SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing.

Mutations in the U2 snRNP component SF3B1 are prominent in myelodysplastic syndromes (MDSs) and other cancers and have been shown recently to alter branch site (BS) or 3' splice site selection in splicing. However, the molecular mechanism of altered splicing is not known. We show here that hsh155 mutant alleles in Saccharomyces cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal BS pre-mRNA substrates. We found that Hsh155p interacts directly with Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regions to HEAT (Huntingtin, EF3, PP2A, and TOR1) motifs in SF3B1 associated with disease mutations. Furthermore, we show that mutations in these motifs from both human disease and yeast genetic screens alter the physical interaction with Prp5p, alter branch region specification, and phenocopy mutations in Prp5p. These and other data demonstrate that mutations in Hsh155p and Prp5p alter splicing because they change the direct physical interaction between Hsh155p and Prp5p. This altered physical interaction results in altered loading (i.e., "fidelity") of the BS-U2 duplex into the SF3B complex during prespliceosome formation. These results provide a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease.

Association between a new dietary protein quality index and micronutrient intake adequacy: a cross-sectional study in a young adult Spanish Mediterranean cohort.

PURPOSE: There is no evidence of a dietary index that measures not only the quantity but also the quality of protein. The aim is to investigate the association between a new dietary protein quality index (PQI) and micronutrient intake adequacy in a Mediterranean cohort. DESIGN: We assessed 17,535 participants' diet at baseline using a semi-quantitative FFQ. The PQI was calculated according to the ratio of protein (g/d) sources: [fish, seafood, lean meat, pulses, eggs, nuts, low-fat dairy, and whole grains]/[red and ultra-processed meats, whole-fat or semi-skimmed dairy, potatoes and refined grains]. Participants were classified into quintiles of PQI. We evaluated the intakes of Fe, Cr, I, K, Mg, Ca, P, Na, Se, Zn and vitamins A, B1, B2, B3, B6, B12, C, E and folic acid. Micronutrient adequacy was evaluated using DRIs. Logistic regression analysis was used to assess the micronutrient adequacy according to quintiles of PQI. RESULTS: In this cross-sectional analysis, a total of 24.2% and 4.3% participants did not to meet DRIs in ≥ 4 and ≥ 8 micronutrients, respectively. The odds of failing to meet ≥ 4 and ≥ 8 DRI were lower in participants in the highest quintile of protein quality (OR = 0.22; IC 95% = 0.18, 0.26; P-trend < 0.001; and OR = 0.08; IC 95% = 0.05, 0.14; P-trend < 0.001, respectively) as compared to participants in the lowest quintile. CONCLUSION: Higher PQI was found to be strongly associated with better micronutrient intake adequacy in this Mediterranean cohort. The promotion of high-quality protein intake may be helpful for a more adequate intake of micronutrients. The odds of failing to meet certain numbers of DRIs were lower rather than saying lower risk.

High consumption of ultra-processed foods is associated with increased risk of micronutrient inadequacy in children: The SENDO project.

Due to its rising prevalence, which parallels that of ultraprocessed food (UPF) consumption, inadequate micronutrient intake in childhood is a public health concern. This study aimed to evaluate the association between UPF consumption and inadequate intake of 20 micronutrients in a sample of children from the Mediterranean area. Cross-sectional information from participants in the "Seguimiento del Niño para un Desarrollo Óptimo" (SENDO) project 2015-2021 was used. Dietary information was gathered with a previously validated 147-item semi-quantitative food frequency questionnaire and the NOVA system was used to classify food items. Children were classified by tertiles of energy intake from UPF. Twenty micronutrients were evaluated, and inadequate intake was defined using the estimated average requirement as a cutoff. Crude and multivariable adjusted OR (95% CI) for the inadequacy of ≥ 3 micronutrients associated with UPF consumption were calculated fitting hierarchical models to take into account intra-cluster correlation between siblings. Analyses were adjusted for individual and family confounders. This study included 806 participants (51% boys) with a mean age of 5 years old (SD: 0.90) and an average energy intake from UPF of 37.64% (SD: 9.59). An inverse association between UPF consumption and the intake of 15 out of the 20 micronutrients evaluated was found (p < 0.01). After the adjustment for individual and family confounders, compared with children in the first tertile of UPF consumption, those in the third tertile showed higher odds of inadequate intake of ≥ 3 micronutrients (OR 2.57; 95%CI [1.51-4.40]).    Conclusion: High UPF consumption is associated with increased odds of inadequate intake of micronutrients in childhood. What is Known: • Micronutrient deficiency is among the 20 most important risk factors for disease and affect around two billion people worldwide. • UPF are rich in total fat, carbohydrates and added sugar, but poor in vitamins and minerals. What is New: • Compared with children in the 1st tertile of UPF consumption, those in the 3rd tertile had 2.57 times higher odds (95% CI: 1.51-4.40) of inadequate intake of ≥ 3 micronutrients after adjusting for potential confounders. • The adjusted proportions of children with inadequate intake of ≥ 3 micronutrients were 23%, 27% and 35% in the 1st, 2nd, and 3rd tertiles of UPF consumption respectively.

