Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.

Exploiting Self-Association to Evaluate Enantiomeric Composition by Cyclic Ion Mobility-Mass Spectrometry.

The characterization of enantiomers is an important analytical challenge in the chemical and life sciences. Thorough evaluation of the purity of chiral molecules is particularly required in the pharmaceutical industry where safety concerns are paramount. Assessment of the enantiomeric composition is still challenging and time-consuming, meaning that alternative approaches are required. In this study, we exploit the formation of dimers as diastereomeric pairs of enantiomers to affect separation by high resolution cyclic ion mobility-mass spectrometry. Using the example of (R/S)-thalidomide, we show that even though this is not an enantiomer separation, we can determine which enantiomer is in excess and obtain quantitative information on the enantiomer composition without the need for a chiral modifier. Further examples of the approach are presented, including d/l-tryptophan and (R/S)-propanolol, and demonstrate the need for mobility resolving power in excess of 400 (CCS/ΔCCS).

Structural characterization and analysis of different epimers of neutral glycosphingolipid LcGg4 by ion mobility spectrometry-mass spectrometry.

LcGg4, a neutral glycosphingolipid (GSL) and cancer antigen, its epimers GalNAc-LcGg4 and GlcNAc-LcGg4, and three lipid forms of GalNAc-LcGg4 were studied by mass spectrometry (MS). It was found that different forms of GalNAc-LcGg4 carrying homologous (d16:1/18:0) and (d18:1/18:0) lipids were easily separated and identified using liquid chromatography (LC)-MS. In addition, like gangliosides, homologous lipid forms of GalNAc-LcGg4 showed the same fragmentation pattern, except for a uniform shift of their glycolipid product ions by a certain m/z number determined by the varied lipid structure. It was also disclosed that LcGg4 and its epimers GalNAc-LcGg4 and GlcNAc-LcGg4, which are different only in the C4-configuration of their non-reducing end sugar residues, gave the same MS/MS product ions in similar relative intensities, as well as the same LC retention time, suggesting the challenge to differentiate epimeric GSLs by LC-MS. However, ion mobility spectrometry (IMS)-MS was able to efficiently separate and distinguish these epimers. This study has demonstrated the promise of IMS-MS for isomeric GSL characterization and the IMS-MS and LC-MS/MS combination for natural GSL analysis.

Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer.

BACKGROUND: Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival. PATIENTS AND METHODS: A total of 254 samples from 143 patients with rectal adenocarcinomas were analyzed for the presence and abundance of F. nucleatum using RNA in situ hybridization and digital image analysis. Assay accuracy was determined using infected cell lines and tumor samples with available quantitative PCR data. We studied the impact of F. nucleatum load on pathologic complete response and relapse-free survival. Treatment-induced changes were evaluated in paired pre- and post-nCRT samples (n = 71). Finally, tumor microenvironment changes during nCRT were assessed in paired samples (n = 45) by immune contexture analysis. RESULTS: F. nucleatum tissue levels by RNA in situ hybridization strongly correlated with quantitative PCR (r = 0.804, P < 0.001). F. nucleatum abundance was higher in untreated [median, 7.4; 95% confidence interval (3.7-16.2)] compared with treated [median, 1.6; 95% confidence interval (1.3-2.4)] tumors (P <0.001) with 58% (73/126) and 26% (22/85) positive tumors, respectively (P < 0.001). Baseline F. nucleatum levels were not associated with pathologic complete response. F. nucleatum positivity after nCRT, but not baseline status, significantly increased risk of relapse [hazard ratio = 7.5, 95% confidence interval (3.0-19.0); P < 0.001]. Tumors that turned F. nucleatum-negative after nCRT had a strong increase in CD8+ T cells post-nCRT (P < 0.001), while those that persisted F. nucleatum-positive after nCRT lacked CD8+ T cells induction in post-nCRT samples compared with baseline (P = 0.69). CONCLUSION: F. nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity.

Direct Drug Analysis in Polymeric Implants Using Desorption Electrospray Ionization - Mass Spectrometry Imaging (DESI-MSI).

