Absence Of Alcohol Research Articles

The Association Between Dextromethorphan/Bupropion with Alcohol and Substance Misuse: Reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).

Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability. We evaluated spontaneous reports of terms such as "alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse" in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA. We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for "drug abuse." In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method. The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.

Causal attributions of impulsive and compulsive behaviors.

Aggression, and therefore gender-based violence, can be an impulsive or compulsive behavior, depending on the consumption of alcohol and/or drugs. In Europe, the prevalence of gender-based violence is 16 to 23%. This prevalence shows that there is a need to make further progress in the treatment of aggression against women. Qualitative techniques allow us to understand perceptions and attributions holistically by analyzing what people who commit the crime say, why they say it and how they say it. To explore the experience of physical and verbal aggression by a partner, dependent on the presence or absence of alcohol and drug use, in the prison population. A mixed methodology was used (combining qualitative and quantitative techniques). The sample was made up of 140 men divided into two focus groups [with alcohol and/or drug consumption (SAD) and without alcohol and/or drug consumption (NSAD)] who completed the Demographic, Criminal and Behavioral Interview in Penitentiary Institutions; the Gender Violence Questionnaire (both developed for this study) and the MultiCAGE CAD-4 Questionnaire. Qualitative data were analyzed using thematic analysis and quantitative data were obtained using contingency tables. It was found that the SAD group attributed the crime committed to alcohol and/or drug consumption, while the NSAD group attributed it to jealousy and to their partner. The SAD group revealed that the consequence of the physical aggressions was to get what they were looking for from their partner and the consequences of the verbal aggressions was regret, unlike the NSAD group that did not get anything from the aggressions. The SAD group recognized that to avoid future aggressions they would have to avoid alcohol and/or drug use, while the NSAD group mentioned that they would have to avoid contact with their partner. The need to include perceptions and attributions as well as the use of alcohol and/or drugs is emphasized when assessing individuals who commit the crime of gender-based violence.

MiR-9 utilizes precursor pathways in adaptation to alcohol in mouse striatal neurons.

microRNA-9 (miR-9) is one of the most abundant microRNAs in the mammalian brain, essential for its development and normal function. In neurons, it regulates the expression of several key molecules, ranging from ion channels to enzymes, to transcription factors broadly affecting the expression of many genes. The neuronal effects of alcohol, one of the most abused drugs in the world, seem to be at least partially dependent on regulating the expression of miR-9. We previously observed that molecular mechanisms of the development of alcohol tolerance are miR-9 dependent. Since a critical feature of alcohol action is temporal exposure to the drug, we decided to better understand the time dependence of alcohol regulation of miR-9 biogenesis and expression. We measured the effect of intoxicating concentration of alcohol (20 mM ethanol) on the expression of all major elements of miR-9 biogenesis: three pri-precursors (pri-mir-9-1, pri-mir-9-2, pri-mir-9-3), three pre-precursors (pre-mir-9-1, pre-mir-9-2, pre-mir-9-3), and two mature microRNAs: miR-9-5p and miR-9-3p, using digital PCR and RT-qPCR, and murine primary medium spiny neurons (MSN) cultures. We subjected the neurons to alcohol based on an exposure/withdrawal matrix of different exposure times (from 15 min to 24 h) followed by different withdrawal times (from 0 h to 24 h). We observed that a short exposure increased mature miR-9-5p expression, which was followed by a gradual decrease and subsequent increase of the expression, returning to pre-exposure levels within 24 h. Temporal changes of miR-9-3p expression were complementing miR-9-5p changes. Interestingly, an extended, continuous presence of the drug caused a similar pattern. These results suggest the presence of the adaptive mechanisms of miR-9 expression in the presence and absence of alcohol. Measurement of miR-9 pre- and pri-precursors showed further that the primary effect of alcohol on miR-9 is through the mir-9-2 precursor pathway with a smaller contribution of mir-9-1 and mir-9-3 precursors. Our results provide new insight into the adaptive mechanisms of neurons to alcohol exposure. It would be of interest to determine next which microRNA-based mechanisms are involved in a transition from the acute, intoxicating effects of alcohol to the chronic, addictive effects of the drug.

