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College students with learning disabilities face a number of challenges in postsecondary education and a lower graduation rate when compared with their peers who do not have a learning disability (Fernandez & Santi, 2016; Kreider, 2020). In response to this discrepancy, we designed a peer mentoring program utilizing mentors who are enrolled in a graduate counseling program that emphasizes a solution-focused (SF) approach. Two students, both women and diagnosed with dyslexia, engaged in six meetings with their respective mentors. These meetings involved solution-focused conversations about their strengths, goals, and successes, as well as academic coaching in the form of study skills psychoeducation for areas that they had identified. The LASSI was used both for goal exploration and assessment of executive functioning. Both participants showed increases on the Anxiety, Concentration, and Time Management scales on the LASSI, and they reported benefits to their study strategies, personal insights on their self-efficacy, and improvements to their mental health.

In response to an unprecedented demand for services, college counseling centers have been forced to innovate new strategies to meet student demand and protect staff from burnout. One private university developed a unique Comprehensive Collaborative Care Model. Drawing on the tradition of collegiate recovery communities, this model includes the use of Peer Support Communities (PSCs). This brief discusses the structure of PSCs, as well as the positive response from both students and staff.

Higher education is a predictor of employment for individuals who have an autism spectrum disorder (ASD), and an increasing number of students with ASD are enrolling in college. However, deficits in executive functioning (EF) make academic success difficult. This systematic review of literature identified ten research studies examining the effects of college supports for students with ASD that targeted an aspect of EF, specifically working memory, cognitive flexibility, inhibitory control, self-regulation, organization, and time management. Common supports included mentorship and group therapy, with interventions often facilitated by graduate or peer students. Although outcomes were generally positive, most researchers relied on participant feedback rather than objective measures of executive function.

Accurately estimating the risk of sensitive populations subjected to toxicant disturbances is central to our ability to protect ecosystem services. While the gold standard for assessing risk historically involves static measures such as the LD50 or LC50, more sophisticated approaches have been developed in an attempt to capture more nuanced outcomes. In the 1980s the International Organization for Biological Control (IOBC) developed a tiered approach to determine the compatibility of pesticides and natural enemies in the context of integrated pest management (IPM). We analyzed the IOBC approach using stage-based matrix models to project population outcomes for four parasitoid species, Diaeretiella rapae, McIntosh, Fopius arisanus, (Sonan), Diachasmimorpha longicaudata Ashmead, Psyttalia fletcheri (Silvestri) and the predator, Coccinella septempunctata L. By imposing mortality levels in matrix models equivalent to those outlined in the IOBC Tier 1 Class 1 (29 %) (harmless) and Class 2 (79 %) (slightly harmful) mortality classes, we explored discrepancies between the IOBC approach and population outcomes generated by these models. Our results highlight that the IOBC Class 1 and 2 levels of mortality are too high to protect many natural enemies from pesticides, setting the stage for unrealistically optimistic views of pesticide compatibility in many cases. Furthermore, a one size fits all approach to protect natural enemies from pesticides does not work because of differences in demographic rates among species which will be less negatively affected by Tier 1 levels of mortality and those that do not reproduce quickly and will thus be more vulnerable to pesticides. Therefore, the IOBC method should be used cautiously if at all, and results should be interpreted with the caveats and pitfalls highlighted here. Results of this study indicate that it is time to reevaluate how we estimate pesticide compatibility with natural enemies and adjust the methods and mortality thresholds based on more realistic measures of toxicity.

