Systematic study on date palm seeds (Phoenix dactylifera L.) extraction optimisation using natural deep eutectic solvents and ultrasound technique.

Natural deep eutectic solvents (NADES) are emerging, environment-friendly solvents that have garnered attention for their application in extracting phenolic compounds. This study investigated the effects of four synthetic NADES on polyphenols extracted from date seeds (DS) using choline chloride (ChCl) as a hydrogen-bond acceptor and lactic acid (La), citric acid (Citri), glycerol (Gly), and fructose (Fruc) as hydrogen-bond donors, in comparison with DS extracts extracted by conventional solvents (water, 70% methanol, and 70% ethanol). The antioxidant activity (DPPH), total phenolic content (TPC) and 6 phenolic compounds were determined using HPLC. The results showed that the ChCl-La and ChCl-Citri systems exhibited a high extraction efficiency regarding TPC, and DPPH in the DS extracts extracted by NADES compare to those DS extracts extracted with conventional solvents (p ˂ 0.001). HPLC results demonstrated that DS extracted by ChCl-La contained all measured phenolic compounds. Also gallic acid and catechin were the major compounds identified in the DS extracts. In addition DS extracted by ChCl-Citri and ChCl-Gly had the highest concentration of catechin. In conclusion, combining NADES is a promising and environment-friendly alternative to the conventional solvent extraction of phenolic compounds from DS.

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes.

Maternal nutrition during pregnancy and lactation plays an important role in the neurodevelopment of offspring. One-carbon (1C) metabolism, which centers around folic acid and choline, as well as other B vitamins, plays a key role during the closure of the neural tube of the developing fetus. However, the impact of these maternal nutritional deficiencies during pregnancy on offspring health outcomes after birth remains relatively undefined. Furthermore, maternal dietary deficiencies in folic acid or choline may impact other health outcomes in offspring - making this a valuable model. This protocol aims to outline the procedure for inducing a deficiency in 1C metabolism in female mice through dietary modifications. Females are placed on diets at weaning, up to 2 months of age, for 4-6 weeks prior to mating and remain on diet throughout pregnancy and lactation. Offspring from these females can be evaluated for health outcomes. Females can be used multiple times to generate offspring, and tissues from females can be collected to measure for 1C metabolite measurements. This protocol provides an overview of how to induce maternal dietary deficiencies in folic acid or choline to study offspring health outcomes.

Association of Methyl Donor Nutrients' Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Frontal cortex neurometabolites and mobility in older adults: a preliminary study.

BACKGROUND: The frontal cortex, relevant to global cognition and motor function, is recruited to compensate for mobility dysfunction in older adults. However, the in vivo neurophysiological (e.g., neurometabolites) underpinnings of the frontal cortex compensation for mobility dysfunction remain poorly understood. The purpose of this study was to investigate the relationships among frontal cortex neurophysiology, mobility, and cognition in healthy older adults. METHODS: Magnetic Resonance Spectroscopy (MRS) quantified N-acetylasparate (tNAA) and total choline (tCho) concentrations and ratios in the frontal cortex in 21 older adults. Four inertial sensors recorded the Timed Up & Go (TUG) test. Cognition was assessed using the Flanker Inhibitory Control and Attention Test which requires conflict resolution because of response interference from flanking distractors during incongruent trials. Congruent trials require no conflict resolution. RESULTS: tNAA concentration significantly related to the standing (p = 0.04) and sitting (p = 0.03) lean angles. tCho concentration (p = 0.04) and tCho ratio (p = 0.02) significantly related to TUG duration. tCho concentration significantly related to incongruent response time (p = 0.01). tCho ratio significantly related to both congruent (p = 0.009) and incongruent (p < 0.001) response times. Congruent (p = 0.02) and incongruent (p = 0.02) Flanker response times significantly related to TUG duration. CONCLUSIONS: Altered levels of frontal cortex neurometabolites are associated with both mobility and cognitive abilities in healthy older adults. Identifying neurometabolites associated with frontal cortex compensation of mobility dysfunction could improve targeted therapies aimed at improving mobility in older adults.

Choline consumption reduces CVD risk via body composition modification.

Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target.

Joint k-ω Space Image Reconstruction and Data Fitting for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k-ω reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies ω, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively.

Modulation of choline and lactate metabolism by basic fibroblast growth factor mitigates neuroinflammation in type 2 diabetes: Insights from 1H-NMR metabolomics analysis.

