Association of Candidate Single-Nucleotide Polymorphism Genotypes With Plasma and Skin Carotenoid Concentrations in Adults Provided a Lycopene-Rich Juice.

BACKGROUND: Carotenoids are fat-soluble phytochemicals with biological roles, including ultraviolet protective functions in skin. Spectroscopic skin carotenoid measurements can also serve as a noninvasive biomarker for carotenoid consumption. Single-nucleotide polymorphisms (SNPs) in metabolic genes are associated with human plasma carotenoid concentrations; however, their relationships with skin carotenoid concentrations are unknown. OBJECTIVES: The objective of this study was to determine the relationship between 13 candidate SNPs with skin and plasma carotenoid concentrations before and after a carotenoid-rich tomato juice intervention. METHODS: In this randomized, controlled trial, participants (n = 80) were provided with lycopene-rich vegetable juice providing low (13.1 mg), medium (23.9 mg), and high (31.0 mg) daily total carotenoid doses for 8 wk. Plasma carotenoid concentrations were measured by high-pressure liquid chromatography, and skin carotenoid score was assessed by reflection spectroscopy (Veggie Meter) at baseline and the end-of-study time point. Thirteen candidate SNPs in 5 genes (BCO1, CD36, SCARB1, SETD7, and ABCA1) were genotyped from blood using PCR-based assays. Mixed models tested the effects of the intervention, study time point, interaction between intervention and study time point, and SNP genotype on skin and plasma carotenoids throughout the study. Baseline carotenoid intake, body mass index, gender, and age are covariates in all models. RESULTS: The genotype of CD36 rs1527479 (P = 0.0490) was significantly associated with skin carotenoid concentrations when baseline and the final week of the intervention were evaluated. Genotypes for BCO1 rs7500996 (P = 0.0067) and CD36 rs1527479 (P = 0.0018) were significant predictors of skin carotenoid concentrations in a combined SNP model. CONCLUSIONS: These novel associations between SNPs and skin carotenoid concentrations expand on the understanding of how genetic variation affects interindividual variation in skin carotenoid phenotypes in humans. This trial was registered at clinicaltrials.gov as NCT03202043.

Exploring Factors Associated With Accelerometer Validity Among Ethnically Diverse Toddlers.

PURPOSE: Studying physical activity in toddlers using accelerometers is challenging due to noncompliance with wear time (WT) and activity log (AL) instructions. The aims of this study are to examine relationships between WT and AL completion and (1) demographic and socioeconomic variables, (2) parenting style, and (3) whether sedentary time differs by AL completion. METHODS: Secondary analysis was performed using baseline data from a community wellness program randomized controlled trial for parents with toddlers (12-35 mo). Parents had toddlers wear ActiGraph wGT3x accelerometers and completed ALs. Valid days included ≥600-minute WT. Analysis of variance and chi-square analyses were used. RESULTS: The sample (n = 50) comprised racial and ethnically diverse toddlers (mean age = 27 mo, 58% male) and parents (mean age = 31.7 y, 84% female). Twenty-eight families (56%) returned valid accelerometer data with ALs. Participants in relationships were more likely to complete ALs (P < .05). Toddler sedentary time did not differ between those with ALs and those without. CONCLUSIONS: We found varied compliance with WT instructions and AL completion. Returned AL quality was poor, presenting challenges in correctly characterizing low-activity counts to improve internal validity of WT and physical activity measures. Support from marital partners may be important for adherence to study protocols.

Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Preterm Pigs Fed Donor Human Milk Have Greater Liver ß-Carotene Concentrations than Pigs Fed Infant Formula.

