Hepatic steatosis induced by nicotine plus Coca-Cola™ is prevented by nicotinamide riboside (NR).

Introduction: Cigarettes containing nicotine (Nic) are a risk factor for the development of cardiovascular and metabolic diseases. We reported that Nic delivered via injections or e-cigarette vapor led to hepatic steatosis in mice fed with a high-fat diet. High-fructose corn syrup (HFCS) is the main sweetener in sugar-sweetened beverages (SSBs) in the US. Increased consumption of SSBs with HFCS is associated with increased risks of non-alcoholic fatty liver disease (NAFLD). Nicotinamide riboside (NR) increases mitochondrial nicotinamide adenine dinucleotide (NAD+) and protects mice against hepatic steatosis. This study evaluated if Nic plus Coca-Cola™ (Coke) with HFCS can cause hepatic steatosis and that can be protected by NR. Methods: C57BL/6J mice received twice daily intraperitoneal (IP) injections of Nic or saline and were given Coke (HFCS), or Coke with sugar, and NR supplementation for 10 weeks. Results: Our results show that Nic+Coke caused increased caloric intake and induced hepatic steatosis, and the addition of NR prevented these changes. Western blot analysis showed lipogenesis markers were activated (increased cleavage of the sterol regulatory element-binding protein 1 [SREBP1c] and reduction of phospho-Acetyl-CoA Carboxylase [p-ACC]) in the Nic+Coke compared to the Sal+Water group. The hepatic detrimental effects of Nic+Coke were mediated by decreased NAD+ signaling, increased oxidative stress, and mitochondrial damage. NR reduced oxidative stress and prevented mitochondrial damage by restoring protein levels of Sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor coactivator 1-alpha (PGC1) signaling. Conclusion: We conclude that Nic+Coke has an additive effect on producing hepatic steatosis, and NR is protective. This study suggests concern for the development of NAFLD in subjects who consume nicotine and drink SSBs with HFCS.

Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences.

Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child's development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in the effects of ELS on 1) adolescent neuroendocrine development; 2) pubertal brain maturation; and 3) development of internalizing symptoms and subsequent substance use. We posit that ELS may generate larger hormonal dysregulation in females than males during puberty, increasing internalizing symptoms and substance use. Future research should consider sex and gender differences in neuroendocrine developmental processes when studying the link between ELS and negative health outcomes.

Implementation of Specialty Tobacco Use Disorder Services in a Community Health Setting: Support for Enhanced Prescription Practices.

OBJECTIVES: Although public efforts to reduce tobacco use have been successful, millions of US adults currently smoke tobacco. Reducing the public health burden of tobacco use disorder (TUD) and eliminating disparities experienced by underresourced communities requires increased accessibility to services. The goal of this study was to assess whether prescriptions for evidence-based medications for tobacco treatment showed steeper growth rates among community health clinics providing specialty TUD services as compared with treatment as usual. METHODS: Clinic-wide data on prescriptions for smoking cessation pharmacotherapy at 18 primary care or mental health community clinics operated by Los Angeles County were retrieved for 4 years of an ongoing implementation trial. Specialty services included behavioral counseling and medications for tobacco treatment. Descriptive statistics characterized prescriptions rates across clinics and time. Analyses compared the slopes of the changes between intervention groups across time for primary care and mental health sites. RESULTS: Within primary care clinics, the most commonly prescribed smoking cessation medications were nicotine patches, nicotine gum, and varenicline. Throughout the trial, all clinics displayed increased rates of prescribing smoking cessation medications. Analytic results supported overall steeper increases in prescription rates for these medications among clinics randomized to specialty services versus treatment as usual within primary care ( P = 0.020) and mental health sites ( P = 0.004). CONCLUSIONS: This work provides support for the effectiveness of community-based implementation interventions that promote prescribing smoking cessation medications with the potential to reduce health disparities among communities at greater risk for TUD and its consequences.

