Quality of plant-based diets and frailty incidence: a prospective analysis of UK biobank participants.

BACKGROUND: Substantial evidence supports the inverse association between adherence to healthy dietary patterns and frailty risk. However, the role of plant-based diets, particularly their quality, is poorly known. OBJECTIVE: To examine the association of two plant-based diets with incidence of physical frailty in middle-aged and older adults. DESIGN: Prospective cohort. SETTING: United Kingdom. SUBJECTS: 24,996 individuals aged 40-70 years, followed from 2009-12 to 2019-22. METHODS: Based on at least two 24-h diet assessments, we built two diet indices: (i) the healthful Plant-based Diet Index (hPDI) and (ii) the unhealthful Plant-based Diet Index (uPDI). Incident frailty was defined as developing ≥3 out of 5 of the Fried criteria. We used Cox models to estimate relative risks (RR), and their 95% confidence interval (CI), of incident frailty adjusted for the main potential confounders. RESULTS: After a median follow-up of 6.72 years, 428 cases of frailty were ascertained. The RR (95% CI) of frailty was 0.62 (0.48-0.80) for the highest versus lowest tertile of the hPDI and 1.61 (1.26-2.05) for the uPDI. The consumption of healthy plant foods was associated with lower frailty risk (RR per serving 0.93 (0.90-0.96)). The hPDI was directly, and the uPDI inversely, associated with higher risk of low physical activity, slow walking speed and weak hand grip, and the uPDI with higher risk of exhaustion. CONCLUSIONS: In British middle-age and older adults, greater adherence to the hPDI was associated with lower risk of frailty, whereas greater adherence to the uPDI was associated with higher risk.

Salud cardiovascular en España basada en el Life's Essential 8 y su asociación con mortalidad general y cardiovascular: la cohorte ENRICA / Cardiovascular health in Spain based on the Life's Essential 8 and its association with all-cause and cardiovascular mortality: the ENRICA cohort

Introducción y objetivos: La American Heart Association ha desarrollado el índice Life's Essential 8 (LE8) para promover la prevención de la enfermedad cardiovascular (ECV). Este estudio examinó la distribución del LE8 en la población adulta española y su asociación con la mortalidad general y por ECV.MétodosSe analizaron datos de 11.616 personas de edad≥ años (el 50,5% mujeres) del estudio ENRICA, reclutadas en 2008-2010 y seguidas hasta 2020-2022. El LE8 incluye 8 parámetros (dieta, actividad física, exposición a la nicotina, sueño, índice de masa corporal, lípidos y glucosa en sangre y presión arterial) y se puntúa de 0 a 100. La asociación entre LE8 y mortalidad se resumió mediante hazardratio obtenidas de modelos de Cox.ResultadosEl 13,2% de los participantes (del 6,1 al 16,9% según la comunidad autónoma) mostraron mala salud cardiovascular (LE8≤49). Tras una mediana de 12,9 años de seguimiento, ocurrieron 908 muertes totales y, durante una mediana de 11,8 años de seguimiento, 207 muertes por ECV. Tras ajustar por los principales factores de confusión y comparados con el cuartil más bajo (menos saludable) de LE8, los HR (IC 95%) de mortalidad general en el segundo, el tercer y el cuarto cuartil fueron, respectivamente, 0,68 (0,56-0,83), 0,63 (0,51-0,78) y 0,53 (0,39-0,72). Los resultados correspondientes a la mortalidad cardiovascular, considerando riesgos competitivos de muerte, fueron 0,62 (0,39-0,97), 0,55 (0,32-0,93) y 0,38 (0,16-0,89).ConclusionesUna proporción sustancial de los españoles mostraron mala salud cardiovascular. Una mayor puntación de LE8, desde el segundo cuartil, se asocia con menores mortalidad general y cardiovascular. (AU)

