Is impulsivity related to attentional bias in cigarette smokers? An exploration across levels of nicotine dependency and deprivation.

Research has largely focused on how attentional bias to smoking-related cues and impulsivity independently influence the development and maintenance of cigarette smoking, with limited exploration of the relationship between these mechanisms. The current experiments systematically assessed relationships between multiple dimensions of impulsivity and attentional bias, at different stages of attention, in smokers varying in nicotine dependency and deprivation. Nonsmokers (NS; n  = 26), light-satiated smokers (LS; n  = 25), heavy-satiated smokers (HS; n  = 23) and heavy 12-hour nicotine-deprived smokers (HD; n  = 30) completed the Barratt Impulsivity Scale, delayed discounting task, stop-signal task, information sampling task and a visual dot-probe assessing initial orientation (200 ms) and sustained attention (2000 ms) toward smoking-related cues. Sustained attention to smoking-related cues was present in both HS and LS, while initial orientation bias was only evident in HS. HS and LS also had greater levels of trait motor and nonplanning impulsivity and heightened impulsive choice on the delay discounting task compared with NS, while heightened trait attentional impulsivity was only found in HS. In contrast, in HD, nicotine withdrawal was associated with no attentional bias but heightened reflection impulsivity, poorer inhibitory control and significantly lower levels of impulsive choice relative to satiated smokers. Trait and behavioral impulsivity were not related to the extent of attentional bias to smoking-related cues at any stage of attention, level of nicotine dependency or state of deprivation. Findings have both clinical and theoretical implications, highlighting the unique and independent roles impulsivity and attentional bias may play at different stages of the nicotine addiction cycle.

Estrogen signaling modulates behavioral selection toward pups and amygdalohippocampal area in the rhomboid nucleus of the bed nucleus of the stria terminalis circuit.

Gonadal steroid hormone influences behavioral choice of adult animals toward pups, parental or aggressive. We previously reported that long-term administration of 17ß-estradiol (E2) to male mice during sexual maturation induces aggressive behavior toward conspecific pups, which is called "infanticide," and significantly enhanced excitatory synaptic transmission in the rhomboid nucleus of bed nucleus of the stria terminalis (BSTrh), which is an important brain region for infanticide. However, it is unclear how estrogen receptor-dependent signaling after sexual maturity regulates neural circuits including the BSTrh. Here we revealed that E2 administration to gonadectomized mice in adulthood elicited infanticidal behavior and enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of glutamate release from the presynaptic terminalis. Next, we performed whole-brain mapping of E2-sensitive brain regions projecting to the BSTrh and found that amygdalohippocampal area (AHi) neurons that project to the BSTrh densely express estrogen receptor 1 (Esr1). Moreover, E2 treatment enhanced synaptic connectivity in the AHi-BSTrh pathway. Together, these results suggest that reinforcement of excitatory inputs from AHi neurons into the BSTrh by estrogen receptor-dependent signaling may contribute to the expression of infanticide.

A role of anterior cingulate cortex in the emergence of worker-parasite relationship.

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.

Preferences of first-degree relatives of gastric cancer patients for gastric cancer screening: a discrete choice experiment.

BACKGROUND: It is very necessary to implement gastric cancer screening in China to reduce the mortality of gastric cancer, but there are no national screening guidelines and programs. Understanding of individual preferences is conducive to formulating more acceptable screening strategies, and discrete choice experiments can quantify individual preferences. In addition, the first-degree relatives of gastric cancer patients are at high risk for gastric cancer. Compared with those without a family history of gastric cancer, the risk of gastric cancer in first-degree relatives of gastric cancer patients is increased by 60%. Therefore, a discrete choice experiment was carried out to quantitatively analyse the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening to serve as a reference for the development of gastric cancer screening strategies. METHODS: A questionnaire was designed based on a discrete choice experiment, and 342 first-degree relatives of gastric cancer patients were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULTS: The five attributes included in our study had a significant influence on the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening (P < 0.05). Participants most preferred the sensitivity of the screening program to be 95% (coefficient = 1.424, P < 0.01) with a willingness to pay 2501.902 Yuan (95% CI, 738.074-4265.729). In addition, the participants' sex and screening experiences affected their preferences. An increase in sensitivity 35 to 95% had the greatest impact on the participants' willingness to choose a gastric cancer screening program. CONCLUSION: The formulation of gastric cancer screening strategies should be rooted in people's preferences. The influence of sex differences and screening experiences on the preferences of people undergoing screening should be considered, and screening strategies should be formulated according to local conditions to help them play a greater role.