The lipolysis inhibitor acipimox reverses the cardiac phenotype induced by electronic cigarettes.

Electronic cigarettes (e-cigarettes) are a prevalent alternative to conventional nicotine cigarettes among smokers and people who have never smoked. Increased concentrations of serum free fatty acids (FFAs) are crucial in generating lipotoxicity. We studied the effects of acipimox, an antilipolytic drug, on e-cigarette-induced cardiac dysfunction. C57BL/6J wild-type mice on high fat diet were treated with saline, e-cigarette with 2.4% nicotine [e-cigarette (2.4%)], and e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction were diminished in mice exposed to e-cigarettes (2.4%) compared with saline and acipimox-treated mice. Mice exposed to e-cigarette (2.4%) had increased circulating levels of inflammatory cytokines and FFAs, which were diminished by acipimox. Gene Set Enrichment Analysis revealed that e-cigarette (2.4%)-treated mice had gene expression changes in the G2/M DNA damage checkpoint pathway that was normalized by acipimox. Accordingly, we showed that acipimox suppressed the nuclear localization of phospho-p53 induced by e-cigarette (2.4%). Additionally, e-cigarette (2.4%) increased the apurinic/apyrimidinic sites, a marker of oxidative DNA damage which was normalized by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1 protein levels and 4-hydroxynonenal (4-HNE). These markers of oxidative stress were decreased by acipimox. Therefore, inhibiting lipolysis with acipimox normalizes the physiological changes induced by e-cigarettes and the associated increase in inflammatory cytokines, oxidative stress, and DNA damage.

The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression.

Type 2 diabetes mellitus (T2DM) and depression are significant public health and socioeconomic issues. They commonly co-occur, with T2DM occurring in 11.3% of the US population, while depression has a prevalence of about 9%, with higher rates among youths. Approximately 31% of patients with T2DM suffer from depressive symptoms, with 11.4% having major depressive disorders, which is twice as high as the prevalence of depression in patients without T2DM. Additionally, over 80% of people with T2DM are overweight or obese. This review describes how T2DM and depression can enhance one another, using the same molecular pathways, by synergistically altering the brain's structure and function and reducing the reward obtained from eating. In this article, we reviewed the evidence that eating, especially high-caloric foods, stimulates the limbic system, initiating Reward Deficiency Syndrome. Analogous to other addictive behaviors, neurochemical changes in those with depression and/or T2DM are thought to cause individuals to increase their food intake to obtain the same reward leading to binge eating, weight gain and obesity. Treating the symptoms of T2DM, such as lowering HbA1c, without addressing the underlying pathways has little chance of eliminating the disease. Targeting the immune system, stress circuit, melatonin, and other alterations may be more effective.

Fatty Acid Excess Dysregulates CARF to Initiate the Development of Hepatic Steatosis.

CARF (CDKN2AIP) regulates cellular fate in response to various stresses. However, its role in metabolic stress is unknown. We found that fatty livers from mice exhibit low CARF expression. Similarly, overloaded palmitate inhibited CARF expression in HepG2 cells, suggesting that excess fat-induced stress downregulates hepatic CARF. In agreement with this, silencing and overexpressing CARF resulted in higher and lower fat accumulation in HepG2 cells, respectively. Furthermore, CARF overexpression lowered the ectopic palmitate accumulation in HepG2 cells. We were interested in understanding the role of hepatic CARF and underlying mechanisms in the development of NAFLD. Mechanistically, transcriptome analysis revealed that endoplasmic reticulum (ER) stress and oxidative stress pathway genes significantly altered in the absence of CARF. IRE1α, GRP78, and CHOP, markers of ER stress, were increased, and the treatment with TUDCA, an ER stress inhibitor, attenuated fat accumulation in CARF-deficient cells. Moreover, silencing CARF caused a reduction of GPX3 and TRXND3, leading to oxidative stress and apoptotic cell death. Intriguingly, CARF overexpression in HFD-fed mice significantly decreased hepatic steatosis. Furthermore, overexpression of CARF ameliorated the aberrant ER function and oxidative stress caused by fat accumulation. Our results further demonstrated that overexpression of CARF alleviates HFD-induced insulin resistance assessed with ITT and GTT assay. Altogether, we conclude that excess fat-induced reduction of CARF dysregulates ER functions and lipid metabolism leading to hepatic steatosis.