Faith-Based Organizations' Support of Veteran Congregants at Risk for Mental Health Conditions and Suicide: A Qualitative Study of Clergy Experiences in Los Angeles County.

Faith-based organizations (FBOs) are often "gatekeepers" to mental health care for congregants at risk of mental illness and suicide, especially U.S. military Veterans, but data to inform better collaboration are needed. We conducted focus groups with clergy in Los Angeles County to understand the mental health support FBOs provide and barriers to collaboration with the mental healthcare system. Clergy detailed strategies used to support the mental health of Veteran congregants. Barriers included stigma, limits in clergy training, and incomplete knowledge about community and VA mental health resources. Results suggest strategies to improve collaboration between FBOs and the mental healthcare system in Los Angeles County.

Association between pre-conceptional carbohydrate quality index and the incidence of gestational diabetes: the SUN cohort study.

The aim of the study was to investigate the association between pre-gestational carbohydrate quality index (CQI) and the incidence of gestational diabetes mellitus (GDM). Data from the 'Seguimiento Universidad de Navarra' (SUN) cohort were used, which includes 3827 women who notified at least one pregnancy between December 1999 and December 2019. We used a validated semi-quantitative 136-item FFQ to evaluate dietary exposures at baseline and at 10-year follow-up. The CQI was defined by four criteria: glycaemic index, whole-grain/total-grain carbohydrate, dietary fibre intake and solid/total carbohydrate ratio. We fitted generalised estimating equations with repeated measurements of the CQI to assess its relationship with incident GDM. A total of 6869 pregnancies and 202 new cases of incident GDM were identified. The inverse association between the global quality of carbohydrate and the development of GDM was not statistically significant: OR the highest v. the lowest CQI category: 0·67, 95 % CI (0·40, 1·10), Pfor trend = 0·10. Participants at the highest CQI category and with daily carbohydrate amounts ≥50 % of total energy intake had the lowest incidence of GDM (OR = 0·29 (95 % CI (0·09, 0·89)) compared with those with the lowest quality (lowest CQI) and quantity (≤40 %). Further studies are needed to overcome the limitations of our study. Those studies should jointly consider the quality and the quantity of dietary carbohydrates, as the quality might be of importance, especially in women with a higher intake of carbohydrates.

Macronutrient quality index and cardiovascular disease risk in the Seguimiento Universidad de Navarra (SUN) cohort.

PURPOSE: To assess the association between a multi-dimensional Macronutrient Quality Index (MQI) and the risk of cardiovascular disease (CVD) in a Mediterranean cohort. METHODS: Prospective analyses among 18,418 participants (mean age 36 years, 60.8% women) of the Seguimiento Universidad de Navarra (SUN) cohort. Dietary intake information was obtained through a validated semi-quantitative food-frequency questionnaire (FFQ). The MQI (expressing high-quality macronutrient intake) was calculated based on three previously reported quality indices: the Carbohydrate Quality Index (CQI), the Fat Quality Index (FQI), and the Healthy Plate Protein source Quality Index (HPPQI). Adherence to the Mediterranean diet (MedDiet) and Provegetarian Diet was evaluated using the Trichopoulou index and the score proposed by Martínez-González, respectively. CVD was defined as new-onset stroke, myocardial infarction, or CVD death. RESULTS: After a median follow-up time of 14 years (211,744 person-years), 171 cases of CVD were identified. A significant inverse association was found between the MQI and CVD risk with multivariable-adjusted HR for the highest vs. the lowest quartile of 0.60 (95% IC, 0.38-0.96; Ptrend = 0.024). CONCLUSION: In this Mediterranean cohort, we found a significant inverse relationship between a multidimensional MQI (expressing high-quality macronutrient intake) and a lower risk of CVD.