The Medial Orbitofrontal Cortex-Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice.

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC-BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLA→mOFC pathway is not needed to use the identity of an expected reward to guide choice but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, the data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.SIGNIFICANCE STATEMENT To make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding outcomes can be expected and how desirable they currently are. Such prospective considerations are critical for adaptive decision making but disrupted in many psychiatric diseases. Here, we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.

Delay discounting rate by a surrogate decision maker depends on the smoking status of the recipient.

The tendency to devalue future rewards is known as delay discounting. Discounting is measured using a series of intertemporal choices between smaller, sooner outcomes and larger, later outcomes. We used a surrogate delay discounting task to explore whether such choices would differ if a hypothetical recipient was a smoker or was an individual with good health habits. Across three studies, the descriptions of the recipient included only information about smoking status (n = 66), smoking status and equal annual income (n = 47), and smoking status and equal weekly expenditures (n = 42). Higher rates of delay discounting for the smoker recipient compared to the nonsmoker recipient were observed across all three studies. These results parallel previous findings showing group differences in discounting between actual smokers and nonsmokers. We discuss the similarities between the present results and previous studies in light of an extension of Bem's (1967) self-perception theory, which posits that choices in laboratory-based delay discounting tasks are informed by observation of real-world intertemporal choice. The theory asserts that there is no fundamental difference between a first-person account of such knowledge and a third-person account. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effects of vapourized THC and voluntary alcohol drinking during adolescence on cognition, reward, and anxiety-like behaviours in rats.

Cannabis and alcohol co-use is prevalent in adolescence, but the long-term behavioural effects of this co-use remain largely unexplored. The aim of this study is to investigate the effects of adolescent alcohol and Δ9-tetrahydracannabinol (THC) vapour co-exposure on cognitive- and reward-related behaviours. Male Sprague-Dawley rats received vapourized THC (10 mg vapourized THC/four adolescent rats) or vehicle every other day (from post-natal day (PND) 28-42) and had continuous voluntary access to ethanol (10% volume/volume) in adolescence. Alcohol intake was measured during the exposure period to assess the acute effects of THC on alcohol consumption. In adulthood (PND 56+), rats underwent behavioural testing. Adolescent rats showed higher alcohol preference, assessed using the two-bottle choice test, on days on which they were not exposed to THC vapour. In adulthood, rats that drank alcohol as adolescents exhibited short-term memory deficits and showed decreased alcohol preference; on the other hand, rats exposed to THC vapour showed learning impairments in the delay-discounting task. Vapourized THC, alcohol or their combination had no effect on anxiety-like behaviours in adulthood. Our results show that although adolescent THC exposure acutely affects alcohol drinking, adolescent alcohol and cannabis co-use may not produce long-term additive effects.

Effect of Initial Treatment Choice on 2-year Quality of Life in Patients with Low-risk Papillary Thyroid Microcarcinoma.

CONTEXT: The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear. OBJECTIVE: The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months. MAJOR OUTCOME MEASURE: We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation. RESULTS: Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression. CONCLUSIONS: This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment.

Indirect exposure to socially defeated conspecifics using recorded video activates the HPA axis and reduces reward sensitivity in mice.

Rodents perceive the emotional states of conspecifics using vision. In the present study, we demonstrated that exposure to the video-recorded distress of conspecifics induces stress responses in male C57BL/6J mice. A single exposure to a video-recorded scene of the social defeat stress (SDS) increased plasma corticosterone levels in these mice. This physiological change was suppressed by blocking the visual information, suggesting that vision plays a crucial role in inducing stress responses. Furthermore, after exposure to the video, there were increased numbers of c-Fos-positive neurons in the anterior cingulate cortex and other brain areas that are associated with the negative valence and empathy systems, but not in the regions related to the pain signaling. In addition, repeated exposure to SDS videos induced an apparent reduction in reward sensitivity in the sucrose preference test, but did not affect avoidance behaviour in the social interaction test or immobility behaviour in the forced swim test. Reduced reward sensitivity in mice reflects anhedonia, which is a core symptom of depression in humans. Our video SDS model therefore provides a unique opportunity to not only understand the mechanisms underlying stress-induced anhedonia, but also to screen effective candidate molecules for stress-related disorders with greater reproducibility.

Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences.

