Habitual Users Research Articles

Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC-MS/MS Analysis.

Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC-MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjects̀ compliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.

Understanding addictive behaviour of a group of slum dwelling female SLT users on the basis of PRIME theory: A case study in Odisha, India

ABSTRACT Context: Tobacco addiction is an important public health problem. Among several theories of addiction proposed, PRIME theory of motivation is found to be a comprehensive one to synthesise prevention strategies. Aims: This case study was conducted on the basis of PRIME theory to explain smokeless tobacco (SLT) addiction patterns among slum dwelling female residents of Cuttack district, Odisha. Settings and Design: Cuttack district of Odisha state and Qualitative synthesis. Methods and Material: Qualitative semistructured face-to-face interviews and framework analysis techniques were employed. The study was conducted over a period of 2 months between February 2020 and March 2020. Face-to-face interviews of 26 participants of Dasha Sahi slum using a semistructured questionnaire assessing responses based on five main themes including P, Plans; R, Responses; I, Impulses And Inhibitory Forces; M, Motives; and E, Evaluations of the said theory. Statistical Analysis Used: Verbatim transcripts were analysed using thematic framework analysis. Results: A majority of the participants were multiple SLT product users, and they did not have an immediate plan to quit. Most of the participants showed strong emotional attachment with these products and considered them the only source of pleasure (want) in a life full of miseries. The words “Tobacco” and “Nicotine” were medical jargons for them. Though they were aware of the harmful effects, they had a positive evaluative belief about its use because of cognitive dissonance. Most of them were habitual users living in an environment full of physical and social cues. Conclusions: This case study is well in line with the PRIME theory in explaining the addictive behaviour; a comprehensive multi-strategic approach was formulated for inculcating quitting behaviour among this disadvantaged section of the population as suggested by the proposer of this theory.

Psychosocial characteristics of the general population who habitually use hypnotics: Results from a national survey on drug use among the Japanese.

The aim of this study was to examine the characteristics of habitual hypnotic users in Japan. This nationwide, cross-sectional survey used self-administered questionnaires. Data were collected from four national surveys conducted every 2 years between 2015 and 2021. The participants were Japanese individuals who had taken prescription hypnotics in the past year or had never taken them. We divided 13,396 participants into three groups to compare the social background and status of taking medication and controlled drugs, drinking, and smoking among the three groups: people who use hypnotics habitually daily (habitual hypnotic users [HUs]), people who use them only occasionally (occasional hypnotic users [OUs]), and people who do not use them (hypnotic non-users [NUs]). We compared the perception of using hypnotics between the HU and OU groups. HUs were more likely to be older, unemployed, and to habitually use anxiolytics and analgesics than NUs. The main reasons for taking anxiolytics in HUs were alleviating insomnia and reducing anxiety, whereas the main reason for taking analgesics was improving joint pain. Additionally, the HU group had a higher proportion of habitual smokers than the OU group. There was no difference in drinking status or taking of controlled drugs among the three groups. HUs were more likely to use hypnotics and to have concerns about their side-effects than OUs. HUs were more likely to be unemployed, habitually use anxiolytics and analgesics, smoke heavily, and take hypnotic drugs with concerns regarding side-effects. These results may help encourage the appropriate use of hypnotics.

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine.

Only a subset of individuals who encounter drugs of abuse become habitual users. Aversive subjective effects like coughing and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop a clinically relevant model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigating whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions. Twenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2 hr/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR). We identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who "overindulge" on their first use and subsequently find self-administration to be aversive. Our novel model mimics real-world variability in initial interactions with drugs of abuse and yields three distinct groups that differ in self-administration patterns and aversive cue valuation.

Effects of Smokeless Tobacco on Oral Health: A Cross-Sectional Study.

