Association of polysubstance use disorder with treatment quality among Medicaid beneficiaries with opioid use disorder.

INTRODUCTION: The opioid crisis is transitioning to a polydrug crisis, and individuals with co-occurring substance use disorder (SUDs) often have unique clinical characteristics and contextual barriers that influence treatment needs, engagement in treatment, complexity of treatment planning, and treatment retention. METHODS: Using Medicaid data for 2017-2018 from four states participating in a distributed research network, this retrospective cohort study documents the prevalence of specific types of co-occurring SUD among Medicaid enrollees with an opioid use disorder (OUD) diagnosis, and assesses the extent to which different SUD presentations are associated with differential patterns of MOUD and psychosocial treatments. RESULTS: We find that more than half of enrollees with OUD had a co-occurring SUD, and the most prevalent co-occurring SUD was for "other psychoactive substances", indicated among about one-quarter of enrollees with OUD in each state. We also find some substantial gaps in MOUD treatment receipt and engagement for individuals with OUD and a co-occurring SUD, a group representing more than half of individuals with OUD. In most states, enrollees with OUD and alcohol, cannabis, or amphetamine use disorder are significantly less likely to receive MOUD compared to enrollees with OUD only. In contrast, enrollees with OUD and other psychoactive SUD were significantly more likely to receive MOUD treatment. Conditional on MOUD receipt, enrollees with co-occurring SUDs had 10 % to 50 % lower odds of having a 180-day period of continuous MOUD treatment, an important predictor of better patient outcomes. Associations with concurrent receipt of MOUD and behavioral counseling were mixed across states and varied depending on co-occurring SUD type. CONCLUSIONS: Overall, ongoing progress toward increasing access to and quality of evidence-based treatment for OUD requires further efforts to ensure that individuals with co-occurring SUDs are engaged and retained in effective treatment. As the opioid crisis evolves, continued changes in drug use patterns and populations experiencing harms may necessitate new policy approaches that more fully address the complex needs of a growing population of individuals with OUD and other types of SUD.

Psychosocial Stress, Health, and the Hippocampus.

Psychoneuroimmunology (PNI) is an interdisciplinary field that examines the relationships between psychological factors and changes in endocrine and immune function, with possible consequences for health status. There is a growing literature suggesting that psychosocial stressors can impact negatively on health through deleterious changes in immune function. In their 2005 review, Glaser and Kiecolt-Glaser examined the mechanisms by which these changes might occur, and summarized some of the findings showing stress-related health consequences in a number of human populations. Buchanan et al. (2009) examined the cortisol response in individuals sustaining damage to the hippocampus, when challenged with a psychosocial stressor. Individuals with damage to the hippocampus, but not those with damage in other regions of the brain, showed abnormal cortisol responses to the psychosocial stressor. These papers were used successfully in an undergraduate Neuroscience course to stimulate class discussion; other possible uses for these articles are discussed.

Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor and small heterodimer partner in murine hepatic taurine metabolism.

AIM: Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms. METHODS: Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent pathways, we utilized GW4064 (FXR agonist), FGF19 or T-0901317 (liver X receptor [LXR] agonist) and Shp-/- mice. Tissue mRNA was determined by quantitative reverse transcription polymerase chain reaction. Amino acids were measured by high-performance liquid chromatography. RESULTS: Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA while those receiving cholestyramine exhibited increased mRNA. Activation of FXR suppressed CSAD mRNA expression whereas CSAD expression was increased in Shp-/- mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp-/- mice with a corresponding increase in serum taurine conjugated BA. FGF19 administration suppressed hepatic cholesterol 7-α-hydroxylase (CYP7A1) mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. CONCLUSION: BA regulate CSAD mRNA expression in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These findings implicate BA as regulators of CSAD mRNA via mechanisms shared with CYP7A1.

Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease.

UNLABELLED: Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes, also modulates HSC FA utilization and in turn regulates the fibrogenic program. L-Fabp expression decreased 10-fold following HSC activation, concomitant with depletion of LDs. Primary HSCs isolated from L-FABP(-/-) mice contain fewer LDs than wild-type (WT) HSCs, and exhibit up-regulated expression of genes involved in HSC activation. Adenoviral L-Fabp transduction inhibited activation of passaged WT HSCs and increased both the expression of prolipogenic genes and also augmented intracellular lipid accumulation, including triglyceride and FA, predominantly palmitate. Freshly isolated HSCs from L-FABP(-/-) mice correspondingly exhibited decreased palmitate in the free FA pool. To investigate whether L-FABP deletion promotes HSC activation in vivo, we fed L-FABP(-/-) and WT mice a high-fat diet supplemented with trans-fatty acids and fructose (TFF). TFF-fed L-FABP(-/-) mice exhibited reduced hepatic steatosis along with decreased LD abundance and size compared to WT mice. In addition, TFF-fed L-FABP(-/-) mice exhibited decreased hepatic fibrosis, with reduced expression of fibrogenic genes, compared to WT mice. CONCLUSION: L-FABP deletion attenuates both diet-induced hepatic steatosis and fibrogenesis, despite the observation that L-Fabp paradoxically promotes FA and LD accumulation and inhibits HSC activation in vitro. These findings highlight the importance of cell-specific modulation of hepatic lipid metabolism in promoting fibrogenesis in nonalcoholic fatty liver disease. (Hepatology 2013).

Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice.

Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp (-/-) mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol "Western" diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption between the genotypes, and fatty acid (FA) oxidation was reduced, rather than increased, in SF-fed L-fabp (-/-) mice as evidenced by decreased heat production and serum ketones. In contrast to mice fed with a SF diet, L-fabp (-/-) mice fed with a high PUFA diet were not protected against obesity and hepatic steatosis. These observations together suggest that L-fabp (-/-) mice exhibit a specific defect in the metabolism of SFA, possibly reflecting altered kinetics of FA utilization. In support of this possibility, microarray analysis of muscle from Western diet-fed mice revealed alterations in genes regulating glucose uptake and FA synthesis. In addition, intestinal cholesterol absorption was decreased in L-fabp (-/-) mice. On the other hand, and in striking contrast to other reports, female L-fabp (-/-) mice fed with low fat, high cholesterol diets gained slightly less weight than control mice, with minor reductions in hepatic triglyceride content. Together these data indicate a role for L-FABP in intestinal trafficking of both SFA and cholesterol.

Diet-induced obesity and hepatic steatosis in L-Fabp / mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation.

Liver fatty acid (FA)-binding protein (L-Fabp), a cytoplasmic protein expressed in liver and small intestine, regulates FA trafficking in vitro and plays an important role in diet-induced obesity. We observed that L-Fabp(-/-) mice are protected against Western diet-induced obesity and hepatic steatosis. These findings are in conflict, however, with another report of exaggerated obesity and increased hepatic steatosis in female L-Fabp(-/-) mice fed a cholesterol-supplemented diet. To resolve this apparent paradox, we fed female L-Fabp(-/-) mice two different cholesterol-supplemented low-fat diets and discovered (on both diets) lower body weight in L-Fabp(-/-) mice than in congenic wild-type C57BL/6J controls and similar or reduced hepatic triglyceride content. We extended these comparisons to mice fed low-cholesterol, high-fat diets. Female L-Fabp(-/-) mice fed a high-saturated fat (SF) diet were dramatically protected against obesity and hepatic steatosis, whereas weight gain and hepatic lipid content were indistinguishable between mice fed a high-polyunsaturated FA (PUFA) diet and control mice. These findings demonstrate that L-Fabp functions as a metabolic sensor with a distinct hierarchy of FA sensitivity. We further conclude that cholesterol supplementation does not induce an obesity phenotype in L-Fabp(-/-) mice, nor does it play a significant role in the protection against Western diet-induced obesity in this background.

Subjective assessment of listening environments in university classrooms: perceptions of students.

A questionnaire is developed to evaluate perception of the listening environment by university students. The objectives were to develop a questionnaire-based measurement tool, derive a measure of perceived classroom-listening quality, use the questionnaire to investigate factors that enhance, impair, or do not affect perceived listening quality, and consider the implications for classroom design. The questionnaire was administered to over 5700 students in 30 classrooms at one university. Physical and acoustical measurements were also performed in each classroom. The questionnaire included items that recorded aspects of student perception, as well as individual, course-, and instructor-specific factors. Responses to 19 perception items generated a perception of listening ease (PLE) score for each student and a classroom-average score. Decreased PLE was associated with women, English-second-larguage students, those with hearing impairment, students not interested in the course material, and those who found the material difficult. Increased PLE was associated with higher speech transmission index, acceptable lighting, temperature and seating, better instructor voice, increased visual-aid use, and easier course material. Results indicate that PLE is a useful measure of student perception of the classroom-listening environment, and that optimal classroom acoustical design must take into consideration "in-use" conditions, as well as classroom physical characteristics.