BACKGROUND: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition. OBJECTIVES: We tested whether tissue and plasma ß-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF. METHODS: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n = 7) or premature IF (n = 7) from 2 to 7 d of age. The diets provided similar ß-carotene (32 nM), but DHM had higher lutein, zeaxanthin, and lycopene, whereas IF had higher total vitamin A. Plasma, liver, and jejunum carotenoid and vitamin A concentrations were measured by HPLC-PDA. Jejunal expression of 12 genes associated with carotenoid and lipid metabolism were measured. RESULTS: Liver ß-carotene concentrations were higher in DHM- than IF-fed piglets (23 ± 4 compared with 16 ± 2 µg/g, respectively, P = 0.0024), whereas plasma and jejunal ß-carotene concentrations were similar between diets. Liver vitamin A stores were higher in piglets fed IF than DHM (50.6 ± 10.1 compared with 30.9 ± 7.2 µg/g, respectively, P=0.0013); however, plasma vitamin A was similar between groups. Plasma, liver, and jejunum concentrations of lutein, zeaxanthin, and lycopene were higher with DHM than IF feeding. Relative to piglets fed DHM, jejunal low density lipoprotein receptor (Ldlr) expression was higher (61%, P = 0.018) and cluster determinant 36 (Cd36) expression (-27%, P = 0.034) was lower in IF-fed piglets. CONCLUSIONS: Preterm pigs fed DHM accumulate more liver ß-carotene than IF-fed pigs. Future studies should further investigate infant carotenoid bioactivity and bioavailability.

Noninvasive Reflection Spectroscopy Measurement of Skin Carotenoid Score in Infants Is Feasible and Reliable.

BACKGROUND: Skin carotenoid measurement by reflection spectroscopy (RS) offers a noninvasive biomarker of carotenoid intake, but feasibility, reliability, and validity are not established in infants. OBJECTIVES: In this study we aimed to determine the feasibility and reliability of 4-mo-old infant skin carotenoid score (SCS) measurement and its correlation with total carotenoid intake and plasma concentrations. METHODS: SCSs were measured in a prospective, observational study with a modified, portable RS device at the index finger and heel of the foot in 4-mo-olds (n = 21). Infant plasma, human milk, and formula carotenoid concentrations were measured by HPLC-photodiode array, and carotenoid intake was estimated from 7-d food diaries corrected for actual milk carotenoid content. Mean SCS, time to acquire measurements, replicate intraclass correlations, and bivariate correlations between SCS, carotenoid intake, and plasma carotenoids were examined. Exploratory analyses of returning 6- (n = 12) and 8-mo-old (n = 9) infants were conducted. RESULTS: Mean ± SD finger and heel SCSs in 4-, 6-, and 8-mo-olds were 92 ± 57 and 92 ± 51; 109 ± 41 and 119 ± 44; and 161 ± 89 and 197 ± 128 units, respectively. Replicate SCS measurements were reliable, with high intraclass correlation (≥0.70) of within-subject visit measurements. Finger SCSs in 4-mo-olds were correlated with carotenoid intake (ρ = 0.48, P = 0.0033), and finger and heel SCS were correlated with total plasma carotenoid concentrations (ρ = 0.71, P < 0.0001 and ρ = 0.57, P = 0.0006, respectively). Eight-mo-olds' finger and heel SCSs were correlated with total carotenoid intake (ρ = 0.73, P < 0.001; ρ = 0.58, P = 0.0014, respectively), whereas SCSs in 6-mo-olds, in transition from exclusive milk to complementary feeding, did not correlate with plasma carotenoid or dietary carotenoids, despite correlation between plasma and dietary carotenoid intake (ρ = 0.86, P = 0.0137). Mixed models suggest plasma total carotenoid concentration, age, carotenoid intake, and age × carotenoid intake, but not measurement site, are determinants of infant SCS. CONCLUSIONS: Infant skin carotenoids are feasibly and reliably measured by RS and may provide a biomarker of carotenoid intake in 4-mo-olds. This trial was registered at clinicaltrials.gov as NCT03996395.

Examining Potential Modifiers of Human Skin and Plasma Carotenoid Responses in a Randomized Trial of a Carotenoid-Containing Juice Intervention.

BACKGROUND: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. OBJECTIVES: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. METHODS: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. RESULTS: In bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. CONCLUSIONS: Changes in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores. This trial was registered at clinicaltrials.gov as NCT04056624.

Orchestration of miRNA Patterns by Testosterone and Dietary Tomato Carotenoids during Early Prostate Carcinogenesis in TRAMP Mice.