Introduction and objectives: The American Heart Association has recently developed the Life's Essential 8 (LE8) score to encourage prevention of cardiovascular disease (CVD). This study assessed the distribution of LE8 in the Spanish adult population and its association with all-cause and CVD death.MethodsWe used data from 11 616 individuals aged 18 years and older (50.5% women) from the ENRICA study, recruited between 2008 and 2010 and followed up until 2020 to 2022. The LE8 score includes 8 metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids and glucose, and blood pressure) and ranges from 0 to 100. The association of LE8 score with mortality was summarized with hazard ratios (HR), obtained from Cox regression.ResultsIn total, 13.2% of participants (range, 6.1%-16.9% across regions) had low cardiovascular health (LE8≤49). During a median follow-up of 12.9 years, 908 total deaths occurred, and, during a median follow-up of 11.8 years, 207 CVD deaths were ascertained. After adjustment for the main potential confounders and compared with being in the least healthy (lowest) quartile of LE8, the HR (95%CI) of all-cause mortality for the second, third and fourth quartiles were 0.68 (0.56-0.83), 0.63 (0.51-0.78), and 0.53 (0.39-0.72), respectively. The corresponding figures for CVD mortality, after accounting for competing mortality risks, were 0.62 (0.39-0.97), 0.55 (0.32-0.93), and 0.38 (0.16-0.89).ConclusionsA substantial proportion of the Spanish population showed low cardiovascular health. A higher LE8 score, starting from the second quartile, was associated with lower all-cause and CVD mortality. (AU)

Dietary vitamin C intake and changes in frequency, severity, and location of pain in older adults.

BACKGROUND: Oral vitamin C supplementation has been associated with lower risk of chronic postsurgical pain. However, the effect of dietary vitamin C on pain in a non-surgical setting is unknown. We aimed to investigate the association between dietary vitamin C intake and changes over time in chronic pain and its characteristics in community-dwelling adults aged 60+ years. METHODS: We pooled data from participants of the Seniors-ENRICA-1 (n=864) and Seniors-ENRICA-2 (n=862) cohorts who reported pain at baseline or at follow-up. Habitual diet was assessed with a face-to-face diet history and dietary vitamin C intake was estimated using standard food composition tables. Pain changes over time were the difference between scores at baseline and follow-up obtained from a pain scale that considered the frequency, severity, and number of pain locations. Multivariable-adjusted relative risk ratios (RRR) were obtained using multinomial logistic regression. RESULTS: After a median follow-up of 2.6 years, pain worsened for 696 (40.3%) participants, improved for 734 (42.5%), and did not change for 296 (17.2%). Compared to the lowest tertile of energy-adjusted vitamin C intake, those in the highest tertile had a higher likelihood of overall pain improvement (RRR 1.61 [95% confidence interval 1.07-2.41],p-trend 0.02). Higher vitamin C intake was also associated with lower pain frequency (1.57 [1.00-2.47],p-trend=0.05) and number of pain locations (1.75 [1.13-2.70],p-trend=0.01). CONCLUSIONS: Higher dietary vitamin C intake was associated with improvement of pain and with lower pain frequency and number of pain locations in older adults. Nutritional interventions to increase dietary vitamin C intake with the aim of improving pain management require clinical testing.

Incorporating Cardiovascular Risk Assessment into Adolescent Reproductive Health and Primary Care Visits.

STUDY OBJECTIVE: This study aimed to evaluate the usability and feasibility of incorporating a cardiovascular risk assessment tool into adolescent reproductive health and primary care visits. DESIGN, SETTING, AND PARTICIPANTS: We recruited 60 young women ages 13-21 years to complete the HerHeart web-tool in 2 adolescent clinics in Atlanta, GA. MAIN OUTCOME MEASURES: Participants rated the tool's usability via the Website Analysis and Measurement Inventory (WAMMI, range 0-95) and their perceived 10-year and lifetime risk of cardiovascular disease (CVD) on a visual analog scale (range 0-10). Participants' perceived risk, blood pressure, and body mass index were measured at baseline and 3 months after enrollment. Health care providers (HCP, n = 5) completed the WAMMI to determine the usability and feasibility of incorporating the HerHeart tool into clinical practice. RESULTS: Adolescent participants and HCPs rated the tool's usability highly on the WAMMI with a median of 79 (interquartile range [IQR] 65, 84) and 76 (IQR 71, 84). At the baseline visit, participants' median perceived 10-year risk of a heart attack was 1 (IQR 0, 3), and perceived lifetime risk was 2 (IQR 0, 4). Immediately after engaging with the tool, participants' median perceived 10-year risk was 2 (IQR 1, 4.3), and perceived lifetime risk was 3 (IQR 1.8, 6). Thirty-one participants chose to set a behavior change goal, and 12 participants returned for follow-up. Clinical metrics were similar at the baseline and follow-up visits. CONCLUSION: HerHeart is acceptable to young women and demonstrates potential for changing risk perception and improving health habits to reduce risk of CVD. Future research should focus on improving retention in studies to promote cardiovascular health within reproductive health clinics.