Smokeless tobacco (SLT) consumption poses a significant global public health challenge because of its adverse effects on oral health. Although the detrimental impact of SLT on oral tissues is well-documented, understanding its multifaceted effects is essential for effective prevention and intervention strategies. This study aimed to comprehensively assess the impact of SLT on oral health, focusing on various clinical parameters and their differences between placement and non-placement sites of SLT. A cross-sectional study involving 528 habitual users of SLT was conducted. Clinical parameters included the plaque index (PI), gingival index (GI), gingival bleeding index (GBI), gingival recession (GR), and probing depth (PD). Oral mucosal changes at SLT placement sites have also been reported. Statistical analysis was performed to compare parameters between the placement and non-placement sites. The study involved 528 subjects, mostly male (82%) and aged 21-40 years (mean±SD=31.14±9.10), habitual users of SLT. Prevalent SLT types included tobacco with betel nuts/masala/gutkha (59.9%) and tobacco with lime (54.5%). Significant differences were observed between SLT placement and non-placement sites: higher gingival inflammation (GI) at placement sites (1.54±0.61 vs. 1.45±0.54, p=0.01), lower GBI at placement sites (40.0% vs. 84.3%, p=0.001), and more prevalent GR (65.7% vs. 34.3%, p=0.03) at placement sites. Probing depths ≥ 3 mm were also less frequent at placement sites (2.67±0.72) than non-placement sites (3.37±1.03, p=0.001). These results highlight the detrimental impact of SLT on periodontal health, emphasizing the need for targeted interventions among SLT users. SLT use is associated with adverse effects on oral health, including GI, plaque accumulation, gingival bleeding, GR, and changes in the oral mucosa. Targeted interventions and public health policies are needed to address these issues effectively.

Right prefrontal activation associated with deviations from expected lipstick texture assessed with functional near-infrared spectroscopy.

There is a continuous consumer demand for ever superior cosmetic products. In marketing, various forms of sensory evaluation are used to measure the consumer experience and provide data with which to improve cosmetics. Nonetheless, potential downsides of existing approaches have led to the exploration of the use of neuroimaging methods, such as functional near-infrared spectroscopy (fNIRS), to provide addition information about consumers' experiences with cosmetics. The aim of the present study was to investigate the feasibility of a real-time brain-based product evaluation method which detects the incongruency between a product, in this case lipstick, and a consumer's expectations. Thirty healthy, female, habitual lipstick users were asked to apply six different lipsticks varying in softness and to rate the softness of and their willingness to pay (WTP) for each lipstick. Cerebral hemodynamic responses in frontal areas were measured with fNIRS during lipstick application and analyzed using the general linear model (GLM). Incongruency scores between softness and expectation were calculated in order to understand how far removed each lipstick was from a participant's optimal softness preference. The correlation between brain activation (beta scores) during the application of each lipstick and the respective incongruency scores from each participant were acquired using semi-partial correlation analysis, controlling for the effects of WTP. We revealed a significant intra-subject correlation between incongruency scores and activation in the right inferior frontal gyrus (IFG). This confirms that as the texture incongruency scores increased for the lipstick samples, activation in each individual's right IFG also increased. The correlation observed between incongruency perceived by participants and activation of the right IFG not only suggests that the right IFG may play an important role in detecting incongruity when there is a discrepancy between the perceived texture and the consumer's expectations but also that measuring activity in the IFG may provide a new objective measurement of the consumer experience, thus contributing to the development of superior cosmetics.

Abstract 3139: Evidence Of Vascular Endothelial Dysfunction In Habitual Hookah (i.e., Waterpipe) Users: Insights For Cardiovascular Disease Risk

Introduction: Flavored hookah tobacco smoking among young adults continues to be a public health concern. While short-term exposure to flavored hookah tobacco smoking impairs vascular function, data on the long-term impact of habitual use are not clearly delineated. Research Question: Is habitual flavored hookah tobacco smoking associated with vascular endothelial dysfunction in young healthy adults? Goals: Investigate the impact of regular flavored hookah tobacco smoking on vascular endothelial function, as compared to regular cigarette smoking and never tobacco use, in young healthy adults. Methods: We assessed brachial artery flow-mediated dilation (FMD)—a well-established index of vascular endothelial function—in 22 exclusive chronic hookah smokers (25±1 years of age, 23% women; mean±SE), who reported smoking flavored hookah tobacco on average two times per week for 9±1 years, 22 exclusive cigarette smokers who reported 4±1 pack years, and 23 non-smokers. FMD and vascular endothelium-independent nitroglycerin-mediated vasodilation was assessed using high resolution ultrasound. Results: Whereas baseline brachial artery diameter was comparable between groups ( P =ns), brachial artery FMD was significantly lower in habitual hookah users and cigarette users as compared to never smokers (cigarette smokers: 5.22±0.42; hookah smokers: 6.43±0.50; non-smokers: 9.80±0.83; P <0.05). Endothelium-independent dilation of the brachial artery in response to sublingual nitroglycerin did not significantly differ between groups. Conclusions: Despite claims of safety advertised by the growing hookah tobacco industry, our findings provide evidence that, as compared to non-tobacco users, young and apparently healthy adults who regularly smoke flavored hookah tobacco exhibit reduced vascular endothelial function. These results suggest that flavored hookah tobacco smoking is not without harm and has potential harmful vascular effects, associated with increased cardiovascular disease risk.