Xeroderris stuhlmannii (Fabaceae) is a medicinal reported in Cameroonian herbal medicine to treat hypertension. The aim of the study was to assess the antihypertensive and antioxidant activities of X. stuhlmannii aqueous leaf extract (AEXS) on cadmium chloride-induced hypertensive rats. The in vitro antioxidant activities of AEXS were investigated for their radical scavenging potency using 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric reducing antioxidant power (FRAP), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), Nitric oxide (NO) and OH- assays completed with oxidative stress markers analyses. Antihypertensive activity of AEXS (35, 100, and 300 mg/kg) was assessed in CdCl2 induced-hypertensive rats. Antihypertensive activities performed include systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) variation, followed by evaluation of selected biochemical parameters in urine, blood (Alanine aminotransferase (ALT), aspartate aminotransferase (AST)), creatinine, urea and total protein) and histological examination of tissue samples (aorta, heart, kidneys and liver). The amount of the phenols of the leaf extract was estimated in mg gallic acid equivalent and identification of some compounds was done by UPLC-UV-ESI-TOF-MS. Accordingly, the identified phenols were stuhlmannione A (1), formononetin (2), stuhlmarotenoid A (3), 9-methoxymaackiain (4), 4-hydroxymaackiain (5) and 7-hydroxy-3′,4′-methylenedioxy-isoflavone (6). The extract exhibited a significant (P

Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.

Objective: Lipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health. Methods: Male and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10–12 and 16–18 weeks of age. Markers of kidney health and blood lipid and hormone concentrations were analyzed. Kidney and blood lysophosphatidic acid (LPA) levels were measured, and a role for LPA in mediating impaired glycemic control was evaluated using the LPA receptor 1/3 inhibitor Ki-16425. Results: All groups remained insulin sensitive, but 16- to 18-week-old male RT-SAKO mice became glucose intolerant, without developing kidney inflammation or fibrosis. Rather, these mice displayed lower circulating insulin and glucagon-like peptide 1 (GLP-1) levels. Impaired first-phase glucose-stimulated insulin secretion was detected and restored by Exendin-4. Kidney and blood LPA levels were elevated in older male but not female RT-SAKO mice, associated with increased kidney diacylglycerol kinase epsilon. Inhibition of LPA-mediated signaling restored serum GLP-1 levels, first-phase insulin secretion, and glucose tolerance. Conclusions: TAG over-storage alone is insufficient to cause renal tubule lipotoxicity. This work is the first to show that endogenously derived LPA modulates GLP-1 levels in vivo, demonstrating a new mechanism of kidney-gut-pancreas crosstalk to regulate insulin secretion and glucose homeostasis.

Abstract The frequency, severity, and spatial extent of destructive wildfires have increased in several regions globally over the past decades. While direct impacts from wildfires are devastating, the hazardous legacy of wildfires affects nearby communities long after the flames have been extinguished. Post‐wildfire soil conditions control the persistence, severity, and timing of cascading geohazards in burned landscapes. The interplay and feedback between geohazards and wildfire‐induced changes to soil properties, land cover conditions, and near‐surface and surface processes are still poorly understood. Here, we synthesize wildfire‐induced processes that can affect the critical attributes of burned soils and their conditioning of subsequent geohazards. More specifically, we discuss the state of knowledge pertaining to changes in mineralogical, hydraulic, mechanical, and thermal properties of soil due to wildfire with a focus on advances in the past decade. We identify how these changes in soil properties alter evapotranspiration, interception, sediment transport, infiltration, and runoff. We then link these alterations to the evolution of different geohazards, including dry raveling, erosion, rockfalls, landslides, debris flows, and land subsidence. Finally, we identify research gaps and future directions to advance knowledge on how wildfires control the evolution of various earth surface processes and geohazards over time.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Total ankle arthroplasty (TAA) is a common procedure to treat end stage ankle osteoarthritis. Despite recent increase in popularity, there is limited literature assessing clinical and patient-reported outcomes (PROs) in TAA procedures using 5 current generation implants. These measures are an important tool for physicians to better assess patient performance in daily activities. The purpose of this study is to characterize both PROs and clinical outcomes in primary and revision TAA surgeries using current generation prostheses performed by non-design surgeons at a single institution. Methods: Our institution maintains a prospective outcomes registry for patients undergoing TAA at our institution. Patient demographics, relevant case information, PROs and complications are collected. Collected PROs include PROMIS Physical Function (PF), Pain Interference (PI), Depression, Global Physical Health (GPH), Global Mental Health (GMH), and Foot and Ankle SANE. Records are categorized as a primary TAA, or revision involving either a polyethylene only exchange or complete hardware removal and replacement. Differences between groups were determined non-parametrically using Mann-Whitney U tests. In all statistical tests, a p value of less than 0.05 was considered significant. Results: A total of 259 patients were included for analysis; 223 primary and 36 partial or full revision. Average length of stay was 1.6 ± 1 days. There were 18 reoperations (6.95%), with no implant failures within 1 year. Five patients underwent implant revision at an average of 2.5 years. Of these, one was related to delayed infection at year 3, two due to hardware failure in year 2, and 2 polyethylene exchanges in years 2 and 5. All physical health PRO measures showed significant improvements post-operatively (p < 0.0001). Patients reported significant reductions in pain following TAA at 3-months (Figure 1a), and significant improvement of physical function after 6-months (Figure 1b). There were no significant changes in Depression or GMH (Figure 1d). Conclusion: Total ankle arthroplasty is a safe and effective procedure for end-stage ankle arthritis. Patients experience improvement in all physical health PRO metrics at all post-operative time points after 3 months. Complication and early failure rates are lower than that reported in the literature. Long term outcomes and implant longevity will be tracked using the CU Total Ankle Registry. Total ankle arthroplasty improves quality of life in patients suffering from ankle osteoarthritis. Further follow-up and patient enrollment in the CU Total Ankle Registry will help us to identify risk factors for complications and define implant lifespan.

Category: Hindfoot; Ankle Introduction/Purpose: Both prefabricated and custom-made foot orthoses have long been effective treatment foot and ankle conditions and deformities. Foot orthoses function by replacing the insole of a shoe to redistribute forces during weightbearing activities and can be a cost-effective and noninvasive treatment modality. Custom foot orthoses are created using a 3D scan or weightbearing impression of the patient’s foot and are intended to accommodate a patient’s foot anatomy, whereas prefabricated (off the shelf) orthoses are often prescribed unaltered or minimally modified. Custom orthoses have a much higher cost and are variably covered by insurance. The aim of this study is to compare the effectiveness of custom versus prefabricated foot orthoses for foot and ankle conditions using validated patient-reported outcome scales. Methods: Consecutive patients prescribed custom or prefabricated orthoses at a single institution were retrospectively reviewed. Following IRB approval, a follow-up research survey was distributed to patients to collect patient-reported outcomes. Collected outcome measures included the Foot and Ankle Single Assessment Numeric Evaluation (FA SANE), PROMIS Mobility, PROMIS Pain Interference (PI), and PROMIS Physical Function (PF). All patients with a baseline and minimum three-month follow-up score were included in the final sample. Statistical analysis was conducted using the ANOVA statistical test. In all cases, a p-value of less than 0.05 was considered significant. Results: A total of 238 patient records were included. 152 patients received a custom orthosis, while 86 patients received a prefabricated orthosis. Both groups reported significant improvement from baseline to follow-up in the FA SANE, PROMIS PI and PROMIS PF (p < 0.001). However, assessing PROMIS Mobility, we did not observe a significant difference in improvement from baseline to follow-up in either group. Comparing outcomes between groups, patients receiving custom orthoses reported significantly greater PF at follow-up compared to the prefabricated group (p < 0.05). However, at follow-up there was no significant difference between the custom and prefabricated groups in PI, Mobility, or FA SANE. Mean satisfaction scores were significantly higher for patients with custom orthotics compared to prefabricated orthotics (8.1 vs. 7.5, p < 0.01). Conclusion: Both custom and prefabricated foot orthoses result in improvement in pain and physical function over time. Although the results found in this study lacked definitive evidence in favor of the custom orthoses over prefabricated orthoses, overall patient-reported outcomes were higher for patients receiving custom orthoses. Further research, including longer term follow up, differentiation based on specific clinical diagnoses and deformities, and subsequent need for surgery may ultimately lead to definitive guidelines for custom versus prefabricated orthoses.

Abstract Barth syndrome (BTHS) is caused by mutations in the TAZ gene encoding the cardiolipin remodeling enzyme, Tafazzin. The study objective was to quantitatively examine growth characteristics and mitochondrial morphology of transformed lymphoblast cell lines derived from five patients with BTHS relative to five healthy controls, as well as the therapeutic potential of oleoylethanolamide (OEA) and linoleoylethanolamide (LEA). These bioactive lipids both activate PPARα, which may be therapeutic. BTHS lymphoblasts grew more slowly than controls, suggesting lymphopenia merits clinical investigation. Treatment of BTHS lymphoblasts with OEA, but not LEA, significantly restored mitochondrial membrane potential, as well as colony growth in all BTHS lymphoblast lines, although a full growth rescue was not achieved. Quantification analysis of electron micrographs from three BTHS and healthy lymphoblast donors indicated similar numbers of mitochondria per cell, but lower average cristae length per mitochondrion, and higher mitochondrial density. Additionally, BTHS lymphoblasts had larger mitochondria, and a higher percentage of abnormally large mitochondria (> 1 μm2) than healthy controls. Notably, OEA treatment significantly restored mitochondrial size, without affecting density or cristae lengths. Cardiolipin total content, relative linoleic acid content and monolysocardiolipin:cardiolipin ratios were not improved by OEA, indicating that effects on growth, and mitochondrial morphology and function, occurred without resolving this deficit. However, immunoblotting showed higher levels of OPA1, a biomarker for mitochondrial fusion, in BTHS lymphoblasts, which was attenuated by OEA treatment, implicating altered mitochondrial dynamics in the pathology and treatment of BTHS.

The common daisy (Bellis perennis) belongs to the family Asteraceae and, in recent years, some new research has been published on the bioactive compounds and biological activities of its extracts. In 2014, the knowledge was partially summarized, but several new studies have been published in the last nine years. In addition, the substances were tabularly consolidated to give a comprehensive overview of over 310 individual components, compound classes, and bioactivities, as well as their accurate plant organ origin. The latest results have shown that the plant has antioxidative, antimicrobial, anticancerogenic, wound healing, antidepressive, anxiolytic, nephroprotective, and insulin mimetic effects, as well as an effect on lipid metabolism. Some studies in the field of homeopathy were also listed. Ideally, a biological effect and one or several compound(s) can be correlated. However, the compounds of the extracts used have often been qualified and quantified, but it remains unclear which of these substances have an activity. The works often stick at the level of the crude extract or a fraction, but not at a single purified and tested compound and, consequently, they are hampered by a missing comprehensive bioactivity workflow. This review provides a critical overview and gaps and offers a basis for further research in this area.

Barth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but age-related changes have been reported in female carriers of other X-linked disorders. Therefore, we examined the phenotype of female mice heterozygous for deletion of the tafazzin gene (Taz-HET) at 3 and 12 months of age. Food intakes, body masses, lean tissue and adipose depot weights, daily activity levels, metabolic measures, and exercise capacity were assessed. Age-related changes in mice resulted in small but significant genotype-specific differences in Taz-HET mice compared with their female Wt littermates. By 12 months, Taz-HET mice weighed less than Wt controls and had smaller gonadal, retroperitoneal, and brown adipose depots and liver and brain masses, despite similar food consumption. Daily movement, respiratory exchange ratio, and total energy expenditure did not vary significantly between the age-matched genotypes. Taz-HET mice displayed improved glucose tolerance and insulin sensitivity at 12 months compared with their Wt littermates but had evidence of slightly reduced exercise capacity. Tafazzin mRNA levels were significantly reduced in the cardiac muscle of 12-month-old Taz-HET mice, which was associated with minor but significant alterations in the heart cardiolipin profile. This work is the first to report the characterization of a model of female carriers of heterozygous tafazzin deficiency and suggests that additional study, particularly with advancing age, is warranted.

This paper analyzes two tailings dam databases and recent failures to assess the local and global failure rates of upstream, downstream, and centerline raised tailings dams. Since 2000, the failure rate for all three raising methods has decreased except in Brazil, which helps explain the recent Brazilian regulations banning upstream raising. However, the failure rates also show that the downstream and centerline raising methods of tailings dams are not immune to failure, so, if mining continues, one of these three raising methods will be used, and all have been involved in prior failures. The paper also presents data on failure mechanisms, showing that slope stability, earthquakes, and overtopping are the three primary causes of tailings dam failures. To continue decreasing the failure rate of tailings dams, the following features and practices should be used in all types of tailings dams: drainage systems, engineering analyses, instrumentation, monitoring, inspection, and qualified external peer review to further reduce the failure rates, especially in Brazil. Finally, a section containing data on release volume as a function of dam height and total storage volume is presented.

The phytochemical study of the ethanolic extract of the leaf of Xeroderris stuhlmannii led to the isolation of five hitherto unreported compounds including two isoflavones (1–2), and three rotenoids (3–5), along with eight known isoflavonoid derivatives (6–13) and one pterocarpan derivative (14). The structures of the new compounds and those of the known ones were established by the spectroscopic (1D and 2D NMR) and spectrometric (HRESIMS) techniques as well as a comparison of their spectroscopic data with those reported in the literature. The leaf extract, fractions, and isolated compounds were tested for their antibacterial effects against nine bacterial strains. Compounds 3, 8, 11, and 12 showed a significant antibacterial effect, with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL each, against Salmonella typhi, Staphylococcus aureus, Klessiella pneumonae, and Escherichia coli, respectively. In addition, the leaf extract, fractions, and isolated compounds were tested for their antifungal effects against four fungal strains. The hexane fraction showed a significant antifungal effect with an MIC value of 125 µg/mL against Candida parasilosis, whereas compounds 3, 8, and 12 showed significant antifungal activity with an MIC value of 62.5 µg/mL, each against Candida parasilosis, Candida albicans, and Candida krusei, respectively.

Bacillus cereus plays an often unrecognized role in food borne diseases. Food poisoning caused by this pathogen is manifested by either diarrhea or emesis. Due to the relatively high prevalence of emetic toxin cereulide associated food poisoning, methods for simple and reliable detection of cereulide producing strains are of utmost importance. Recently, two different studies reported on the application of MALDI-ToF MS for either the differentiation of emetic and non-emetic strains of B. cereus or for direct detection of cereulide from bacterial colony smears. However, for implementation of cereulide detection using MALDI-ToF MS in routine microbiological diagnostics additional investigations on the sensitivity and specificity as well as on the fitting into common workflows for bacterial identification are needed. These aspects prompted us to investigate open issues and to test sample preparation methods, commonly used for microbial identification for their suitability to detect the emetic toxin from bacteria. Based on our experimental findings we propose a workflow that allows identification of B. cereus and sensitive detection of cereulide in parallel, using linear-mode MALDI-ToF MS equipment. The protocol was validated in a blinded study and is based on the well-established ethanol/formic acid extraction method. Cereulide is detected in the ethanol wash solution of samples identified as B. cereus as peaks at m/z 1175 and 1191. Peak position difference of 16 Th (Thomson) indicates detection of the sodium and potassium adducts of cereulide. This sample treatment offers possibilities for further characterization by more sophisticated LC-MS-based methods. In summary, the ease of use and the achieved level of analytical sensitivity as well as the wide-spread availability of MALDI-ToF MS equipment in clinical microbiological laboratories provides a promising tool to improve and to facilitate routine diagnostics of B. cereus associated food intoxications.

Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.

The aroma of pea protein (Pisum sativum L.) was decrypted for knowledge-based flavor optimization of new food products containing pea protein. Sensomics helped to determine several volatiles via ultra-high performance liquid chromatography tandem mass spectrometry and 3-nitrophenylhydrazine derivatization. Among the investigated volatiles, representatives of aldehydes, ketones, and acids were reported in literature as especially important in pea and pea-related matrices. After validation of the method and quantitation of the corresponding analytes, sensory reconstitution as well as omission studies of a selected pea protein were performed and revealed nine odor-active compounds as key food odorants (3-methylbutanal, hexanal, acetaldehyde, (E,E)-2,4-nonadienal, (E)-2-octenal, benzaldehyde, heptanal, 2-methylbutanal, and nonanoic acid). Interestingly, eight out of nine compounds belonged to the chemical class of aldehydes. Statistical heatmap and cluster analysis of all odor activity values of different pea proteins confirmed the obtained sensory results and generalize these nine key food odorants in other pea proteins. The knowledge of key components gained shows potential for simplifying industrial flavor optimization of pea protein-based food.

The emetic Bacillus cereus toxin cereulide (1) poses a significant safety risk in the food industry, causing emesis and nausea after consumption of contaminated foods. Analogously to cereulide, the structures of various isocereulides, namely, isocereulides A–G, have been recently reported and could also be identified in B. cereus-contaminated food samples. The HPLC fractionation of B. cereus extracts allows us to isolate additional isocereulides. By applying MSn sequencing, post-hydrolytic dipeptide, amino acid and α-hydroxy acid analyses using UPLC-ESI-TOF-MS to purify the analytes, seven new isocereulides H–N (2–8) could be elucidated in their chemical structures. The structure elucidation was supported by one-dimensional and two-dimensional NMR spectra of the isocereulides H (2), K (5), L and N (6 + 8) and M (7). The toxicity of 2–8 was investigated in a HEp-2 cell assay to determine their respective 50% effective concentration (EC50). Thus, 2–8 exhibited EC50 values ranging from a 0.4- to 1.4-fold value compared to cereulide (1). Missing structure-activity correlations indicate the necessity to determine the toxic potential of all naturally present isocereulides as single compounds to be able to perform a thorough toxicity evaluation of B. cereus-contaminated foods in the future.

Abstract Background Human biomonitoring represents an important tool for health risk assessment, supporting the characterization of contaminant exposure and nutrient status. In communities where country foods (locally harvested foods: land animals, fish, birds, plants) are integrated in the daily diet, as is the case in remote northern regions where food security is a challenge, such foods can potentially be a significant route of contaminant exposure. To assess this issue, a biomonitoring project was implemented among Dene/Métis communities of the Dehcho region of the Northwest Territories, Canada. Methods Participants completed dietary surveys (i.e., a food frequency questionnaire and 24-h recall) to estimate food consumption patterns as well as a Health Messages Survey to evaluate the awareness and perception of contaminants and consumption notices. Biological sampling of hair, urine and blood was conducted. Toxic metals (e.g., mercury, lead, cadmium), essential metals (e.g., copper, nickel, zinc), fatty acids, and persistent organic pollutants (POPs) were measured in samples. Results The levels of contaminants in blood, hair and urine for the majority of participants were below the available guidance values for mercury, cadmium, lead and uranium. However, from the 279 participants, approximately 2% were invited to provide follow up samples, mainly for elevated mercury level. Also, at the population level, blood lead (GM: 11 μg/L) and blood cadmium (GM: 0.53 μg/L) were slightly above the Canadian Health Measures Survey data. Therefore, although country foods occasionally contain elevated levels of particular contaminants, human exposures to these metals remained similar to those seen in the Canadian general population. In addition, dietary data showed the importance and diversity of country foods across participating communities, with the consumption of an average of 5.1% of total calories from wild-harvested country foods. Conclusion This project completed in the Mackenzie Valley of the Northwest Territories fills a data gap across other biomonitoring studies in Canada as it integrates community results, will support stakeholders in the development of public health strategies, and will inform environmental health issue prioritization.

DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma DHA increases, but the mechanism is not fully understood. Using rats fed a fixed-formula diet (DHA as 0.07% total energy), plasma and liver were collected for fatty acid profiling before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. Phosphatidylethanolamine methyltransferase (PEMT) and enzymes involved in PUFA synthesis were examined in liver. Ad hoc transcriptomic and lipidomic analyses were also performed. With pregnancy, DHA increased in liver and plasma lipids, with a large increase in plasma DHA between day 15 and day 20 that was mainly attributed to an increase in 16:0/DHA phosphatidylcholine (PC) in liver (2.6-fold) and plasma (3.9-fold). Increased protein levels of Δ6 desaturase (FADS2) and PEMT at day 20 and increased Pemt expression and PEMT activity at day 15 suggest that during pregnancy, both DHA synthesis and 16:0/DHA PC synthesis are upregulated. Transcriptomic analysis revealed minor changes in the expression of genes related to phospholipid synthesis, but little insight on DHA metabolism. Hepatic PEMT appears to be the mechanism for increased plasma 16:0/DHA PC, which is supported by increased DHA biosynthesis based on increased FADS2 protein levels.

Cultivated carrot is one of the most important vegetable plants in the world and favored by consumers for its typically sweet flavor. Unfortunately, the attractive sensory quality is hindered by a sporadic bitter off-taste. To evaluate the influence of the abiotic stress conditions, waterlogging and drought, on the bitter sensometabolome as well as agronomical traits of six genotypes of Daucus carota, a field trial was performed. Enabling the accurate tracing of carrots’ bitter compounds and therefore their metabolic changes, a fast and robust high-throughput UHPLC-MS/MS was developed and validated. Remarkably, the genotypes are the driving source for the biological fate of the bitter metabolites that are reflected in concentrations, dose-over-threshold factors, and fold changes. A certain influence of the irrigation level is observable but is overruled by its cultivar. Therefore, metabolic stress response in carrots seems to be genotype dependent. Hence, this study might help to plant specific carrot genotypes that are adapted to stress conditions evoked by future climatic changes.

Acylglycerophosphate acyltransferase 4 (AGPAT4)/lysophosphatidic acid acyltransferase delta catalyzes the formation of phosphatidic acid (PA), a precursor of triacyl­glycerol (TAG). We investigated the effect of Agpat4 gene ablation on white adipose tissue (WAT) after finding consistent expression across depots. Epididymal WAT mass was 40% larger in male Agpat4−/− mice than wild-type littermates, but unchanged in perirenal, retroperitoneal, and inguinal WAT and subscapular brown adipose tissue. Metabolic changes were identified in epididymal WAT that were not evident in perirenal WAT, which was analyzed for comparison. The total epididymal TAG content doubled, increasing adipocyte cell size without changing markers of differentiation. Enzymes involved in de novo lipogenesis and complex lipid synthesis downstream of phosphatidic acid production were also unchanged. However, total epididymal TAG hydrolase activity was reduced, and there were significant decreases in total ATGL and reduced phosphorylation of hormone-sensitive lipase at the S563 and S660 PKA-activation sites. Analysis of Agpats 1, 2, 3, and 5, as well as Gpats 1, 2, 3, and 4, demonstrated compensatory upregulation in perirenal WAT that did not occur in epididymal WAT. Our findings therefore indicate depot-specific differences in the redundancy of Agpat4 and highlight the molecular and metabolic heterogeneity of individual visceral depots.

Long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) have in some studies been associated with cognitive and socioemotional outcomes in children, but results are inconsistent possibly due to the use of different tests and potential gender-specific effects. The objective of this cross-sectional study was to explore overall patterns in neuropsychological scores as well as correlations between scores within specific domains, and to examine potential gender differences and consistency in associations with n-3 LCPUFA status. In 199 Danish 8-9 year-old children, we performed a large battery of tests and questionnaires on attention, processing speed, executive functions, memory, and socioemotional traits, and measured erythrocyte fatty acid composition. Principal component analyses (PCA) showed that most of the variation in both cognitive performance and socioemotional traits was explained by overall performance, followed by speed-accuracy trade off and externalizing vs. internalizing problems, respectively. Boys had higher speed, lower attention and higher externalizing problem scores than girls. Measures of performance within both processing speed and attention domains correlated moderately, whereas no correlations were found for measures of executive functions apart from some weak correlations for impulsivity. Parent-rated scores for both externalizing and internalizing problems correlated strongly, whereas correlations with child-rated scores were weak. Scores within specific domains did not consistently associate with n-3 LCPUFA, except for processing speed measures which all pointed to faster processing with increased n-3 LCPUFA status. Gender differences in the associations were observed for attention and impulsivity. Child- but not parent-rated internalizing and social problems tended to associate directly with n-3 LCPUFA, supported by increased internalizing problems measured by the PCA component. In conclusion, measures of speed and attention seem to represent these domains in general, whereas single measures of more complex cognitive functions should be interpreted with caution. One approach could be to use multiple tests and create multivariate scores to guide interpretations. Furthermore, the results indicate a need to consider both parent- and child-rated socioemotional scores and gender differences in neuropsychological functions e.g. in investigations of n-3 LCPUFA effects.

In order to gain a more comprehensive knowledge of the chemical nature of creaminess-related flavor compounds in milk chocolates on a molecular level, crumb chocolate was analyzed by means of activity guided screening techniques. Sensory studies of a triglyceride-free lipid emulsion indicated that the n-pentane extract showed the highest impact regarding creaminess sensation. Enhancement of creaminess by adding anhydrous milk fat fractions to chocolate was demonstrated by fractionated high-vacuum distillation of different fats associated with the chocolate production combined with sensory experiments. Syntheses of various δ-lactones and the quantification of these sensory active semi-volatiles led to the conclusion that the anhydrous milk fat contains a series of γ- and δ-lactones. Cocoa butter revealed a high concentration of δ-hexadecalactone, too. Experiments suggested that lactones are generated from the potential precursors monohydroxyalkanoic acid(s) esterified (mono-tri)glyceride(s) during heating. Sensory studies exhibited recognition thresholds of 29–40 µmol/kg for the long-chain δ-lactones in crumb chocolate. Furthermore, significant enhancement of the retro-nasal creamy flavor was found for δ-tetradecalactone.

The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A–G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an l-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESI-TOF-MS, as well as MSn sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the l-O-Leu as assumed to date, one l-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(d-O-Leu-d-Ala-l-O-Val-l-Val)2(d-O-Leu-d-Ala-l-O-Ile-l-Val)].

Data are presented on the fatty acyl composition of phospholipid from retroperitoneal white adipose tissue of female mice that were either given ad libitum access to food or fasted for 16 h overnight prior to sacrifice. Our data show that total adipose phospholipid concentrations were more than 2-fold higher in the fasted animals compared with the fed animals (33.48±7.40 versus 16.57±4.43 μg phospholipid fatty acids/100 mg tissue). Concentrations of several individual phospholipid fatty acyl species, including palmitic acid (16:0), vaccenic acid (18:1n-7), linoleic acid (18:2n-6), dihomo-gamma-linolenic acid (20:3n-6), arachidonic acid (20:4n-6), eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), as well as total phospholipid saturated fatty acids, n-6 polyunsaturated fatty acids and n-3 polyunsaturated fatty acids, were significantly higher in adipose tissue from the fasted animals compared with the fed animals. However, when the relative abundance of phospholipid fatty acyl species was analyzed, only 20:4n-6 was specifically enriched (by ~2.5-fold) in adipose phospholipid with fasting.

Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg-1 body weight to study acute effects or using daily doses of 10 μg cereulide kg-1 body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations.