Biosynthesis of vitamin B3 and NAD+: incubating HepG2 cells with the alkaloid myosmine.

BACKGROUND: In the kynurenine pathway, it is reported that the essential amino acid tryptophan forms nicotinic acid (NA, vitamin B3) in biological systems. This pathway is part of the de novo pathway to perform nicotinamide adenine dinucleotide (NAD+) biosynthesis. Additionally, biosynthesis of NAD+ via the Preiss-Handler pathway involves NA and its analogue nicotinamide, both designated as niacin. Previous attempts were successful in converting myosmine (MYO) by organic synthesis to NA, and the assumption was that the alkaloid MYO, which is taken in from food, can be converted into NA by biological oxidation. RESULT: Incubation of HepG2 cells with MYO yielded NA. Moreover, a significant increase of NAD+ compared with the control has been found. CONCLUSION: Hence, MYO could be assumed to be the hitherto unknown origin of an alternative NA biosynthesis additionally influencing NAD+ biosynthesis positively. This novel MYO pathway may open new perspectives to improve knowledge and relevance of NA and NAD+ biosynthesis and bioactivation in cells and, moreover, in food staples, food, and diet. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The Role of Positive and Negative Affect in Illicit Substance Use and Alcohol Use: An Ecological Momentary Assessment Study.

BACKGROUND: Theories suggest that experiences of negative and positive affect are important precursors to alcohol and illicit substance use. Research utilizing ecological momentary assessments (EMA) has generally supported the relation between momentary experiences of positive affect, but not negative affect, and subsequent substance use. Unfortunately, most of these studies have focused on alcohol use and not other substance use. The goal of this paper was to further explore the relation between momentary affect and use of both alcohol and illicit substances within a population of individuals with a history of substance use. Additionally, this study aimed to understand whether the relations between affect and substance use would vary depending on the timing of EMA assessments of affect prior to substance use. METHOD: Participants with a history of heavy substance use (N = 59) completed EMA's measuring affect and substance use using random prompts 4 times a day for 14 days. RESULTS: We found that positive affect was significantly related to later engagement in drinking, illicit substance use, and marijuana use. Moreover, timing of the affect was important. When affect was assessed in the last hour prior to substance use, relative to 7 hours prior, the relation between positive affect and illicit substance use was stronger. Negative affect was related to a lower likelihood of subsequent marijuana use, but more so when it was measured a few hours versus several hours before the use. CONCLUSION: This study further supported the relation between positive affect and both alcohol and illicit substance use.

Contextualizing Bicultural Competence Across Youths' Adaptation From High School to College: Prospective Associations With Mental Health and Substance Use.

Bicultural competence, the ability to navigate bicultural demands, is a salient developmental competency for youth of color linked with positive adjustment. This study investigated how discrimination experiences informed developmental trajectories of behavioral and affective bicultural competence across youth's adaptation from high school to college, and how these biculturalism trajectories predicted later adjustment (i.e., internalizing symptoms and binge drinking). Data were collected between 2016 through 2020 and included 206 U.S. Latino youth (Mage=17.59, 64% female, 85% Mexican origin, 11% first and 62% second generation immigrants). Linear latent growth analyses revealed that youth who experienced greater time-varying discrimination demonstrated lower concurrent behavioral and affective bicultural competence. Higher behavioral bicultural competence intercepts were associated with fewer internalizing symptoms in the third college year. No other significant associations emerged for internalizing symptoms or binge drinking. These findings have implications for mental health equity among Latino youth during a critical period of psychopathology onset.

Posttraumatic stress disorder, Veterans Health Administration use, and care-seeking among recent-era U.S. veterans.

The current study investigated the associations among probable posttraumatic stress disorder (PTSD), recent Veterans Health Administration (VHA) health care use, and care-seeking for PTSD in U.S. military veterans. Analyses were conducted among 19,691 active duty military personnel enrolled in the Millennium Cohort Study who separated from the military between 2000 and 2012 and were weighted to the 1,130,103 active duty personnel who separated across this time period. VHA utilization was identified from electronic medical records in the year before survey completion, and PTSD care-seeking and PTSD symptoms were assessed through self-report on the 2014-2016 survey; thus, the observation period regarding care-seeking and VHA use encompassed 2013-2016. Veterans with probable PTSD were more likely to use VHA services than those without probable PTSD, aOR = 1.12, 95% CI [1.01, 1.24], although the strongest association with recent VHA use was a depression diagnosis, aOR = 2.47, 95% CI [2.26, 2.70]. Among veterans with probable PTSD, the strongest predictor of care-seeking was recent VHA use compared to community care, aOR = 4.01, 95% CI [3.40, 4.74); reporting a diagnosis of depression was the second strongest predictor of PTSD care-seeking, OR = 2.99, 95% CI [2.53, 3.54]. However, the absolute number of veterans with probable PTSD who were not seeking care was approximately equivalent between veterans using VHA services and those not using VHA services. Additionally, certain groups were identified as being at risk of not seeking care, namely Air Force veterans and veterans with high physical and mental functioning despite substantial PTSD symptoms.

Within-person reciprocal links between stress, sleep, and depressive symptoms across Latino/a adolescents' transition to and through college.

Evidence suggests bidirectional relations between stress, sleep, and depressive symptoms in adolescence and young adulthood. Less research has disaggregated within- and between-person variance in these associations over time or within Latino/a college students. This study examined longitudinal, within-person reciprocal relations between stress, sleep, and depressive symptoms among 181 Latino/a adolescents (M age = 18.10; SD = 0.41, 35% male) transitioning to college. Participants were assessed in their senior year of high school and annually until their fourth year of college. A random intercept cross-lagged panel model (RI-CLPM) was used to parse out within- and between-person sources of variance. Results indicated overall (between-person) relations among depressive symptoms and school/college stress and sleep problems. There were reciprocal within-person links between stress and sleep problems across the first two years of college. Within-person increases in depressive symptoms during the second year of college predicted more stress than usual in the third year, which predicted increased depressive symptoms in the fourth year. More sleep problems than usual in the third year of college predicted higher stress in the fourth year. Findings provide evidence for within-person cross-lagged relations among various domains of adjustment during college and may inform future prevention efforts for incoming Latino/a college students targeting mental health and sleep problems.

Nonsense-mediated decay machinery in Plasmodium falciparum is inefficient and non-essential.

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite Plasmodium falciparum shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the P. falciparum orthologs of two core NMD components: PfUPF1 (PF3D7_1005500) and PfUPF2 (PF3D7_0925800). We localize both PfUPF1 and PfUPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in P. falciparum, they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in P. falciparum has no functional role and that NMD is not required for parasite growth ex vivo. IMPORTANCE In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.

A Review of CAR-T Therapy in Pediatric and Young Adult B-Lineage Acute Leukemia: Clinical Perspectives in Singapore.

Approximately 10-15% of pediatric B-cell acute lymphoblastic leukemia (B-ALL) are high risk at diagnosis or relapsed/ refractory. Prior to the availability of chimeric antigen receptor T-cell (CAR-T) in Singapore and the region, the treatment options for these paediatric and young adults are conventional salvage chemotherapy or chemo-immunotherapy regimens as a bridge to allogeneic total body irradiation-based hematopoietic stem cell transplantation (allo-HSCT). This results in significant acute and long-term toxicities, with suboptimal survival outcomes. Finding a curative salvage therapy with fewer long-term toxicities would translate to improved quality-adjusted life years in these children and young adults. In this review, we focus on the burden of relapsed/refractory pediatric B-ALL, the limitations of current strategies, the emerging paradigms for the role of CAR-T in r/r B-ALL, our local perspectives on the health economics and future direction of CAR-T therapies in pediatric patients.

Ethnic-Racial Identity Developmental Trajectories Across the Transition to College.

There is limited longitudinal research examining multiple ethnic-racial identity (ERI) components from adolescence into young adulthood. The current study modeled Latino adolescents' ERI trajectories across the college transition (N = 206; Mage = 18.10 years, SD = 0.41; 65.0% female). Longitudinal data from a survey administered on five occasions across 3 years were analyzed using multilevel growth modeling. Prior to college, Latino heritage culture orientation was positively associated with ERI exploration and resolution. ERI exploration increased over time. ERI resolution was high with no average change; Latino heritage culture orientation predicted variability in resolution over time. Before college, male-identifying youth reported higher ERI public regard from teachers/professors compared to female-identifying youth. Public regard increased to a greater extent for female compared to male adolescents. The findings join evidence for lifespan and intersectional models of ERI development.

Reactions to Amyloid PET Scan Results and Levels of Anxious and Depressive Symptoms: CARE IDEAS Study.

BACKGROUND AND OBJECTIVES: Few studies have examined care partners' reactions to their loved ones receiving amyloid-ß positron emission tomography (PET) scan results, which can be indicative of Alzheimer's disease. We explored care partners' reactions qualitatively, and checked the association of scan results and diagnostic category (dementia vs mild cognitive impairment [MCI]) with care partner anxious and depressive symptoms through quantitative analysis. RESEARCH DESIGN AND METHODS: Using data from 1,761 care partners in the Caregivers' Reactions and Experience, a supplemental study of the Imaging Dementia Evidence for Amyloid Scanning study, we applied an exploratory sequential mixed-methods design and examined the reactions of 196 care partners to receiving amyloid PET scan results through open-ended interview questions. Based on the qualitative content analysis, we hypothesized there would be an association of care partners' depressive (Patient Health Questionnaire-2) and anxious (6-item State-Trait Anxiety Inventory) symptoms with scan results and diagnostic category which we then tested with logistic regression models. RESULTS: Content analysis of open-ended responses suggests that when scan results follow the care partner's expectations, for example, elevated amyloid in persons with dementia, care partners report relief and gratitude for the information, rather than distress. Adjusted logistic regression models of survey responses support this finding, with significantly higher odds of anxiety, but not depressive symptoms, among care partners of persons with MCI versus dementia and elevated amyloid. DISCUSSION AND IMPLICATIONS: Care partners of persons with MCI reported distress and had higher odds of anxiety after receiving elevated amyloid PET scan results than care partners of persons with dementia. This has the potential to inform clinical practice through recommendations for mental health screening and referrals.

The DAS-6: A Short Form of the Dementia Attitudes Scale.

Attitudes toward persons with dementia (PWD) are important predictors of emotional and behavioral outcomes for PWD and their caregivers. It is often desirable to have short, psychometrically-sound measures of such attitudes for inclusion in large community-based surveillance surveys and quick training assessments. The Dementia Attitudes Scale (DAS) is a 20-item scale that examines person-centered knowledge and perceptions of comfort working with PWD. Shorter versions of this scale have been used in various settings, although the psychometric properties of this abbreviated scale are unknown. This study used a principal components analysis to examine the properties associated with scales using a reduced number of items. Our final scale, the DAS-6 includes three items in each of the comfort and person-centered knowledge subscales.

Association Between Opioid Use and Outpatient Visits for Dysphagia: An Analysis of the National Ambulatory Medical Care Survey in 2008-2018.

INTRODUCTION: Opioid-induced esophageal dysfunction has been described with characteristic manometric patterns, but the population burden of dysphagia attributable to opioid use remains unclear. METHODS: The National Ambulatory Medical Care Survey from 2008 to 2018 was used to assess the relationship between opioid use and outpatient visits for dysphagia. RESULTS: After controlling for potential confounders, there were no significant difference in ambulatory visits for dysphagia between opioid users and nonusers (adjusted odds ratio = 0.98, confidence interval: 0.59-1.65). DISCUSSION: No correlation between opioid use and ambulatory visits for dysphagia was found in a nationwide sample. Opioid-related manometric changes may be clinically relevant only in a small proportion of patients.

Shifting the discourse on disability: Moving to an inclusive, intersectional focus.

Individuals with disabilities comprise one of the largest marginalized groups in the United States and experience systemic barriers in health care. In Westernized communities, disability has historically been conceptualized via the medical model, which considers disability an individual-level deficit in need of correction. Although other models of disability (e.g., social model) have been developed to address the medical model's ableist shortcomings, these fail to consistently acknowledge intersectionality. Specifically, these models fail to consider that (a) a disabled individual may hold other marginalized or oppressed identities and (b) these intersecting oppressions may exacerbate health inequities. Intersectionality, which originates from Black feminist literature, describes the ways that systems of power and oppression (e.g., racism, sexism) interact to form an individual's unique experience. To date, the intersection of disability and other marginalized identities has been neglected in psychology and related fields, leaving little guidance for how scholars, clinicians, and other stakeholders can address disability via an intersectional lens. The present article discusses how a disability-affirmative, intersectional approach can serve as a strategy for challenging and reforming oppressive systems across the field of psychology. We assert that, ultimately, this approach has the potential to optimize and expand access to equitable, inclusive mental health care, and we propose actionable steps psychologists can take in research, practice, training, and policy in pursuit of this aim. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Endogenous Levels of Circulating Androgens Are Not Associated with Risk of Microscopic Colitis.

BACKGROUND: Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. AIM: To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. METHODS: We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. RESULTS: Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all Ptrend > 0.52). CONCLUSION: Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis.

Advance directives among cognitively impaired persons who had an amyloid PET scan and their care partners: a mixed-methods study.

BACKGROUND: Little research exists on the role of ß-amyloid PET scans as part of Alzheimer's diagnostic tests and documentation of end-of-life preferences for persons with cognitive impairment. The study objectives were to examine the association of amyloid PET scan results (elevated vs. not elevated amyloid levels) and diagnostic category (mild cognitive impairment vs. dementia) with the likelihood of having an advance directive (reported a median of 4.5 months post-scan); to explore perceptions of PET scan results and their influence on planning for the future among persons with cognitive impairment and their care partners. METHODS: Sequential, explanatory mixed-methods design using data from dyads in the CARE-IDEAS study: advance directives as a factor of diagnostic category and scan result using multivariable logistic regression models; thematic analysis of semi-structured interviews with persons with cognitive impairment and care partners to explore how scan results influenced documentation of future healthcare preferences. Participants included 1784 persons with cognitive impairment and care partners from the CARE-IDEAS study, and a subsample of 100 semi-structured telephone interviews. RESULTS: 81.6% of dyads reported an advance directive. Non-Hispanic, White participants had higher rates of advance directives. There was no significant association between having an advance directive and scan results. Qualitative analysis provided insight into perceived urgency to have advance directives, evolving healthcare preferences, and the context of completing advance directives. CONCLUSIONS: Although amyloid PET scans prompted persons with cognitive impairment and care partners to consider progressive cognitive impairment as part of evolving healthcare preferences, we found substantial variability in the perceived urgency of documentation.

Pilot RCT Testing A Mailing About Sleeping Pills and Cognitive Behavioral Therapy for Insomnia: Impact on Benzodiazepines and Z-Drugs.

OBJECTIVES: The aim is to pilot a low-touch program for reducing benzodiazepine receptor agonist (BZRA; benzodiazepines, z-drugs) prescriptions among older veterans. METHODS: Pilot randomized controlled trial consists of 2,009 veterans aged ≥ 65 years who received BZRA prescriptions from a Veterans Health Administration pharmacy (Colorado or Montana) during the prior 18 months. Active: Arm 1 was a mailed brochure about BZRA risks that also included information about a free, online cognitive behavioral therapy for the insomnia (CBTI) program. Arm 2 was a mailed brochure (same as arm 1) and telephone reinforcement call. Control: Arm 3 was a mailed brochure without insomnia treatment information. Active BZRA prescriptions at follow-up (6 and 12 months) were measured. RESULTS: In logistic regression analyses, the odds of BZRA prescription at 6- and 12-month follow-ups were not significantly different for arm 1 or 2 (active) versus arm 3 (control), including models adjusted for demographics and prescription characteristics (p-values >0.36). CONCLUSIONS: Although we observed no differences in active BZRA prescriptions, this pilot study provides guidance for conducting a future study, indicating a need for a more potent intervention. A full-scale trial testing an optimized program would provide conclusive results. CLINICAL IMPLICATIONS: Mailing information about BZRA risks and CBTI did not affect BZRA prescriptions.

The Influence of the Rural Transitions Nurse Program for Veterans on Healthcare Utilization Costs.

BACKGROUND: The Veterans Affairs (VA) Healthcare System Rural Transitions Nurse Program (TNP) addresses barriers veterans face when transitioning from urban tertiary VA hospitals to home. Previous clinical evaluations of TNP have shown that enrolled veterans were more likely to follow up with their primary care provider within 14 days of discharge and experience a significant reduction in mortality within 30 days compared to propensity-score matched controls. OBJECTIVE: Examine changes from pre- to post-hospitalization in total, inpatient, and outpatient 30-day healthcare utilization costs for TNP enrollees compared to controls. DESIGN: Quantitative analyses modeling the changes in cost via multivariable linear mixed-effects models to determine the association between TNP enrollment and changes in these costs. PARTICIPANTS: Veterans meeting TNP eligibility criteria who were discharged home following an inpatient hospitalization at one of the 11 implementation sites from April 2017 to September 2019. INTERVENTION: The four-step TNP transitional care intervention. MAIN MEASURES: Changes in 30-day total, inpatient, and outpatient healthcare utilization costs were calculated for TNP enrollees and controls. KEY RESULTS: Among 3001 TNP enrollees and 6002 controls, no statistically significant difference in the change in total costs (p = 0.65, 95% CI: (- $675, $350)) was identified. However, on average, the increase in inpatient costs from pre- to post-hospitalization was approximately $549 less for TNP enrollees (p = 0.02, 95% CI: (- $856, - $246)). The average increase in outpatient costs from pre- to post-hospitalization was approximately $421 more for TNP enrollees compared to controls (p = 0.003, 95% CI: ($109, $671)). CONCLUSIONS: Although we found no difference in change in total costs between veterans enrolled in TNP and controls, TNP was associated with a smaller increase in direct inpatient medical costs and a larger increase in direct outpatient medical costs. This suggests a shifting of costs from the inpatient to outpatient setting.

Bicultural competence and academic adjustment across Latino youth adaptation from high school to college.

This study investigated the association between bicultural competence and academic adjustment (i.e., engagement, efficacy, achievement) among 193 Latino youth (65.3% female; 89.1% U.S.-born) followed from their senior high school year (Mage  = 17.58 years, SD = 0.53) to their fifth college semester (2016-2019). Latent growth analyses revealed that youth's overall bicultural competence trajectory was moderately high and stable across this period. Youth who maintained or increased bicultural competence levels over time (slopes) demonstrated greater self-efficacy. Youth with greater high school bicultural competence (intercepts) demonstrated higher engagement but lower achievement. No other associations emerged. This study highlights that the promoting influence of bicultural competence may not extend to all indicators of academic adjustment but may depend upon the contexts and demands they navigate.

Defects in meristem maintenance, cell division, and cytokinin signaling are early responses in the boron deficient maize mutant tassel-less1.

Meristems house the stem cells needed for the developmental plasticity observed in adverse environmental conditions and are crucial for determining plant architecture. Meristem development is particularly sensitive to deficiencies of the micronutrient boron, yet how boron integrates into meristem development pathways is unknown. We addressed this question using the boron-deficient maize mutant, tassel-less1 (tls1). Reduced boron uptake in tls1 leads to a progressive impairment of meristem development that manifests in vegetative and reproductive defects. We show, that the tls1 tassel phenotype (male reproductive structure) was partially suppressed by mutations in the CLAVATA1 (CLV1)-ortholog, thick tassel dwarf1 (td1), but not by other mutants in the well characterized CLV-WUSCHEL pathway, which controls meristem size. The suppression of tls1 by td1 correlates with altered signaling of the phytohormone cytokinin. In contrast, mutations in the meristem maintenance gene knotted1 (kn1) enhanced both vegetative and reproductive defects in tls1. In addition, reduced transcript levels of kn1 and cell cycle genes are early defects in tls1 tassel meristems. Our results show that specific meristem maintenance and hormone pathways are affected in tls1, and suggest that reduced boron levels induced by tls1 are the underlying cause of the observed defects. We, therefore, provide new insights into the molecular mechanisms affected by boron deficiency in maize, leading to a better understanding of how genetic and environmental factors integrate during shoot meristem development.