Association of Cannabis Use Disorder with Major Adverse Cardiac and Cerebrovascular Events in Older Non-Tobacco Users: A Population-Based Analysis.

Tobacco use disorder (TUD) adversely impacts older patients with established cardiovascular disease (CVD) risk. However, CVD risk in chronic habitual cannabis users without the confounding impact of TUD hasn't been explored. We aimed to determine the risk of major adverse cardiac and cerebrovascular events (MACCE) in older non-tobacco smokers with established CVD risk with vs. without cannabis use disorder (CUD). We queried the 2019 National Inpatient Sample for hospitalized non-tobacco smokers with established traditional CVD risk factors aged ≥65 years. Relevant ICD-10 codes were used to identify patients with vs. without CUD. Using multivariable logistic regression, we evaluated the odds of MACCE in CUD cohorts compared to non-CUD cohorts. Prevalence of CUD in the sample was 0.3% (28,535/10,708,815, median age 69), predominantly male, black, and non-electively admitted from urban teaching hospitals. Of the older patients with CVD risk with CUD, 13.9% reported MACCE. The CUD cohort reported higher odds of MACCE (OR 1.20, 95% CI 1.11-1.29, p < 0.001) compared to the non-CUD cohort. Comorbidities such as hypertension (OR 1.9) and hyperlipidemia (OR 1.3) predicted a higher risk of MACCE in the CUD cohort. The CUD cohort also had higher unadjusted rates of acute myocardial infarction (7.6% vs. 6%) and stroke (5.2% vs. 4.8%). Among older non tobacco smokers with known CVD risk, chronic cannabis use had a 20% higher likelihood of MACCE compared to those who did not use cannabis.

RESISTIN GENE POLYMORPHISMS: POTENTIAL BIOMARKER FOR ORAL SQUAMOUS CELL CARCINOMA

Objective: The objective of the work is to study the association between Resistin Gene polymorphisms and susceptibility of Oral Squamous Cell carcinoma. Methods: In the present study, we scrutinize the connection between four genetic polymorphisms present in RETN gene with the susceptibility, progression, and clinical outcome of OSCC among 200 OSCC patients and 200 healthy controls. Results: The results of the study reveal that among 260 smokers, the risk of developing OSCC is significantly more among the subjects having history of using betel quid in comparison to those who are not habitual users of betel quid. Conclusion: The study reveals that patients with OSCC exhibiting G/A heterozygous genotype of RETN rs3219175 polymorphism have lesser risk for developing high-grade tumor compared to the patients with G/G homozygotes in North Indian population.

Post-occlusive reactive hyperemia in habituated caffeine users: Effects of abstaining versus consuming typical doses.

Post-occlusive reactive hyperemia (PORH) typically requires caffeine abstinence. For habitual users, it is unknown if abstinence affects PORH. Compare PORH after habitual users consume or abstain from caffeine. On separate visits (within-subject), PORH was measured in 30 participants without abstinence from typical caffeine doses (CAFF) and with abstinence (ABS). Measurements included baseline and peak hyperemic velocity, tissue saturation index slopes during ischemia (Slope 1) and following cuff deflation (Slope 2), resting arterial occlusion pressure (AOP), heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure. All variables were compared using Bayesian paired t-tests. BF10 = likelihood of alternative vs null. Results are mean±SD. Comparing baseline velocity (cm/s) between CAFF (9.3±4.8) and ABS (7.5±4.9) yielded anecdotal evidence (BF10 = 1.0). Peak hyperemic velocity (cm/s) was similar (CAFF = 77.3±16.7; ABS = 77.6±19.0, BF10 = 0.20). For slopes (TSI% /s), CAFF Slope 1 = -0.11±0.04 and Slope 2 = 1.9±0.46 were similar (both BF10≤0.20) to ABS Slope 1 = -0.12±0.03 and Slope 2 = 1.8±0.42. SBP and DBP (mmHg) were both similar (CAFF SBP = 116.0±9.8, DBP = 69.6±5.8; ABS SBP = 115.5±10.7, DBP = 69.5±5.4; both BF10≤0.22). Comparing AOP (mmHg) (CAFF = 146.6±15.0; ABS = 143.0±16.4) yielded anecdotal evidence (BF10 = 0.46). HR (bpm) was similar (CAFF = 66.5±12.3; ABS = 66.9±13.0; BF10 = 0.20). In habitual users, consuming or abstaining from typical caffeine doses does not appear to affect post-occlusive reactive hyperemia.

Visual Performance in Myopic Adolescents Fitted with Pupil-Optimised Multifocal Soft Contact Lenses

Objective: This study aims to assess the influence of a newly developed pupil-optimized multifocal soft contact lens (MFSCL) in comparison to single-vision contact lenses (SVCL) on visual performance among adolescent myopes. Materials and Methods: Myopic adolescents, aged 14 to 18 years, who were habitual SVCL users, were subjected to a trial involving MFSCL with a mid-addition power. Various visual parameters including distance and near visual acuity (VA), maximum reading speed (MRS), reading acuity, contrast sensitivity, and stereoacuity under photopic conditions were measured for MFSCL and compared to SVCL. Results: No statistically significant differences were observed between SVCL and MFSCL in terms of near VA, MRS, contrast sensitivity, and stereoacuity (p &gt; 0.05 for all). However, a decrease in distance VA was noted with MFSCL (p = 0.021). Moreover, reading acuity, which denotes the smallest print size comprehensible without significant errors, was found to be smaller when using MFSCL (p &lt; 0.001). Conclusion: In adolescent myopic patients, mid-add power in MFSCL did not significantly impact near VA and contrast sensitivity when compared to SVCL, while a decrease in distance VA was observed. Moreover, MFSCL did not affect reading speed but did enable the reading of smaller font sizes.

How Social Media Algorithms Shape Offline Civic Participation: A Framework of Social-Psychological Processes

Even though social media platforms have created opportunities for more efficient and convenient civic participation, they are unlikely to bring about social change if the online actions do not propagate to offline civic participation. This article begins by reviewing the meta-analytic evidence on the relation between social media use and offline civic participation. Following this discussion, we present a theoretical framework that incorporates the attitudinal, motivational, and relational processes that may mediate the effect of social media use on offline civic participation. The framework highlights how social media algorithms may shape attitudes on important societal issues, promote generalized action goals among habitual users, and build social capital. We further discuss factors that may strengthen or undermine each of these processes, suggest ways to design and implement algorithms that may promote offline civic participation, and propose questions for future research.

Less vigilant in the mobile era? A comparison of information processing on mobile phones and personal computers

Do people process information differently on mobile phones compared to computers? We investigate this question by conducting two online field experiments. We randomly assigned participants to use their mobile phones or personal computers (PCs) to process different kinds of information. Study 1 ( N = 116) discovered that participants using mobile phones process emails more efficiently (i.e., spend less time) than those using PCs. Study 2 ( N = 241) extended this to online deceptive content and found that individuals using mobile phones, especially habitual users, are more efficient, but engage in less information processing, are less attentive and less vigilant about misinformation, compared to those using PCs. However, the latter are more likely to succumb to phishing emails by clicking on malicious links. We discuss theoretical implications for information processing across media devices and practical implications for combating misinformation and cybersecurity attacks.

Mediating Effect of Stress Recognition on the Effect of Generalized Anxiety Disorder on Smartphone Dependence

The widespread adoption of the smartphone has led to both positive and negative consequences for adolescents’ mental health. This study examines the interplay between smartphone dependence (SPD), generalized anxiety disorder (GAD), and various mental health outcomes among Korean adolescents. Data from the 16th Adolescence Health Behavior Survey (2020), including 54,948 middle and high school students, were analyzed. Adolescents were categorized into three groups based on SPD severity. The GAD-7 scale assessed anxiety, and other factors such as subjective health recognition, happiness, weight control efforts, and body mass index (BMI) were considered. Adolescents with higher SPD exhibited lower academic performance, decreased happiness, and increased perception of stress. GAD levels were positively correlated with SPD, with higher SPD linked to more severe GAD symptoms. Additionally, higher SPD was associated with increased loneliness, sadness, and suicidal thoughts, plans, and attempts as well as a greater likelihood of habitual drug use. Gender differences revealed that females were more prone to sadness, hopelessness, and suicidal thoughts, while males exhibited higher rates of drug use. This study highlights the complex relationship between SPD, GAD, and mental health outcomes among Korean adolescents. Stress recognition was found to mediate the association between GAD and SPD. The process-macro result of the total effect between SPD on GAD and the direct effect of the SPD pathway on GAD was significant; thus, the stress recognition was mediated. Effective interventions should target stress management, especially among adolescents with high smartphone dependence, to mitigate the risk of mental health issues. These findings underscore the importance of addressing smartphone dependence and its impact on the mental well-being of adolescents.

Promoting Minority Language Use to Foster Revitalisation: Insights From New Speakers of West Frisian

Abstract Language planners are increasingly aware of the importance of new speakers (individuals acquiring a language outside the home, typically later-on in life) for the revitalisation of minority languages. Yet, little is known about new speakers’ activation (the process by which they become active and habitual minority language users). This article presents a questionnaire-based investigation of new speakers’ (n = 264) use of West Frisian in Fryslân, Netherlands—and the role traditional speakers play in new speakers’ activation. Qualitative and quantitative data show that participants use West Frisian only rarely; and when they do use it, it is mainly in the classroom. Minority language interactions outside the classroom, with traditional speakers, consist mostly of a few tokenistic words or phrases. The findings show to what extent different behaviours by traditional speakers discourage and/or encourage new speakers’ minority language use, highlighting how the complex dynamics between the speaker groups are hindering revitalisation efforts. The article discusses the implications of these findings for language planning to promote the activation of new speakers, and thereby the revitalisation of West Frisian.

An Integrated Ordered Probit Model for Evaluating University Commuters’ Satisfaction with Public Transport

Transport policymakers need to have an in-depth understanding of public transport (PT) customers in order to effectively manage transport systems and maintain the attractiveness of these systems to potential users. This research aims to compare the perceptions and satisfaction levels of two groups of PT users (habitual and occasional) among university staff and students regarding the quality of PT through a new integrated approach. A sample of 500 participants from Budapest, Hungary was used. Two stages of analysis were conducted: a descriptive analysis was conducted in the first stage, and Student’s t-tests of two independent samples were applied to identify the varying perceptions and overall satisfaction. Second, a new integrated ordered probit model (OPM) and an importance–performance analysis (IPA) were used to envisage how best to prioritize actions for transport enhancement. The results show that in the circle of commuters, the habitual PT users were more satisfied with the existing PT service than the occasional PT users. According to the findings of the IPA, for habitual users, the attribute “information provided” has a high priority for improvement, whereas the cost for both user types was found to be significant for all models, contributing to overall satisfaction. This factor was included in the possible overkill quadrant, suggesting that there might be more cost resources than needed. The new model, along with the case study results, may help policymakers and transport operators to make better decisions regarding the identification of service priority areas.

Caffeine Enhances 10-km Cycling Performance in Habitual Users Only When Preceded by Caffeine Abstinence.

The primary objective was to assess the performance benefits of caffeine (CAF) supplementation in habitual users. Importantly, this investigation was designed to account for the potential confounding effects of CAF withdrawal(CAFW), which are inherent and common in previous work. Ten CAF-consuming (394 [146]mg·d-1) recreational cyclists (age 39.1 [14.9]y; maximum oxygen consumption 54.2 [6.2]mL·kg-1·min-1) completed four 10-km time trials (TTs) on a cycle ergometer. On each trial day, 8hours before reporting to the laboratory, subjects consumed 1.5mg·kg-1 CAF to prevent withdrawal (no withdrawal [N]) or a placebo (PLA; withdrawal [W]). Then, 1hour prior to exercise, they received either 6mg·kg-1 CAF or PLA. These protocols were repeated 4 times, employing all combinations of N/W and CAF/PLA. CAFW did not impair TT power output (PLAW vs PLAN P = .13). However, preexercise CAF only improved TT performance when compared to PLA in the W condition (CAFN vs PLAW P = .008, CAFW vs PLAW P = .04), not when W was mitigated (PLAN vs CAFN P = .33). These data indicate that preexercise CAF only improves recreational cycling performance when compared to bouts preceded by CAF abstinence, suggesting that habitual users may not benefit from 6mg·kg-1 of CAF and that previous work may have overstated the value of CAF supplementation for habitual users. Future work should examine higher doses of CAF for habitual users.