Racial/ethnic and gender disparity in the severity of NAFLD among people with diabetes or prediabetes.

Aim: Non-alcoholic fatty liver disease (NAFLD) exhibits a racial disparity. We examined the prevalence and the association between race, gender, and NAFLD among prediabetes and diabetes populations among adults in the United States. Methods: We analyzed data for 3,190 individuals ≥18 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values: S0 (none) < 238, S1 (mild) = 238-259, S2 (moderate) = 260-290, S3 (severe) > 290. Data were analyzed using Chi-square test and multinomial logistic regression, adjusting for confounding variables and considering the design and sample weights. Results: Of the 3,190 subjects, the prevalence of NAFLD was 82.6%, 56.4%, and 30.5% (p < 0.0001) among diabetes, prediabetes and normoglycemia populations respectively. Mexican American males with prediabetes or diabetes had the highest prevalence of severe NAFLD relative to other racial/ethnic groups (p < 0.05). In the adjusted model, among the total, prediabetes, and diabetes populations, a one unit increase in HbA1c was associated with higher odds of severe NAFLD [adjusted odds ratio (AOR) = 1.8, 95% confidence level (CI) = 1.4-2.3, p < 0.0001; AOR = 2.2, 95% CI = 1.1-4.4, p = 0.033; and AOR = 1.5, 95% CI = 1.1-1.9, p = 0.003 respectively]. Conclusion: We found that prediabetes and diabetes populations had a high prevalence and higher odds of NAFLD relative to the normoglycemic population and HbA1c is an independent predictor of NAFLD severity in prediabetes and diabetes populations. Healthcare providers should screen prediabetes and diabetes populations for early detection of NAFLD and initiate treatments including lifestyle modification to prevent the progression to non-alcoholic steatohepatitis or liver cancer.

Electronic Cigarette Use and the Risk of Cardiovascular Diseases.

Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolescents. Despite the widespread use of e-cigarettes and the known detrimental cardiac consequences of nicotine, the effects of e-cigarettes on the cardiovascular system are not well-known. Several in vitro and in vivo studies delineating the mechanisms of the impact of e-cigarettes on the cardiovascular system have been published. These include mechanisms associated with nicotine or other components of the aerosol or thermal degradation products of e-cigarettes. The increased hyperlipidemia, sympathetic dominance, endothelial dysfunction, DNA damage, and macrophage activation are prominent effects of e-cigarettes. Additionally, oxidative stress and inflammation are unifying mechanisms at many levels of the cardiovascular impairment induced by e-cigarette exposure. This review outlines the contribution of e-cigarettes in the development of cardiovascular diseases and their molecular underpinnings.

A New Ingenious Enemy: Heat-Not-Burn Products.

While cigarette smoking is still a major source of morbidity and mortality, e-cigarette usage is skyrocketing, and the tobacco industry is finding new ways to market nicotine. With updated published research highlighting the dangers of cigarette smoking and now vaping, the industry has been developing new techniques and devices that circumvent this research to hook users on tobacco and nicotine. The FDA allowed Philip Morris International (PMI) to sell their heat not burn tobacco products known as iQOS in 2019. By 2019, 49 countries had permitted the sale of iQOS. This commentary summarizes the recent research on heat not burn cigarettes, also known as heated tobacco products and their effects on public policy. We urge policy makers to consider the research published regarding these new products and prevent the widespread use of these products that will harm public health.