A score appraising Paleolithic diet and the risk of cardiovascular disease in a Mediterranean prospective cohort.

PURPOSE: To assess the association between a score appraising adherence to the PaleoDiet and the risk of cardiovascular disease (CVD) in a Mediterranean cohort. METHODS: We included 18,210 participants from the Seguimiento Universidad de Navarra (SUN) cohort study. The PaleoDiet score comprised six food groups promoted within this diet (fruit, nuts, vegetables, eggs, meat and fish) and five food groups whose consumption is discouraged (cereals and grains, dairy products, legumes, culinary ingredients, and processed/ultra-processed foods). CVD was defined as acute myocardial infarction with or without ST elevation, non-fatal stroke and cardiovascular death. Cox proportional hazards models adjusted for potential confounders were fitted to assess the association between the PaleoDiet score and CVD risk, and the PaleoDiet and MedDiet indices to explore differences between both diets. RESULTS: During 12.2 years of follow-up, 165 incident CVD cases were confirmed. A significant inverse association was found between the PaleoDiet score and CVD (HR Q5 vs. Q1: 0.45, 95% CI 0.27-0.76, P for trend = 0.007). A weaker association that became non-significant was observed when the item for low consumption of ultra-processed foods was removed from the score. Joint analysis of PaleoDiet and MedDiet Trichopoulou scores suggested that the inverse association between PaleoDiet and CVD was mainly present when adherence to the MedDiet was also high (HR for high adherence vs low adherence to both diet scores: 0.22, 95% CI 0.08-0.64). CONCLUSIONS: Our findings suggest that the PaleoDiet may have cardiovascular benefits in participants from a Mediterranean country. Avoidance of ultra-processed foods seems to play a key role in this inverse association.

Healthful and unhealthful provegetarian food patterns and micronutrient intake adequacy in the SUN cohort.

OBJECTIVE: To investigate the association between different versions of a provegetarian food pattern (FP) and micronutrient inadequacy. DESIGN: Cross-sectional analysis. Dietary intake was assessed at baseline through a validated 136-item FFQ. Participants were classified according to groups of different versions of a provegetarian FP: overall, healthful and unhealthful. The prevalence of inadequate intake of vitamins B1, B2, B3, B6, B12, C, A, D, E, folic acid, Zn, I, Se, Fe, Ca, K, P, Mg and Cr was evaluated using the estimated average requirement (EAR) cut-point method and the probabilistic approach. Logistic regression analyses were conducted to estimate the probability of failing to meet EAR for either ≥ 3 or ≥ 6 micronutrients. SETTING: Seguimiento Universidad de Navarra (SUN) cohort. PARTICIPANTS: 17 825 Spanish adults. RESULTS: Overall, subjects in the highest group of the unhealthful provegetarian FP had the highest prevalence of inadequate dietary intake for every vitamin and mineral, compared to those in the lowest group. The adjusted OR of failing to meet ≥ 3 EAR (highest v. lowest group) was 0·65 (0·54, 0·69) for the overall, 0·27 (0·24, 0·31) for the healthful and 9·04 (7·57, 10·4) for the unhealthful provegetarian FP. CONCLUSION: A higher adherence to an overall and healthful provegetarian FP was inversely associated with the risk of failing to meet EAR values, whereas the unhealthful version was directly associated with micronutrient inadequacy. Provegetarian FP should be well planned, prioritising nutrient-dense plant foods and minimising ultra-processed and unhealthy ones.

Scoping review of Paleolithic dietary patterns: a definition proposal.

The Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.

Added sugars and sugar-sweetened beverage consumption, dietary carbohydrate index and depression risk in the Seguimiento Universidad de Navarra (SUN) Project.