PURPOSE: Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) coupled with gas-phase ion mobility spectrometry was used to characterize the drug distribution in polymeric implants before and after exposure to accelerated in vitro release (IVR) media. DESI-MSI provides definitive chemical identification and localization of formulation components, including 2D chemical mapping of individual components with essentially no sample preparation. METHODS: Polymeric implants containing 40% (w/w) entecavir and poly(D,L-lactide) (PLA) were prepared and then exposed to either acidified PBS (pH 2.5) or MeOH:H2O (50:50, v/v) medias during a 7-day IVR test using continuous flow-through (CFT) cell dissolution. The amount of drug released from the polymer matrix during the 7-day IVR test was monitored by online-ultraviolet spectroscopy (UV) and HPLC-UV. After that period, intact implants and radial sections of implants were analyzed by DESI-MSI with ion mobility spectrometry. The active ingredient along with impurities and contaminants were used to generate chemical maps before and after exposure to the release medias. RESULTS: Bi-phasic release profiles were observed for implants during IVR release using both medias. During the second phase of release, implants exposed to PBS, pH 2.5, released the entecavir faster than the implants exposed to MeOH:H2O (50:50, v/v). Radial images of the polymer interior show that entecavir is localized along the central core of the implant after exposure to MeOH:H2O (50:50, v/v) and that the drug is more uniformly distributed throughout the implant after exposure to acidified PBS (pH 2.5). CONCLUSIONS: DESI-MSI coupled with ion mobility analysis produced chemical images of the drug distribution on the exterior and interior of cylindrical polymeric implants before and after exposure to various release medias. These results demonstrated the utility of this technique for rapid characterization of drug and impurity/degradant distribution within polymeric implants with direct implications for formulation development as well as analytical method development activities for various solid parenteral and oral dosage forms. These results are especially meaningful since samples were analyzed with essentially no preparative procedures.

MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.

Early evolutionary divergence between papillary and anaplastic thyroid cancers.

Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC. Patients and methods: We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data. Results: Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones. Conclusion: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.

Morphological development in the first life phase of Adriatic sturgeon Acipenser naccarii under controlled conditions.

Early development of the Adriatic sturgeon Acipenser naccarii from its free embryo after hatching (stage 36), until late embryo stage, when the transition to exogenous feeding starts (stage 45) is described. Special emphasis is given to morphological development and description of the different structures that are formed at each life stage. After hatching, free embryos still present embryonic characteristics, little pigmentation and an ovoid yolk sac. The mouth begins to open on the second day post hatch (dph) and is fully open at 3 dph. The head begins to separate from the body at 4 dph and straightens at 6 dph. The first fins to appear are the pectoral fins on the yolk sac and an embryological fin fold that extends from behind the head to the posterior part of the yolk sac. All other fins will develop from this fold. At 7 dph the caudal fin begins to take a heterocercal form and dorsal scutes are observed. This study provides information that will assist aquaculturists by establishing a reference for the normal development of A. naccarii, which may be useful for evaluating the suitability and quality of fish produced for restocking.

Ion mobility-derived collision cross section as an additional measure for lipid fingerprinting and identification.

Despite recent advances in analytical and computational chemistry, lipid identification remains a significant challenge in lipidomics. Ion-mobility spectrometry provides an accurate measure of the molecules' rotationally averaged collision cross-section (CCS) in the gas phase and is thus related to ionic shape. Here, we investigate the use of CCS as a highly specific molecular descriptor for identifying lipids in biological samples. Using traveling wave ion mobility mass spectrometry (MS), we measured the CCS values of over 200 lipids within multiple chemical classes. CCS values derived from ion mobility were not affected by instrument settings or chromatographic conditions, and they were highly reproducible on instruments located in independent laboratories (interlaboratory RSD < 3% for 98% of molecules). CCS values were used as additional molecular descriptors to identify brain lipids using a variety of traditional lipidomic approaches. The addition of CCS improved the reproducibility of analysis in a liquid chromatography-MS workflow and maximized the separation of isobaric species and the signal-to-noise ratio in direct-MS analyses (e.g., "shotgun" lipidomics and MS imaging). These results indicate that adding CCS to databases and lipidomics workflows increases the specificity and selectivity of analysis, thus improving the confidence in lipid identification compared to traditional analytical approaches. The CCS/accurate-mass database described here is made publicly available.

COPD patient profiles in primary care. Referral criteria.

COPD is a disease with a high prevalence that diminishes the quality of life of many patients. Despite this, there are still high rates of under-diagnosis in Spain, partly due to a lack of recognition of the pathology by patients. In this context, the role played by primary care teams becomes fundamental, as they are one of the first lines of entry into the health system. In this paper we explain the different COPD profiles that may be present, and update the tools for diagnosis and treatment, which, together with an attitude of active suspicion of the disease, can help in the correct management of patients, whether they are undiagnosed or have subsequent complications.

Taming Conformational Heterogeneity on Ion Racetrack to Unveil Principles that Drive Membrane Permeation of Cyclosporines.