Estradiol receptors inhibit long-term potentiation in the dorsomedial striatum.

Estradiol, a female sex hormone and the predominant form of estrogen, has diverse effects throughout the brain including in learning and memory. Estradiol modulates several types of learning that depend on the dorsomedial striatum (DMS), a subregion of the basal ganglia involved in goal-directed learning, cued action-selection, and motor skills. A cellular basis of learning is synaptic plasticity, and the presence of extranuclear estradiol receptors ERα, ERβ, and G protein-coupled estrogen receptor (GPER) throughout the DMS suggests that estradiol may influence rapid cellular actions including those involved in plasticity. To test whether estradiol affects synaptic plasticity in the DMS, corticostriatal long-term potentiation (LTP) was induced using theta-burst stimulation in ex vivo brain slices from intact male and female C57BL/6 mice. Extracellular field recordings showed that female mice in the diestrus stage of the estrous cycle exhibited LTP similar to male mice, while female mice in estrus did not exhibit LTP. Furthermore, antagonists of ERα or GPER rescued LTP in estrus females and agonists of ERα or GPER reduced LTP in diestrus females. In males, activating ERα but not GPER reduced LTP. These results uncover an inhibitory action of estradiol receptors on cellular learning in the DMS and suggest a cellular mechanism underlying the impairment in certain types of DMS-based learning observed in the presence of high estradiol. Due to the dorsal striatum's role in drug addiction, these findings may provide a mechanism underlying an estradiol-mediated progression from goal-directed to habitual drug use.Significance StatementThis study examined the role of the female reproductive cycle and female sex hormones in synaptic plasticity, a cellular process that underlies learning behavior, in a brain region involved in goal-directed learning. Synaptic plasticity was similar between male mice and female mice in the low estradiol phase of the cycle. In contrast, female mice in a high estradiol phase of the cycle did not exhibit synaptic plasticity. The effect of estradiol was mediated by two of the three estradiol receptors found in the brain. The results have implications for the role of the female reproductive cycle in the development of drug addiction, which involves a progression from goal-directed learning to habit-based learning as drug use switches from recreational to compulsive.

Habitual fish oil use and risk of COVID-19-related outcomes: Evidence from a large scale cohort study and Mendelian randomization analysis

Previous findings for the effects of fish oil on COVID-19-related outcomes remain largely inconclusive and controversy persists. Large population-based studies in real-life settings are required to explore the impact of habitual fish oil use on Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, Coronavirus disease 2019 (COVID-19)-related hospitalization and death. To investigate the associations between habitual fish oil use and SARS-CoV-2infection, COVID-19-related outcome. Cohort study based on the UK Biobank. 466,572 participants were enrolled. For Mendelian randomization (MR) study, single-nucleotide variants were selected for exposures of fish-oil-derived n-3 PUFAs, including docosapentaenoic acid (DPA). 146,969 (31.5%) participants reported their habitual fish oil use at baseline. Compared with non-fish-oil-users, the hazard ratios for habitual users were 0.97 (95% confidence interval [CI] 0.94 to 0.99) for SARS-CoV-2 infection, 0.92 (95% CI 0.85 to 0.98) for COVID-19-related hospitalization and 0.86 (95% CI 0.75 to 0.98) for COVID-19-related death. MR showed that a higher level of circulating DPA is casually associated with a lower risk of severe COVID-19 (IVW, odds ratio=0.26, 95% CI 0.08-0.88, P=0.030). In this large cohort, we found that habitual fish oil use was significantly associated with lower risks of SARS-CoV-2 infection, hospitalization and death from COVID-19. MR analyses further support a possible causal role of DPA, one of the components of fish oil and valid biomarkers of dietary intake, in reducing the risk of severe COVID-19.

A Common East Asian aldehyde dehydrogenase 2*2 variant promotes ventricular arrhythmia with chronic light-to-moderate alcohol use in mice

Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.