The association between added sugars or sugar-sweetened beverage consumption and the risk of depression, as well as the role of carbohydrate quality in depression risk, remains unclear. Among 15 546 Spanish university graduates from the Seguimiento Universidad de Navarra (SUN) prospective cohort study, diet was assessed with a validated 136-item semi-quantitative FFQ at baseline and at 10-year follow-up. Cumulative average consumption of added sugars, sweetened drinks and an overall carbohydrate quality index (CQI) were calculated. A better CQI was associated with higher whole-grain consumption and fibre intake and lower glycaemic index and consumption of solid (instead of liquid) carbohydrates. Clinical diagnoses of depression during follow-up were classified as incident cases. Multivariable time-dependent Cox regression models were used to estimate hazard ratios (HR) of depression according to consumption of added sugars, sweetened drinks and CQI. We observed 769 incident cases of depression. Participants in the highest quartile of added sugars consumption showed a significant increment in the risk of depression (HR=1·35; 95 % CI 1·09, 1·67, P=0·034), whereas those in the highest quartile of CQI (upper quartile of the CQI) showed a relative risk reduction of 30 % compared with those in the lowest quartile of the CQI (HR=0·70; 95 % CI 0·56, 0·88). No significant association between sugar-sweetened beverage consumption and depression risk was found. Higher added sugars and lower quality of carbohydrate consumption were associated with depression risk in the SUN Cohort. Further studies are necessary to confirm the reported results.

Micronutrient intake adequacy and depression risk in the SUN cohort study.

PURPOSE: The aim of the study was to prospectively assess the association between micronutrient intake adequacy and risk of depression. METHODS: This dynamic cohort study involves Spanish university graduates (SUN Project). Dietary intake was assessed at baseline and after 10 years of follow-up with a semi-quantitative food frequency questionnaire. Micronutrient intake adequacy for vitamins B1, B2, B3, B6, B12, C, A, D, E, folic acid, zinc, iodine, selenium, iron, calcium, potassium, phosphorus, magnesium and chrome was estimated. Inadequate intake for each nutrient was defined when the intake of the nutrient was below the estimated average requirements (EAR) if available or the adequate intake levels, if EARs were not available. We compared participants with inadequate intake for ≥4 nutrients vs. those with one nutrient. Participants were classified as having incident depression if they had no previous history of depression or antidepressants use at baseline, but they reported during follow-up a new clinical diagnosis of depression by a physician, use of antidepressant drugs, or both. Time-dependent multivariable Cox regression models were fitted. RESULTS: After a median follow-up of 8.5 years, 953 new cases of depression were observed among 13,983 participants. Participants with inadequate intake for ≥4 nutrients showed a significantly higher risk of depression [multivariable hazard ratio (HR) = 1.37; 95% confidence interval (CI) 1.01-1.85]. When the analyses were updated with repeated assessments of intakes, the association was attenuated and it was no longer statistically significant (Multivariable HR = 1.11; 95% CI 0.82-1.51). CONCLUSIONS: Micronutrient inadequacy in four or more micronutrients could exert a moderate role in the development of depression.

Self-perceived level of competitiveness, tension and dependency and depression risk in the SUN cohort.

BACKGROUND: Emerging evidence suggests a possible etiologic role of certain personality traits (not necessary dysfunctional) in the risk of depression, but the longitudinal long-term available evidence is currently scarce. We longitudinally assessed whether 3 common personality traits (competitiveness, tension and dependency) were associated with the risk of depression after a maximum follow-up of 15 years. METHODS: We assessed 15,604 university graduates free of depression at baseline through a self-administered questionnaire including personality traits. Simple, Likert-type, questions with 11 possible answers ranging from 0 to 10 were used at baseline to assess the 3 personality traits. We compared participants with high scores (7-10) versus those with low scores (0-4). New medical diagnoses of depression during follow-up were used as the outcome. RESULTS: During a median follow-up of 10.1 y, we prospectively identified 902 new medical diagnoses of depression. The multivariable-adjusted hazard ratios (95% confidence intervals) for depression were 1.85 (1.52-2.24) for participants with higher baseline tension (7-10 versus 0 to 4), P-trend < 0.001; and 1.23 (1.06-1.44) for high versus low baseline dependence levels, P-trend = 0.004. Higher levels of competitiveness were marginally associated with lower risk of depression, with hazard ratio = 0.78 (0.61-1.01), P-trend = 0.105. CONCLUSION: A simple scoring system of personality traits shows an independent association with the future occurrence of depression. This finding underscores, with now prospective evidence, the importance of personality traits in the aetiology of depression and can provide a clinically useful tool for gathering valid information about depression-related personality traits.

Ten-Year Changes in Healthy Eating Attitudes in the SUN Cohort.