Menthol has been shown to contribute to the appeal of tobacco products in humans. However, factors such as sex, age and menthol concentration remain unclear in the interaction between menthol and nicotine. To understand these factors, we utilized a mouse model to determine the impact of menthol on oral nicotine consumption. A range of menthol concentrations (oral and systemic) were tested with or without oral nicotine using the two-bottle choice paradigm in adolescent and adult female and male C57BL/6J mice. Moreover, genetically modified mice were used to investigate the role of α7 nicotinic acetylcholine receptors (nAChRs) on the effects of menthol. Menthol addition to nicotine solution increased oral nicotine consumption in C57BL/6J mice in a sex- and menthol concentration-dependent manner. At lower menthol concentrations, female mice demonstrated an enhancement of nicotine consumption and male mice showed a similar behavior at higher menthol concentrations. Menthol drinking alone was only significantly different by sex at 60 µg/ml menthol concentration where female mice had higher menthol intake than males. Menthol administered both orally and systemically (intraperitoneal) increased oral nicotine consumption. Adolescent female mice had a higher nicotine intake at lower menthol concentrations compared to their adult counterparts. While α7 nAChR wild type mice consumed more mentholated nicotine solution than nicotine only solution, this effect was abolished in KO mice. Effects of menthol are concentration-, sex-, age-, and α7 nAChR-dependent. Oral and intraperitoneal menthol increases nicotine intake, suggesting that sensory, peripheral, and/or central mechanisms are involved in effects of menthol on oral nicotine consumption.

Determinants of surgeon choice in cases of suspected implant rupture following mastectomy or aesthetic breast surgery: Clinical implications.

Implant ruptures may be diagnosed by physical examination, ultrasound (US), and magnetic resonance imaging (MRI). The absence of standard guidelines to approach to implant ruptures may cause unnecessary surgical revisions in the absence of radiological confirmation of prosthetic damages.The purpose of this study was to analyze the diagnostic procedures applied to patients with suspected prosthetic rupture and surgeon choices to perform a revision or to plan a clinical and radiological follow-up.We conducted a retrospective study on 62 women submitted to revision surgery due to radiological diagnosis of suspected implant rupture, following mastectomy or aesthetic reconstruction, and admitted to a Plastic Surgery Department between 2008 and 2018.Seventy-three implants, believed to be ruptured, were explanted. One-third of these were intact and unnecessarily explanted. US associated with MRI evaluation resulted in the most helpful diagnostical method.A standardized clinical and radiological approach is essential to manage breast implant ruptures successfully. An innovative protocol is proposed in order to: ensure the appropriate management of implant ruptures and prevent unnecessary surgical revisions; reduce the risk of claims for medical malpractice in cases of unsatisfactory final aesthetic results or worse than before.

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice.

BACKGROUND: The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion. METHODS: Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine. RESULTS: Mice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone. CONCLUSIONS: Our data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.

Social interaction in the emergence of toddler's mealtime spoon use.

The use of a spoon for eating is among the important daily skills in early development. The article provides an analysis of how caregiver-toddler interactions guides the attention of toddlers who were first learning how to use a spoon to spoon-related action opportunities that were relevant to the mealtime context. Our analysis revealed several related results. First, caregivers often manipulated objects on the table (i.e., food and dishes), and toddlers were more likely than chance to use their spoon to contact food immediately after watching these caregiver manipulations. Second, toddlers looked more often at the caregiver's hand than at their face. Third, toddlers tended to look at the caregiver's hand when the caregiver was manipulating objects on the table, and after these looks, toddlers were more likely than chance to contact food with their spoon. Finally, the toddlers' choices about when to look at the caregiver were influenced by their own behavior, as if they wanted to know how the caregiver would react to what they had done. We discuss these results in terms of the learning of socially promoted action opportunities for meal-related spoon use.

Visual stimulation with food pictures in the regulation of hunger hormones and nutrient deposition, a potential contributor to the obesity crisis.

Food cues affect hunger and nutritional choices. Omnipresent stimulation with palatable food contributes to the epidemics of obesity. The objective of the study was to investigate the impact of food cues on appetite-related hormones and to assess the functionality of the secreted hormones on macronutrient uptake in healthy subjects. Additionally, we aimed at verifying differences in the response of total and active ghrelin to stimulation with food pictures and to a meal followed by the stimulation. We were also interested in the identification of factors contributing to response to food cues. We recruited healthy, non-obese participants for two independent cross-over studies. During the first study, the subjects were presented random non-food pictures on the first day and pictures of foods on the second day of the study. Throughout the second study, following the picture session, the participants were additionally asked to drink a milkshake. Concentrations of blood glucose, triglycerides and hunger-related hormones were measured. The results showed that concentrations of several hormones measured in the blood are interdependent. In the case of ghrelin and gastric inhibitory peptide (GIP) as well as ghrelin and glucagon-like peptide-1 (GLP-1), this co-occurrence relies on the visual cues. Regulation of total ghrelin concentration following food stimulation is highly individual and responders showed upregulated total ghrelin, while the concentration of active ghrelin decreases following a meal. Protein content and colour intensity of food pictures reversely correlated with participants' rating of the pictures. We conclude that observation of food pictures influences the concentration of several appetite-related hormones. The close link of visual clues to physiological responses is likely of clinical relevance. Additionally, the protein content of displayed foods and green colour intensity in pictures may serve as a predictor of subjective attractiveness of the presented meal.

Differences in acute reinforcement across reduced nicotine content cigarettes.

RATIONALE: The smallest difference in nicotine that can change a smoker's cigarette preference is not clearly known. OBJECTIVE: A procedure to efficiently identify the difference in nicotine needed to change cigarette preference could help inform research to gauge effects of a nicotine reduction policy. METHODS: Using a within-subject design, we assessed preference for research cigarettes varying in nicotine contents (NIC; 18.7, 10.8, 5.3, 2.3, and 1.3 mg/g of tobacco), relative to a very low nicotine cigarette (VLNC; 0.4 mg/g), in 17 adult-dependent non-menthol smokers abstinent overnight. Only one NIC was compared vs. the VLNC per session, with order of the five NIC contents randomized across sessions on five separate days. Preference for each NIC vs. VLNC was determined by validated forced choice procedure, with those NIC chosen more than VLNC indicating greater reinforcement due to greater nicotine per se. Secondarily, less preference for lower NIC (vs. VLNC), relative to choice for the highest NIC, 18.7 mg/g (vs. VLNC), indexed reduced reinforcement. RESULTS: Overall, NIC choices increased as their nicotine increased, as anticipated. Relative to the 0.4 mg/g VLNC, choice was greater for NIC ≥ 5.3 mg/g but not ≤ 2.3 mg/g. Correspondingly, relative to choice for 18.7 mg/g, choice was less for NIC ≤ 2.3 mg/g but not ≥ 5.3 mg/g. CONCLUSIONS: Although replication with larger samples and longer access is needed, results indicate that nicotine reduction to ≤ 2.3 mg/g in cigarettes would attenuate reinforcement. This choice procedure may efficiently inform future clinical trials to assess relative reinforcing effects of smoking reduced nicotine cigarettes.

Perceptual salience influences food choices independently of health and taste preferences.

BACKGROUND: Making decisions about food is a critical part of everyday life and a principal concern for a number of public health issues. Yet, the mechanisms involved in how people decide what to eat are not yet fully understood. Here, we examined the role of visual attention in healthy eating intentions and choices. We conducted two-alternative forced choice tests of competing food stimuli that paired healthy and unhealthy foods that varied in taste preference. We manipulated their perceptual salience such that, in some cases, one food item was more perceptually salient than the other. In addition, we manipulated the cognitive load and time pressure to test the generalizability of the salience effect. RESULTS: Manipulating salience had a powerful effect on choice in all situations; even when an unhealthy but tastier food was presented as an alternative, healthy food options were selected more often when they were perceptually salient. Moreover, in a second experiment, food choices on one trial impacted food choices on subsequent trials; when a participant chose the healthy option, they were more likely to choose a healthy option again on the next trial. Furthermore, robust effects of salience on food choice were observed across situations of high cognitive load and time pressure. CONCLUSIONS: These results have implications both for understanding the mechanisms of food-related decision-making and for implementing interventions that might make it easier for people to make healthy eating choices.

Co-occurrence and relational information in evaluative learning: A multinomial modeling approach.

