Replacement of Saturated Fatty Acids from Meat by Dairy Sources in Relation to Incident Cardiovascular Disease: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.

BACKGROUND: Prospective observational data revealed lower cardiovascular disease (CVD) incidence with modeled replacement of saturated fatty acids (SFA) from total meat by total dairy, but it is unknown what the associations are of replacing SFA from types of meat by types of dairy with CVD incidence. OBJECTIVES: This study aimed to investigate the associations of replacing SFA from total, red, processed, and poultry meat by SFA from total dairy, milk, cheese, and yogurt with the incidence of CVD. METHODS: We analyzed longitudinal data from 21,841 participants of the European Prospective Investigation into Cancer and Nutrition-Norfolk study (56.4% female; age, 40-79 years). Dietary data were collected by food frequency questionnaires at baseline (1993-1997). Incident fatal or nonfatal CVD (n = 5902), coronary artery disease (CAD; n = 4215), stroke (total: n = 2544; ischemic: n = 1113; hemorrhagic: n = 449) were identified up to 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression for the risk associated with replacement of 2.5% of energy from SFA from meat by dairy, adjusted for sociodemographic, lifestyle, energy, dietary, and cardiometabolic factors. RESULTS: Replacing SFA from total meat by total dairy was associated with a lower CVD incidence (HR: 0.89; 95% CI: 0.82, 0.96) and CAD (HR: 0.88; 95% CI: 0.80, 0.96). Replacing SFA from processed meat by cheese was associated with lower CVD (HR: 0.77; 95% CI: 0.68, 0.88); CAD (HR: 0.77; 95% CI: 0.66, 0.90), and stroke (HR: 0.81; 95% CI: 0.67, 0.99). Similarly, replacing SFA from red meat by cheese was associated with lower CVD (HR: 0.86; 95% CI: 0.76, 0.97). Higher incidence of stroke was found with replacement of SFA from poultry by milk (HR: 2.06; 95% CI: 1.09, 3.89), yogurt (HR: 2.55; 95% CI: 1.27, 5.13), or cheese (HR: 1.96; 95% CI: 1.04, 3.70), but the CI were relatively large, owing to low, narrow range of poultry SFA intake. CONCLUSIONS: Findings indicate that different SFA-rich foods at baseline have differential associations with CVD risk. If confirmed by further studies, these findings could be used to inform specific food-based dietary guidance.

Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.

BACKGROUND: Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive. OBJECTIVES: To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke. METHODS: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested. RESULTS: Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke. CONCLUSION: Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.

Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries.

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study. METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants. RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing. CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

Plasma Metabolites Related to the Consumption of Different Types of Dairy Products and Their Association with New-Onset Type 2 Diabetes: Analyses in the Fenland and EPIC-Norfolk Studies, United Kingdom.

SCOPE: To identify metabolites associated with habitual dairy consumption and investigate their associations with type 2 diabetes (T2D) risk. METHODS AND RESULTS: Metabolomics assays were conducted in the Fenland (n = 10,281) and EPIC-Norfolk (n = 1,440) studies. Using 82 metabolites assessed in both studies, we developed metabolite scores to classify self-reported consumption of milk, yogurt, cheese, butter, and total dairy (Fenland Study-discovery set; n = 6035). Internal and external validity of the scores was evaluated (Fenland-validation set, n = 4246; EPIC-Norfolk, n = 1440). The study assessed associations between each metabolite score and T2D incidence in EPIC-Norfolk (n = 641 cases; 16,350 person-years). The scores classified low and high consumers for all dairy types with internal validity, and milk, butter, and total dairy with external validity. The scores were further associated with lower incident T2D: hazard ratios (95% confidence interval) per standard deviation: milk 0.71 (0.65, 0.77); butter 0.62 (0.57, 0.68); total dairy 0.66 (0.60, 0.72). These associations persisted after adjustment for known dairy-fat biomarkers. CONCLUSION: Metabolite scores identified habitual consumers of milk, butter, and total dairy products, and were associated with lower T2D risk. These findings hold promise for identifying objective indicators of the physiological response to dairy consumption.

Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Suppression of BMP signaling restores mitral cell development impaired by FGF signaling deficits in mouse olfactory bulb.

Fibroblast growth factors (FGFs) and bone morphogenic proteins (BMPs) play various important roles in the development of the central nervous system. However, the roles of FGF and BMP signaling in the development of the olfactory bulb (OB) are largely unknown. In this study, we first showed the expression of FGF receptors (FGFRs) and BMP receptors (BMPRs) in OB RGCs, radial glial cells (RGCs) in the developing OB, which generate the OB projection neurons, mitral and tufted cells. When the FGF signaling was inhibited by a dominant-negative form of FGFR1 (dnFGFR1), OB RGCs accelerated their state transition to mitral cell precursors without affecting their transcription cascade and fate. However, the mitral cell precursors could not radially migrate to form the mitral cell layer (MCL). In addition, FGF signaling inhibition reduced the expression of a BMP antagonist, Noggin, in the developing OB. When BMP signaling was suppressed by the ectopic expression of Noggin or a dominant-negative form of BMPR1a (dnBMPR1a) in the developing OB, the defect in MCL formation caused by the dnFGFR1 was rescued. However, the dnBMPR1a did not rescue the accelerated state transition of OB RGCs. These results demonstrate that FGF signaling is important for OB RGCs to maintain their self-renewal state and MCL formation. Moreover, the suppression of BMP signaling is required for mitral cells to form the MCL. This study sheds new light on the roles of FGFs and BMPs in OB development.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

n-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies.