BACKGROUND: Type 2 diabetes (T2D), a chronic metabolic disease, occurs brain dysfunction accompanied with neuroinflammation and metabolic disorders. The neuroprotective effects of the basic fibroblast growth factor (bFGF) have been well studied. However, the mechanism underlying the anti-inflammatory effects of bFGF remains elusive. METHODS: In this study, db/db mice were employed as an in vivo model, while high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells were used as in vitro models. Liposomal transfection of MyD88 DNA plasmid was used for MyD88-NF-κB pathway studies. And western blotting, flow cytometry and qPCR were employed. 1H-NMR metabolomics was used to find out metabolic changes. RESULTS: bFGF mitigated neuroinflammatory and metabolic disorders by inhibiting cortical inflammatory factor secretion and microglia hyperactivation in the cortex of db/db mice. Also, bFGF was observed to inhibit the MyD88-NF-κB pathway in high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells in in vitro experiments. Moreover, the 1H-NMR metabolomics results showed that discernible disparities between the cortical metabolic profiles of bFGF-treated db/db mice and their untreated counterparts. Notably, excessive lactate and choline deficiency attenuated the anti-inflammatory protective effect of bFGF in SY5Y cells. CONCLUSION: bFGF ameliorates neuroinflammation in db/db mice by inhibiting the MyD88-NF-kB pathway. This finding expands the potential application of bFGF in the treatment of neuroinflammation-related cognitive dysfunction.

Investigation of antifungal and antibacterial potential of green extracts of propolis.

Propolis extracts have been used in traditional medicines since ages due to its advantageous complex chemical composition. However, the antibacterial and antifungal activity of poplar propolis extracts prepared in Natural Deep Eutectic Solvent (NADES) are seldom studied. This study investigates suitable alternate for ethanol as a solvent for extraction for Polish poplar propolis. It also attempts to identify suitable extraction condition for the efficient transfer of compounds from propolis to the solvents. The extraction efficiency of NADES extracts was assessed in terms of total phenolic content, antioxidant activity and antimicrobial activity. The chemical composition of the extracts was analysed using UHPLC-DAD-QqTOF-MS. Four extracts, prepared in Propylene Glycol, Choline Chloride:Propylene Glycol (1:3), Choline Chloride:Propylene Glycol (1:4) and Choline Chloride:Glycerol (1:2), demonstrated activity and properties similar to ethanolic extract and extraction at 50 °C was found the most suitable for propolis. HPLC analysis confirmed that the chemical cocktail extracted by these solvents from propolis were identical with minor variations in their concentration as compared to its ethanolic extract. Thus, extracts of propolis at 50 °C in Propylene Glycol, Choline Chloride:Propylene Glycol (1:3) and Choline Chloride:Propylene Glycol (1:4) can be alternates for ethanolic extracts.

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

Usual Choline Intake of Australian Children 6-24 Months: Findings from the Australian Feeding Infants and Toddlers Study (OzFITS 2021).

(1) Background: Despite the important role choline plays in child development, there are no data on dietary choline intake in early childhood in Australia. (2) Aim: In this cross-sectional study, we estimated the usual total choline intake and the proportion exceeding the Adequate Intake (AI) and determined the main dietary sources of choline in infants 6-12 months (n = 286) and toddlers 12-24 months (n = 475) of age. (3) Methods: A single 24-h food record with repeats collected during the 2021 Australian Feeding Infants and Toddlers Study (OzFITS 2021) was used to estimate dietary choline intake. (4) Results: The mean choline intake was 142 ± 1.9 mg/day in infants and 181 ± 1.2 mg/day in toddlers. Only 35% of infants and 23% of toddlers exceeded the AI for choline based on Nutrient Reference Values (NRVs) for Australia and New Zealand. Breastmilk was the leading source of choline, contributing 42% and 14% of total choline intake in infants and toddlers, respectively; however, egg consumers had the highest adjusted choline intakes and probability of exceeding the AI. (5) Conclusions: Findings suggest that choline intake may be suboptimal in Australian infants and toddlers. Further research to examine the impact of low choline intake on child development is warranted.

Solidification of deep eutectic solvent containing fimasartan through wet impregnation and exploration of flow attributes by modified SeDeM-SLA expert system.