Calcium-Driven In Silico Inactivation of a Human Olfactory Receptor.

Conformational changes as well as molecular determinants related to the activation and inactivation of olfactory receptors are still poorly understood due to the intrinsic difficulties in the structural determination of this GPCR family. Here, we perform, for the first time, the in silico inactivation of human olfactory receptor OR51E2, highlighting the possible role of calcium in this receptor state transition. Using molecular dynamics simulations, we show that a divalent ion in the ion binding site, coordinated by two acidic residues at positions 2.50 and 3.39 conserved across most ORs, stabilizes the receptor in its inactive state. In contrast, protonation of the same two acidic residues is not sufficient to drive inactivation within the microsecond timescale of our simulations. Our findings suggest a novel molecular mechanism for OR inactivation, potentially guiding experimental validation and offering insights into the possible broader role of divalent ions in GPCR signaling.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort.

INTRODUCTION: The impact of residential green spaces on cardiovascular health in older adults remains uncertain. METHODS: Cohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF-15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). RESULTS: After adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of -5.56 % (95 %CI: -9.77; -1.35), -5.05 % (-9.58; -0.53), -4.24 % (-8.19, -0.19), and -4.16 % (-7.59; -0.74), respectively; and mean differences in hs-TnT among diabetic participants of -8.03 % (95 %CI: -13.30; -2.77), -9.52 % (-16.08; -2.96), -8.05 % (-13.94, -2.16) and -5.56 % (-10.75; -0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. CONCLUSION: Increased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Lifestyle behaviors, social and economic disadvantages, and all-cause and cardiovascular mortality: results from the US National Health Interview Survey.

Aim: To examine the independent relationships of lifestyle and social and economic factors with all-cause and cardiovascular disease (CVD) mortality in a large representative sample of the US adult population. Furthermore, the association between the combination of lifestyle and social and economic factors with mortality was analyzed in detail. Methods: The sample included 103,314 participants with valid records and eligible for mortality follow-up, and information on lifestyle factors and social and economic disadvantages (NHIS waves 2000, 2005, 2010, and 2015). An unhealthy lifestyle score was constructed using information on physical activity, alcohol consumption, diet, and smoking status. Social and economic disadvantages were assessed using information on education, receipt of dividends, employment, family's home, and access to private health. Information on mortality data was determined by the National Death Index records. Results: Compared with favorable lifestyle, unfavorable lifestyle was associated with higher all-cause (HR 2.07; 95% CI 1.97-2.19) and CVD (HR 1.84; 95% CI 1.68-2.02) mortality. Higher social and economic disadvantages were also associated with higher all-cause (HR 2.44; 95% CI 2.30-2.59) and CVD mortality (HR 2.44; 95% CI 2.16-2.77), compared to low social and economic disadvantages. In joint associations, participants in the high social and economic disadvantage and unfavorable lifestyle showed a greater risk of all-cause (HR 4.06; 95% CI 3.69-4.47) and CVD mortality (HR 3.98; 95% CI 3.31-4.79). Conclusion: Lifestyle and social and economic disadvantages are associated with all-cause and CVD mortality. The risk of mortality increases as the number of social and economic disadvantages and unhealthy lifestyles increases.

Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women.

Importance: Previous research has found that vegetarian diets are associated with lower bone mineral density and higher risk of fractures, but these studies did not differentiate the quality of the plant-based foods. Objective: To examine the association between the quality of plant-based diets (not necessarily vegan but also omnivorous) and hip fracture risk among postmenopausal women in the Nurses' Health Study. Design, Setting, and Participants: This cohort study analyzed data from 70 285 postmenopausal women who participated in the US Nurses' Health Study from 1984 through 2014. Data were analyzed from January 1 to July 31, 2023. Main outcomes and Measures: Hip fractures were self-reported on biennial questionnaires. Diet was assessed every 4 years using a validated semiquantitative food frequency questionnaire. Plant-based diet quality was assessed using 2 previously established indices: the healthful Plant-Based Diet Index (hPDI), for which healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee) received positive scores, whereas less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, and sweets or desserts) and animal foods received reversed scores; and the unhealthful Plant-Based Diet Index (uPDI), for which positive scores were given to less healthy plant foods and reversed scores to healthy plant and animal foods. Quintile scores of 18 food groups were summed, with a theoretical range for both indices of 18 to 90 (highest adherence). Cox proportional hazards regression with time-varying covariates was used to compute hazard ratios (HRs) and 95% CIs for hip fracture. Results: In total, 70 285 participants (mean [SD] age, 54.92 [4.48] years; 100% White women) were included, and 2038 cases of hip fracture were ascertained during the study and for up to 30 years of follow-up. Neither the hPDI (HR for highest vs lowest quintile, 0.97 [95% CI, 0.83-1.14]) nor the uPDI (HR for highest vs lowest quintile, 1.02 [95% CI, 0.87-1.20]) for long-term diet adherence was associated with hip fracture risk. However, when examining recent intake for the highest vs lowest quintiles, the hPDI was associated with 21% lower risk of hip fracture (HR, 0.79 [95% CI, 0.68-0.92]; P = .02 for trend), and the uPDI was associated with 28% higher risk (1.28 [95% CI, 1.09-1.51]; P = .008 for trend). Conclusions and Relevance: Findings of this cohort study indicated that long-term adherence to healthful or unhealthful plant-based diets as assessed by hPDI and uPDI scores was not associated with hip fracture risk. Future research should clarify whether the associations observed with recent dietary intake are due to short-term effects of these dietary patterns, reverse causality, or both.

Exposure to residential traffic and trajectories of unhealthy ageing: results from a nationally-representative cohort of older adults.

BACKGROUND: Traffic exposure has been associated with biomarkers of increased biological ageing, age-related chronic morbidities, and increased respiratory, cardiovascular, and all-cause mortality. Whether it is associated with functional impairments and unhealthy ageing trajectories is unknown. METHODS: Nationally representative population-based cohort with 3,126 community-dwelling individuals aged ≥60 years who contributed 8,291 biannual visits over a 10 year period. Unhealthy ageing was estimated with a deficit accumulation index (DAI) based on the number and severity of 52 health deficits, including 22 objectively-measured impairments in physical and cognitive functioning. Differences in DAI at each follow-up across quintiles of residential traffic density (RTD) at 50 and 100 meters, and closest distance to a petrol station, were estimated using flexible marginal structural models with inverse probability of censoring weights. Models were adjusted for sociodemographic and time-varying lifestyle factors, social deprivation index at the census tract and residential exposure to natural spaces. RESULTS: At baseline, the mean (SD) age and DAI score of the participants were 69.0 (6.6) years and 17.02 (11.0) %, and 54.0% were women. The median (IQR) RTD at 50 and 100 meters were 77 (31-467) and 509 (182-1802) vehicles/day, and the mean (SD) distance to the nearest petrol station of 962 (1317) meters. The average increase in DAI (95%CI) for participants in quintiles Q2-Q5 (vs Q1) of RTD at 50 meters was of 1.51 (0.50, 2.53), 0.98 (-0.05, 2.01), 2.20 (1.18, 3.21) and 1.98 (0.90, 3.05), respectively. Consistent findings were observed at 100 meters. By domains, most of the deficits accumulated with increased RTD were of a functional nature, although RTD at 50 meters was also associated with worse self-reported health, increased vitality problems and higher incidence of chronic morbidities. Living closer to a petrol station was associated with a higher incidence of functional impairments and chronic morbidities. CONCLUSIONS: Exposure to nearby residential traffic is associated with accelerated trajectories of unhealthy ageing. Diminishing traffic pollution should become a priority intervention for adding healthy years to life in the old age.

Animal and vegetable protein intake and malnutrition in older adults: a multicohort study.

OBJECTIVES: Malnutrition is a global concern in older adults, as it negatively affects morbidity and mortality. While higher animal protein intake may help prevent and treat malnutrition, it might also increase the risk of chronic diseases and death. Conversely, vegetable protein intake might have a lower anabolic effect and not be as effective to improve nutritional status. We studied whether animal and vegetable protein intake are associated with changes in nutritional status in older adults. DESIGN: We used pooled data from two Spanish cohorts: the Seniors-ENRICA 1 and Seniors-ENRICA 2. SETTINGS AND PARTICIPANTS: 2,965 community-dwelling adults aged 62-92 years. MEASUREMENTS: Protein intake was estimated at baseline via an electronic, validated diet history. Nutritional status was assessed at baseline and after 2.6 years with the GLIM (Global Leadership Initiative on Malnutrition) phenotypic criteria: weight loss, low body mass index, and reduced muscle mass. The odds of improvements in nutritional status were assessed with logistic regression models, extensively adjusted for potential confounders. RESULTS: Higher animal and vegetable protein intake were associated with improvements in nutritional status [odds ratios (95% confidence intervals) per 0.25 g/kg/day were 1.15 (1.00, 1.32) and 1.77 (1.35, 2.32), respectively]. Cereal protein intake drove most of the latter association [2.07 (1.44, 2.98)]. Replacing 0.25 g/kg/day of total animal protein, meat, or fish protein (but not dairy or egg protein) with vegetable protein was associated with improvements in nutritional status [1.54 (1.13, 2.09), 1.70 (1.20, 2.41), and 1.77 (1.18, 2.64), respectively]. CONCLUSIONS: Higher animal and, especially, vegetable protein intake were associated with improvements in nutritional status in older adults. Replacing total animal protein, meat, or fish protein with vegetable protein may help improve malnutrition.

Association of a Mediterranean Lifestyle With All-Cause and Cause-Specific Mortality: A Prospective Study from the UK Biobank.

OBJECTIVE: To examine the association between the Mediterranean lifestyle and all-cause, cancer, and cardiovascular disease (CVD) mortality in a British population. PATIENTS AND METHODS: We studied 110,799 individuals 40 to 75 years of age from the UK Biobank cohort, free of CVD or cancer between 2009 and 2012 who were followed-up to 2021. The Mediterranean lifestyle was assessed at baseline through the Mediterranean Lifestyle (MEDLIFE) index, derived from the lifestyle questionnaire and diet assessments and comprising three blocks: (1) "Mediterranean food consumption," (2) "Mediterranean dietary habits," and (3) "physical activity, rest, social habits, and conviviality." Death information was retrieved from death register records. Cox regression models were used to analyze the study associations. RESULTS: During a median 9.4-year follow-up, 4247 total deaths, 2401 cancer deaths, and 731 CVD deaths were identified. Compared with the first quartile of the MEDLIFE index, increasing quartiles had HRs of 0.89 (95% CI, 0.81 to 0.97), 0.81 (95% CI, 0.74 to 0.89), and 0.71 (95% CI, 0.65 to 0.78) (P-trend<.001 for all-cause mortality). For cancer mortality, the quartiles had HRs of 0.90 (95% CI, 0.80 to 1.01), 0.83 (95% CI, 0.74 to 0.93), and 0.72 (95% CI, 0.64 to 0.82) (P-trend<.001). All MEDLIFE index blocks were independently associated with lower risk of all-cause and cancer death, and block 3 was associated with lower CVD mortality. CONCLUSION: Higher adherence to the Mediterranean lifestyle was associated with lower all-cause and cancer mortality in British middle-aged and older adults in a dose-response manner. Adopting a Mediterranean lifestyle adapted to the local characteristics of non-Mediterranean populations may be possible and part of a healthy lifestyle.

Mediterranean lifestyle index and 24-h systolic blood pressure and heart rate in community-dwelling older adults.

Specific foods, nutrients, dietary patterns, and physical activity are associated with lower blood pressure (BP) and heart rate (HR), but little is known about the joint effect of lifestyle factors captured in a multidimensional score. We assessed the association of a validated Mediterranean-lifestyle (MEDLIFE) index with 24-h-ambulatory BP and HR in everyday life among community-living older adults. Data were taken from 2,184 individuals (51% females, mean age: 71.4 years) from the Seniors-ENRICA-2 cohort. The MEDLIFE index consisted of 29 items arranged in three blocks: 1) Food consumption; 2) Dietary habits; and 3) Physical activity, rest, and conviviality. A higher MEDLIFE score (0-29 points) represented a better Mediterranean lifestyle adherence. 24-h-ambulatory BP and HR were obtained with validated oscillometric devices. Analyses were performed with linear regression adjusted for the main confounders. The MEDLIFE-highest quintile (vs Q1) was associated with lower nighttime systolic BP (SBP) (-3.17 mmHg [95% CI: -5.25, -1.08]; p-trend = 0.011), greater nocturnal-SBP fall (1.67% [0.51, 2.83]; p-trend = 0.052), and lower HR (-2.04 bpm [daytime], -2.33 bpm [nighttime], and -1.93 bpm [24-h]; all p-trend < 0.001). Results were similar for each of the three blocks of MEDLIFE and by hypertension status (yes/no). Among older adults, higher adherence to MEDLIFE was associated with lower nighttime SBP, greater nocturnal-SBP fall, and lower HR in their everyday life. These results suggest a synergistic BP-related protection from the components of the Mediterranean lifestyle. Future studies should determine whether these results replicate in older adults from other Mediterranean and non-Mediterranean countries.