BACKGROUND: The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined. OBJECTIVES: This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. METHODS: Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 wk. Mice were killed at 10 wk, and dorsolateral prostate expression of 602 miRNAs was assessed. RESULTS: We detected expression of 88 miRNAs (15% of 602), all of which were present in the TRAMP, in comparison with 49 miRNAs being detectable (8%) in WT. Expression of 61 miRNAs differed by TRAMP genotype, with the majority upregulated in TRAMP. Of the 61 miRNAs, 42 were responsive to androgen status. Diet affected 41% of the miRNAs, which differed by genotype (25/61) and 48% of the androgen-sensitive miRNAs (20/42), indicating overlapping genetic and dietary influences on prostate miRNAs. Tomato and lycopene feeding influenced miRNAs previously associated with the regulation of androgen (miR-145 and let-7), MAPK (miR-106a, 204, 145/143, and 200b/c), and p53 signaling (miR-125 and miR-98) pathways. CONCLUSIONS: Expression of miRNAs in early prostate carcinogenesis is sensitive to genetic, endocrine, and diet drivers, suggesting novel mechanisms by which tomato and lycopene feeding modulate early prostate carcinogenesis.

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive to Change in Carotenoid Intake in a 6-Week Randomized Controlled Feeding Trial in a Racially/Ethnically Diverse Sample.

BACKGROUND: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake. OBJECTIVES: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial. METHODS: In this 6-wk trial, participants (n = 162) who self-identified as one of 4 US racial/ethnic groups (25% Black, 25% Asian, 27% non-Hispanic White, 23% Hispanic) were randomized to a control group, receiving negligible carotenoids (177 mL apple juice/d), moderate-dose group, receiving 4 mg total carotenoids/d (177 mL orange-carrot juice/d), or high-dose group, receiving 8 mg total carotenoids/d (355 mL orange-carrot juice/d). Skin carotenoid score and plasma total carotenoid concentrations (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein, zeaxanthin) were assessed at baseline, 3 wk, and 6 wk (n = 158 completed the trial). Repeated measures linear models were used to examine skin and plasma carotenoids over time and between groups. RESULTS: At 6 wk, participants in the high-dose and moderate-dose groups had significantly higher mean skin carotenoid scores [414.0 (SD = 100.6) and 369.7 (SD = 100.3), respectively] compared with those in the control group [305.2 (100.5)]. In the high-dose group, there was a 42% change in skin carotenoids from baseline (mean = 290.4) to a 6-wk follow-up (increase of 123, 123/290 = 42.4%). There was a 61% change in the plasma carotenoids in the high-dose group. CONCLUSIONS: The Veggie Meter is sensitive to increases in daily carotenoid intake in diverse racial/ethnic groups over 6 wk. CLINICAL TRIALS REGISTRY NUMBER: This trial was registered at clinicaltrials.gov as ID: NCT04056624. Study URL: https://clinicaltrials.gov/ct2/show/NCT04056624.

COVID-19-Associated Hospitalizations Among U.S. Adults Aged ≥65 Years - COVID-NET, 13 States, January-August 2023.

Adults aged ≥65 years remain at elevated risk for severe COVID-19 disease and have higher COVID-19-associated hospitalization rates compared with those in younger age groups. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to estimate COVID-19-associated hospitalization rates during January-August 2023 and identify demographic and clinical characteristics of hospitalized patients aged ≥65 years during January-June 2023. Among adults aged ≥65 years, hospitalization rates more than doubled, from 6.8 per 100,000 during the week ending July 15 to 16.4 per 100,000 during the week ending August 26, 2023. Across all age groups, adults aged ≥65 years accounted for 62.9% (95% CI = 60.1%-65.7%) of COVID-19-associated hospitalizations, 61.3% (95% CI = 54.7%-67.6%) of intensive care unit admissions, and 87.9% (95% CI = 80.5%-93.2%) of in-hospital deaths associated with COVID-19 hospitalizations. Most hospitalized adults aged ≥65 years (90.3%; 95% CI = 87.2%-92.8%) had multiple underlying conditions, and fewer than one quarter (23.5%; 95% CI = 19.5%-27.7%) had received the recommended COVID-19 bivalent vaccine. Because adults aged ≥65 years remain at increased risk for COVID-19-associated hospitalization and severe outcomes, guidance for this age group should continue to focus on measures to prevent SARS-CoV-2 infection, encourage vaccination, and promote early treatment for persons who receive a positive SARS-CoV-2 test result to reduce their risk for severe COVID-19-associated outcomes.

Tomatoes, Lycopene, and Prostate Cancer: What Have We Learned from Experimental Models?

