Altered reward processing following an acute social stressor in adolescents

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development

Conversion of deoxynivalenol to 3-acetyldeoxynivalenol in barley-derived fuel ethanol co-products with yeast expressing trichothecene 3-O-acetyltransferases

<p>Abstract</p> <p>Background</p> <p>The trichothecene mycotoxin deoxynivalenol (DON) may be concentrated in distillers dried grains with solubles (DDGS; a co-product of fuel ethanol fermentation) when grain containing DON is used to produce fuel ethanol. Even low levels of DON (≤ 5 ppm) in DDGS sold as feed pose a significant threat to the health of monogastric animals. New and improved strategies to reduce DON in DDGS need to be developed and implemented to address this problem. Enzymes known as trichothecene 3-<it>O-</it>acetyltransferases convert DON to 3-acetyldeoxynivalenol (3ADON), and may reduce its toxicity in plants and animals.</p> <p>Results</p> <p>Two <it>Fusarium </it>trichothecene 3-<it>O-</it>acetyltransferases (FgTRI101 and FfTRI201) were cloned and expressed in yeast (<it>Saccharomyces cerevisiae</it>) during a series of small-scale ethanol fermentations using barley (<it>Hordeum vulgare</it>). DON was concentrated 1.6 to 8.2 times in DDGS compared with the starting ground grain. During the fermentation process, FgTRI101 converted 9.2% to 55.3% of the DON to 3ADON, resulting in DDGS with reductions in DON and increases in 3ADON in the Virginia winter barley cultivars Eve, Thoroughbred and Price, and the experimental line VA06H-25. Analysis of barley mashes prepared from the barley line VA04B-125 showed that yeast expressing FfTRI201 were more effective at acetylating DON than those expressing FgTRI101; DON conversion for FfTRI201 ranged from 26.1% to 28.3%, whereas DON conversion for FgTRI101 ranged from 18.3% to 21.8% in VA04B-125 mashes. Ethanol yields were highest with the industrial yeast strain Ethanol Red^®, which also consumed galactose when present in the mash.</p> <p>Conclusions</p> <p>This study demonstrates the potential of using yeast expressing a trichothecene 3-<it>O</it>-acetyltransferase to modify DON during commercial fuel ethanol fermentation.</p

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

Risk Factors, Screening, Diagnosis, and Treatment of Osteoporosis in HIV-Infected Adults in an HIV Primary Care Clinic

Background: The population of people living with HIV is aging, and with aging come emergent comorbidities, including osteoporosis, for which screening and treatment are becoming increasingly important. Osteoporosis prevalence among those living with HIV is 3 times greater than among HIV-uninfected controls. Objective: To assess and describe osteoporosis risk factors, screening, diagnosis, and treatment for people 50 years of age or older living with HIV and receiving care at a multidisciplinary HIV primary care clinic. Methods: A retrospective chart review of people 50 years of age or older living with HIV was conducted at the John Ruedy Clinic in Vancouver, British Columbia, between June 1, 2016, and June 1, 2019. Patients who had had fewer than 2 yearly follow-up appointments were excluded. Results: A total of 146 patients were included in the analysis; most were male (n = 134, 92%), and the median age was 55 years. Patients had a median of 3 osteoporosis risk factors (in addition to age and  HIV infection), and 145 patients had at least 1 risk factor. All screening for osteoporosis was conducted by dual-energy X-ray absorptiometry  (DXA). Thirty-nine (27%) of the patients were screened with DXA, 92 (63%) were not screened, and 15 (10%) already had a diagnosis of osteoporosis. The DXA screening identified osteoporosis in an additional 10 patients and osteopenia in 22 patients. Treatments for patients with osteoporosis included bisphosphonates (n = 15, 60%) and vitamin D or calcium (or both), without any other medications (n = 4, 16%). In the overall study population, 32 (22%) of the patients were taking calcium and 46 (32%) were taking vitamin D. Conclusions: Many patients aged 50 years or older and receiving HIV care at the John Ruedy Clinic had or were at risk for osteoporosis. An opportunity exists to increase screening and treatment of these individuals. A multidisciplinary team may be crucial in achieving this goal. RÉSUMÉ Contexte : La population des personnes vivant avec le VIH vieillit et, avec le vieillissement, des comorbidités émergent, dont l’ostéoporose, pour laquelle le dépistage et le traitement sont de plus en plus importants. La prévalence de l’ostéoporose chez les personnes vivant avec le VIH est 3 fois plus élevée que chez les témoins non infectés. Objectif : Évaluer et décrire les facteurs de risque, le dépistage, le diagnostic et le traitement de l’ostéoporose chez les personnes d’au moins 50 ans vivant avec le VIH et qui reçoivent des soins dans une clinique pluridisciplinaire de soins primaires pour le VIH. Méthodes : Un examen rétrospectif des dossiers des personnes d’au moins 50 ans vivant avec le VIH a été effectué à la clinique John Ruedy à Vancouver (Colombie-Britannique) entre le 1er juin 2016 et le 1er juin 2019. Les patients qui avaient eu moins de 2 rendez-vous de suivi annuels ont été exclus de l’étude. Résultats : Au total, 146 patients ont été inclus dans l’analyse; la plupart étaient des hommes (n = 134, 92 %) et l’âge médian était de 55 ans. Les patients avaient une médiane de 3 facteurs de risque d’ostéoporose (en plus de l’âge et de l’infection par le VIH), et 145 patients avaient au moins 1 facteur de risque. Tous les dépistages de l’ostéoporose ont été réalisés par absorption biphotonique à rayons X (DXA). Trente-neuf patients (27 %) ont été dépistés par DXA, 92 (63 %) ne l’ont pas été et 15 (10 %) avaient déjà un diagnostic d’ostéoporose. Le dépistage par DXA a permis d’identifier l’ostéoporose chez 10 patients supplémentaires et l’ostéopénie chez 22 patients. Le traitement des patients atteints d’ostéoporose comprenait des bisphosphonates (n = 15, 60 %) et de la vitamine D ou du calcium (ou les deux) sans autre médicament (n = 4, 16 %). Dans la population générale de l’étude, 32 patients (22 %) prenaient du calcium et 46 (32 %) prenaient de la vitamine D. Conclusions : De nombreux patients d’au moins 50 ans recevant des soins pour le VIH à la clinique John Ruedy présentaient un risque d’ostéoporose ou l’avaient déjà développée. Il est possible d’accroître leur dépistage et leur traitement, et une équipe multidisciplinaire peut être cruciale pour atteindre cet objectif

Changes in lipids over twelve months after initiating protease inhibitor therapy among persons treated for HIV/AIDS

Background: Protease inhibitors are known to alter the lipid profiles in subjects treated for HIV/AIDS. However, the magnitude of this effect on plasma lipoproteins and lipids has not been adequately quantified. Objective: To estimate the changes in plasma lipoproteins and triglycerides occurring within 12 months of initiating PI-based antiretroviral therapy among HIV/AIDS afflicted subjects. Methods: We included all antiretroviral naïve HIV-infected persons treated at St-Paul's Hospital, British Columbia, Canada, who initiated therapy with protease inhibitor antiretroviral (ARV) drugs between August 1996 and January 2002 and who had at least one plasma lipid measurement. Longitudinal associations between medication use and plasma lipids were estimated using mixed effects models that accounted for repeated measures on the same subjects and were adjusted for age, sex, time dependent CD4+ T-cell count, and time dependent cumulative use of non-nucleoside reverse transcriptase inhibitors and adherence. The cumulative number of prescriptions filled for PIs was considered time dependent. We estimated the changes in the 12 months following any initiation of a PI based regimen. Results: A total of 679 eligible subjects were dispensed nucleoside analogues and PI at the initiation of therapy. Over a median 47 months of follow-up (interquartile range (IQR): 29–62), subjects had a median of 3 (IQR: 1–6) blood lipid measurements. Twelve months after treatment initiation of PI use, there was an estimated 20% (95% confidence interval: 17% – 24%) increase in total cholesterol and 22% (12% – 33%) increase in triglycerides. Conclusions: Twelve months after treatment initiation with PIs, statistically significant increases in total cholesterol and triglycerides levels were observed in HIV-infected patients under conditions of standard treatment. Our results contribute to the growing body of evidence implicating PIs in the development of blood lipid abnormalities. In conjunction with the predominance or men, high rates of smoking, and aging of the treated HIV-positive population, elevated lipoproteins and triglycerides may mean that patients such as these are at elevated risk for cardiovascular events in the future.Health Care and Epidemiology, Department ofMedicine, Department ofMedicine, Faculty ofOther UBCNon UBCReviewedFacult