Associations of physical activity type, volume, intensity, and changes over time with all-cause mortality in older adults: The Seniors-ENRICA cohorts.

OBJECTIVE: To assess the association of physical activity (PA) type, volume, intensity, and changes over time with all-cause mortality in older adults. METHODS: We used data from 3518 and 3273 older adults recruited in the Seniors-ENRICA-1 and 2 cohorts. PA was assessed with the EPIC questionnaire. Participants reported how many hours they spent a week in walking, cycling, gardening, do-it-yourself (DIY), sports, and housework. Then, time at each intensity (moderate PA [MPA], vigorous PA [VPA], moderate-to-vigorous PA [MVPA] and total PA) was calculated. Changes in PA were calculated from the date of the baseline interview to Wave 1. All-cause mortality was ascertained up January 31, 2022. Analyses were performed with Cox regression models, adjusting for the main confounders. RESULTS: Walking, gardening, sports, and housework was associated with lower mortality (ranged 20%-46%). Also, MPA, VPA, MVPA was associated with lower risk of mortality (ranged 28%-53%). Analyses of PA change showed that, compared no PA participation (at baseline nor Wave 1), maintain walking, sports, and housework (ranged 28%-53%) and maintaining MPA, VPA, and MVPA (ranged 32%-36%) levels was linked to decreased mortality risk. Those who increased, maintained, or even decreased total PA had lower mortality (57%, 52%, and 36%, respectively) than those with consistently very low PA. CONCLUSIONS: The lower mortality was observed in those with a high baseline level of total PA. Maintaining PA levels such as walking, gardening, and housework, or at all analyzed intensities, was related to lower mortality.

Blood Selenium Concentrations Are Inversely Associated with the Risk of Undernutrition in Older Adults.

BACKGROUND: Selenium is an essential trace element with an antioxidant and anti-inflammatory capacity that has been associated in experimental studies with beneficial effects on appetite control, the regulation of the gut microbiota, and control of the anabolic-catabolic balance. The main aim of the present study was to evaluate the association between circulating selenium concentrations and the risk of developing undernutrition in older adults. METHODS: This was a cohort study with 1398 well-nourished community-dwelling individuals aged ≥ 65 years residing in Spain in 2017, who were followed for a mean of 2.3 years. Whole blood selenium was measured at baseline using inductively coupled plasma-mass spectrometry. Undernutrition was assessed at baseline and at follow-up, and defined as having at least one of the three GLIM phenotypic criteria (involuntary weight loss, a low body mass index, and a reduced muscle mass) and at least one of the two etiologic criteria (reduced food consumption or nutrient assimilation and inflammation/disease burden). RESULTS: During the follow-up, 142 participants (11%) developed moderate undernutrition and 113 (8.8%) severe undernutrition. The standardized relative risks of moderate and severe undernutrition at the 75th percentile of Se levels versus the 25th were 0.90 and 0.70, respectively. In dose-response analyses, the risk of severe undernutrition decreased linearly with increasing selenium concentrations. This association was independent of protein intake or diet quality and was stronger among participants with a diagnosis of a musculoskeletal disorder. CONCLUSIONS: The results suggest that an adequate dietary selenium status is needed to prevent undernutrition in older adults. Also, this may open the door for clinical trials with selenium supplementation, at doses considered as safe, to prevent undernutrition.

Surviving & Thriving; a healthy lifestyle app for new US firefighters: usability and pilot study protocol.

In the United States (US), new firefighters' fitness and health behaviors deteriorate rapidly after fire academy graduation. Over the long-term, this increases their risks for chronic diseases. This study protocol describes the proposed usability testing and pilot study of a newly designed and developed healthy lifestyle smartphone app, "Surviving & Thriving", tailored towards young US firefighters. "Surviving & Thriving" will provide interactive educational content on four lifestyle factors; nutrition, sleep, physical activity, and resilience, and include a personalized journey, habit tracker, and elements of gamification to promote engagement and long-term healthy behavior change. The first phase of the app development entails alpha testing by the research team and pre-beta testing by a fire service expert panel which will help refine the app into a pre-consumer version. Upon completion of the full app prototype, beta 'usability' testing will be conducted among new fire academy graduates from two New England fire academies to collect qualitative and quantitative feedback via focus groups and satisfaction surveys, respectively. A last phase of piloting the app will evaluate the app's efficacy at maintaining/improving healthy lifestyle behaviors, mental health metrics, and physical fitness metrics. We will also evaluate whether firefighters' perceived "health cultures" scores (ratings of each fire station's/fire department's environments as to encouraging/discouraging healthy behaviors) modify the changes in health metrics after utilizing the app for three to six months. This novel user-friendly app seeks to help new firefighters maintain/improve their health and fitness more effectively, reducing their risk of lifestyle-related chronic disease. Firefighters who can establish healthy habits early in their careers are more likely to sustain them throughout their lives.

Cardiovascular health in Spain based on the Life's Essential 8 and its association with all-cause and cardiovascular mortality: the ENRICA cohort.

INTRODUCTION AND OBJECTIVES: The American Heart Association has recently developed the Life's Essential 8 (LE8) score to encourage prevention of cardiovascular disease (CVD). This study assessed the distribution of LE8 in the Spanish adult population and its association with all-cause and CVD death. METHODS: We used data from 11 616 individuals aged 18 years and older (50.5% women) from the ENRICA study, recruited between 2008 and 2010 and followed up until 2020 to 2022. The LE8 score includes 8 metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids and glucose, and blood pressure) and ranges from 0 to 100. The association of LE8 score with mortality was summarized with hazard ratios (HR), obtained from Cox regression. RESULTS: In total, 13.2% of participants (range, 6.1%-16.9% across regions) had low cardiovascular health (LE8 ≤ 49). During a median follow-up of 12.9 years, 908 total deaths occurred, and, during a median follow-up of 11.8 years, 207 CVD deaths were ascertained. After adjustment for the main potential confounders and compared with being in the least healthy (lowest) quartile of LE8, the HR (95%CI) of all-cause mortality for the second, third and fourth quartiles were 0.68 (0.56-0.83), 0.63 (0.51-0.78), and 0.53 (0.39-0.72), respectively. The corresponding figures for CVD mortality, after accounting for competing mortality risks, were 0.62 (0.39-0.97), 0.55 (0.32-0.93), and 0.38 (0.16-0.89). CONCLUSIONS: A substantial proportion of the Spanish population showed low cardiovascular health. A higher LE8 score, starting from the second quartile, was associated with lower all-cause and CVD mortality.

Association between a mediterranean lifestyle and Type 2 diabetes incidence: a prospective UK biobank study.

BACKGROUND: There is mounting evidence that the Mediterranean diet prevents type 2 diabetes, but little is known about the role of Mediterranean lifestyles other than diet and among non-Mediterranean populations. This work aimed to examine the association between a comprehensive Mediterranean-type lifestyle and type 2 diabetes incidence in a British adult population. METHODS: We used data from 112,493 individuals free of cardiovascular disease and type 2 diabetes mellitus, aged 40-69 years, from the UK Biobank cohort, who were followed from 2009 to 2010 to 2021. The Mediterranean lifestyle was assessed through the 25-item MEDLIFE index, which comprises three blocks: (a) "Mediterranean food consumption", (b) "Mediterranean dietary habits", (c) "Physical activity, rest, social habits, and conviviality". Diabetes incidence was obtained from clinical records. Cox proportional-hazards regression models were used to analyze associations and adjusted for the main potential confounders. RESULTS: After a median follow-up of 9.4 years, 2,724 cases of type 2 diabetes were ascertained. Compared to the first quartile of MEDLIFE adherence, the hazard ratios (95% confidence interval) for increasing quartiles of adherence were 0.90 (0.82-0.99), 0.80 (0.72-0.89) and 0.70 (0.62-0.79) (p-trend < 0.001). All three blocks of MEDLIFE were independently associated with lower risk of diabetes. CONCLUSIONS: Higher adherence to the MEDLIFE index was associated with lower risk of type 2 diabetes in the UK Biobank. A Mediterranean-type lifestyle, culturally adapted to non-Mediterranean populations, could help prevent diabetes.

Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.

The RNA-binding protein human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. This protein has been progressively recognized as a relevant therapeutic target for several pathologies, like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here, we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatic approaches, high-throughput virtual screening, and RNA-protein pulldown assays, we demonstrate that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits a dose-dependent HuR inhibition effect in binding experiments. Importantly, the chemical scaffold is new with respect to the currently known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Effect of a Nutrition Intervention on Mediterranean Diet Adherence Among Firefighters: A Cluster Randomized Clinical Trial.

Importance: US firefighters are a working population at risk of chronic diseases, including obesity, cardiovascular disease, and cancer. This risk may be mitigated by a healthy diet. Objective: To evaluate the effect of a Mediterranean nutrition intervention using a behavioral/environmental approach (firefighter/fire station/home) at the individual participant level. Design, Setting, and Participants: This 12-month cluster randomized clinical trial included US career firefighters from fire stations and homes within 2 Indiana fire departments. Participants were randomized by fire station to either Mediterranean diet or control (usual care). The study was conducted from October 2016 to December 2019, and data were analyzed in November 2022. Intervention: For the first 12 months of the study, firefighters located at fire stations randomized to the intervention group were provided with access to supermarket discounts and free samples of Mediterranean diet foods, online nutrition education platforms, email announcements and reminders, family and peer education and support, and chef demonstrations. Firefighters in fire stations allocated to the control group received no intervention and were instructed to follow their usual diet. Main Outcomes and Measures: Change in dietary habits at 12 months as measured by a modified Mediterranean diet score (range, 0 to 51 points) at baseline and 6-month and 12-month follow-up. Cardiometabolic parameters were secondary outcomes. Results: Of 485 included firefighters, 458 (94.4%) were male, and the mean (SD) age was 47 (7.5) years. A total of 241 firefighters (27 fire stations) were randomized to the Mediterranean nutrition intervention, and 244 (25 fire stations) were randomized to usual diet. Outcomes were analyzed using generalized linear mixed models for modified Mediterranean diet score at 6 months (n = 336) and 12 months (n = 260), adjusting for baseline age, sex, race and ethnicity, fire department, physical activity, and waist circumference. In the intervention group compared with the control group, the modified Mediterranean diet score significantly increased by 2.01 points (95% CI, 0.62-3.40; P = .005) at 6 months and by 2.67 points (95% CI, 1.14-4.20; P = .001) at 12 months. Among secondary outcomes, changes in cardiometabolic risk factors were not statistically significant at 1 year. Results from analyses with multilevel multiple imputation for missingness were similar. Conclusions and Relevance: In this Mediterranean nutrition intervention of multicomponent behavioral/environmental changes, career firefighters had increased adherence to a Mediterranean diet. Trial Registration: ClinicalTrials.gov Identifier: NCT02941757.

Fluoride permeation mechanism of the Fluc channel in liposomes revealed by solid-state NMR.

Solid-state nuclear magnetic resonance (ssNMR) methods can probe the motions of membrane proteins in liposomes at the atomic level and propel the understanding of biomolecular processes for which static structures cannot provide a satisfactory description. In this work, we report our study on the fluoride channel Fluc-Ec1 in phospholipid bilayers based on ssNMR and molecular dynamics simulations. Previously unidentified fluoride binding sites in the aqueous vestibules were experimentally verified by 19F-detected ssNMR. One of the two fluoride binding sites in the polar track was identified as a water molecule by 1H-detected ssNMR. Meanwhile, a dynamic hotspot at loop 1 was observed by comparing the spectra of wild-type Fluc-Ec1 in variant buffer conditions or with its mutants. Therefore, we propose that fluoride conduction in the Fluc channel occurs via a "water-mediated knock-on" permeation mechanism and that loop 1 is a key molecular determinant for channel gating.