Our study reveals the underlying principles governing the passive membrane permeability in three large N-methylated macrocyclic peptides (N-MeMPs): cyclosporine A (CycA), Alisporivir (ALI), and cyclosporine H (CycH). We determine a series of conformers required for robust passive membrane diffusion and those relevant to other functions, such as binding to protein targets or intermediates, in the presence of solvent additives. We investigate the conformational interconversions and establish correlations with the membrane permeability. Nuclear magnetic resonance (NMR) and cyclic ion-mobility spectrometry-mass spectrometry (cIMS-MS) are employed to characterize conformational heterogeneity and identify cis-amides relevant for good membrane permeability. In addition, ion mobility selected cIMS-MS and infrared (IR) multiple-photon dissociation (IRMPD) spectroscopy experiments are conducted to evaluate the energy barriers between conformations. We observe that CycA and ALI, both cyclosporines with favorable membrane permeabilities, display multiple stable and well-defined conformers. In contrast, CycH, an epimer of CycA with limited permeability, exhibits fewer and fewer stable conformers. We demonstrate the essential role of the conformational shift from the aqueous cis MeVal11-MeBmt1 state (A1) to the closed conformation featuring cis MeLeu9-MeLeu10 (C1) in facilitating membrane permeation. Additionally, we highlight that the transition from A1 to the all-trans open conformation (O1) is specifically triggered by the presence of CaCl2. We also capture a set of conformers with cis Sar3-MeLeu4, MeLeu9-MeLeu10, denoted as I. Conformationally selected cIMS-MS and IRMPD data of [CycA+Ca]2+ show immediate repopulation of the original population distribution, suggesting that CaCl2 smooths out the energy barriers. Finally, our work presents an improved sampling molecular dynamics approach based on a refined force field that not only consistently and accurately captures established conformers of cyclosporines but also exhibits strong predictive capabilities for novel conformers.

Cryo-EM Unveils the Processivity Mechanism of Kinesin KIF1A and the Impact of its Pathogenic Variant P305L.

Mutations in the microtubule-associated motor protein KIF1A lead to severe neurological conditions known as KIF1A-associated neurological disorders (KAND). Despite insights into its molecular mechanism, high-resolution structures of KIF1A-microtubule complexes remain undefined. Here, we present 2.7-3.4 Å resolution structures of dimeric microtubule-bound KIF1A, including the pathogenic P305L mutant, across various nucleotide states. Our structures reveal that KIF1A binds microtubules in one- and two-heads-bound configurations, with both heads exhibiting distinct conformations with tight inter-head connection. Notably, KIF1A's class-specific loop 12 (K-loop) forms electrostatic interactions with the C-terminal tails of both α- and ß-tubulin. The P305L mutation does not disrupt these interactions but alters loop-12's conformation, impairing strong microtubule-binding. Structure-function analysis reveals the K-loop and head-head coordination as major determinants of KIF1A's superprocessive motility. Our findings advance the understanding of KIF1A's molecular mechanism and provide a basis for developing structure-guided therapeutics against KAND.

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

N-acetylneuraminate pyruvate lyase controls sialylation of muscle glycoproteins essential for muscle regeneration and function.

Deleterious variants in N-acetylneuraminate pyruvate lyase (NPL) cause skeletal myopathy and cardiac edema in humans and zebrafish, but its physiological role remains unknown. We report generation of mouse models of the disease: NplR63C, carrying the human p.Arg63Cys variant, and Npldel116 with a 116-bp exonic deletion. In both strains, NPL deficiency causes drastic increase in free sialic acid levels, reduction of skeletal muscle force and endurance, slower healing and smaller size of newly formed myofibers after cardiotoxin-induced muscle injury, increased glycolysis, partially impaired mitochondrial function, and aberrant sialylation of dystroglycan and mitochondrial LRP130 protein. NPL-catalyzed degradation of sialic acid in the muscle increases after fasting and injury and in human patient and mouse models with genetic muscle dystrophy, demonstrating that NPL is essential for muscle function and regeneration and serves as a general marker of muscle damage. Oral administration of N-acetylmannosamine rescues skeletal myopathy, as well as mitochondrial and structural abnormalities in NplR63C mice, suggesting a potential treatment for human patients.

The use of pedicled buccal fat pad combined with sequestrectomy in bisphosphonate-related osteonecrosis of the maxilla.

The use of pedicled buccal fat pad flap (BFP) has proved of value for the closure of oroantral and oronasal communications and is a well-established tool in oral and maxillofacial surgery. Otherwise, the perceived limitations of surgical therapy for bisphosphonate-related osteonecrosis of the jaws (BRONJ) have been widely discussed, and recommendations have largely been made to offer aggressive surgery only to stage 3 patients refractary to conservative management. Oroantral communication may be a common complication after sequestrectomy and bone debridement in upper maxillary BRONJ. We report a case series of stage 3 recalcitrant maxillary BRONJ surgically treated with extensive sequestrectomy and first reconstruction using pedicled BFP. All the cases presented an uneventful postoperative healing was uneventful without dehiscence, infection, necrosis or oroantral communication. We postulate that managing initially the site with BFP and primary closure may ensure a sufficient blood supply and adequate protection for an effective bone-healing response to occur. This technique may represent a mechanic protection and an abundant source of adipose-derived adult stem cells after debridement in upper maxillary BRONJ. We evaluate in this work results, advantages and indications of this technique.