BACKGROUND: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVES: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS: We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (aged ≥18 y). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS: Biomarkers of n-6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Nutritional Intake after Liver Transplant: Systematic Review and Meta-Analysis.

Cardiovascular disease and its concurrent risk factors are prevalent after liver transplant (LT). Most of these risk factors are modifiable by diet. We aimed to synthesise the literature reporting the nutritional intake of liver transplant recipients (LTR) and the potential determinants of intake. We performed a systematic review and meta-analyses of studies published up until July 2021 reporting the nutritional intake of LTR. The pooled daily mean intakes were recorded as 1998 (95% CI 1889, 2108) kcal, 17 (17, 18)% energy from protein, 49 (48, 51)% energy from carbohydrates, 34 (33, 35)% energy from total fat, 10 (7, 13)% energy from saturated fat, and 20 (18, 21) g of fibre. The average fruit and vegetable intake ranged from 105 to 418 g/day. The length of time post-LT and the age and sex of the cohorts, as well as the continent and year of publication of each study, were sources of heterogeneity. Nine studies investigated the potential determinants of intake, time post-LT, gender and immunosuppression medication, with inconclusive results. Energy and protein requirements were not met in the first month post-transplant. After this point, energy intake was significantly higher and remained stable over time, with a high fat intake and low intake of fibre, fruits and vegetables. This suggests that LTR consume a high-energy, low-quality diet in the long term and do not adhere to the dietary guidelines for cardiovascular disease prevention.

A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.

BACKGROUND: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P-value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations (P-value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was -0·63 (95 % CI - 1·02, -0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity -0·43(-0·82, -0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes.

The Impact of Controlling Nutritional Status (CONUT) score on functional prognosis in hospitalized elderly patients with acute osteoporotic vertebral fractures.

BACKGROUND: Nutritional status, which is associated with osteoporosis and muscle weakness is considered an important factor in the management of acute osteoporotic vertebral fracture (AOVF). However, few reports have investigated the nutritional status of hospitalized patients with AOVF and the impact of malnutrition on their functional prognosis. This study aimed to evaluate the nutritional status of hospitalized elderly patients with AOVF using the Controlling Nutritional Status (CONUT) score and to determine the usefulness of the CONUT score in predicting their functional prognosis. METHODS: The CONUT score on admission was retrospectively calculated for 134 hospitalized elderly patients (mean age 83 ± 7.6 years, 66% female) with AOVF who received conservative treatment between 2017 and 2020. Functional outcome was assessed by comparing ambulatory ability before the onset of AOVF and upon discharge. Patients were divided into two groups: CONUT-high ( ≥ 4) and CONUT-low ( ≤ 3), according to receiver operating characteristic (ROC) analysis to predict decline in ambulatory ability upon discharge. Logistic regression analysis was performed to obtain odds ratios (OR) and 95% confidence intervals (CI) of the relationships between the nutritional status and ambulatory ability. The discriminative power of the CONUT score was then compared with other nutritional assessment tools such as the Geriatric Nutritional Risk Index (GNRI) and prognostic nutritional index (PNI) by ROC analysis. RESULTS: 81% of hospitalized patients with an AOVF were malnourished at the time of admission. The CONUT-high group had a significantly higher rate of decline in ambulatory ability (P < 0.001) than the CONUT-low group. Logistic regression analysis revealed the CONUT score ( ≥ 4) as an independent risk factor for a decline in ambulatory ability (OR 3.44, 95% CI 1.61-7.37, P = 0.0014). ROC analysis showed that the area under the curve (AUC) for the CONUT score (AUC = 0.724) was significantly greater than that for the GNRI (AUC = 0.624, P = 0.021) and PNI (AUC = 0.636, P = 0.0008). CONCLUSIONS: This study showed that 81% of hospitalized elderly patients with AOVFs were malnourished and that the CONUT score was a useful predictive factor of functional prognosis.

Effects of nasal inflammation on the olfactory bulb.

Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases as some of the most common medical conditions in the world. Exposure to environmental pathogens and toxicants via the nasal cavity can result in a severe inflammatory state commonly observed in these conditions. It is well understood that the epithelial and neuronal cells lining the olfactory mucosa, including olfactory sensory neurons (OSNs), are significantly damaged in these diseases. Prolonged inflammation of the nasal cavity may also lead to hyposmia or anosmia. Although various environmental agents induce inflammation in different ways via distinct cellular and molecular interactions, nasal inflammation has similar consequences on the structure and homeostatic function of the olfactory bulb (OB) which is the first relay center for olfactory information in the brain. Atrophy of the OB occurs via thinning of the superficial OB layers including the olfactory nerve layer, glomerular layer, and superficial external plexiform layer. Intrabulbar circuits of the OB which include connectivity between OB projection neurons, OSNs, and interneurons become significantly dysregulated in which synaptic pruning and dendritic retraction take place. Furthermore, glial cells and other immune cells become hyperactivated and induce a state of inflammation in the OB which results in upregulated cytokine production. Moreover, many of these features of nasal inflammation are present in the case of SARS-CoV-2 infection. This review summarizes the impact of nasal inflammation on the morphological and physiological features of the rodent OB.

Association between circulating 25-hydroxyvitamin D and cardiometabolic risk factors in adults in rural and urban settings.

BACKGROUND: An inverse association between vitamin D status and cardiometabolic risk has been reported but this relationship may have been affected by residual confounding from adiposity and physical activity due to imprecise measures of these variables. We aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk factors, with adjustment for objectively-measured physical activity and adiposity. METHODS: This was a population-based cross-sectional study in 586 adults in Cameroon (63.5% women). We assessed markers of glucose homoeostasis (fasting blood glucose (BG), 2 h post glucose load BG, HOMA-IR)) and computed a metabolic syndrome score by summing the sex-specific z-scores of five risk components measuring central adiposity, blood pressure, glucose, HDL cholesterol and triglycerides. RESULTS: Mean±SD age was 38.3 ± 8.6 years, and serum 25(OH)D was 51.7 ± 12.5 nmol/L. Mean 25(OH)D was higher in rural (53.4 ± 12.8 nmol/L) than urban residents (50.2 ± 12.1 nmol/L), p = 0.002. The prevalence of vitamin D insufficiency (<50 nmol/L) was 45.7%. There was an inverse association between 25(OH)D and the metabolic syndrome score in unadjusted analyses (ß = -0.30, 95% CI -0.55 to -0.05), which became non-significant after adjusting for age, sex, smoking status, alcohol intake and education level. Serum 25(OH)D was inversely associated with fasting BG (-0.21, -0.34 to -0.08)), which remained significant after adjustment for age, sex, education, smoking, alcohol intake, the season of data collection, BMI and physical activity (-0.17, -0.29 to -0.06). There was an inverse association of 25(OH)D with 2-h BG (-0.20, -0.34 to -0.05) and HOMA-IR (-0.12, -0.19 to -0.04) in unadjusted analysis, but these associations became non-significant after adjustment for potential confounders. CONCLUSION: Vitamin D insufficiency was common in this population. This study showed an inverse association between vitamin D status and fasting glucose that was independent of potential confounders, including objectively measured physical activity and adiposity, suggesting a possible mechanism through insulin secretion.

Development and validation of a metabolite score for red meat intake: an observational cohort study and randomized controlled dietary intervention.

BACKGROUND: Self-reported meat consumption is associated with disease risk but objective assessment of different dimensions of this heterogeneous dietary exposure in observational and interventional studies remains challenging. OBJECTIVES: We aimed to derive and validate scores based on plasma metabolites for types of meat consumption. For the most predictive score, we aimed to test whether the included metabolites varied with change in meat consumption, and whether the score was associated with incidence of type 2 diabetes (T2D) and other noncommunicable diseases. METHODS: We derived scores based on 781 plasma metabolites for red meat, processed meat, and poultry consumption assessed with 7-d food records among 11,432 participants in the EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort. The scores were then tested for internal validity in an independent subset (n = 853) of the same cohort. In focused analysis on the red meat metabolite score, we examined whether the metabolites constituting the score were also associated with meat intake in a randomized crossover dietary intervention trial of meat (n = 12, Lyon, France). In the EPIC-Norfolk study, we assessed the association of the red meat metabolite score with T2D incidence (n = 1478) and other health endpoints. RESULTS: The best-performing score was for red meat, comprising 139 metabolites which accounted for 17% of the explained variance of red meat consumption in the validation set. In the intervention, 11 top-ranked metabolites in the red meat metabolite score increased significantly after red meat consumption. In the EPIC-Norfolk study, the red meat metabolite score was associated with T2D incidence (adjusted HR per SD: 1.17; 95% CI: 1.10, 1.24). CONCLUSIONS: The red meat metabolite score derived and validated in this study contains metabolites directly derived from meat consumption and is associated with T2D risk. These findings suggest the potential for objective assessment of dietary components and their application for understanding diet-disease associations.The trial in Lyon, France, was registered at clinicaltrials.gov as NCT03354130.

Using genetic variation to disentangle the complex relationship between food intake and health outcomes.

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons.

Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the olfactory bulb (OB). Although chronic rhinosinusitis patients have smaller OBs, the consequences of olfactory inflammation on OB neurons are largely unknown. In this study, we investigated the neurological consequences of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and AIS reconstruction both took place following a 10-week recovery period. Our findings suggest that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress.