Search

Comprehensive in-depth structural characterization of free mono-unsaturated and polyunsaturated fatty acids often requires the determination of carbon-carbon double bond positions due to their impact on physiological properties and relevance in biological samples or during impurity profiling of pharmaceuticals. In this research, we report on the evaluation of disulfides as suitable derivatization reagents for the determination of carbon-carbon double bond positions of unsaturated free fatty acids by UHPLC-ESI-QTOF-MS/MS analysis and SWATH (sequential windowed acquisition of all theoretical mass spectra) acquisition. Iodine-catalyzed derivatization of C = C double bonds with dimethyl disulfide (DMDS) enabled detection of characteristic carboxy-terminal MS2 fragments for various fatty acids in ESI negative mode. The determination of double bond positions of fatty acids with up to three double bonds, the transfer of the method to plasma samples, and its limitations have been shown. To achieve charge-switching for positive ion mode MS-detection, derivatization with 2,2'-dipyridyldisulfide (DPDS) was investigated. It enabled detection of both corresponding characteristic omega-end- and carboxy-end-fragments for fatty acids with up to two double bonds in positive ion mode. It provides a straightforward strategy for designing MRM transitions for targeted LC-MS/MS assays. Both derivatization techniques represent a simple and inexpensive way for the determination of double bond positions in fatty acids with low number of double bonds. No adaptation of MS hardware is required and the specific isotopic pattern of resulting sulfur-containing products provides additional structural confirmation. This reaction scheme opens up the avenue of structural tuning of disulfide reagents beyond DMDS and DPDS using reagents like cystine and analogs to achieve enhanced performance and sensitivity., (© 2024. The Author(s).)

Limited research on diabetes education and support implementation in Appalachia, which is a critical knowledge gap considering barriers to care, and high prevalence rates. The aim was to understand what each facility is providing regarding diabetes education and services within West Virginia. This study reports cognitive interview qualitative findings from a multi-methods study. Individuals were recruited through an online search to identify clinics, organizations, and hospital staff that provided diabetes education in the state of West Virginia. Eligible participants were individuals who facilitated and managed diabetes education and support in counties of West Virginia. The interviews followed an 11-item interview guide, approved, and reviewed by a practicing Registered Dietitian and Certified Diabetes Care Education Specialist in West Virginia. All qualitative data from the interviews were hand-coded using grounded theory, by two researchers. 15 participating organizations from the state of West Virginia were included and described three phenomena: Diabetes Education Implementation (differences in: evaluation measures, modality, delivery format, topical areas); Barriers to Care (staffing, lack of training, evaluation, loss of research partnerships and funding); and Facilitators to Care (community-based involvement, interdisciplinary collaboration, capacity building (trainings). There are concerns with program drift and "risky" adaptations such as inconsistent evaluative measures, lack of training for program facilitators, variety of delivery formats, and content material. Findings recommend more alignment in program delivery to better implementation. Further studies should assess patient experiences with implemented diabetes education programs in West Virginia to further support the current research findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cathepsins (Cats) are proteases that mediate the successful entry of SARS-CoV-2 into host cells. We designed and synthesized a tailored series of 21 peptidomimetics and evaluated their inhibitory activity against human cathepsins L, B, and S. Structural diversity was realized by combinations of different C-terminal warhead functions and N-terminal capping groups, while a central Leu-Phe fragment was maintained. Several compounds were identified as promising cathepsin L and S inhibitors with K i values in the low nanomolar to subnanomolar range, for example, the peptide aldehydes 9a and 9b ( 9a , 1.76 nM, CatL; 0.512 nM, CatS). The compounds' inhibitory activity against the main protease of SARS-CoV-2 (M 9b ) was additionally investigated. Based on the results at CatL, CatS, and M pro ) was additionally investigated. Based on the results at CatL, CatS, and M pro , selected inhibitors were subjected to investigations of their antiviral activity in cell-based assays. In particular, the peptide nitrile 11e exhibited promising antiviral activity with an EC 50 value of 38.4 nM in Calu-3 cells without showing cytotoxicity. High metabolic stability and favorable pharmacokinetic properties make 11e suitable for further preclinical development., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF 2 X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF 2 X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF 2 X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, reveals a highly interesting binding mode for fragment 23 in JNK3, featuring an XB of CF 2 Br toward the P-loop, as well as chalcogen bonds. We suggest that underexplored chemical space combined with unconventional binding modes provides excellent opportunities for patentable chemotypes for therapeutic intervention.

The prevalence of obesity continues to rise. Preventing obesity, especially childhood obesity, is critically important. Parents, especially mothers, play a vital role in preventing childhood obesity. Numerous factors, such as maternal employment, may influence maternal weight-related practices and home environment characteristics that affect the risk of childhood obesity. Given the prevalence of both childhood obesity and maternal employment, this study was conducted to examine how weight-related maternal, child, and household behaviors as well as home environment characteristics differ by maternal employment hours and extends existing research by examining work impact on behaviors and home characteristics. U.S. mothers (n = 527) with at least one school-age child (6 to 11 years), who were between the ages of 25 and 54 years and the main food gatekeeper in the household completed an online survey. ANOVA comparisons of non-working, part-time employed, and full-time employed mothers revealed few differences in any of the variables studied. Cluster analysis of the 336 employed mothers based on six work impact scale scores found three unique clusters characterized as Enthusiastic Earners, Indifferent Earners, and Strained Earners. Few differences in sociodemographic and job characteristics occurred among clusters and the differences noted had small effect sizes. Clusters did not differ by maternal BMI or perceived child weight status. However, the clusters differed in numerous weight-related behaviors and home environment characteristics. Future research should aim to determine the direction of the associations of work impact with weight-related behaviors and home environments as well as identify potential strategies for overcoming the negative effects of employment on weight-related behaviors and environments and weight status as well as clarify other factors that may affect maternal work impact, such as time management, reasons for employment, and stress.

Background: The prevalence of food insecurity and its relationship to diet quality are factors impacting the health of persons living across the United States-affiliated Pacific region (USAP)., Objectives: The aim of this study was to describe characterize the relationship between household food security status and diet quality of 2- to 8-y-old children across jurisdictions in the USAP., Methods: Baseline data from 2- to 8-y-olds (n = 3099) enrolled in the Children's Healthy Living Program for Remote Underserved Minority Populations in the Pacific region, an obesity prevention study conducted in communities across Alaska, American Samoa, Commonwealth of the Northern Mariana Islands (CNMI), Guam, and Hawaii, and a concomitant prevalence study in communities across the Freely Associated States (FAS) (the Federated States of Micronesia: Kosrae, Pohnpei, Chuuk, Yap; Republic of Marshall Islands; Republic of Palau) were collected in 2012. Caregivers self-reported sociodemographic data and food insecurity. Assisted by their caregiver, children completed two dietary records on nonconsecutive, randomly assigned days. The Healthy Eating Index 2005 (HEI-2005) was used to assess the diet quality. Data were summarized overall and by jurisdiction. Differences in HEI-2005 and HEI component scores among jurisdictions and by household food security status were tested using 1-factor ANOVA., Results: Half or more of participants from American Samoa, Guam, CNMI, and FAS reported household food insecurity (n = 295, 59.7%; n = 292, 49.9%; n = 267, 54.6%; n = 572, 69.0%, respectively). HEI-2005 scores varied by jurisdiction (P < 0.001) and were significantly lower among FAS participants (54.7 ± 1.2) than among all other jurisdictions (P < 0.05). Total diet quality scores did not differ by food security status (59.9 ± 0.8 food secure compared with 58.3 ± 1.1 food insecure, P = 0.07); however, most diet quality adequacy component scores were significantly higher and moderation component scores significantly lower among participants in food secure households than those in food insecure households., Conclusions: Significant differences in children's diet quality and household food security existed across USAP jurisdictions., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

This work reports on targeted UHPLC-tandem mass spectrometry methods for the chiral separation of anteiso-methyl branched fatty acids (aiFAs). The methods involve precolumn derivatization with 1-naphthylamine and chiral separation on Chiralpak IG-U. anteiso-Methyl branched fatty acids with up to eight carbons can be separated. A method was used for the assignment of the absolute configuration of an aiFA present as fatty acyl residue of the teicoplanin mixture, namely teicoplanin RS3. Furthermore, the excellent methylene selectivity and improved selectivity for constitutional isomers of the polysaccharide columns was exploited for the elucidation and structural confirmation of previously unknown fatty acyl residues in teicoplanin. This shows the versatility and practical applicability of polysaccharide columns as orthogonal stationary phases to reversed-phase for structural elucidation of natural compounds. The developed methods are useful tools for related subdisciplines such as targeted metabolomics and lipidomics., 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 © 2022 Elsevier B.V. All rights reserved.)

The present work reports on a novel stable-bonded amino silica stationary phase obtained by crosslinking of surface aminopropyl moieties using triglycidyl isocyanurate. The obtained cross-linked amido-amino network silica material exhibited superior hydrolytic stability compared to classical 3-aminopropyl phases and showed, inter alia, excellent separation of nine therapeutically effective sulfonamides in hydrophilic interaction/weak anion exchange chromatography elution mode. Additionally, the separation of carbohydrates was investigated under classical hydrophilic interaction chromatography conditions as well proving the suitability of the novel phase for such applications. For the evaluation of the hydrolytic stability the prepared material, as well as two commercially available benchmark columns and a set of in-house synthesized amino-modified materials, were exposed to harsh aqueous mobile phase conditions for in total of 50 h at elevated temperature. In this context, the materials were examined by elemental analysis, ( 13 C and 29 Si cross-polarization/magic angle spinning) solid-state nuclear magnetic resonance, and a chromatographic test before and subsequent to the exposure to these stress conditions. Lastly, the new stationary phase was classified in comparison to a set of commercially available stationary phases by principal component analysis of resultant retention factors gained from chromatographic standard tests., (© 2022 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)

This research reports on the development of a comprehensive two-dimensional liquid chromatography (2D-LC) method hyphenated to inline DAD-UV and ESI-QTOF-MS/MS-detection for the separation of conjugated polyunsaturated fatty acid isomers and structurally related (saturated, unconjugated, oxidized) compounds. In pharmaceutical lipid formulations conjugated fatty acids can be found as impurities, generated by oxidation of polyunsaturated fatty acids. Due to the structural complexity of resultant multi-component samples one dimensional liquid chromatography may be suboptimal for quality control and impurity profiling. The screened reversed-phase columns showed a lack of selectivity for the conjugated fatty acid isomers but the resolutions improved with the shape selectivity of the stationary phases (C18- < C30- < cholesteryl-ether-bonded). Further enhanced selectivity for the non-chiral conjugated FAs could be achieved with amylose/cellulose-based chiral stationary phases (CSPs) which harbor cavities for selective inclusion depending on E/Z configurations of the double bonds of the analytes. Amylose-based CSPs showed higher selectivity for conjugated fatty acids than the cellulose-based polysaccharide CSPs. Hyphenating the chiral and reversed-phase columns in a comprehensive 2D-LC-setup was favorable since they showed orthogonality and good compatibility, because both were operated under RP-conditions. The chiral dimension ( 1 D) mainly separated the different isomers, while the reversed-phase dimension ( 2 D) separated according to number of double bonds and degree of oxidation. Using this setup, advanced structural annotation of unknowns was possible based on UV-, MS1- and MS2-spectra. Data-independent acquisition (by SWATH) enabled differentiation of positional isomers of oxidized lipids by characteristic MS2-fragments and elucidation of co-eluted compounds by selective extracted ion chromatograms of fragment ions (MS2 EICs)., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Nursing students in Canada are typically enrolled in a four-year bachelor degree program that provides students with the necessary skills and knowledge to enter a highly demanding and challenging workforce. Strong critical thinking, clinical reasoning, and clinical judgment skills are essential skills for safe nursing practice. Therefore, educational institutes and their mentors are mandated to teach and assess these skills. In addition, nursing programs operate under an apprenticeship model, which entails the fulfillment of practical experience during which students are expected to develop and refine their skills in critical thinking, clinical reasoning, and clinical judgment., Purpose: The purpose of this scoping review of the literature is to assess the available evidence of how higher-level thinking, including critical thinking, clinical reasoning, and clinical judgment are evaluated in undergraduate nursing students in clinical settings., Methods: The inclusion criteria consisted of quantitative research articles published in the last 10 years. Search databases accessed included CINAHL Plus (EBSCO), Medline, and PubMed., Results: Seven articles that fit the inclusion criteria became the focus of this scoping review. Four tools to evaluate higher-thinking processes in clinical settings were located and scrutinized: Lasater Clinical Judgment Rubric (LCJR), Script Concordance Testing, and Yoon's Critical Thinking Disposition Instrument. Relevance to practice : The scoping review will provide direction and contextualize future studies that focus on the appraisal of nursing students' critical thinking, clinical reasoning, and clinical judgment in clinical settings., (© Copyright 2022 Springer Publishing Company, LLC.)

The inter-provincial migration patterns of family physicians in canada show that some provinces like newfoundland and saskatchewan experience persistent net out-migration, while others, including ontario and british columbia, are destinations more often than origins of migrants. Governments in provinces exhibiting net out-migration have responded with a number of incentive and recruitment programs. In this study, we investigate the determinants of the stated interprovincial migration intentions of 3,995 rural and urban family physicians in the 2010 wave of the national physician survey. We consider a range of physician characteristics, community attributes and working conditions. We find that in the intention to move, higher compensation has a modest effect, while the community characteristics have a consistently important influence. Our results suggest that policy and program designers should acknowledge the critical role of community-level living and working conditions in their family physician recruitment and retention efforts., (Copyright © 2015 Longwoods Publishing.)

Objective: To develop a tailored, theory-based, Web-delivered intervention to prevent excessive weight gain in young adults using a Community-Based Participatory Research model., Design: Investigators from 14 universities developed the intervention and supporting administrative portal using the 4 phases of the PRECEDE model. Steering committees were composed of the target audience (aged 19-24 years) and key health/wellness personnel were formed at each institution and provided information during each phase that was used to guide development of the intervention, Project YEAH (Young Adults Eating and Active for Health). Piloting results were used to refine the curriculum and identify and avoid barriers to delivery., Results: Qualitative and quantitative data collected at each phase informed Project YEAH development. In Phase 1, factors of highest priority to young adults were identified. In Phase 2, environmental supports for healthful lifestyles were elucidated. In Phase 3, behavior and environmental changes considered important and changeable were identified. In Phase 4, the 10-week, theory-based, stage-tailored, interactive-learning intervention with a 10-month reinforcement period was developed., Conclusions and Implications: Applying the PRECEDE model with fidelity during development of Project YEAH resulted in an intervention that pilot participants found relevant and useful, gained attention, instilled confidence in the ability to apply the information, and provided a sense of satisfaction., (Copyright © 2014. Published by Elsevier Inc.)

Objective: The study examines metabolic syndrome (MetS) among college students at 3 geographically distinct US campuses., Participants: Undergraduates (N = 360; 68% women), 18 to 24 years of age, were recruited at each public university in January and February 2011. MetS prevalence was evaluated in 83% (n = 299) participants., Methods: Anthropometric, biochemical, and clinical measures were collected in the fasted state., Results: Twelve percent of college men and 6% of college women met the clinical definition of MetS. Males were more likely to have ≥ 2 individual MetS criteria than females (33% vs 16%; p < .05). Prevalence and individual criteria of MetS differed between the 3 regions. Obese and overweight students met significantly more MetS criteria and had higher C-reactive protein levels than normal-weight students (both p < .05)., Conclusion: Findings suggest that MetS prevalence among college students differs by sex, weight status, and region. Further research is needed to identify effective, targeted interventions that are regionally appropriate for this population.

Objective: The present study evaluated the restaurant and dining venues on and near post-secondary campuses varying in institution size., Design: The Nutrition Environment Measures Survey for Restaurants (NEMS-R) was modified to evaluate restaurants as fast food, sit down and fast casual; and campus dining venues as dining halls, student unions and snack bar/cafe´s. ANOVA with post hoc Tukey’s B and T tests were used to distinguish differences between dining venues and associated institutions by size., Setting: The study was conducted at fifteen US post-secondary institutions, 2009–2011., Subjects: Data presented are from a sample of 175 restaurants and sixty-eight on-campus dining venues., Results: There were minimal differences in dining halls by institution size, although medium-sized institutions as compared with small-sized institutions offered significantly more healthful side dish/salad bar items. Dining halls scored significantly higher than student unions or snack bar/cafe´s on healthful entre´es, side dish/salad bar and beverages offerings, but they also had the most barriers to healthful dietary habits (i.e. all-you-can-eat). No differences were found by restaurant type for NEMS-R scores for total restaurant dining environment or healthful entre´es and barriers. Snack bars had more healthful side dishes (P50?002) and fast-food restaurants had the highest level of facilitators (i.e. nutrition information; P50?002)., Conclusions: Based on this evaluation in fifteen institutions, the full campus dining environment provides limited support for healthy eating and obesity prevention. The quality of campus dining environments can be improved via healthful offerings, providing nutrition information and other supports to facilitate healthy eating and prevent unwanted weight gain.

Objective: Recent evidence suggests physical activity may be protective against smoking initiation and increased smoking among youth. The present study explored the effects of a teen smoking cessation intervention supplemented with a physical activity module on participants' physical activity outcomes. A secondary aim examined the relationship between participants' physical activity outcomes and postprogram smoking intensity., Design: The study reports primary data from a 3-arm randomized group trial consistent with CONSORT guidelines (Registry # NCT01242657)., Setting: Public high schools (N = 19) in West Virginia., Participants: Teens aged 14-19 years (N = 233) who reported current smoking, ≥1 cigarette in the past 30 days., Intervention: High schools were randomly selected, then randomly assigned to Brief Intervention (standard of care), Not-On-Tobacco (N-O-T, teen cessation program), or N-O-T plus a physical activity module (N-O-T+FIT)., Outcome Measures: Standardized instruments at baseline and end of treatment/3-months postbaseline measured physical activity outcomes. The study assessed smoking intensity using cigarettes smoked per day. We conducted ANCOVA controlling for school-level variance to measure physical activity changes. Multiple linear and logistic regression analyses explored favorable change influence of physical activity on smoking cessation outcomes, controlling for potential clustering., Results: Teens who increased the number of days on which they received at least 20 minutes of exercise were significantly more likely to reduce their daily cigarette use, with those in the N-O-T+FIT condition having the highest likelihood of reducing smoking. Teens in the N-O-T+FIT condition who increased the number of days on which they received at least 30 minutes of exercise were significantly more likely than those in other groups to quit smoking., Conclusion: Findings suggest that it is possible to alter simultaneously more than one health behavior among teens-favorable changes in physical activity and smoking cessation may be particularly compatible targets for dual behavior change., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated the food stores on and near postsecondary campuses varying in institutional size., Design: The design of the study is an environmental audit survey., Setting: Fifteen U.S. postsecondary education institutions participated in this study between 2009-2011., Subjects: Eighty-one stores (44% grocery, 17% campus, and 39% convenience/drug) were evaluated., Measures: The Nutrition Environment Measures Survey for Stores was modified to evaluate food stores. Analysis. Analysis of variance with post hoc Tukey B and t-tests assessed differences between store types and by institutional size., Results: Grocery stores had significantly higher scores than campus/convenience stores for healthy foods (19.5 ± 3.8 vs. 2.4 ± 1.7), and for the availability (19.5 ± 3.8 vs. 2.4 ± 1.7) and quality (5.9 ± 0.5 vs. 1.8 ± 2.2) of fruits/vegetables (p < .001). Healthy foods and beverages were significantly more expensive (-0.6 ± 3.4 vs. 0.9 ± 2.0; p < .031) than their less healthful alternatives in grocery stores, but not in convenience stores. There were no differences by institutional size for grocery stores; however, smaller institutions' convenience stores had significantly lower availability and quality of fruits/vegetables and total food store environment scores., Conclusion: A college campus provides a food environment with an array of shopping venues, most of which are not consistent with dietary recommendations for obesity prevention. The limited quality of healthy food in on-campus and convenience stores and the exacerbated deficiencies for small postsecondary institutions provide evidence to support environmental and policy initiatives to improve the quality of campus food store environments.

Long-term exposure of humans and many mammals to hypoxia leads to the activation of several cellular mechanisms within skeletal muscles that compensate for a limited availability of cellular oxygen. One of these cellular mechanisms is to increase the expression of a subset of hypoxia-inducible genes, including the expression of vascular endothelial growth factor (VEGF). The VEGF promoter contains a hypoxic response element (HRE) that can bind the transcription factor, hypoxia-inducible factor-1alpha; (HIF-1alpha), and initiate transcriptional activation of the VEGF gene. VEGF gene expression is critically important for skeletal muscle angiogenesis and VEGF gene deletion in the mouse has been shown to greatly reduce skeletal muscle capillarity. However, HIF-1alpha-dependent transcriptional activation of the VEGF gene may not be the only signaling pathway that leads to increased or maintained VEGF levels under conditions of acute or long-term hypoxia. Additional mechanisms, induced during hypoxic exposure that could signal skeletal muscle VEGF activation include inflammation, possibly linked to reactive O(2) species generation, or a change in cellular energy status as reflected by AMP kinase activity. These pathways may provide quite different mechanisms for VEGF upregulation in the context of muscular activity during long-term exposure to a hypoxic environment such as occurs at high altitude. This review will accordingly discuss the potential cellular signals or stimuli resulting from hypoxic exposure that could increase myocyte VEGF expression. These cellular signals include 1) a decrease in intracellular P(O(2)), 2) skeletal muscle inflammation, associated cytokines and oxidative stress, and 3) an increase in AMP kinase activity and adenosine accompanying a reduction in cellular energy potential.