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We aimed to investigate the clinico-radiologic features of acute Marchiafava-Bignami disease (MBD) and its evolutionary process after effective treatment through subgroup comparison. The clinical and MRI data of 23 patients with acute MBD were retrospectively analyzed and divided into type A (12 cases, with entire callosal involvement) and type B (11 cases, with focal callosal involvement). The clinical assessments and MRI findings (before and after treatment) were compared between the two subtypes. Compared with type B, type A had lower MoCA (Montreal Cognitive Assessment) scores at admission (16.50 ± 1.73 vs 18.27 ± 1.68, P = 0.021) and were more common with extracallosal involvement (66.67% vs 18.18%, P = 0.036) and longer illness duration (18.3 ± 2.1 days vs 15.6 ± 2.4 days, P = 0.012). During the treatment, the residual lesion in the splenium was more common in type A (58.33% vs 9.09%, P = 0.027). After treatment, the MoCa scores of both subtypes gradually increased (P < 0.001), and the callosal and extracallasal lesions disappeared completely. Clinico-radiologic typing of acute MBD is related to the severity of early symptoms, but not to the prognosis. Complete clinico-radiologic recovery is possible for both subtypes with combined treatment. The clinico-radiologic reversibility is helpful for accurate diagnosis and therapeutic evaluation., (© 2023. The Author(s).)

Objective: To investigate the effect of long-term ethanol consumption on learning-memory functions in mice and the mechanisms involved., Methods: Thirty male C57BL6/J mice were randomly assigned to 3 groups, with 10 mice in each group. The three groups included a control group in which the mice were given water ad libitum for 30 days, a long-term ethanol consumption group, or the EtOH group, in which the mice were given 6% (volume fraction) ethanol ad libitum for 30 days, and a long-term alcoholism group, or the EtOH+G group, in which the mice were given 5% (volume fraction) ethanol ad libitum for 30 days plus intermittent intragastric gavage of 20% ethanol at 3.5 g per kilogram body mass once every three days. After 30 days, the learning-memory functions of the mice were evaluated. At the conclusion of the experiment, the brain tissue of the mice was collected in order to examine the oxygen consumption rate (OCR) of mitochondria, the levels of pan-acetylation and protein oxidative stress in the hippocampal tissue, and the expression of sirtuin-3 (SIRT3) in hippocampus., Results: Morris water maze test showed that, compared with those of the control group, the times of crossing the platform and the percentage of platform time in the EtOH group and the EtOH+G group were both lower, and the EtOH+G group had the lowest results ( P <0.05). Western blot results showed that long-term ethanol intake increased the levels of protein oxidative stress and pan-acetylation in the hippocampal tissue and down-regulated SIRT3 expression of hippocampal mitochondria. The results of mitochondrial complex Ⅱ respiration showed that the brain mitochondrial 3-state respiration in the EtOH group and the EtOH+G group was lower than that in the control group ( P <0.05). Compared that with the control group, the mitochondrial maximum respiration in EtOH+G group was decreased ( P <0.05)., Conclusions: Both long-term ethanol consumption and long-term alcoholism can reduce learning-memory functions and long-term alcoholism has the greater impact of the two. The potential mechanism may involve the down-regulation of the expression of SIRT3 protein in the hippocampus, which results in an increased level of pan-acetylation and enhanced expression of oxidative stress protein in the hippocampus, affects the mitochondrial functions of the brain, inhibits the oxidative phosphorylation capacity of mitochondrial complex Ⅱ, reduces the ATP energy supply of the brain tissue, and thus affects the learning-memory function., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro . Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Syed, Yu, Yang, Xia, Relich, Russell, Zhang, Khalili, Huang, Kacena, Zheng and Yu.)

Alcohol is the most frequently-used addictive drug. However, the mechanism by which its consumption leads to addiction remains largely elusive. Given the conservation of behavioral reactions to alcohol, Caenorhabitis elegans (C. elegans) has been effectively used as a model system to investigate the relevant molecular targets and pathways mediating these responses. In this article, we review the roles of BK channels (also called SLO-1), the lipid microenvironment, receptors, the synaptic machinery, and neurotransmitters in both the acute and chronic effects of alcohol. We provide an overview of the genes and mechanisms involved in alcoholismrelated behaviors in C. elegans.

Previous post-mortem and structural magnetic resonance imaging (MRI) studies in patients with alcohol dependence have demonstrated abnormalities of brain white matter. The present study investigated the microstructural integrity in the corpus callosum and the associations of this integrity with neurobehavioral assessments. Twenty-five male cases fulfilling the DSM-IV diagnosis of alcohol dependence and 15 male control subjects were scanned using a 3T MRI system. Callosal fiber tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into seven functionally distinct segments. The microstructural integrity was quantified in terms of generalized fractional anisotropy (GFA). Compared with normal subjects, men with alcohol dependence showed lower GFA values on all segments of the corpus callosum. The segment interconnecting the bilateral orbitofrontal cortices was the most affected. The score on the Barratt Impulsivity Scale showed an inverse relationship with GFA on the callosal fiber tracts connecting the bilateral orbitofrontal cortices. Furthermore, the duration of regular use was negatively associated with GFA on the callosal fiber tracts connecting the bilateral temporal and parietal cortices. Our findings suggest that a high self-rated impulsivity level was associated with low anisotropy in white matter of corpus callosum sectors extending to the orbitofrontal cortex., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: The purpose of this study was to explore the concepts and processes for successful abstinence from alcohol for Taiwanese Alcoholics Anonymous members., Background: Attempting to identify the psychological and social influences upon alcohol consumption remission outside of alcoholism treatment could help professionals to engage in a broad array of community interventions in an informed fashion., Methods: Grounded theory method was utilized in this study. The study chose nine participants who had succeeded in abstinence, using theoretical sampling and conducted in-depth interviews by an open-ended questionnaire., Results: The results of this study indicated that the core of the process during which alcoholic individuals succeeded in abstaining from further alcohol consumption was an empowerment process for the involved individual. Alcoholics felt that their family, interpersonal relationships, jobs and personal finances all had been at 'rock-bottom' level following a long period of alcohol dependence. This feeling caused the individual to experience an emotion of a loss of control and provoked the arousal of an alcoholic's inner consciousness levels, this then resulting in the generation of a driving force for abstinence from alcohol for these individuals., Conclusions: The expansion of an individual's internal awakening power helps the individual to obtain assistance and to resist the temptation of further alcohol consumption. Therefore, the power derived by individuals from the stages of repositioning, releasing, active sharing, resistance and assistance are the maintenance factors for an individual's empowerment process that help maintain the successful recovery from alcohol for the involved individual., Relevance to Clinical Practice: A good comprehension of the recovery processes for alcoholics, we believe, will trigger clinical professionals to pay appropriate attention to the specific problems and needs of alcoholic individuals, to build an effective resource network for treatment and to help solve alcoholics' physical and psychosocial problems.

Internal control beliefs appear to be important factors in recovery from alcoholism. However, no instrument for assessing drinking-related locus of control has been developed in Taiwan. After translating the drinking-related locus-of-control scale (DRIE) into Chinese, we examined the psychometric properties of the Chinese version of the DRIE in alcohol-dependent patients. A total sample of 161 alcohol-dependent patients received treatment for alcoholism in psychiatric hospital outpatient and inpatient units. Confirmatory factor analyses were conducted on three-factor, two-factor, and one-factor measurement models of the DRIE based on prior studies. The results indicated that the one-factor model of the DRIE provided goodness of fit to the data in this study. The Chinese version of the DRIE has been demonstrated to be a reliable and valid tool for the assessment of locus-of-control beliefs in alcohol-dependent patients.

Aim: To investigate the correlation between the gastric adaptive cytoprotection and the low concentration alcohol intake in a chronic drinking rat model and the effect of chronic ethanol exposures on the cell turnover of the gastric mucosa and its possible role in adaptive cytoprotection., Methods: Sprague-Dawley rats received the drinking water containing 6% (v/v) ethanol as their only water intake for 28 days. In the different stages of the 28 days (1st, 3rd, 7th, 14th and 28th days), the stomachs of the rats were cannulated and perfused with pure ethanol, and the severity of mucosal lesions was measured in 2 hours at the end of perfusion respectively. The cell proliferation and apoptosis in gastric mucosa of rats in different groups were analyzed by flow cytometer, immunohistochemistry and computer image analysis., Results: Pure ethanol caused ulcer and haemorrhagic damage in the corpus and antral mucosa of the control rats. These lesions were prevented by pretreatment of the animals with ethanol exposure in the 3 rd to 14 th days. The damage index was decreased by 80%, as compared with those in control rats. There was no significant difference in the rats exposed to the ethanol in the 1st and 28th days. Compared with control, the cell apoptosis in gastric mucosa of the rats was enhanced during they exposure to the ethanol in the 3rd to 28th days. Otherwise the cell proliferation was increased in the 3rd to 28th days, and decreased in the 28th days, respectively., Conclusion: Chronic adequate alcohol intake may enhance the cell turnover of gastric mucosa and lead to an adaptive cytoprotection. Long-term stimulus with the low concentration ethanol may cause the atrophy of gastric mucosa and reduce the gastric mucosal cytoprotective effect.

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.

To track iron accumulation and location in the brain across adolescence, we repurposed diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data acquired in 513 adolescents and validated iron estimates with quantitative susceptibility mapping (QSM) in 104 of these subjects. DTI and fMRI data were acquired longitudinally over 1 year in 245 male and 268 female, no-to-low alcohol-consuming adolescents (12-21 years at baseline) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. Brain region average signal values were calculated for susceptibility to nonheme iron deposition: pallidum, putamen, dentate nucleus, red nucleus, and substantia nigra. To estimate nonheme iron, the corpus callosum signal (robust to iron effects) was divided by regional signals to generate estimated R2 (edwR2 for DTI) and R2 * (eR2 * for fMRI). Longitudinal iron deposition was measured using the normalized signal change across time for each subject. Validation using baseline QSM, derived from susceptibility-weighted imaging, was performed on 46 male and 58 female participants. Normalized iron deposition estimates from DTI and fMRI correlated with age in most regions; both estimates indicated less iron in boys than girls. QSM results correlated highly with DTI and fMRI results (adjusted R2 = 0.643 for DTI, 0.578 for fMRI). Cross-sectional and longitudinal analyses indicated an initial rapid increase in iron, notably in the putamen and red nucleus, that slowed with age. DTI and fMRI data can be repurposed for identifying regional brain iron deposition in developing adolescents as validated with high correspondence with QSM.

Prenatal alcohol exposure can result in long-term cognitive and behavioral deficits. Fetal alcohol spectrum disorder (FASD) refers to a range of permanent birth defects caused by prenatal alcohol exposure, and is the most common neurodevelopmental disorder in the US. Studies by autopsy and conventional structural MRI indicate that the midline structures of the brain are particularly vulnerable to prenatal alcohol exposure. Diffusion tensor imaging (DTI) has shown that abnormalities in brain white matter especially the corpus callosum are very common in FASD. Quantitative susceptibility mapping (QSM) is a novel technique that measures tissue's magnetic property. Such magnetic property is affected by tissue microstructure and molecular composition including that of myelin in the white matter. In this work, we studied three major white matter fiber bundles of a mouse model of FASD and compared it to control mice using both QSM and DTI. QSM revealed clear and significant abnormalities in anterior commissure, corpus callosum, and hippocampal commissure, which were likely due to reduced myelination. Our data also suggested that QSM may be even more sensitive than DTI for examining changes due to prenatal alcohol exposure. Although this is a preclinical study, the technique of QSM is readily translatable to human brain.