Do couple drinking episodes lead to intimate partner aggression? An ecological momentary assessment study of same-sex and mixed-sex couples.

Alcohol use is an established risk factor for intimate partner aggression (IPA); however, few studies have considered whether couple drinking episodes increase the short-term likelihood of IPA episodes. The present ecological momentary assessment study considered the temporal effects of alcohol consumption on IPA perpetration and victimization within a sample of community couples at elevated risk of aggression. Mixed-sex (n = 191), same-sex male (n = 31), and same-sex female (n = 27) cohabiting couples (total N = 249; ages 21-35) made three independent, random reports for 30 consecutive days. Dyadic multilevel modeling was used to examine the impact of each partner's drinking episodes on the occurrence of verbal and physical perpetration and victimization events within the next 4 hr, using the actor-partner interdependence model. Actor and partner alcohol use increased the likelihood of conflict and likelihood of conflicts involving verbal perpetration and victimization within the next 4 hr; alcohol effects on physical aggression were weaker. Actor alcohol effects on IPA remained significant after the addition of several control variables; partner effects did not. The absence of Alcohol × Gender interaction effects suggests that alcohol effects on IPA do not depend on actor or partner gender or their combination. There are robust alcohol effects on the occurrence of verbal aggression perpetration and victimization episodes, with weak effects on physical aggression perpetration. Conflicts that include alcohol are not more likely to include aggression; rather, alcohol increases the likelihood of conflict occurring, with a proportion of those involving verbal aggression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The age-related dynamics of brain stem volume in women

Aim to study the dynamics of brain stem volumetric parameters in women from the early adulthood period to the middle old age according to magnetic resonance imaging (MRI) data.
 Material and methods.The material for the study was the MRI data of 94 female patients. The MRI was prescribed to exclude a probable pathology of the central nervous system in these patients. All the subjects gave their consent to participate in the study. The study sample included individuals without pathology of central and peripheral nervous system, with absence of alcohol or drug addiction, with skulls of average shape mesocranes. The cranial index was calculated according to the protruding extreme points on the axial section in 3D reconstruction mode. The subjects were divided into four groups according to selected age periods. The first group consisted of 25 women of the early adulthood (21-35 years); the second group included 25 women of the middle and late adulthood (36-55 years); the third group included 23 early old age women (56-74 years); the fourth group consisted of 21 middle old age women (75-88 years).
 Results. The brain stem volume in women decreased by 1.21% (t=3.84; p0.01) during the whole period of adulthood and by 0.82% (t=2.32; p0.01) from the late adulthood to early old age. From early old age to middle old age, there was only a tendency for volume to decrease by 0.83% (t=1.75; p0.05). In early adulthood period women, the brain stem volume was 2.8% higher than in middle old age women (t=6.47; p0.01).
 Conclusion.The results of intravital comparative analysis of the brain stem volume in women of the adulthood period, early and middle old age contribute to the knowledge about its relation to age and sex parameters and can be used in further morphofunctional studies and in clinical practice in gerontology, neurology and rehabilitation.

Stress-related neuropeptide systems as targets for treatment of alcohol addiction: A clinical perspective.

Alcohol use is a major cause of disability and death globally. These negative consequences disproportionately affect people who develop alcohol addiction, a chronic relapsing condition characterized by increased motivation to use alcohol, choice of alcohol over healthy, natural rewards, and continued use despite negative consequences. Available pharmacotherapies for alcohol addiction are few, have effect sizes in need of improvement, and remain infrequently prescribed. Research aimed at developing novel therapeutics has in large part focused on attenuating pleasurable or "rewarding" properties of alcohol, but this targets processes that primarily play a role as initiation factors. As clinical alcohol addiction develops, long-term changes in brain function result in a shift of affective homeostasis, and rewarding alcohol effects become progressively reduced. Instead, increased stress sensitivity and negative affective states emerge in the absence of alcohol and create powerful incentives for relapse and continued use through negative reinforcement, or "relief." Based on research in animal models, several neuropeptide systems have been proposed to play an important role in this shift, suggesting that these systems could be targeted by novel medications. Two mechanisms in this category, antagonism at corticotropin-releasing factor type 1, and neurokinin 1/substance P receptors, have been subject to initial evaluation in humans. A third, kappa-opioid receptor antagonism, has been evaluated in nicotine addiction and could soon be tested for alcohol. This paper discusses findings with these mechanisms to date, and their prospects as future targets for novel medications.

ВОЗРАСТНЫЕ ИЗМЕНЕНИЯ ОБЪЕМА СТВОЛА МОЗГА В ПОЖИЛОМ И СТАРЧЕСКОМ ВОЗРАСТЕ

One of the tasks of a developed society with a high standard of living is to increase life expectancy. It is worth understanding that the increasing number of young-old and old-old population causes the importance of developing gerontology and geriatrics. Causes and consequences of aging of the central nervous system departments have been studied sufficiently; nevertheless, anatomical data on the brain structures in the age aspect, namely on changes in the brain stem volume, are poorly presented. The aim of the investigation was to carry out a comparative analysis of brain stem volume parameters in young-old and old-old men and women according to magnetic resonance imaging data. The data of magnetic resonance imaging were analyzed in 94 patients examined in the Department of Radiation Diagnostics of State Autonomous Healthcare Institution of Perm Krai «City Clinical Hospital №» in the period of 2020-2022. The patients were divided into two groups according to age periodization. The first group consists of young-old people: 27 men aged 61-74 years and 23 women aged 56-73 years. The second group was represented by old-old individuals: 23 men aged 75-88 and 21 women aged 75-88. The study sample included persons without pathologies of central and peripheral nervous system, with absence of alcohol or drug addiction, with skulls of medium shape – mesocranes. The volume of the brain stem was determined in the 3D reconstruction mode. A tendency to the prevalence of parameters of the trunk volume in the young-old men and women in comparison with representatives of the old-old age (p>0.05) was established. In each age group studied, there was a tendency for prevalence of brain stem volume parameters in men compared to women (p>0.05). Thus, the obtained data add to the scientific knowledge about age-related anatomical features of the brain stem, which, in turn, will allow their use in assessing its volume in elderly and senile patients.

Pendampingan Sosialisasi Cemaran Khamr dan Alkohol Dalam Makanan Sebagai Persiapan Menghadapi Sertifikasi Halal

One of the food-product halalness indicator is the absence of alcohol. In this case, traders as business actors must know about the contamination of khamr and alcohol in food ingredients that are traded so as not to endanger themselves and consumersas a condition when applying for halal certification. Because the content of khamr and alcohol besides endangering health, the Qur'an also clearly forbids them.Therefore this community service aims to increase the knowledge of shop owners around IAIN Surakarta regarding the contamination of khamr and alcohol in food as an effort to prepare for halal certification. This activity is carried out using the socialization method, namely by giving lectures and questions and answers to 10 food stall owners. Activity evaluation is carried out by providing a pre-test and post-test on the topic presented. From this community service activity, there was an increase in knowledge which could be seen from the pre-test and post-test scores, which were respectively 36 and 86. Specifically, the increase in knowledge about the definition of alcohol and khamr was 50%, the rules of the beverage trade. alcohol in Indonesia is 50%, types of alcoholic drinks are 60%, and the law of alcohol and khamr in Islam is 30%.

N-alkyl-β-ketoiminate zinc complexes: Synthesis, structure, and reactivity in ring-opening polymerization of lactide

A series of N-alkyl-β-ketoiminate monozinc complexes [{tBuCN(R)CHC(O)CtBu}2Zn] (R = Me, 2a; Et, 2b; Pr, 2c; iPr, 2d; Cy, 2e) were synthesized from the reaction of diethyl zinc with the corresponding β-ketimines. All these zinc complexes were characterized by NMR, elemental analysis and HRMS spectroscopy. The molecular structures of complexes 2b-2e were further confirmed by single-crystal X-ray diffraction. The structures exhibit that each zinc center is four-coordinate, and surrounded by two bidentate β-ketoiminate ligands, forming a distorted tetrahedral geometry. These homoleptic bis(β-ketoiminate) zinc complexes are active towards the ring-opening polymerization of rac-lactide in the absence of alcohol, yielding over 90 % conversions within 1 h at 70 °C in toluene with the ratio of monomer to catalyst being 100.

Trait- and State-Fear of Missing Out: Influences on Alcohol Craving and Drinking Likelihood.

A growing body of research implicates Fear of Missing Out (FoMO) as a risk factor for collegiate alcohol use. However, little research has explored the causal mechanisms of this association, which may depend on examining FoMO at both trait and state levels. We therefore examined how predispositions toward experiencing FoMO (i.e., trait-FoMO) interacted with state-level cues indicating that one was "missing out" (i.e., state-FoMO) and cues indicating the presence or absence of alcohol. College students (n = 544) participating in an online experiment completed a measure of trait-FoMO and were then randomly assigned to one of four guided-imagery script conditions (FoMO/Alcohol cue, FoMO/No Alcohol cue, No FoMO/Alcohol cue, No FoMO/No Alcohol cue). Participants then completed measures of alcohol craving and drinking likelihood for the given scenario. Two hierarchical regressions (one per dependent variable) revealed significant two-way interactions. Greater trait-FoMO demonstrated the strongest, positive associations with alcohol craving following scenarios with FoMO cues present. Reported drinking likelihood was strongest when state-level cues for FoMO and alcohol were both present, moderate when either cue was independently present, and lowest when both cues were absent. FoMO's impact on alcohol craving and drinking likelihood varied across trait/state levels. Although trait-FoMO was associated with alcohol craving, state-level cues indicating "missing out" affected both alcohol-related variables and interacted with alcohol cues in imagery scenarios to predict drinking likelihood. Although additional research is needed, targeting psychological variables related to meaningful social connection may reduce collegiate alcohol use with respect to FoMO.

Metabolic and nutritional aspects of non-alcoholic fatty liver disease

Currently, in the structure of liver pathology, the leading position is occupied by non-alcoholic fatty liver disease (NAFLD), ahead of viral hepatitis C and alcoholic liver disease. The previous concept of NAFLD as a harmless disease has undergone significant changes. In the modern understanding, non-alcoholic fatty liver disease is a progressive disease with a high risk of developing fibrosis, cirrhosis of the liver and hepatocellular carcinoma. The number of liver transplants in patients with cirrhosis as a result of NAFLD is steadily increasing and ranks second after cirrhosis of the liver of viral etiology. Nevertheless, non-alcoholic fatty liver disease is still considered a «diagnosis of exclusion» due to the lack of specific diagnostic criteria, and the term itself has been criticized since it focuses only on the absence of alcohol’s contribution to the development of the disease. For this reason, an international expert consensus statement was published in 2020, proposing a new concept – metabolically associated fatty liver disease (MAFLD), highlighting the leading role of nutritional metabolic predictors in the development of disease. We performed a systematic review to summarize the clinical nutritional aspects of MAFLD. The authors discuss the fundamental clinical and functional, nutritional, metabolic, hormonal, microbiotic factors of the pathological process that determine the course and prognosis of the disease. Information on the topic was used from publications based on the disserCat, PubMed, and eLibrary databases.

Subregional Differences in Alcohol Modulation of Central Amygdala Neurocircuitry.

Alcohol use disorder is a highly significant medical condition characterized by an impaired ability to stop or control alcohol use, compulsive alcohol seeking behavior, and withdrawal symptoms in the absence of alcohol. Understanding how alcohol modulates neurocircuitry critical for long term and binge-like alcohol use, such as the central amygdala (CeA), may lead to the development of novel therapeutic strategies to treat alcohol use disorder. In clinical studies, reduction in the volume of the amygdala has been linked with susceptibility to relapse to alcohol use. Preclinical studies have shown the involvement of the CeA in the effects of alcohol use, with lesions of the amygdala showing a reduction in alcohol drinking, and manipulations of cells in the CeA altering alcohol drinking. A great deal of work has shown that acute alcohol, as well as chronic alcohol exposure via intake or dependence models, alters glutamatergic and GABAergic transmission in the CeA. The CeA, however, contains heterogeneous cell populations and distinct subregional differences in neurocircuit architecture which may influence the mechanism by which alcohol modulates CeA function overall. The current review aimed to parse out the differences in alcohol effects on the medial and lateral subregions of the CeA, and what role neuroinflammatory cells and markers, the endocannabinoid system, and the most commonly studied neuropeptide systems play in mediating these effects. A better understanding of alcohol effects on CeA subregional cell type and neurocircuit function may lead to development of more selective pharmacological interventions for alcohol use disorder.