The solidification of deep eutectic solvent (DES) through wet impregnation techniques on inert solid carriers is an interesting approach that offers better processing attributes and excellent stability. Herein, DES of Fimasartan (FS) was developed to improve its solubility and bioavailability. The selected DES-FS was solidified by wet impregnation method employing Nesulin US2 and Aerosil 200. The SeDeM-SLA (solid-liquid adsorption) system was employed to investigate flow attributes of solidified DES-FS. Further, the selected solidified DES-FS (A) was characterized by Fourier transforms infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM). The DES comprising Choline Chloride (ChCl): Glycerol (Gly) (1:3) revealed maximum drug solubility (35.6 ± 2.2 mg/mL) and thus opted for solidification. Solidification through wet impregnation was employed using 1:0.5 ratios (DES-FS to carriers). The Index of Good Flow (IGF) value was calculated from the SeDeM-SLA expert system, which indicates the better flow characteristics of solidified DES-FS, particularly with Neusilin US2 [SDES-FS (A)]. The solid-state evaluation data of SDS-FS (A) suggested a transition of FS to an amorphous form, resulting in an increment in solubility and dissolution. A similar trend was reported in the in vivo pharmacokinetic study, which indicated a 2.9 folds increment in the oral bioavailability of FS. Furthermore, excellent stability, i.e., a shelf life of 28.44 months, reported by SDES-FS (A) in accelerated stability studies, suggests better formulation perspectives. In a nutshell, the present study evokes the potentiality of performing solidification through wet impregnation and successful implementation of the SeDeM-SLA expert model, which could find wide applications in pharmaceutical science.

Region-specific Cerebral Metabolic Alterations in Parkinson's Disease Patients With/without Mild Cognitive Impairment.

N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) are brain metabolites involved in some key neuronal functions within the brain, such as cognitive function. The aim of this study was to investigate whether Parkinson's disease (PD) with different cognitive status induces regional brain metabolite differences. 38 diagnosed PD patients, including 18 PD patients with normal cognitive (PDN), 20 PD subjects with cognitive impairment (PDMCI) and 25 healthy controls (HC) participated in this study. All subjects underwent a single-voxel proton MR spectroscopy (1H-MRS) on a 3T scanner. 1H-MRS were obtained from bilateral PCC, left thalamus and PFC regions in all subjects, respectively. Region-specific cerebral metabolic alterations existed in PD patients with different cognitive status. PDMCI patients showed a significant reduction of NAA, Cho and tCr in the PCC and left thalamus, compared to healthy controls; whereas lower levels of NAA and Cho in thalamus were found in PDN patients. Moreover, Cho and tCr levels were positively correlated with MMSE scores. Both NAA and tCr in PCC levels were positively correlated with MMSE and MoCA scores. The combination of thalamic and PCC metabolites showed a 75.6% accuracy in distinguishing PDMCI patients from PDN patients. This study provides preliminary evidence that thalamic, PCC and PFC neurometabolic alterations occur in PD patients with cognition decline. Findings of this study indicate that NAA and tCr abnormalities in PCC and thalamus might be used as a biomarker to track cognitive decline in Parkinson's disease in clinical settings.

Longitudinal Analysis of Mitochondrial Function in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis Mouse Model.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF1-ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF1-ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF1-ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF1-ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.

Dynamic Changes in Gut Microbiota-Derived Metabolite Trimethylamine-N-Oxide and Risk of Type 2 Diabetes Mellitus: Potential for Dietary Changes in Diabetes Prevention.

BACKGROUND: A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with type 2 diabetes mellitus (T2DM). Few previous prospective studies have addressed associations between the changes in TMAO and T2DM incidence. METHODS: Data were derived from a longitudinal cohort conducted from 2019 to 2021 in rural areas of Fuxin County, Liaoning Province, China, and 1515 diabetes-free participants aged above 35 years were included. The concentrations of serum TMAO and its precursors were measured at two time points, namely in 2019 and 2021. TMAO and TMAO changes (ΔTMAO) were separately tested in a logistic regression model. For further examination, the odds ratios (ORs) for T2DM were calculated according to a combination of TMAO levels and ΔTMAO levels. RESULTS: During a median follow-up of 1.85 years, 81 incident cases of T2DM (5.35%) were identified. Baseline TMAO levels exhibited a nonlinear relationship, first decreasing and then increasing, and only at the highest quartile was it associated with the risk of T2DM. The OR for T2DM in the highest quartile of serum TMAO was 3.35 (95%CI: 1.55-7.26, p = 0.002), compared with the lowest quartile. As for its precursors, only choline level was associated with T2DM risk and the OR for T2DM in the Q3 and Q4 of serum choline was 3.37 (95%CI: 1.41-8.05, p = 0.006) and 4.72 (95%CI: 1.47-15.13, p = 0.009), respectively. When considering both baseline TMAO levels and ΔTMAO over time, participants with sustained high TMAO levels demonstrated a significantly increased risk of T2DM, with a multivariable-adjusted OR of 8.68 (95%CI: 1.97, 38.34). CONCLUSION: Both initial serum TMAO levels and long-term serum TMAO changes were collectively and significantly associated with the occurrence of subsequent T2DM events. Interventions aimed at normalizing TMAO levels, such as adopting a healthy dietary pattern, may be particularly beneficial in T2DM prevention.

Choline-An Underappreciated Component of a Mother-to-Be's Diet.

The nutritional status of the mother-to-be has a key impact on the proper development of the fetus. Although all nutrients are important for the developing baby, recent research indicates the importance of adequate choline intake during the periconceptional period, pregnancy, and lactation. Choline plays a key role in the biosynthesis of cell membranes, supporting liver function, neurotransmission, brain development, and DNA and histone methylation. Choline participates in the formation of a child's nervous system, supports its cognitive development, and reduces the risk of neural tube defects. The human body is incapable of producing sufficient choline to meet its needs; therefore, it must be obtained from the diet. Current data indicate that most women in their reproductive years do not achieve the recommended daily intake of choline. The presented narrative review indicates the importance of educating mothers-to-be and thereby increasing their awareness of the effects of choline on maternal and child health, which can lead to a more aware and healthy pregnancy and proper child development.

α7 nicotinic receptor activation mitigates herpes simplex virus type 1 infection in microglia cells.

Herpes simplex virus type 1 (HSV-1), a neurotropic DNA virus, establishes latency in neural tissues, with reactivation causing severe consequences like encephalitis. Emerging evidence links HSV-1 infection to chronic neuroinflammation and neurodegenerative diseases. Microglia, the central nervous system's (CNS) immune sentinels, express diverse receptors, including α7 nicotinic acetylcholine receptors (α7 nAChRs), critical for immune regulation. Recent studies suggest α7 nAChR activation protects against viral infections. Here, we show that α7 nAChR agonists, choline and PNU-282987, significantly inhibit HSV-1 replication in microglial BV2 cells. Notably, this inhibition is independent of the traditional ionotropic nAChR signaling pathway. mRNA profiling revealed that choline stimulates the expression of antiviral factors, IL-1ß and Nos2, and down-regulates the apoptosis genes and type A Lamins in BV2 cells. These findings suggest a novel mechanism by which microglial α7 nAChRs restrict viral infections by regulating innate immune responses.

Sensitive detection of choline and nicotine in real samples by switching upconversion luminescence.

Nicotine (3-(1-methyl-2-pyrrolidinyl)pyridine) is one of the most common addictive substances, causing the trace detection of nicotine to be very necessary. Herein, we designed and prepared a functionalized nanocomposite CS-PAA (NaYF4:19.5%Yb,0.5%Tm@NaYF4-PAA) using a simple method. The nicotine concentration was quantitatively detected through the inhibition of choline oxidase activity by nicotine and the luminescence intensity of CS-PAA being quenched by Fe3+. The mechanism of Fe3+ quenching CS-PAA emission was inferred by luminescence lifetime and UV-vis absorption spectra characterization. During the nicotine detection, both excitation (980 nm) and emission (802 nm) wavelengths of CS-PAA enable the avoidance of the interference of background fluorescence in complicated food objects, thus providing high selectivity and sensitivity with a linear range of 5-750 ng/mL and a limit of detection of 9.3 nM. The method exhibits an excellent recovery and relative standard deviation, indicating high accuracy and repeatability of the detection of nicotine.

Dietary choline intake in European and non-european populations: current status and future trends-a narrative review.

BACKGROUND: Choline is a nutrient necessary for the proper functioning of the body with a multidimensional impact on human health. However, comprehensive studies evaluating the dietary intake of choline are limited. The aim of this narrative review is to analyze current trends in choline intake in European and non-European populations. The secondary aim was to discuss possible future choline trends. METHODS: The search strategy involved a systematic approach to identifying relevant literature that met specific inclusion criteria. Observational studies and randomized clinical trials were searched for in PubMed and Scopus databases from January 2016 to April 2024. This review includes the characteristics of study groups, sample sizes, methods used to assess choline intake and time period, databases used to determine intake, choline intakes, and the main sources of choline in the diet. The review considered all population groups for which information on choline intake was collected. RESULTS: In most studies performed in Europe after 2015 choline intake did not exceed 80% of the AI standard value. The mean choline intake for adults in different European countries were 310 mg/day, while the highest value was reported for Polish men at 519 mg/day. In non-European countries, mean choline intakes were 293 mg/day and above. The main reported sources of choline in the diet are products of animal origin, mainly eggs and meat. The available data describing the potential intake of these products in the EU in the future predict an increase in egg intake by another 8% compared to 2008-2019 and a decrease in meat intake by about 2 kg per capita from 2018 to 2030. CONCLUSIONS: In the last decade, choline intake among adults has been insufficient, both in Europe and outside it. In each population group, including pregnant women, choline intake has been lower than recommended. Future choline intake may depend on trends in meat and egg consumption, but also on the rapidly growing market of plant-based products. However, the possible changes in the intake of the main sources of choline may lead to either no change or a slight increase in overall choline intake.

A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation.

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). DISCUSSION: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. TRIAL REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).