Background: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Materials and methods: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Results: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745–0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0–A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B–D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Conclusion: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarette (e-cigarette) and cannabis (marijuana) use is rapidly increasing. Objectives: To report percentage prevalence and changes over time in current (past 30 days) e-cigarette, cannabis, and dual (concurrent) use in the population of reproductive age women (18–44 years old) in the United States. Methods: Our cross-sectional analysis involved data of 11, 004 women from Waves 1 to 3 of the Population Assessment of Tobacco and Health (PATH) Study (2013–2016). We estimated weighted percentage prevalence and 95% confidence intervals (CIs) and changes between 2013 and 2016 in current e-cigarette, cannabis, and dual use at each wave overall and across race/ethnicity, age, education, cigarette smoking status, alcohol use, and perceived mental health. Changes were reported as p for trend. Results: Between 2013 and 2016, e-cigarette use increased 13.6% (p for trend <.001) [15.2% (95% CI:14.2, 16.2) in 2013–2014; 22.2% (95% CI: 20.2, 24.3) in 2014–2015; and 28.8% (95% CI: 26.3, 31.3) in 2015–2016]; cannabis use increased 6.2% (p for trend <.001) [23.6% (95% CI: 22.1, 25.1) in 2013–2014; 28.5% (95% CI: 26.0, 31.0) in 2014–2015; and 29.8% (95% CI: 27.9, 31.1) in 2015–2016]; and dual use declined 0.3% (p for trend <.001) [5.8% (95% CI: 5.2, 6.3) in 2013–2014; 4.8% (95% CI: 3.7, 5.8) in 2014–2015; and 5.5% (95% CI: 4.2, 6.7) in 2015–2016]. Increases and declines in prevalence varied across sociodemographic characteristics, cigarette smoking status, alcohol use, and perceived mental health. Conclusions: Continued monitoring can capture further changes in prevalence and patterns to inform targeted public health intervention programs. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic has taken a detrimental toll on the lives of individuals globally. In addition to the direct effect (e.g., being infected with the virus), this pandemic has negatively ravaged many industries, particularly food retail, food services, and hospitality. Given the novelty of the disease, the true impact of COVID-19 remains to be determined. Because of the nature of their work, and the characteristics of the workers, individuals in the food retail, food service, and hospitality industries are a group whose vulnerability is at its most fragile state during this pandemic. Through this qualitative study, we explored workers' perspectives on the impact of COVID-19 on their mental health and coping, including screening for post-traumatic stress disorder (PTSD) and alcohol use disorder symptoms. Twenty-seven individual interviews were conducted, audio-recorded, transcribed, and analyzed using qualitative content analysis. Four key themes emerged: being infected and infecting others, the unknown, isolation, and work and customer demands. Considering the many uncertainties of COVID-19, workers in these three industries were experiencing heightened levels of mental distress because of where they worked and the already existing disparities they faced on a daily basis before the pandemic started. Yet they remained hopeful for a better future. More studies are needed to fully understand the magnitude, short-term, and long-term effects of COVID-19. Based on this study's findings, programs are critically needed to promote positive coping behaviors among at-risk and distressed workers. Recommendations for employers, occupational health and safety professionals, and policy stakeholders to further support these service workers are discussed. [ABSTRACT FROM AUTHOR]

Background: Heavy alcohol consumption disrupts gut epithelial integrity, leading to increased permeability of the gastrointestinal tract and subsequent translocation of microbes. Regenerating islet‐derived protein 3α (REG3α) and Trefoil factor 3 (TFF3) are mainly secreted to the gut lumen by Paneth and Goblet cells, respectively, and are functionally linked to gut barrier integrity. Circulating levels of REG3α and TFF3 have been identified as biomarkers for gut damage in several human diseases. We examined whether plasma levels of REG3α and TFF3 were dysregulated and correlated with conventional markers of microbial translocation (MT) and pro‐inflammatory mediators in heavy drinkers with and without alcoholic hepatitis (AH). Methods: Cross‐sectional and longitudinal studies were performed to monitor plasma levels of REG3α and TFF3 in 79 AH patients, 66 heavy drinkers without liver disease (HDC), and 46 healthy controls (HC) at enrollment and at 6‐ and 12‐month follow‐ups. Spearman correlation was used to measure the relationships of REG3α and TFF3 levels with MT, disease severity, inflammation, and effects of abstinence from alcohol. Results: At enrollment, AH patients had significantly higher levels of REG3α and TFF3 than HDC and HC. The elevated REG3α levels were positively correlated with the 30‐day fatality rate. Plasma levels of REG3α and TFF3 in AH patients differentially correlated with conventional MT markers (sCD14, sCD163, and LBP) and several highly up‐regulated inflammatory cytokines/chemokines/growth factors. At follow‐ups, although REG3α and TFF3 levels were decreased in AH patients with alcohol abstinence, they did not fully return to baseline levels. Conclusions: Circulating levels of REG3α and TFF3 were highly elevated in AH patients and differentially correlated with AH disease severity, MT, and inflammation, thereby serving as potential biomarkers of MT and gut epithelial damage in AH patients. [ABSTRACT FROM AUTHOR]

Background: Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up‐regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM‐1, VCAM‐1, and VEGF‐A) and the effect of alcohol abstinence on the reversal of these abnormalities in heavy drinkers with and without AH. Methods: ELISA and multiplex immunoassays were used to measure soluble EC activation markers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6‐month follow‐up, and 18 AH patients and 25 HDC at 12‐month follow‐up. Results: At baseline, the 4 soluble markers were significantly up‐regulated in AH patients compared with HDC and HC, whereas only sVCAM‐1 was elevated in HDC relative to HC. At follow‐ups, plasma levels of CD146, VCAM‐1, and VEGF‐A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several soluble inflammatory factors. Conclusions: The levels of soluble CD146, ICAM‐1, VCAM‐1, and VEGF‐A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities. [ABSTRACT FROM AUTHOR]

Background: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. Objectives: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). Methods: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. Results: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. Conclusions: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP. [ABSTRACT FROM AUTHOR]

Introduction: there is a lack of longitudinal studies investigating daily tobacco use and problem drinking in Africa. The aim of this study was to explore the prevalence of daily tobacco use and problem drinking and to determine the factors associated with daily tobacco use and problem drinking among urban dwellers in a longitudinal study in South Africa. Methods: electronic interview data were collected from 2213 adults (mean age 45.7 years, SD=15.1; range 20-97) at time 1 (baseline assessment) and Time 2 (12 months follow-up assessment) from one urban centre in South Africa. Results: daily tobacco use only, was at time 1 24.0% and at time 2 23.4%, a decrease of 0.5%. Problem drinking only was at time 1 19.6% and at time 2 21.1%, an increase of 1.5%. Concurrent daily tobacco use and problem drinking increased from time 1 9.5% to 10.3% at time 2, an increase of 0.8%. In longitudinal regression analyses, being male and being born in current city were significantly associated with all three substance use indicators (daily tobacco use; problem drinking; and concurrent daily tobacco use and problem drinking). In addition, older age, not currently married, lower education, underweight and higher levels of perceived stress were associated with daily tobacco use and younger age was associated with problem drinking. Conclusion: high prevalence of daily tobacco use and problem drinking were found among urban dwellers and several sociodemographic (being male, being born in the city, not married and lower education) and health variables (being underweight and perceived stress) were identified which can guide substance use intervention programmes for this population. [ABSTRACT FROM AUTHOR]