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There has been an increasing use of cannabis during pregnancy in recent years. Studies have indicated that THC exposure in utero may increase the risk of attention deficits and memory impairments in adolescence. The goal of the present study is to investigate the effects of vaporized THC exposure during pregnancy on offspring memory and attention performance in early and late adolescence. Pregnant dams were exposed to vaporized THC (10 mg or 40 mg) daily from gestational day 2 until labor. Pups were given either a standard or a high-fat diet at weaning and tested in early and late adolescence in two memory tests, the Novel Object Recognition (NOR) test and the Morris Water Maze (MWM) test, and a test of attention, the Object-Based Attention (OBA) test. Rats exposed to low-dose THC showed significantly decreased object exploration in both the NOR and OBA tests, indicating decreased attention. Object exploration time in OBA was significantly lower in females than males. Additionally, post hoc analysis of MWM tests showed some differences in learning patterns for HD THC offspring in early adolescence, possibly due to diet interaction, but ultimate performance was not impacted. While there are existing studies examining prenatal exposure to THC in rodents, this is the first to our knowledge examining memory and attention in adolescence following vaporized THC exposure in utero, and we find indications that prenatal THC exposure may lead to attention deficits and altered memory performance., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale Clinical research has shown that prenatal exposure to nicotine may result in increased obesity risk later in life. Preclinical research has corroborated this finding, but few studies have investigated inhaled nicotine or the interaction with diet on obesity risk. Objective The aim of this study was to investigate the effects of prenatal nicotine exposure on both direct and indirect obesity measures, with both sex and diet as factors. Methods Pregnant rats were exposed to either vehicle or nicotine vapor (24 mg/mL or 59 mg/mL) throughout the entire gestational period. Offspring from each treatment group were given either a normal diet or a high fat diet starting at postnatal day 22. Caloric intake, body weight, spontaneous locomotion, sleep/wake activity, and voluntary exercise were measured throughout adolescence. Pregnancy weight gain and pup birthweights were collected to further measure developmental effects of prenatal nicotine exposure. Results Both maternal weight gain during pregnancy and pup weight at birth were decreased with prenatal nicotine exposure. Early adolescent males showed increased spontaneous activity in the open field following prenatal nicotine exposure compared to vehicle counterparts, particularly those given high-fat diet. Additionally, high dose nicotine prenatal treated males ran significantly less distance on the running wheel in late adolescence compared to vehicle counterparts, in the normal diet group only. Conclusion The results presented here show decreased birthweight, hyperactivity, and decreased voluntary exercise in adolescence following prenatal nicotine exposure in dose, sex, and diet dependent manners, which could lead to increased obesity risk in adulthood., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Preclinical studies have found that chronic ∆9-tetrahydrocannabinol (THC) treatment is directly associated with weight gain when introduced during adolescence and adulthood, but the effect of prenatal THC is unclear. Clinical studies have demonstrated prenatal exposure to THC is a prospective predictor of increased health risks associated with obesity. Our study aims to examine prenatal THC impact on obesity risks in males and females throughout adolescence using a clinically relevant inhalation model., Methods: Pregnant rats were exposed to one of the following from gestational day 2 through birth: 10 mg THC, 40 mg THC, or air. Daily 10-min inhalations were conducted in each animal from 0900 to 1200. Offspring from each treatment group were given either a high-fat diet (HFD) or a normal diet (ND). Food and bodyweights were collected daily, while circadian activity, locomotion, and exercise were measured periodically (PND 21-60). Pregnancy weight gain and birth weight were collected to determine early-life developmental effects., Results: Rats prenatally treated with low-dose THC (LDTHC) generally had lower dark-cycle activity compared with control counterparts, but this altered activity was not observed at the higher dose of THC (HDTHC). In terms of open-field activity, THC doses displayed a general increase in locomotion. In addition, the LDTHC male rats in the ND showed significantly greater exploratory behavior. Prenatal THC had dose-dependent effects on maternal weight gain and birth weight., Conclusions: Overall, our findings indicate there are some activity-related and developmental effects of prenatal THC, which may be related to obesity risks later in life., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Acute and chronic Δ 9 -THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ 9 -THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ 9 -THC's effects on CB1R and MOR levels and locomotor activity., Main Methods: Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ 9 -THC [0.75mg/kg (low dose or LD) or 2.0 mg/kg (high dose or HD)] or vehicle for 24 days, and locomotion in the open field was tested after the first and fourth weeks of chronic Δ 9 -THC exposure. Brains were harvested at the end of treatment. [ 3 H] SR141716A and [ 3 H] DAMGO autoradiography assessed CB1R and MOR levels, respectively., Key Findings: Relative to each other, chronic HD rats showed reduced vertical plane (VP) entries and time, while LD rats had increased VP entries and time for locomotion, as assessed by open-field testing; no effects were found relative to the control. Autoradiography analyses showed that HD Δ 9 -THC significantly decreased CB1R binding relative to LD Δ 9 -THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ 9 -THC rats displayed elevated binding in the primary motor (33% increase) and hypothalamic (33% increase) regions compared with controls. No significant differences were observed in MOR binding for the LD or HD compared to the control., Significance: These results demonstrate that chronic Δ 9 -THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Yeasts are reported to be rich in folates, a group of vitamers known to be involved in several biosynthetic reactions such as methylation reactions, oxidation and reduction processes, and nucleotide synthesis. Not being able to synthesize folates, humans rely on external folate supply. Here, we show the application of LC/MS-MS methods using SIDA (stable isotope dilution analysis) assays for the quantitative analysis of different folate mono- and polyglutamates during growth of Saccharomyces cerevisiae . Molecular networking (MN) was applied for detailed analysis of further folate metabolites. Highest folate contents of 13,120 μg/100 g were observed after 20 h of cultivation. The main vitamers 5-CH 3 -H 4 folate and H 4 folate decreased during cultivation, while 5-CHO-H 4 folate increased during cultivation. The hexa- and heptaglutamate of 5-CH 3 -H 4 folate accounted for >96% of the total 5-CH 3 -H 4 folate content. A shift of the major polyglutamate from hexa- to heptaglutamate was observed after 29 h. MN unraveled two groups of novel folates which could be assigned to a potentially existing C 2 -metabolism in yeast. In detail, 5,10-ethenyl-tetrahydrofolate and a further CO-substituted 5-CH 3 -H 4 folate were identified as hexa- and heptaglutamates. The latter was neither identified as 5-acetyl-tetrahydrofolate nor as EthylFox, the oxidation product of 5-ethyl-tetrahydrofolate. The structure needs to be elucidated in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schillert, Wirtz, Weber, Schaller, Striegel, Schmitt-Kopplin and Rychlik.)

Folate is a fundamental vitamin for metabolism in plants and humans. A modelling approach has been developed to characterize the reactivity of folates in cowpea seeds during germination at 30 °C, using a water-to-seed ratio of 1:1 (w/w). For this purpose, the concentrations of folic acid, 10-formylfolic acid, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate and tetrahydrofolate were determined in seeds during germination times up to 96 h. Two reaction models were sequentially built and adjusted to experimental data to describe changes in concentration in cowpea seed during two germination phases: before 14 h and after 48 h. Results showed intense enzymatic interconversion of all folate vitamers into 5-methyltetrahydrofolate before 14 h of germination and high enzymatic production of 5-methyltetrahydrofolate, 5-formyltetrahydrofolate and tetrahydrofolate after 48 h of germination. This study suggests that a long germination process could be more beneficial than soaking to increase the production of bioavailable folates within the seed for human consumption., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Choy sum is a commonly consumed Asian green leafy brassica vegetable. A comprehensive spectrum of nutritional important metabolites, including amino acids, plant sugars, essential minerals, vitamins (A, B 9 , E, and K 1 ) and glucosinolates were systematically quantified using LC-QQQ-MS, GC-QQQ-MS and ICP-MS. Significant metabolic profile shifts were observed during the three major developmental stages (microgreen, seedling and adult) studied. Primary metabolites, especially essential amino acids decreased while most plant sugars increased from microgreens to seedlings. Carotenoids, such as violaxanthin, neoxanthin, together with vitamin K 1 were higher in the seedlings whereas CHO-folate vitamers and β-cryptoxanthin were much lower in adult plants. Most essential minerals were concentrated in the microgreens, while sodium increased in adult plants. Aliphatic glucosinolates in microgreens were converted to indolic glucosinolates in the seedlings and further to aromatic glucosinolates in the adults. Overall findings reveal that most of the nutritional metabolites were concentrated either in the microgreens or seedlings., (Copyright © 2021. Published by Elsevier Ltd.)

Quantification of the specific folate vitamers to estimate total folate in foods is not standardized. A collaborative study, including eight European laboratories, was conducted in order to determine the repeatability and reproducibility of the method for folate quantification in foods using the plant-origin γ-glutamyl hydrolase as part of the extraction procedure. The seven food samples analyzed represent the food groups; fruits, vegetables, dairy products, legumes, offal, fish, and fortified infant formula. The homogenization step was included, and six folate vitamers were analyzed using LC-MS/MS. Total folate content, expressed as folic acid equivalent, was 17-490 μg/100 g in all samples. Horwitz ratio values were within the acceptable range (0.60-1.94), except for fish. The results for fortified infant formula, a certified reference material (NIST 1869), confirmed the trueness of the method. The collaborative study is part of a standardization project within the Nordic Committee on Food Analysis (NMKL)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Folates are a group of B 9 vitamins playing an important role in many metabolic processes such as methylation reactions, nucleotide synthesis or oxidation and reduction processes. However, humans are not able to synthesize folates de novo and thus rely on external sources thereof. Baker's yeast ( Saccharomyces cerevisiae ) has been shown to produce high amounts of this vitamin but extensive identification of its folate metabolism is still lacking. Therefore, we optimized and compared different sample preparation and purification procedures applying solid phase extraction (SPE). Strong anion exchange (SAX), C18 and hydrophilic-lipophilic-balanced (HLB) materials were tested for their applicability in future metabolomics studies. SAX turned out to be the preferred material for the quantitative purification of folates. Qualification of several folate vitamers was achieved by ultra-high pressure liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-ToF-MS) measurements and quantification was performed by liquid chromatography tandem mass spectrometry (LC-MS/MS) applying stable isotope dilution assays (SIDAs). The oxidation product s -pyrazino-triazine (MeFox) was included into the SIDA method for total folate determination and validation. Applying the best protocol (SAX) in regard to folate recovery, we analyzed 32 different vitamers in different polyglutamate states up to nonaglutamates, of which we could further identify 26 vitamers based on tandem-MS (MS 2 ) spectra. Total folate quantification revealed differences in formyl folate contents depending on the cartridge chemistry used for purification. These are supposedly a result of interconversion reactions occurring during sample preparation due to variation in pH adjustments for the different purification protocols. The occurrence of interconversion and oxidation reactions should be taken into consideration in sample preparation procedures for metabolomics analyses with a focus on folates.

Innovative programs are needed to build a pipeline of future nurse scientists necessary to generate practice-based evidence for optimal healthcare and to address the serious shortage of PhD-prepared nurses. This paper describes two nurse scholar programs based in one large, Magnet® designated healthcare institution that aim to provide clinical registered nurses (RNs) with mentored research opportunities in order to ultimately build an internal pipeline of practice-based nurse scientists. The Clinical Nurse Scholar Program provides clinical RNs the opportunity to conduct a research study under the mentorship of a senior nurse scientist. The Nursing Research Scholar Program provides a clinical RN enrolled in a PhD program or who recently completed a PhD program with an opportunity to gain enhanced research training and acquire new research skills. These two scholar models have the potential to be replicated in other institutions to enhance the development of future nurse scientists and to address a critical national shortage of PhD-prepared nurse scientists., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A round robin comparison was performed in order to test the performance of a recently developed LC-MS/MS method for quantification of 6 folate forms. Eighty-nine samples representing the food groups of fruits, vegetables, legumes, cereals, dairy products, meat, and offal were analyzed by two LC-MS/MS methods and a microbiological assay (MA). A plant-origin deconjugase enzyme (Arabidopsis thaliana) for deconjugation of folates (PE-LC-MS/MS), or animal-origin deconjugase (rat serum and chicken pancreas) (AE-LC-MS/MS) was used in the LC-MS/MS methods, each in a single enzymatic step. In contrast, the MA involved tri-enzyme extraction including human plasma as a deconjugase. A significant bias of 17% lower and 25% higher results was found when PE-LC-MS/MS was compared to MA and AE-LC-MS/MS, respectively. The PE-LC-MS/MS provides fast quantification of various folate vitamers and total folate content, which could be a proper substitute to the currently standardized but imprecise and time-consuming microbiological assay in the future., (Copyright © 2019. Published by Elsevier Ltd.)

A multitude of human nutritional supplements based on Chlorella vulgaris biomass has recently been introduced to the specialty food market. In this study, an analysis of total folate contents in Chlorella sp. and a series of marine microalgae was conducted to evaluate folate content in alternative algae-based food production strains. For the first time, total folate content and vitamer distribution in microalgae were analyzed by stable isotope dilution assay (SIDA) using LC-MS/MS, which has demonstrated its superiority with respect to folate quantification. Consistently, high folate contents were detected in all examined microalgae samples. High folate concentrations of 3,460 ± 134 μg/100 g dry biomass were detected in freshly cultivated Chlorella vulgaris , notably also in other well-researched microalgae strains. To that end, the highest folate content currently documented for any algae sample was measured in the marine microalgae Picochlorum sp. isolate with values of 6,470 ± 167 μg/100 g dry biomass. This calls for alternative products based on other algae biomass. Our data indicate that freshwater and marine microalgae provide extremely high concentrations of folates, which warrant further studies on the regulation of pteroylpolyglutamates in algae as well as on bioaccessibility, absorption, and retention in humans., (Copyright © 2020 Woortman, Fuchs, Striegel, Fuchs, Weber, Brück and Rychlik.)

As the popularity of tropical fruits has been increasing consistently during the last few decades, nutritional and health-related data about these fruits have been gaining more and more interest. Therefore, we analyzed 35 samples of tropical fruits and vegetables with respect to folate content and vitamer distribution in this study. The fruits and vegetables were selected by their availability in German supermarkets and were grouped according to their plant family. All fruits and vegetables were lyophilized and analyzed by stable isotope dilution assay (SIDA) and liquid chromatography mass spectrometry (LC-MS/MS). The results vary from 7.82 ± 0.17 µg/100 g in the horned melon to 271 ± 3.64 µg/100 g in the yellow passion fruit. The yellow passion fruit is a good source for meeting the recommended requirements, as just 110 g are needed to cover the recommended daily intake of 300 µg folate for adults; however, longan fruits, okras, pete beans, papayas, mangos, jack fruits, and feijoas are also good sources of folates. In conclusion, the study gives a good overview of the total folate content in a broad range of tropical fruits and vegetables and shows that some of these fruits definitely have the potential to improve the supply of this critical vitamin.

Folates play a key role in the prevention of neural tube defects in newborns. Thus, it is important to reliably determine the bioavailability of folates from various foods. Accurate analytical methods are essential for quantifying blood-folates, especially in human studies. Here, we present the development and validation of a sensitive method using stable isotope dilution liquid chromatography coupled with mass spectrometry for determining various folates in plasma. Moreover, this study reports the applicability of the developed method to a human pilot study using strawberries as a test food. Validation of the assay revealed the precision, sensitivity, and accuracy of the method in determining the predominant 5-methyltetrahydrofolate in plasma. This method was also applicable for the screening of individual folate status using finger prick blood and for monitoring the post-absorptive plasma-concentration curve. Moreover, the human study revealed a high recovery of strawberry folates with a calculated relative bioavailability of 96.2%. Thus, the developed method enables prospective bioavailability studies. This work also confirmed, via human studies, that strawberries are a rich and natural source of folates that are available for human metabolism., Competing Interests: The authors have declared that no competing interests exist.

Durian ( Durio zibethinus ) is a tropical fruit grown in Southeast Asia and highly appreciated by consumers throughout Asia. Folates are a group of vitamins and are essential nutrients for humans. Here we present the folate analysis of different durian cultivars as well as diverse durian products. An LC-MS/MS method and the application of a stable isotope dilution assay (SIDA) was used for quantitation of the folate vitamers 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, 10-formylfolate, tetrahydrofolate, and pteroylmonoglutamic acid by using [ 13 C 5 ]-labeled internal standards. Total folates varied from 175 to 440 μg/100 g for durian arils and from 15.0 to 417 μg/100 g for durian products. These contents are extraordinarily high compared to other fruits and may be correlated to the upregulated methionine biosynthesis pathway reported recently. In summary, the tropical fruit durian can be considered as a very rich dietary source of natural folates.

Folates play an important role in the human body and a deficiency of this vitamin can cause several diseases. Therefore, a reliable analytical method is crucial for the determination of folate vitamers in strawberries and other dietary folate sources. A stable isotope dilution LC-MS/MS method for analyzing folates in food was developed and validated. The folate vitamers Pteroylmonoglutamic acid, tetrahydrofolate, 5-methyltetrahydrofolate, and 5-formyltetrahydrofolate were quantified using 13 C-labeled internal standards. Validation of the assay was accomplished by determining linearity, precision, recovery, limit of detection, and limit of quantification and revealed to be a precise, sensitive, and accurate method to determine folate vitamers. Strawberries are worldwide consumed and known to be a good dietary source of nutritive compounds. Using this method, folate concentrations in selected commercial strawberry cultivars and experimental breeding lines grown in Germany and Australia were investigated. Total folates varied from 59 to 153 μg/100 g on fresh weight basis. Furthermore, folate content after lyophilizing or freezing did not show any significant differences compared to fresh strawberries. However, significant losses of total folates in pureed strawberries could be observed after 5 days of storage with only 16% of the original concentration retained. In summary, some of the investigated strawberry cultivars/breeding lines can be considered as rich dietary sources of natural folates.

This study evaluates the potential mechanism of action and bioactivity of black tea and black tea pomace for type 2 diabetes prevention via inhibition of carbohydrate hydrolyzing enzymes. Black tea leaves were extracted in hot water and black tea pomace was extracted in 70% acetone. The phenolic content of the water extract (WBT) and pomace acetone extracts (AOBT) were 5.77 and 8.9 mg/mL, respectively, both based on the same concentration of solid tea in the extract. The water extract was subjected to C18 extraction and the resulting hydrophobic fraction (HBBT) was further subjected to LH-20 extraction to recover a low molecular weight phenolic enriched fraction (LMW) and a high molecular weight enriched fraction (HMW). The phenolic content of the LMW and HMW fraction were 1.42 and 2.66 mg/mL, respectively. Among water extracts the HMW fraction was most bioactive against α-glucosidase (IC50 = 8.97 μg/mL) followed by HBBT fraction (IC50 = 14.83 μg/mL). However, the HBBT fraction was the most bioactive fraction against α-amylase (IC50 = 0.049 mg/mL). The black tea pomace (AOBT) had significant α-glucosidase inhibitory activity (IC50 = 14.72 μg/mL) but lower α-amylase inhibitory activity (IC50 = 0.21 mg/mL). The phenolic profiles for LMW and HMW fractions were evaluated using HPLC and the differences between the two profiles were identified. Further research is underway to identify and evaluate the phenolic compounds that are present in the HMW fraction. Our findings suggest that black tea and black tea pomace has potential for carbohydrate hydrolyzing enzyme inhibition and this activity depends on high molecular weight phenolic compounds.