Embedding comprehensive smoking cessation programs into community clinics: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Cigarette smoking among adults in the USA is a leading cause of preventable death worldwide, even though there has been a decline in prevalence since 2005. The addictive nature of nicotine is the chief reason smokers continue to use tobacco. Although the majority of smokers report a desire to quit smoking, a small minority who attempt to quit achieve long-term cessation. Combined, smoking cessation best practices include coordinated medication and behavioral treatments. However, these treatments are not currently adequately delivered to Medi-Cal beneficiaries in the publicly funded patient-centered medical homes (PCMHs) and community mental health clinics operated by Los Angeles County (LAC)-Department of Health Services (LACDHS) and LAC-Department of Mental Health (LACDMH). METHODS: This is a 5-year implementation, cluster-randomized comparative effectiveness trial that will support the implementation of smoking cessation services delivered in LAC-LACDHS-operated outpatient primary care clinics and in LAC-LACDMH-operated community mental health clinics. We will enroll 1000 participants from clinics that will offer smoking cessation services and 200 from clinics that will offer treatment as usual. Participants will be asked to complete assessments at baseline, 3 months, 6 months, and 12 months. The assessments will include self-reports on smoking history, anxiety, stress, quality of life, and participant satisfaction. Participants who are assigned to clinics that provide smoking cessation services will also be asked about the frequency of their participation in the smoking cessation services during the 12-month period. DISCUSSION: This study will evaluate the effectiveness and feasibility of implementing smoking cessation services in outpatient primary care and community mental health clinics. It will also determine if there will be higher rates of smoking cessation in the implementation sites as compared to the sites with treatment as usual. If the implementation proves to be effective, the plan is to sustain these services using a workflow we will develop in the LAC-operated sites. This would lead to ameliorating the significant smoking cessation treatment gaps among those served within the LAC Health Agency departments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04717544 "Embedding comprehensive smoking cessation programs into community clinics." Registered on January 22, 2021.

Sex-Specific Differences in the Association Between Race/Ethnicity and NAFLD Among US Population.

Non-alcoholic fatty liver disease (NAFLD) is spreading worldwide, with a racial/ethnic disparity. We examined the gender role in the racial/ethnic difference in NAFLD in the US population. We analyzed data for 3,292 individuals ≥18 years old from NHANES 2017-2018, a representative sample of the non-institutionalized adult population in the US. Exclusions were subjects with elevated transferrin level, chronic hepatitis B or C, excessive alcohol use, or prescription medications that might cause hepatic steatosis. NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values: S0 <238, S1 = 238-259, S2 = 260-290, S3 >290. Data were analyzed using Chi square and multinomial regression. The overall prevalence of NAFLD was 47.9% [S2 = 16.1%, and S3 = 31.8%]. The prevalence of S3 was highest among Mexican Americans (46%), lowest among Blacks (22.7%), 29.9% in other Hispanics and 32.1% in Whites (p < 0.05). It was higher among Mexican American males (54.1%) compared to Mexican American females (37.7%) (p < 0.05). In the adjusted model, Mexican Americans were two times more likely than Whites to have S2 and S3 (p < 0.05). Only male Mexican Americans had higher odds of S2 and S3 relative to male White (p < 0.05). Males had higher odds of S3 relative to non-menopausal females (p < 0.05). There was no difference in the odds of S2 or S3 NAFLD among the menopausal females with or without hormone therapy relative to non-menopausal females (p > 0.05). While Mexican Americans had the highest prevalence of severe NAFLD relative to the other racial/ethnic groups, only male Mexican Americans, but not females, had higher likelihood of both moderate and severe NAFLD relative to Whites. Interventions that specifically target Mexican American males are needed to increase awareness about NAFLD and its prevention.

US Tobacco 21 is Paving the Way for a Tobacco Endgame.

The battle against tobacco usage is being fought on all fronts. On December 19, 2019, a measure to raise the minimum age to buy tobacco products to 21 from 18 was passed by the United States Congress and signed by President Donald Trump. This instated banning the sale of all tobacco products and electronic cigarettes to anyone in the US under the age of 21. This follows the raising of the age to buy tobacco in California to 21 in 2016. According to the California Tobacco Control Program: in 2016, roughly 10% of high-school students were smoking cigarettes, but by 2018, only 2%. The percentage of retailers selling tobacco to underaged youth dropped dramatically. These data show that the CA Tobacco 21 law was effective in decreasing the obtainability and usage of tobacco by youth. We expect that US Tobacco 21 will be similarly effective in reducing tobacco use by youth leading to less tobacco addiction in the US.

Implementing texting programs in the P.O.W.E.R. (preventing obesity with eating right) medical group visit for weight loss.

BACKGROUND: The effect of incorporating mobile technology to support participants' lifestyle change and weight loss in medical group visits has not been well studied in a safety-net setting. RATIONALE AND DESIGN: Thus, the rationale of the current study was to examine the effect of text messaging in a medical group visit, and test the effect of two texting programs (12 weeks and 20 weeks), compared to those who did not receive text-messaging in the Preventing Obesity With Eating Right (POWER) group visit program. The primary outcome was weight loss. RESULTS: We found that those enrolled in the 20-week and 12-week texting programs attended more group visit sessions than those enrolled in the POWER group only (p < 0.001). Both POWER and POWER + 20-week texting groups had a significant reduction in weight at their final group visit compared to their baseline (POWER, 114 ± 27 kg vs. 112 ± 26 kg, p < 0.001; POWER + 20-week texting, 111 ± 28 kg vs. 109 ± 28 kg, p < 0.01), but not the 12-week texting group (114 ± 29 kg vs. 113 ± 29 kg, p = 0.22), with no differences between the groups. The number of group visits was correlated with a decrease in weight (rs  = 0.12, p < 0.05). CONCLUSION: In conclusion, text messaging programs led to more attendance in the medical group visits, but not greater weight loss or reduction in HbA1c than the POWER group obesity program alone. Further studies are needed to maximize the beneficial effects of texting programs in medical group visits in underserved minority populations.

Safety Net Provider Attitudes Toward Smoking Cessation Treatment.

Background: Cigarette smoking, which poses significant health risks, is prevalent among vulnerable populations commonly treated by safety net providers. A large-scale implementation science project on specialty tobacco use treatment was launched within the Los Angeles County Health Agency. The first phase of this study seeks to summarize and compare smoking cessation treatment attitudes of providers at the Department of Health Services (DHS) and Department of Mental Health (DMH). Methods: In total, 467 safety net health care providers (DHS = 322; DMH = 145) completed a survey inquiring about attitudes on smoking cessation treatment consisting of locally developed items and those informed by a scale on readiness for organizational change. Descriptive statistics and non-parametric tests were conducted to examine treatment attitudes for DHS and DMH providers. Results: Between agencies, providers largely reported similar attitudes on smoking cessation treatment and expressed positive beliefs regarding the efficacy of smoking cessation aids. Providers slightly or moderately agreed with being prepared to identify and diagnose tobacco use among patients. DMH providers stated that identification of tobacco use was less in line with their job responsibilities (p < 0.0001) and less strongly agreed that varenicline is effective for smoking cessation (p = 0.003), compared with DHS providers. Conclusions: Providers supported smoking cessation aid efficacy but may benefit from additional training on identification and treatment of tobacco use. These findings support the implementation of specialty tobacco cessation treatment programs with training on medications in safety net health care systems, which has the potential to yield large-scale public health benefits.

Reassessment of the Hispanic Disparity: Hepatic Steatosis Is More Prevalent in Mexican Americans Than Other Hispanics.

Hepatic steatosis (HS) is a growing problem in adults worldwide, with racial/ethnic disparity in the prevalence of the disease. The purpose of this study was to characterize the racial/ethnic prevalence of the stages (normal/mild [S0/S1], moderate [S2], and severe [S3]) of HS in Mexican Americans and other Hispanics compared to other racial/ethnic groups. We analyzed data for 5,492 individuals 12 years and older from the newly released National Health and Nutrition Examination Survey 2017-2018, which is a representative sample of the US adult population. HS was diagnosed by FibroScan using controlled attenuation parameter values: S0, <238; S1, 238-259; S2, 260-290; S3, >290. We analyzed the data using the bivariate chi-squared test and multinomial regression. The prevalence of HS overall was 46.9% (S2,16.6%; S3, 30.3%). The prevalence of S3 was highest among Mexican Americans (42.8%), lowest among Blacks (21.6%), 27.6% in other Hispanics, and 30.6% in Whites (P < 0.05). Mexican Americans were about 2 times more likely than Whites to have S2 and S3, while other Hispanics showed no difference from Whites. In an adjusted model, the common risk factors of S2 and S3 were male sex, older ages, high waist-to-hip ratio, body mass index ≥25, and high triglycerides (P < 0.05). Other risk factors for S3 were hemoglobin A1c ≥5.7 and highly sensitive C-reactive protein ≥10 mg/dL (P < 0.05). Conclusion: Our study challenges the paradigm that HS is higher in Hispanics overall; rather, our data show that HS is higher in Mexican Americans and not non-Mexican American Hispanics.

Unhealthy Lifestyle and Gut Dysbiosis: A Better Understanding of the Effects of Poor Diet and Nicotine on the Intestinal Microbiome.

The study of the intestinal or gut microbiome is a newer field that is rapidly gaining attention. Bidirectional communication between gut microbes and the host can impact numerous biological systems regulating immunity and metabolism to either promote or negatively impact the host's health. Habitual routines, dietary choices, socioeconomic status, education, host genetics, medical care and environmental factors can all contribute to the composition of an individual's microbiome. A key environmental factor that may cause negative outcomes is the consumption of nicotine products. The effects of nicotine on the host can be exacerbated by poor dietary choices and together can impact the composition of the gut microbiota to promote the development of metabolic disease including non-alcoholic fatty liver disease. This review explores the contribution of nicotine, poor dietary choices and other unhealthy lifestyle factors to gut dysbiosis.

Decreased 11ß-Hydroxysteroid Dehydrogenase Type 2 Expression in the Kidney May Contribute to Nicotine/Smoking-Induced Blood Pressure Elevation in Mice.

[Figure: see text].

Metabolic parameters in smokers undergoing smoking reduction.

INTRODUCTION: Few human studies have explored the mechanisms of smoking-induced insulin resistance. Aims: To prospectively examine the metabolic changes of smoking reduction. METHODS: Cigarette smokers (n = 22; ½-2 packs per day) were enrolled in a smoking reduction program (counseling plus bupropion × 8 weeks; Phase I) followed by monitoring only (no counseling or bupropion × 16 weeks; Phase II). We serially measured exhaled carbon monoxide (CO) and urine nicotine metabolites; fat distribution, and metabolic parameters by hyperinsulinemic clamps including hepatic glucose output (HGO) and indirect calorimetry, adjusted for total caloric intake and expenditure. RESULTS: CO and nicotine metabolite levels fell with smoking reduction during Phase I (all p < 0.05), without any further changes through Phase II. Central-to-peripheral fat ratio increased during Phase I, but then fell during Phase II (all p < 0.05). Over 24 weeks, basal HGO fell (p = 0.02); and falling CO and nicotine metabolite levels correlated inversely with changes in glucose oxidation, and directly with changes in weight (all p < 0.05). CONCLUSIONS: Smoking reduction produced a transient worsening of central fat redistribution followed by a more significant improvement; along with other net beneficial metabolic effects.

