contribute meaningfully to nutrients and food groups to be encouraged (iron, zinc, and whole grains), as well as some that should be limited (added sugars and sodium). More research is needed to better understand the utility and sensitivities of using Nova for providing dietary guidance for infants and toddlers in the United States.

Application of WeChat Public Account for Lifestyle Management of Polycystic Ovary Syndrome.

Null.

Imbalance of multiple neurotransmitter pathways leading to depression-like behavior and cognitive dysfunction in the triple transgenic mouse model of Alzheimer disease.

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.

Fish-To Eat or Not to Eat? A Mixed-Methods Investigation of the Conundrum of Fish Consumption in the Context of Marine Pollution in Indonesia.

Background: The Indonesian government faces a dilemma of promoting fish consumption for its health benefits and to ease food insecurity, while at the same time seeking effective approaches to reduce the high levels of marine pollution. However, the factors associated with fish consumption in the face of persistent high levels of marine pollution are not well elucidated in the literature. Objectives: This was an explorative study to investigate the sociodemographic factors related to fish consumption and to understand the perspectives of expert informants on marine pollution and its impact on fish quality and availability in Indonesia. Methods: We characterized fish consumption among respondents aged 15 years and older in the fifth wave of the Indonesian Family Life Survey (n = 31,032), based on their sociodemographic profiles, and developed multinomial regression models to assess the relationship between respondents' sociodemographic profiles and quintiles of fish consumption. We also conducted in-depth interviews on fish consumption and marine pollution with key informants from Indonesia (n = 27). We then used a convergent mixed-methods design to synthesize the results of both datasets. Results: Fish was the most frequently consumed animal-source food reported by survey respondents: 2.8 (±2.6) days/week. More younger respondents (15-19 years) reported relatively lower consumption of fish (9.3% in Q1 versus 5.9% in Q5) compared to respondents 50 years and older (37% in Q1 versus 39.9% in Q5; p < 0.01). When classified by region, more respondents from the Java region reported lower consumption of fish (86.5% in Q1 versus 53% in Q5; p < 0.01). Key-informants' perspectives corroborated the survey results by indicating that the younger generation tends not to want to consume fish; informants expanded the survey results by suggesting that fish is scarce in the Java region due to high levels of marine pollution. Informants further implied that there is low awareness about the impact of marine pollution on fish quality among most of the Indonesian population. Conclusion: Evidence from both data sources converge on differential preference for fish consumption by age group. Informants' perspectives also link marine pollution to fish scarcity, which poses a threat to food security among low-income Indonesians and to human health globally. More studies are needed to corroborate our findings and inform policy guidelines to reduce marine pollution while promoting fish consumption in Indonesia.

Measurement of diets that are healthy, environmentally sustainable, affordable, and equitable: A scoping review of metrics, findings, and research gaps.

Introduction: Research on the impacts of dietary patterns on human and planetary health is a rapidly growing field. A wide range of metrics, datasets, and analytical techniques has been used to explore the role of dietary choices/constraints in driving greenhouse gas (GHG) emissions, environmental degradation, health and disease outcomes, and the affordability of food baskets. Many argue that each domain is important, but few have tackled all simultaneously in analyzing diet-outcome relationships. Methods: This paper reviews studies published between January 2015 and December 2021 (inclusive) that examined dietary patterns in relation to at least two of the following four thematic pillars: (i) planetary health, including, climate change, environmental quality, and natural resource impacts, (ii) human health and disease, (iii) economic outcomes, including diet cost/affordability, and (iv) social outcomes, e.g., wages, working conditions, and culturally relevant diets. We systematically screened 2,425 publications by title and abstract and included data from 42 eligible publications in this review. Results: Most dietary patterns used were statistically estimated or simulated rather than observed. A rising number of studies consider the cost/affordability of dietary scenarios in relation to optimized environmental and health outcomes. However, only six publications incorporate social sustainability outcomes, which represents an under-explored dimension of food system concerns. Discussion: This review suggests a need for (i) transparency and clarity in datasets used and analytical methods; (ii) explicit integration of indicators and metrics linking social and economic issues to the commonly assessed diet-climate-planetary ecology relationships; (iii) inclusion of data and researchers from low- and middle-income countries; (iv) inclusion of processed food products to reflect the reality of consumer choices globally; and (v) attention to the implications of findings for policymakers. Better understanding is urgently needed on dietary impacts on all relevant human and planetary domains simultaneously.

What is the cost-effectiveness of menu calorie labelling on reducing obesity-associated cancer burdens? An economic evaluation of a federal policy intervention among 235 million adults in the USA.

OBJECTIVE: To assess the impact of menu calorie labelling on reducing obesity-associated cancer burdens in the USA. DESIGN: Cost-effectiveness analysis using a Markov cohort state-transition model. SETTING: Policy intervention. PARTICIPANTS: A modelled population of 235 million adults aged ≥20 years in 2015-2016. INTERVENTIONS: The impact of menu calorie labelling on reducing 13 obesity-associated cancers among US adults over a lifetime was evaluated for: (1) effects on consumer behaviours; and (2) additional effects on industry reformulation. The model integrated nationally representative demographics, calorie intake from restaurants, cancer statistics and estimates on associations of policy with calorie intake, dietary change with body mass index (BMI) change, BMI with cancer rates, and policy and healthcare costs from published literature. MAIN OUTCOME MEASURES: Averted new cancer cases and cancer deaths and net costs (in 2015 US$) among the total population and demographic subgroups were determined. Incremental cost-effectiveness ratios from societal and healthcare perspectives were assessed and compared with the threshold of US$150 000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters and generated 95% uncertainty intervals (UIs). RESULTS: Considering consumer behaviour alone, this policy was associated with 28 000 (95% UI 16 300 to 39 100) new cancer cases and 16 700 (9610 to 23 600) cancer deaths averted, 111 000 (64 800 to 158 000) QALYs gained, and US$1480 (884 to 2080) million saved in cancer-related medical costs among US adults. The policy was associated with net cost savings of US$1460 (864 to 2060) million and US$1350 (486 to 2260) million from healthcare and societal perspectives, respectively. Additional industry reformulation would substantially increase policy impact. Greater health gains and cost savings were predicted among young adults, Hispanic and non-Hispanic Black individuals. CONCLUSIONS: Study findings suggest that menu calorie labelling is associated with lower obesity-related cancer burdens and reduced healthcare costs. Policymakers may prioritise nutrition policies for cancer prevention in the USA.

The circular RNA Rap1b promotes Hoxa5 transcription by recruiting Kat7 and leading to increased Fam3a expression, which inhibits neuronal apoptosis in acute ischemic stroke.

Circular RNAs can regulate the development and progression of ischemic cerebral disease. However, it remains unclear whether they play a role in acute ischemic stroke. To investigate the role of the circular RNA Rap1b (circRap1b) in acute ischemic stroke, in this study we established an in vitro model of acute ischemia and hypoxia by subjecting HT22 cells to oxygen and glucose deprivation and a mouse model of acute ischemia and hypoxia by occluding the right carotid artery. We found that circRap1b expression was remarkably down-regulated in the hippocampal tissue of the mouse model and in the HT22 cell model. In addition, Hoxa5 expression was strongly up-regulated in response to circRap1b overexpression. Hoxa5 expression was low in the hippocampus of a mouse model of acute ischemia and in HT22-AIS cells, and inhibited HT22-AIS cell apoptosis. Importantly, we found that circRap1b promoted Hoxa5 transcription by recruiting the acetyltransferase Kat7 to induce H3K14ac modification in the Hoxa5 promoter region. Hoxa5 regulated neuronal apoptosis by activating transcription of Fam3a, a neuronal apoptosis-related protein. These results suggest that circRap1b regulates Hoxa5 transcription and expression, and subsequently Fam3a expression, ultimately inhibiting cell apoptosis. Lastly, we explored the potential clinical relevance of circRap1b and Hoxa5 in vivo. Taken together, these findings demonstrate the mechanism by which circRap1b inhibits neuronal apoptosis in acute ischemic stroke.