Human epidemiology suggests a protective effect of tomatoes or tomato phytochemicals, such as lycopene, on prostate cancer risk. However, human epidemiology alone cannot reveal causal relations. Laboratory animal models of prostate cancer provide opportunities to investigate hypotheses regarding dietary components in precisely controlled, experimental systems, contributing to our understanding of diet and cancer risk relations. We review the published studies evaluating the impact of tomatoes and/or lycopene in preclinical models of prostate carcinogenesis and tumorigenesis. The feeding of tomatoes or tomato components demonstrates anti-prostate cancer activity in both transplantable xenograft models of tumorigenesis and models of chemically- and genetically-driven carcinogenesis. Feeding pure lycopene shows anticancer activity in most studies, although outcomes vary by model system, suggesting that the impact of pure lycopene can depend on dose, duration, and specific carcinogenic processes represented in different models. Nonetheless, studies with the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of carcinogenesis typically demonstrate similar bioactivity to that of tomato feeding. In general, interventions that commence earlier in carcinogenesis and are sustained tend to be more efficacious. Accumulated data suggest that lycopene is one, but perhaps not the only, anticancer bioactive compound in tomatoes. Although it is clear that tomatoes and lycopene have anti-prostate cancer activity in rodent models, major knowledge gaps remain in understanding dose-response relations and molecular mechanisms of action. Published and future findings from rodent studies can provide guidance for translational scientists to design and execute informative human clinical trials of prostate cancer prevention or in support of therapy.

ß-Carotene Oxygenase 2 Genotype Modulates the Impact of Dietary Lycopene on Gene Expression during Early TRAMP Prostate Carcinogenesis.

BACKGROUND: Epidemiologic studies suggest lycopene and tomato intake are inversely associated with human prostate cancer incidence. In the genetically driven murine prostate carcinogenesis model transgenic adenocarcinoma of the mouse prostate (TRAMP), prostate cancer is inhibited by feeding of lycopene or tomatoes, and these effects are modulated by the ß-carotene oxygenase 2 (Bco2) genotype. OBJECTIVE: We sought insight into this interaction through evaluation of prostate gene expression patterns during early TRAMP carcinogenesis. METHODS: Three-week-old TRAMP/+ or TRAMP/- × Bco2+/+ or Bco2-/- mice were fed a control, lycopene beadlet, or 10% tomato powder-containing semipurified diet (providing 0, 384 and 462 mg lycopene/kg diet, respectively) for 5 wk. Gene expression patterns were evaluated by prostate cancer- and cholesterol and lipoprotein metabolism-focused arrays at age 8 wk. RESULTS: The TRAMP genotype profoundly alters gene expression patterns, specifically inducing pathways associated with cell survival [z-score = 2.09, -log(P value) = 29.2, p53 signaling (z-score 1.13, -log(P value) = 13.5], and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling [z-score = 0.302, -log(P value) = 12.1], while repressing phosphatase and tensin homolog (PTEN) signaling [(z-score = -0.905, -log(P value) = 12.3], cholesterol synthesis [z-score = -1.941, -log(P-value) = 26.2], and LXR/RXR pathway activation [z-score = -1.941, -log(P value) = 23.1]. In comparison, lycopene- and tomato-feeding modestly modulate strong procarcinogenic TRAMP signaling. Lycopene decreased gene expression related to carcinogenesis [ Nkx3-1(NK3 homeobox 1)], tomato feeding increased expression of a gene involved in circadian regulation [Arntl (aryl hydrocarbon receptor nuclear translocator like)], and tomato and/or lycopene increased expression of genes involved in lipid metabolism [Fasn (fatty acid synthase), Acaca(acetyl-CoA carboxylase alpha), Srebf1 (sterol regulatory element binding transcription factor 1), Hmgcr (3-hydroxy-3-methylglutaryl-coA reductase), and Ptgs1 (prostaglandin-endoperoxide synthase 1)] (all P < 0.05). The impact of Bco2 genotype was limited to a subset of lycopene-impacted genes [Apc (adenomatous polyposis coli), Mto1 (mitochondrial TRNA translation optimization 1), Nfkb1 (nuclear factor kappa B subunit 1), andRbm39 (RNA binding motif protein 39)]. CONCLUSIONS: The TRAMP genotype strongly impacts procarcinogenic gene expression prior to emergence of histopathologic disease. Dietary tomato and lycopene modestly temper these processes, while Bco2 genotype has a limited impact at this early stage. These observed patterns provide insight into the complex interactions between a dietary variable, here tomatoes and lycopene, genes impacting nutrient metabolism, and their modulating influences on oncogene-driven prostate carcinogenesis. These findings provide further mechanistic support, consistent with cancer outcomes in rodents experiments and human epidemiologic studies.