OBJECTIVE: The objective of this study was to assess the within-subject longitudinal changes in self-perceived healthy eating attitudes after 10 years of follow-up and to identify predictors of long-term changes in a middle-aged adult cohort. METHODS: Four thousand five hundred seventy-two participants completed a validated food frequency questionnaire (FFQ) at baseline and after 10 years of follow-up. The FFQ was expanded with a brief 10-item questionnaire about eating attitudes with 2 possible answers: yes or no. A baseline score and a 10-year score were calculated with these 10 items (range from 0 to 10). Participants were categorized into 3 groups according to this score. Linear and logistic regressions were used to examine changes at follow-up and associations between baseline characteristics and improvement in the score. RESULTS: After 10 years of follow-up, a statistically significant favorable change (p < 0.001) was achieved in all questions about eating attitudes, particularly in these items: "Do you try to eat less sweets and pastries?" (12%), "Do you try to eat less meat?" (11.1%), and "Do you try to reduce your fat intake?" (10%). Being female (odds ratio [OR] = 1.19, 95% confidence interval [CI], 1.02-1.39), being 35-50 or ≥ 50 years old (OR = 1.24, 95% CI, 1.07-1.44 and OR = 1.74, 95% CI, 1.38-2.18, respectively), a high level of physical activity (OR for third vs first tertile = 1.20, 95% CI, 1.02-1.41), and a higher Mediterranean diet score (OR for second and third tertiles = 1.18, 95% CI, 1.01-1.37 and OR = 1.26, 95% CI, 1.04-1.52, respectively) were associated with a higher probability of improving the eating attitudes score, while a low body mass index (BMI; OR = 0.71, 95% CI, 0.51-1.00) and snacking between meals (OR = 0.84, 95% CI, 0.73-0.97) were associated with a lower probability of improving their score. CONCLUSIONS: The eating attitudes of the participants in the Seguimiento Universidad de Navarra (SUN) cohort became more favorable after 10 years of follow-up. Certain sociodemographic or clinical variables may predict a positive change.

Healthy-eating attitudes and the incidence of cardiovascular disease: the SUN cohort.

There is an emerging use of brief dietary questionnaires to investigate diet-health relation. We prospectively assess the association between eating attitudes (yes/no) and incident cardiovascular disease (CVD) in 19,138 participants of the Seguimiento Universidad de Navarra (SUN) Cohort. We calculated a baseline healthy-eating attitudes score (in quartiles), positively weighting answers on more fruit, vegetables, fish and fiber and less meat, sweets and pastries, fat, butter, fatty meats and added sugar in drinks. We observed 139 incident cases of CVD. A higher score was associated with a lower risk of CVD [3-5 points Hazard Ratio (HR): 0.38 (95% confidence interval: 0.18-0.81); 6-8 points: 0.57 (0.29-1.12); 9-10 points: 0.31 (0.15-0.67), compared to 0-2 points]. Key contributors were the attitude to increase fruit [HR: 0.59 (0.40-0.87)], vegetables [HR: 0.57 (0.29-1.12)] and fiber intake [HR: 0.69 (0.48-0.98)]. Brief questionnaire on attitudes towards healthy-eating may be a useful tool for the primary prevention of CVD.

Beneficial changes in food consumption and nutrient intake after 10 years of follow-up in a Mediterranean cohort: the SUN project.

BACKGROUND: The assessment of changes in dietary habits provides interesting information on whether or not the observed trends are in line with accepted nutritional guidelines. The objective was to evaluate within-subject longitudinal changes in food consumption and nutrient intake and in a 10-year follow-up study. METHODS: The SUN (Seguimiento Universidad de Navarra) project is a prospective Spanish cohort study. Diet was assessed using a 136-item food-frequency questionnaire (FFQ), previously validated in Spain. The participants were 3036 university graduates (55.8 % women) of Spain and the main outcome measures the changes in dietary quality and in food consumption and nutrient intake. Paired t-tests and conditional logistic regression models were used to evaluate within-subject longitudinal dietary changes and the risk of inadequacy respectively, after 10 years of follow-up. RESULTS: During follow-up, participants showed a relevant and significant increase (p < 0.001) in the consumption of fruits (7.4 %), vegetables (8.6 %), low-fat dairy products (35.2 %), lean meat (12.4 %), fish (2.9 %), whole grains (53.2 %), nuts (52.4 %) and a significant decrease in legumes (-7.4 %), whole-fat dairy products (-44.2 %), red meat (-17.6 %), sugar-sweetened beverages (-58.7 %) and wine (-11.9 %). With respect to nutrients, we found a higher proportion of carbohydrates (3.6 %) and fiber (7.4 %) and a decrease in total energy intake (2.7 %), total fat (-4.5 %), SFA (-9.4 %), MUFA (-4.9 %), PUFA (-12.7 %), w-3 and w-6 fatty acids (-9.1 and -20.5 % respectively) and cholesterol (-9.6 %). CONCLUSIONS: In this Mediterranean cohort study, mainly beneficial changes in the consumption of most foods and macronutrients were observed after 10 years of follow-up.