Purkinje cell-specific deletion of CREB worsens alcohol-induced cerebellar neuronal losses and motor deficits.

Exposure to alcohol during pregnancy can kill developing fetal neurons and lead to fetal alcohol spectrum disorder (FASD) in the offspring. However, not all fetuses are equally vulnerable to alcohol toxicity. These differences in vulnerability among individuals are likely due, at least in part, to genetic differences. Some genes encode neuroprotective molecules that act through signaling pathways to protect neurons against alcohol's toxic effects. One signaling pathway that can protect cultured neurons against alcohol-induced cell death invitro is the cAMP pathway. A goal of this study was to determine whether the cAMP pathway can exert a similar neuroprotective effect against alcohol invivo. A key molecule within the cAMP pathway is cAMP response element binding protein (CREB). In this study, CREB was specifically disrupted in cerebellar Purkinje cells to study its role in protection of cerebellar neurons against alcohol toxicity. Mice with Purkinje cell-specific knockout of CREB were generated with the Cre-lox system. A 2×2 design was used in which Cre-negative and Cre-positive mice received either 0.0 or 2.2mg/g ethanol by intraperitoneal (i.p.) injection daily over postnatal day (PD) 4-9. Stereological cell counts of cerebellar Purkinje cells and granule cells were performed on PD 10. Motor function was assessed on PD 40 using the rotarod. Purkinje cell-specific disruption of CREB alone (in the absence of alcohol) induced only a small reduction in Purkinje cell number. However, the loss of CREB function from Purkinje cells greatly increased the vulnerability of Purkinje cells to alcohol-induced cell death. While alcohol killed 20% of Purkinje cells in the Cre-negative (CREB-expressing) mice, alcohol killed 57% of Purkinje cells in the Cre-positive (CREB-nonexpressing) mice. This large loss of Purkinje cells did not lead to similar alcohol-induced losses of granule cells. In the absence of alcohol, lack of CREB function in Purkinje cells had no effect on rotarod performance. However, in the presence of alcohol, disruption of CREB in Purkinje cells substantially worsened rotarod performance. Disruption of a single gene (CREB) in a single neuronal population (Purkinje cells) greatly increases the vulnerability of that cell population to alcohol-induced cell death and worsens alcohol-induced brain dysfunction. The results suggest that the cAMP pathway can protect cells invivo against alcohol toxicity and underline the importance of genetics in determining the neuropathology and behavioral deficits of FASD.

Fenretinide Reduces Intestinal Mucin-2-Positive Goblet Cells in Chronic Alcohol Abuse

Introduction: Alcohol-induced thickening of the gut mucosal layer and increased expression of goblet cell gel-forming mucins, such as mucin-2 (MUC2) are associated with disruptions to the gut barrier in alcoholic liver disease (ALD). Interest in drugs that can target gut mucins in ALD has grown; however to date, no studies have examined the properties of drugs on expression of gut mucins in models of ALD. We previously demonstrated that at 10 mg/kg/day, the drug fenretinide (N-[4-hydroxyphenyl] retinamide [Fen]), a synthetic retinoid, mitigates alcohol-associated damage to the gut barrier and liver injury in a murine model of ALD. Methods: In this study, we specifically sought to examine the effects of Fen on gut goblet cells, and expression of mucins, including MUC2 using a 25-day Lieber-DeCarli model of chronic alcohol intake. Results: Our results show that chronic alcohol intake increased gut-mucosal thickening, goblet cell numbers, and mRNA and protein expression of MUC2 in both the ileum and colon. Alcohol intake was associated with marked decreases in ileal and colonic Notch signaling, levels of Notch ligands Dll1 and Dll4, and increases in the expression of Notch-associated genes indispensable for goblet cell specification, including Math1 and Spdef. Interestingly, ileal and colonic expression of KLF4, which is involved in terminal differentiation of goblet cells, was reduced in mice chronically fed alcohol. Coadministration of alcohol with Fen at 10 mg/kg/day significantly reduced alcohol-associated increases in ileal and colonic mucosal thickening, ileal Muc2, colonic Muc2, Muc5ac and Muc6 mRNAs, and goblet cell numbers. We also found that Fen strongly prevented alcohol-mediated suppression of the Notch ligand Dll1, Notch signaling, and alcohol-induced increases in expression of Notch-associated goblet cell specification genes in both the ileum and colon. In the absence of alcohol, Fen treatments alone at 10 mg/kg/day had no effects on any of the goblet cell-related endpoints. Conclusion: These data show for the first time that the drug Fen possesses mucosal layer-modulating properties in response to chronic alcohol abuse. These data warrant further preclinical examination of Fen given the need for anti-ALD drugs and emerging evidence of a role for intestinal goblet cell mucins in the progression of ALD.

Association of Serum Apolipoprotein A5 Concentration with Nonalcoholic Fatty Liver Disease in Ningbo, China.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease characterized by the excessive accumulation of hepatocyte fat and steatosis in the absence of alcohol or any other clear contributing factors to liver injury. NAFLD has been confirmed to be closely associated with obesity, insulin resistance, and dyslipidemia. Genetic polymorphism studies have shown the relations between the apolipoprotein A5 gene (APOA5) and NAFLD. However, the association between the serum ApoA5 level and NAFLD remains unclear. Between September 2018 and August 2019, adults who attended the hospital-based health checkup center were enrolled in this study. Anthropometric examination, laboratory investigations on fasting blood, and abdominal ultrasonography were performed. The serum ApoA5 level was determined by enzyme-linked immunosorbent assay. A total of 517 eligible participants (317 females and 200 males) were involved in this study, with a mean age of 54.7 ± 16.7 years. The mean ApoA5 concentration was 28.8 ± 4.7 μg/ml, among which the males had higher concentration levels than females (29.3 ± 4.5 vs. 28.5 ± 4.7 μg/mL, P=0.04). Serum ApoA5 level was not significantly correlated with NAFLD or metabolic profiles. However, the prevalence rate of hypertriglyceridemia (triglyceride ≥ 1.7 mmol/L) showed a significant inverted “U”-shaped trend in individuals with the serum ApoA5 level of quartile one to quartile four after adjusting the confounding factors. Moreover, individuals with higher serum ApoA5 levels were also more likely to suffer from hyperglycemia. The ApoA5 levels and the prevalence of hypertriglyceridemia are in an inverted “U-shaped” correlation, but there is no significant difference between ApoA5 levels, NAFLD, and metabolic syndrome.

The anti-anginal ranolazine does not confer beneficial actions against hepatic steatosis in male mice subjected to high-fat diet and streptozotocin-induced type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver in the absence of alcohol and increases one's risk for both diabetes and cardiovascular disease (e.g., angina). We have shown that the second-line anti-anginal therapy, ranolazine, mitigates obesity-induced NAFLD, and our aim was to determine whether these actions of ranolazine also extend to NAFLD associated with type 2 diabetes (T2D). Eight-week-old male C57BL/6J mice were fed either a low-fat diet or a high-fat diet for 15 weeks, with a single dose of streptozotocin (STZ; 75 mg/kg) administered in the high-fat diet-fed mice at 4 weeks to induce experimental T2D. Mice were treated with either vehicle control or ranolazine during the final 7 weeks (50 mg/kg once daily). We assessed glycemia via monitoring glucose tolerance, insulin tolerance, and pyruvate tolerance, whereas hepatic steatosis was assessed via quantifying triacylglycerol content. We observed that ranolazine did not improve glycemia in mice with experimental T2D, while also having no impact on hepatic triacylglycerol content. Therefore, the salutary actions of ranolazine against NAFLD may be limited to obese individuals but not those who are obese with T2D.

Ring-opening polymerization of cyclic esters by 3- and 4-pyridinyl Schiff base Zn(II) and Cu(II) paddlewheel complexes: kinetic, mechanistic and tacticity studies

We have previously reported a series of highly active N,O-Amino-phenolate Mg(II) and Zn(II) Schiff base complexes for caprolactone and lactide polymerization (Munzeiwa, Nyamori, and Omondi, 2019). Herein we report carboxylate Zn(II) and Cu(II) pyridinyl Schiff base complexes and in particular, those whose ligands have substituents slightly situated away from the metal center. The complexes were fully characterized and for some fully by single-crystal X-ray diffraction studies. The ligands were confirmed to be monodentate and their complexes have the famous paddlewheel conformation. The carboxylate complexes were found to initiate the polymerization of ɛ-caprolactone and lactides in the presence or absence of alcohol, yielding low molecular weight polymers between 1.27 and 5.65 kg mol ‐1 , with broad Ð between 1.7 and 2.0. The Zn(II) complexes were more reactive than their Cu(II) analogues. Activity of the complexes seems to have been influenced by the electronic properties of the substituents with the highest apparent rate constant, k app of 0.4043 h −1 , being obtained for the complex of the ligand with an electron-withdrawing group (chloro). The complex was used to investigate activity and stereo-selectivity towards the ring-opening polymerization of L -lactide and rac -lactide. Tetrad analysis of the polylactides obtained from homonuclear 1 H and 13 C NMR afforded isotactic PLA with L -LA and heterotactic (Pr = 0.68) stereo-block PLA with rac -LA.

Trends in Deaths Fully Attributable to Alcohol in Minnesota, 2000-2018.

Overall trends in rates of fully alcohol-attributable mortality may mask disparities among demographic groups. We investigated overall, demographic, and geographic trends in fully alcohol-attributable mortality rates in Minnesota. We obtained mortality data from Minnesota death certificates and defined fully alcohol-attributable deaths as deaths that would not occur in the absence of alcohol. We calculated age-adjusted death rates during 2000-2018 using 5-year moving averages stratified by decedents' characteristics and geographic location. Chronic conditions accounted for most of the alcohol-attributable deaths in Minnesota (89% during 2014-2018). Alcohol-attributable mortality rates per 100 000 population increased from an average rate of 8.0 during 2000-2004 to 12.6 during 2014-2018. During 2000-2018, alcohol-attributable mortality rates were highest among males (vs females), adults aged 55-64 (vs other ages), and American Indian/Alaska Native people (vs other racial and ethnic groups) and lowest among people aged ≤24 years and Asian or Pacific Islander people. During 2014-2018, the alcohol-attributable mortality rate among American Indian/Alaska Native people was more than 5 times higher than the overall mortality rate in Minnesota. Results from this study may increase awareness of racial and ethnic disparities and continuing health inequities and inform public health prevention efforts, such as those recommended by the Community Preventive Services Task Force, including regulating alcohol outlet density and increasing alcohol taxes.

Fructose and the Liver.

Chronic diseases represent a major challenge in world health. Metabolic syndrome is a constellation of disturbances affecting several organs, and it has been proposed to be a liver-centered condition. Fructose overconsumption may result in insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, and increased triglyceride concentrations in both the blood and liver. Non-alcoholic fatty liver disease (NAFLD) is a term widely used to describe excessive fatty infiltration in the liver in the absence of alcohol, autoimmune disorders, or viral hepatitis; it is attributed to obesity, high sugar and fat consumption, and sedentarism. If untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation and mild fibrosis in addition to fat infiltration and, eventually, advanced scar tissue deposition, cirrhosis, and finally liver cancer, which constitutes the culmination of the disease. Notably, fructose is recognized as a major mediator of NAFLD, as a significant correlation between fructose intake and the degree of inflammation and fibrosis has been found in preclinical and clinical studies. Moreover, fructose is a risk factor for liver cancer development. Interestingly, fructose induces a number of proinflammatory, fibrogenic, and oncogenic signaling pathways that explain its deleterious effects in the body, especially in the liver.

Duodenojejunal intussusception due to an inflammatory fibroid polyp: a mimic of acute pancreatitis.

SUMMARY This report describes an extremely unusual cause of acute pancreatitis. It highlights the value of cross-sectional imaging, in the absence of alcohol and gallstone aetiology, to establish a diagnosis and direct management. Computed tomography (CT) revealed a duodenal jejunal intussusception. A benign inflammatory fibroid tumour, acting as a lead point, was surgically resected and the patient made an unremarkable recovery without further episodes of acute pancreatitis.