The Combination of High-Fat Diet and Oral Marijuana Promotes the Development of Fibrosis in the Mouse Corpora Cavernosa.

INTRODUCTION: The link between cannabis use and erectile dysfunction remains unclear. Moreover, the effect of cannabis in tandem with current Western dietary habits is an area in male sexual health that has yet to be explored. This study seeks to investigate the impact of diet and cannabis on penile health in an animal model. AIM: To determine the effects of diet and oral cannabis extract on fibrosis and oxidative stress within the corpora cavernosa of mice. METHODS: This is a pilot animal study in which groups of 2-month old C57BL/6J male mice were fed a normal chow diet (NCD) or high-fat diet (HFD) daily and treated with or without either MJ or THC extract for 2 months. After euthanization, mouse penises were isolated and processed for immunohistochemical studies to determine: (i) smooth muscle cell to collagen content, (ii) myofibroblast proliferation, and (iii) anti-oxidative activity. MAIN OUTCOME MEASURES: Quantitative assessment of immunohistochemical markers of fibrosis and oxidative stress within the corpora cavernosa of mice fed a high-fat diet in combination with either oral marijuana (MJ) or Δ-9-tetrahydrocannabinol extract (THC). RESULTS: The combination of HFD with MJ resulted in: (i) a decrease in the smooth/collagen ratio in the corpora cavernosa, (ii) an increase in alpha-smooth muscle actin expression in the tunica albuginea compatible with myofibroblast proliferation, and (iii) a decrease in heme oxygenase 1 expression indicating an increase in oxidative stress. Significant histological changes were not observed in the HFD + THC group. CONCLUSIONS: HFD combined with oral MJ extract led to structural alterations in erectile tissue that are associated with accelerated corporal fibrosis. However, the addition of THC to the diet did not exacerbate histological changes within the corpora. Further studies are warranted to elucidate the discrepant effects between MJ and THC in order to optimize the therapeutic potential of cannabis and minimize its adverse effects on penile health. S Nguyen, M Mangubat, S Eleswarapu, et al. The Combination of High-Fat Diet and Oral Marijuana Promotes the Development of Fibrosis in the Mouse Corpora Cavernosa. Sex Med 2021;9:100312.

High Prevalence of Adrenal Remnant Tissue in Patients Undergoing Bilateral Adrenalectomy for Cushing's Disease.

Bilateral adrenalectomy (BLA) is a treatment option for patients with Cushing's Disease (CD) if transsphenoidal pituitary surgery fails or is not a therapeutic option. For most patients, BLA eliminates endogenous glucocorticoid and mineralocorticoid production, but for a small number of patients, endogenous secretion of adrenal hormones from adrenal tissue continues or recurs, leading to signs and symptoms of hypercortisolism. If adrenal tissue is confined to the adrenal bed, it is considered adrenal remnant tissue, while if it is outside the adrenal bed, it is considered adrenal rest tissue. We retrospectively evaluated morning serum cortisol, nighttime serum cortisol, nighttime salivary cortisol, and 24-h urine free cortisol on at least three occasions in 10 patients suspected of having endogenous cortisol production. Imaging of adrenal remnant tissue was also reviewed. Ten of 51 patients who underwent BLA during this time period had adrenal remnant/rest tissue marked by detectable endogenous glucocorticoid production; 9 of the 10 patients had signs and symptoms of hypercortisolism. Localization and treatment proved difficult. We conclude that the incidence of adrenal remnant/rest tissue in those undergoing BLA following unsuccessful pituitary surgery was 12% although there may have been a selection bias affecting this prevalence. The first indication of remnant tissue occurrence is a reduction in glucocorticoid replacement with symptoms of hypercortisolism. If this occurs, endogenous cortisol production should be tested for by cortisol measurements using a highly specific cortisol assay while the patient is taking dexamethasone or no glucocorticoid replacement. Endocrinologists need to monitor the development of both adrenal remnant tissue and Nelson's syndrome following BLA.