Diagnosis and management with botulinum toxin in 11 cases of laryngeal synkinesis.

Laryngeal synkinesis is a vocal fold movement disorder produced by a misdirected reinnervation after a recurrent laryngeal nerve injury. Its symptoms differ greatly between patients, requiring diverse therapeutical approaches. We aim to describe our experience in the diagnosis and treatment of different laryngeal synkinesis presentations. 11 patients diagnosed between 2011 and 2014 in a tertiary referral center with laryngeal synkinesis confirmed by laryngeal electromyography were included in our study. All medical records and laryngoscopic and electromyographic data were reviewed retrospectively. Four patients had previous unilateral vocal fold palsy and seven had a bilateral palsy with different degrees of clinical involvement. All of them showed paradoxical movements during inhalation in videofibrolaryngoscopic examination. Laryngeal electromyography confirmed the diagnosis of laryngeal synkinesis. Dyspnea was the main presentation symptom. Three patients with mild symptoms were not treated. Patients with unilateral vocal fold immobility were successfully treated with periodic botulinum toxin injections. Patients with bilateral immobility had a good initial response to botulinum toxin, although in some of them, a posterior cordectomy had to be finally performed. In conclusion, laryngeal synkinesis is a heterogeneous clinic entity that appears in patients with unilateral or bilateral vocal fold paralysis. Videofibrolaryngoscopy and laryngeal electromyography are essential to a correct diagnosis. Botulinum toxin injections are the main treatment for symptomatic cases, even if in bilateral palsy cases more aggressive treatments are often required.

Two carotenoid oxygenases contribute to mammalian provitamin A metabolism.

Mammalian genomes encode two provitamin A-converting enzymes as follows: the ß-carotene-15,15'-oxygenase (BCO1) and the ß-carotene-9',10'-oxygenase (BCO2). Symmetric cleavage by BCO1 yields retinoids (ß-15'-apocarotenoids, C20), whereas eccentric cleavage by BCO2 produces long-chain (>C20) apocarotenoids. Here, we used genetic and biochemical approaches to clarify the contribution of these enzymes to provitamin A metabolism. We subjected wild type, Bco1(-/-), Bco2(-/-), and Bco1(-/-)Bco2(-/-) double knock-out mice to a controlled diet providing ß-carotene as the sole source for apocarotenoid production. This study revealed that BCO1 is critical for retinoid homeostasis. Genetic disruption of BCO1 resulted in ß-carotene accumulation and vitamin A deficiency accompanied by a BCO2-dependent production of minor amounts of ß-apo-10'-carotenol (APO10ol). We found that APO10ol can be esterified and transported by the same proteins as vitamin A but with a lower affinity and slower reaction kinetics. In wild type mice, APO10ol was converted to retinoids by BCO1. We also show that a stepwise cleavage by BCO2 and BCO1 with APO10ol as an intermediate could provide a mechanism to tailor asymmetric carotenoids such as ß-cryptoxanthin for vitamin A production. In conclusion, our study provides evidence that mammals employ both carotenoid oxygenases to synthesize retinoids from provitamin A carotenoids.

Association between dietary carbohydrate intake quality and micronutrient intake adequacy in a Mediterranean cohort: the SUN (Seguimiento Universidad de Navarra) Project.

Epidemiological research confirms that the prevalence of suboptimal micronutrient intakes across Europe is an emerging concern in terms of public health. The aim of the present study was to investigate the association between a new index of carbohydrate (CHO) quality and micronutrient intake adequacy in the 'Seguimiento Universidad de Navarra (SUN)' cohort. The baseline assessment extended from 1999 to March 2012. We assessed 16,841 participants who completed a validated 136-item semi-quantitative FFQ at baseline. We created a new index to evaluate CHO quality for the following four criteria: dietary fibre intake; glycaemic index; whole grains:total grains ratio; solid CHO:total CHO ratio. The subjects were classified into quintiles according to this index. We evaluated the intakes of Zn, I, Se, Fe, Ca, K, P, Mg, Cr and vitamins B1, B2, B3, B6, B12, C, A, D, E and folic acid. The probability of intake adequacy was evaluated using the estimated average requirement cut-point approach and the probabilistic approach. Logistic regression analysis was used to assess the nutritional adequacy according to the CHO quality index (CQI). Participants in the highest quintile of CQI were found to have the lowest prevalence of inadequacy. A higher quality of CHO intake was found to be associated with a lower risk of nutritional inadequacy in comparison with the lowest quintile of CQI (adjusted OR 0·06, 95 % CI 0·02, 0·16; P for trend < 0·001). A higher CQI was found to be strongly associated with better micronutrient intake adequacy in the young Mediterranean cohort, stressing the importance of focusing nutritional education not only on CHO quantity, but also on quality.

Association between overall quality of macronutrients and incidence of overweight and obesity in the SUN (Seguimiento Universidad de Navarra) cohort.

INTRODUCTION: no previous large prospective studies have assessed the global quality of macronutrients in association with the risk of overweight/obesity. OBJECTIVE: to prospectively assess the association of an overall macronutrient quality index (MQI) with weight change and the incidence of overweight/obesity in the Seguimiento Universidad de Navarra (SUN) cohort. METHODS: the diet of 9,344 Spanish university graduates (mean age: 36.5 [SD, 11.1]) was assessed through a validated 136-item food frequency questionnaire. The MQI was calculated as the sum of the Carbohydrate Quality Index, the Fat Quality Index, and the Healthy Plate Protein Quality Index. Participants were classified into groups according to MQI. Incident overweight/obesity was defined if follow-up questionnaires indicated BMI was ≥ 25 kg/m2. Multiple linear regression models and Cox proportional hazard models were used to assess the average yearly weight change and the risk of overweight/obesity over follow-up time. RESULTS: 2,465 cases of incident overweight/obesity were identified (median follow-up: 10.7 years). Increasing MQI was significantly associated with lower annual weight gain (g): ß coefficient: -99.0, (95 % CI: -173.6 to -24.5) in the Q4 vs Q1, p for trend = 0.007. In the fully adjusted model the incidences of overweight/obesity in Q4 and Q1 were 21.7 % (431 cases) and 29.3 % (954 cases), respectively. The adjusted HR was 0.87 (95 % CI, 0.77-0.98, p for trend = 0.036). When we used repeated analyses updating the MQI after 10 years of follow-up, results remained similar. CONCLUSIONS: a significant inverse association between a multidimensional MQI and the risk of overweight/obesity was found in this Mediterranean cohort of adults.

Association between the Carbohydrate Quality Index (CQI) and Nutritional Adequacy in a Pediatric Cohort: The SENDO Project.

Suboptimal micronutrient intake in children remains a public health concern around the world. This study examined the relationship between a previously defined dietary carbohydrate quality index (CQI) and the risk of micronutrient intake inadequacy in a pediatric cohort of Spanish preschoolers. Children aged 4-5 years old were recruited at their medical center or at school, and information on sociodemographic, dietary, and lifestyle variables were collected through a self-administered online questionnaire. Dietary information was obtained from a validated 147-item semi-quantitative food frequency questionnaire. We calculated the CQI and categorized participants into quartiles according to their scores. We assessed the intakes of 20 micronutrients and evaluated the probability of intake inadequacy by using the estimated average requirement cut-off point. Generalized estimating equations were used to adjust for potential confounders and account for the intra-cluster correlations between siblings. The adjusted proportions of children with an inadequate intake of ≥three micronutrients were 23%, 12%, 11%, and 9% in the first, second, third, and fourth quartiles of the CQI, respectively. Children in the highest quartile of the CQI had 0.22-fold lower odds (95% CI 0.10-0.48) of having ≥three inadequate micronutrient intakes than their peers in the lowest quartile. These findings reinforce the relevance of carbohydrate quality in children's diets.