[Neonatal extracorporeal membrane oxygenation: 9 years of experience]. / Oxigenación por membrana extracorpórea neonatal: 9 años de experiencia.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for reversible respiratory or cardiac diseases. Neonatal pathologies requiring this technique are different from the ones found later in life. OBJECTIVES: To review the main causes requiring ECMO in the neonatal period, to compare the clinical course depending on the initial illness and to identify the sequelae attributable to this technique. MATERIAL AND METHOD: A retrospective review of clinical records of all neonatal patients that received ECMO support in our centre. RESULTS: 45 neonatal ECMO were performed in our unit between January 2001 and June 2009. Forty techniques were due to respiratory failure, 2 secondary to haemodynamic shock and 3 secondary to sepsis. Veno-venous cannulation was used initially in 24 patients (53.3%). The length of technique varied depending on the underlying disease. Patients with congenital diaphragmatic hernia were in ECMO for longer periods. The overall survival to the technique was 86.3% (38/44 patients), also with differences among diseases. Extracorporeal support was withdrawn in 4 children because of a diagnosis of an irreversible pathology and one because of massive brain haemorrhage. No serious adverse outcomes attributable to the technique were found among survivors. CONCLUSIONS: Survival among newborns supported with ECMO in our hospital is similar to that recorded by the ELSO in 2004, although we use veno-venous cannulation in more than a half of the patients. The percentage of moderate to severely impaired neurodevelopmental outcome among survivors after this technique was low.

Multiscale Electrochemomechanics Interaction and Degradation Analytics of Sn Electrodes for Sodium-Ion Batteries.

Sodium-ion batteries have emerged as a strong contender among the beyond lithium-ion chemistries due to elemental abundance and the low cost of sodium. Tin (Sn) is a promising alloying electrode with high capacity, redox reversibility, and earth abundance. Tin electrodes, however, undergo a series of intermediate reactions exhibiting multiple voltage plateaus upon sodiation/desodiation. Phase transformations related to incomplete sodiation in tin during cycling, in the presence of a frail solid electrolyte interphase layer, can quickly weaken the structural stability. The structural dynamics and reactivity of the electrode/electrolyte interface, being further dependent on the size and morphology of the active material particle in the presence of different electrolytes, dictate the electrode degradation and survivability during cycling. In this study, we paint a comprehensive picture of the underpinnings of the electrochemical and mechanics coupling and electrode/electrolyte interfacial interactions in alloying Sn electrodes. We elicit the fundamental role of electrode/electrolyte complexations in the Sn electrode structure-property-performance relationship based on multimodal analytics, including electrochemical, microscopy, and tomography analyses.

Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort.

Background: Current evidence suggests that egg composition might have potential neuroprotective effects. Our aim was to determine the association between egg consumption and the risk of dementia in a Mediterranean population. Methods: This study was carried out in 3 centers from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort, i.e., 25,015 participants aged 30-70 years, recruited in 1992-1996, and followed up for a mean of 21.5 years. Results: A total of 774 incident dementia cases were diagnosed and validated, of which 518 were Alzheimer's disease (AD). Data on egg consumption were estimated using a validated dietary history questionnaire at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses. No association was observed between egg consumption and either total dementia [hazard ratio between extreme quartiles (HRQ4vs.Q1: 1.05; 95% CI 0.85-1.31; p-trend = 0.93)] or AD (HRQ4vs.Q1 0.93; 95% CI 0.72-1.21; p-trend = 0.50) risks. After dividing the population by adherence to the relative Mediterranean diet (rMED) score, a borderline inverse association was found between egg intake and both total dementia (HRQ4vs.Q1: 0.52; 95% CI 0.30-0.90; p-trend = 0.10) and AD (HRQ4vs.Q1: 0.52; 95% CI 0.27-1.01; p-trend = 0.13) risks within participants with low adherence to rMED score. However, no association was observed in participants with medium and high adherence to rMED score. Conclusion: This prospective study suggests that egg consumption is associated with a reduced risk of dementia, and specifically of AD, in the adult population with low adherence to rMED score; whereas it has no impact in subjects with moderate and high MD adherence.