Pressure-Mediated Reflection Spectroscopy Criterion Validity as a Biomarker of Fruit and Vegetable Intake: A 2-Site Cross-Sectional Study of 4 Racial or Ethnic Groups.

BACKGROUND: Valid biomarkers of fruit and vegetable (FV) intake are needed for field-based nutrition research. OBJECTIVES: To examine criterion-related validity of pressure-mediated reflection spectroscopy as a proxy measure of FV intake, using plasma carotenoids and self-reported FV and carotenoid intake as primary and secondary criterion measures, respectively. METHODS: Healthy adults 18-65 y of age, self-identifying as African American/black (n = 61), Asian (n = 53), white (n = 70), or Hispanic (n = 29), in North Carolina and Minnesota were recruited. Skin carotenoids were assessed via pressure-mediated reflection spectroscopy (Veggie Meter), skin melanin via spectrophotometer, and total plasma carotenoid concentration by HPLC-photodiode array detection. Self-reported carotenoid and FV intake was assessed using a semiquantitative FFQ. Relations between skin carotenoids, plasma carotenoids, FV, and carotenoid intake, with differences by race or ethnicity, age, sex, weight status, cholesterol, and melanin index, were examined by bivariate correlations and adjusted multivariate linear regressions. RESULTS: The overall unadjusted correlation between skin and total plasma carotenoids was r = 0.71 and ranged from 0.64 (non-Hispanic black) to 0.80 (Hispanic). Correlations between skin carotenoids and self-reported FV intake ranged from 0.24 (non-Hispanic black) to 0.53 (non-Hispanic white), with an overall correlation of r = 0.35. In models adjusted for age, sex, racial or ethnic group, and BMI, skin carotenoids were associated with plasma carotenoids (R2 = 0.55), FV (R2 = 0.17), and carotenoid intake (R2 = 0.20). For both plasma carotenoid and FV measures, associations with skin carotenoids did not vary by race, but these relations did differ by skin melanin-those with lower melanin had a lower correlation between skin and plasma carotenoids. CONCLUSIONS: Reflection spectroscopy-assessed skin carotenoids may be a reasonable alternative to measurement of plasma carotenoids, a biomarker used to approximate FV intake.

Laboratory-Confirmed COVID-19-Associated Hospitalizations Among Adults During SARS-CoV-2 Omicron BA.2 Variant Predominance - COVID-19-Associated Hospitalization Surveillance Network, 14 States, June 20, 2021-May 31, 2022.

Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).

Exploring qualities of ethnically diverse parents related to the healthy home environment of toddlers.

Parents serve as role models and household policy makers for their children's home social environment. Also, parents may influence the home physical environment through the provision of resources to support their children's dietary, activity, and sleep behaviors. Understanding the parental characteristics related to children's home environment may allow for tailoring obesity interventions to families' needs. This study aimed to explore parental qualities (general parenting styles, parent feeding practices, and parental BMI) related to healthy home food, physical activity, media and sleep environment of toddlers. A total of 50 multi-ethnic parents with toddler age children who were enrolled in a randomized pilot study of a wellness program completed the Structure and Control in Parent Feeding (SCPF) questionnaire and Comprehensive General Parenting Questionnaire (CGPQ). Parental BMI was calculated using self-reported weight and height data. The Healthy Home Survey, the Home Food Inventory, the Sleep Environment Questionnaire, and items developed for this study were standardized and summed to create home food, physical activity, screen media, and sleep environment scores; high scores reflected healthier environments. To examine the relationships between parental qualities and the home environment, Pearson's correlation test was performed. Parental BMI and overall healthy home environment were inversely associated (r = -0.306; p = 0.032). Structure in general parenting and parental feeding practice were positively correlated with the overall healthy home environment (r = 0.336; p = 0.026) and healthy home food environment (r = 0.415; p = 0.003), respectively. The coercive control general parenting was inversely related to overall healthy home environment score (r = -0.333; p = 0.022). Based on the findings from this study, parents who provide clear communication, set consistent rules, avoid pressure to control their child's behavior, and have lower BMI tend to live in a home environment that support children's health behaviors.

Single Nucleotide Polymorphisms in ß-Carotene Oxygenase 1 are Associated with Plasma Lycopene Responses to a Tomato-Soy Juice Intervention in Men with Prostate Cancer.

BACKGROUND: Human plasma and tissue lycopene concentrations are heterogeneous even when consuming controlled amounts of tomato or lycopene. OBJECTIVES: Our objective is to determine whether single nucleotide polymorphisms (SNPs) in or near known or putative carotenoid metabolism genes [ß-carotene 15,15' monooxygenase 1 (BCO1), scavenger receptor class B type 1 (SCARB1), ATP-binding cassette transporter subfamily A member 1 (ABCA1), microsomal triglyceride transfer protein (MTTP), apolipoprotein B-48, elongation of very long chain fatty acids protein 2 (ELOVL2), and ATP-binding cassette subfamily B member 1 (ABCB1), and an intergenic superoxide dismutase 2, mitochondrial-associated SNP] are predictive of plasma lycopene responses to steady state tomato juice consumption. METHODS: Secondary linear regression analyses of data from a dose-escalation study of prostate cancer patients [n = 47; mean ± SEM age: 60 ± 1 y; BMI (in kg/m2): 32 ± 1] consuming 0, 1, or 2 cans of tomato-soy juice/d (163 mL/can; 20.6 mg lycopene 1.2 mg ß-carotene/can) for 24 ± 0.7 d before prostatectomy were conducted to explore 11 SNP genotype effects on the change in plasma lycopene and plasma and prostate tissue concentrations of lycopene, ß-carotene, phytoene, and phytofluene. RESULTS: Two BCO1 SNP genotypes were significant predictors of the change in plasma lycopene, with SNP effects differing in magnitude and direction, depending on the level of juice intake (rs12934922 × diet group P = 0.02; rs6564851 × diet group P = 0.046). Further analyses suggested that plasma ß-carotene changes were predicted by BCO1 rs12934922 (P < 0.01), prostate lycopene by trending interaction and main effects of BCO1 SNPs (rs12934922 × diet group P = 0.09; rs12934922 P = 0.02; rs6564851 P = 0.053), and prostate ß-carotene by BCO1 SNP interaction and main effects (rs12934922 × diet group P = 0.01; rs12934922 P < 0.01; rs7501331 P = 0.02). CONCLUSIONS: In conclusion, SNPs in BCO1 and other genes may modulate human plasma and prostate tissue responses to dietary lycopene intake and warrant validation in larger, human controlled feeding intervention and cohort studies. Genetic variants related to carotenoid metabolism may partially explain heterogeneous human blood and tissue responses and may be critical covariates for population studies and clinical trials. This trial was registered at clinicaltrials.gov as NCT01009736.

A Novel Tomato-Soy Juice Induces a Dose-Response Increase in Urinary and Plasma Phytochemical Biomarkers in Men with Prostate Cancer.

Background: Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies. Objective: On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure. Methods: Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean ± SD duration: 24 ± 4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry. Results: We documented significant dose-response increases (P < 0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, ß-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2 = 0.78 for lycopene, P < 0.001; R2 = 0.59 for dihydrodaidzein, P < 0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P = 0.078). Conclusion: These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis. This trial is registered at clinicaltrials.gov as NCT01009736.

A non-invasive assessment of skin carotenoid status through reflection spectroscopy is a feasible, reliable and potentially valid measure of fruit and vegetable consumption in a diverse community sample.

OBJECTIVE: To assess the feasibility, reliability and validity of reflection spectroscopy (RS) to assess skin carotenoids in a racially diverse sample. DESIGN: Study 1 was a cross-sectional study of corner store customers (n 479) who completed the National Cancer Institute Fruit and Vegetable Screener as well as RS measures. Feasibility was assessed by examining the time it took to complete three RS measures, reliability was assessed by examining the variation between three RS measures, and validity was examined by correlation with self-reported fruit and vegetable consumption. In Study 2, validity was assessed in a smaller sample (n 30) by examining associations between RS measures and dietary carotenoids, fruits and vegetables as calculated from a validated FFQ and plasma carotenoids. SETTING: Eastern North Carolina, USA. RESULTS: It took on average 94·0 s to complete three RS readings per person. The average variation between three readings for each participant was 6·8 %. In Study 2, in models adjusted for age, race and sex, there were statistically significant associations between RS measures and (i) FFQ-estimated carotenoid intake (P<0·0001); (ii) FFQ-estimated fruit and vegetable consumption (P<0·010); and (iii) plasma carotenoids (P<0·0001). CONCLUSIONS: RS is a potentially improved method to approximate fruit and vegetable consumption among diverse participants. RS is portable and easy to use in field-based public health nutrition settings. More research is needed to investigate validity and sensitivity in diverse populations.

Mice lacking ß-carotene-15,15'-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation.

ß-Carotene-15,15'-dioxygenase (BCO1) cleaves dietary carotenoids at the central 15,15' double bond, most notably acting on ß-carotene to yield retinal. However, Bco1 disruption also impacts diverse physiological end points independent of dietary carotenoid feeding, including expression of genes controlling androgen metabolism. Using the Bco1-/- mouse model, we sought to probe the effects of Bco1 disruption on testicular steroidogenesis, prostatic androgen signaling, and prostatic proliferation. Male wild-type (WT) and Bco1-/- mice were raised on carotenoid-free AIN-93G diets before euthanasia between 10 and 14 wk of age. Weights of the prostate and seminal vesicles were significantly lower in Bco1-/- than in WT mice (-18% and -29%, respectively). Serum testosterone levels in Bco1-/- mice were significantly reduced by 73%. Bco1 disruption significantly reduced Leydig cell number and decreased testicular mRNA expression of Hsd17b3, suggesting inhibition of testicular testosterone synthesis. Immunofluorescent staining of the androgen receptor (AR) in the dorsolateral prostate lobes of Bco1-/- mice revealed a decrease in AR nuclear localization. Analysis of prostatic morphology suggested decreases in gland size and secretion. These findings were supported by reduced expression of the proliferation marker Ki-67 in Bco1-/- prostates. Expression analysis of 200 prostate cancer- and androgen-related genes suggested that Bco1 loss significantly disrupted prostatic androgen receptor signaling, cell cycle progression, and proliferation. This is the first demonstration that Bco1 disruption lowers murine circulating testosterone levels and thereby reduces prostatic androgen receptor signaling and prostatic cellular proliferation, further supporting the role of this protein in processes more diverse than carotenoid cleavage.

Absorption and Distribution Kinetics of the 13C-Labeled Tomato Carotenoid Phytoene in Healthy Adults.

BACKGROUND: Phytoene is a tomato carotenoid that may contribute to the apparent health benefits of tomato consumption. Although phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lycopene, suggesting the kinetics of phytoene and lycopene differ. OBJECTIVE: The objective of this study was to characterize the kinetic parameters of phytoene absorption, distribution, and excretion in adults, to better understand why biodistribution of phytoene differs from lycopene. METHODS: Four adults (2 males, 2 females) maintained a controlled phytoene diet (1-5 mg/d) for 42 d. On day 14, each consumed 3.2 mg (13)C-phytoene, produced using tomato cell suspension culture technology. Blood samples were collected at 0, 1-15, 17, 21, and 24 h and 2, 3, 4, 7, 10, 14, 17, 21, and 28 d after (13)C-phytoene consumption. Plasma-unlabeled and plasma-labeled phytoene concentrations were determined using ultra-HPLC-quadrupole time-of-flight-mass spectrometry, and data were fit to a 7-compartment carotenoid kinetic model using WinSAAM 3.0.7 software. RESULTS: Subjects were compliant with a controlled phytoene diet, consuming a mean ± SE of 2.5 ± 0.6 mg/d, resulting in a plasma unlabeled phytoene concentration of 71 ± 14 nmol/L. A maximal plasma (13)C-phytoene concentration of 55.6 ± 5.9 nM was achieved 19.8 ± 9.2 h after consumption, and the plasma half-life was 2.3 ± 0.2 d. Compared with previous results for lycopene, phytoene bioavailability was nearly double at 58% ± 19%, the clearance rate from chylomicrons was slower, and the rates of deposition into and utilization by the slow turnover tissue compartment were nearly 3 times greater. CONCLUSIONS: Although only differing from lycopene by 4 double bonds, phytoene exhibits markedly different kinetic characteristics in human plasma, providing insight into metabolic processes contributing to phytoene enrichment in plasma and tissues compared with lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.