Dual-process theories of evaluative learning suggest that evaluative representations can be formed via two functionally distinct mechanisms: automatic formation of associative links between co-occurring events (associative learning) and nonautomatic generation and truth assessment of mental propositions about the relation between stimuli (propositional learning). Single-process propositional theories reject the idea of automatic association formation, attributing all instances of evaluative learning to propositional processes. A central question in the debate between the two theories concerns the mechanisms underlying unqualified effects of stimulus co-occurrence when the relation between the co-occurring stimuli suggests an evaluation that is opposite to the one implied by the observed co-occurrence (e.g., sunscreen prevents skin cancer). Addressing interpretational ambiguities in previous research on the differential impact of co-occurrence and relational information on implicit and explicit measures, the current research used a multinomial modeling approach to investigate the functional properties of the effects of co-occurrence and relational information on a single measure of evaluative responses. Although the moderating effects obtained for relational information are consistent with the predictions of the two theories, the obtained properties of co-occurrence effects pose an explanatory challenge to both dual-process and single-process propositional theories. The findings demonstrate the value of multinomial modeling in providing deeper insights into the functional properties of the effects of co-occurrence and relational information, which impose stronger empirical constraints on extant theories of evaluative learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Determinants in Initial Treatment Choice for Diabetic Macular Edema.

PURPOSE: To assess how patient choices (out-of-pocket costs, insurance plan, geographic region) impact initiation of therapy for diabetic macular edema (DME). DESIGN: Retrospective cohort study using administrative medical claims data from a large, national insurer. PARTICIPANTS: All patients newly diagnosed with DME from 2013 through 2016 were observed for 90 days after diagnosis or until first treatment was received. METHODS: Multivariate logistic regression was used to create odds ratios comparing different baseline demographic and patient-related factors. MAIN OUTCOME MEASURES: The primary outcome was the odds of receiving the different possible initial treatments for DME (anti-vascular endothelial growth factor [VEGF], focal laser treatment, steroids, or observation), no treatment, and not following up. RESULTS: Of the 6220 newly diagnosed DME patients, 3010 (48.4%) underwent a follow-up examination within 90 days of diagnosis, and of those, 1453 patients (48.3%) received treatment in the observation window, including 614 (20.4%) with bevacizumab, 191 (6.3%) with ranibizumab or aflibercept, 560 (18.6%) with focal laser, 38 (1.3%) with steroid injection, and 50 (1.7%) with an injection of an unspecified drug. Having a copay (vs. $0) lowered the odds of receiving any treatment (odds ratio [OR] = 0.60; 95% confidence interval [CI], 0.51-0.71; P < 0.001) and of receiving each treatment individually (anti-VEGF treatment: OR = 0.72; 95% CI, 0.59-0.88; bevacizumab: OR = 0.73; 95% CI, 0.59-0.91; ranibizumab or aflibercept: OR, 0.70; 95% CI, 0.49-0.99; focal laser: OR = 0.44; 95% CI, 0.35-0.55; P < 0.001). Contrary to having a copay, having a high deductible and type of insurance plan were not associated with initiating treatment (P > 0.41 for all comparisons). Patients in the Northeast showed lower odds of initiating anti-VEGF treatment (OR = 0.60; 95%CI, 0.44-0.82; P < 0.001) and specifically bevacizumab (OR = 0.47; 95% CI, 0.33-0.67; P < 0.001). Furthermore, Northeast patients who were treated with anti-VEGF showed a higher odds of receiving ranibizumab or aflibercept compared with bevacizumab (OR = 2.39; 95% CI, 1.31-4.37; P < 0.001). Southern Midwest patients showed a higher odds of treatment (anti-VEGF: OR = 1.35; 95%CI, 1.02-1.77; P < 0.001; bevacizumab: OR = 1.40; 95% CI, 1.04-1.87; focal laser: OR = 1.39; 95% CI, 1.01-1.89; P < 0.001). CONCLUSIONS: Patient choices such as copays and where they live are important factors in determining the initial choice of treatment for DME.

Impact of Menthol on Oral Nicotine Consumption in Female and Male Sprague Dawley Rats.

INTRODUCTION: One of the preferable flavors in oral nicotine delivery systems is menthol which masks the harshness of tobacco. However, possible interactions between oral menthol and nicotine on intake and preference remain unclear. Therefore, we aimed to determine the impact of menthol on oral nicotine consumption. METHODS: Adult Sprague Dawley female and male rats (n = 8 per group) were given a choice of water or drug solution by using two-bottle free choice paradigm for 2 weeks: vehicle (5% ethanol), nicotine (20 mg/L), menthol (1 g/L) and mentholated nicotine groups. At the end of the study, plasma nicotine levels were determined. RESULTS: When rats were given a choice of nicotine or water, nicotine intake was similar between female and male rats. Menthol addition to nicotine solution significantly increased nicotine intake and preference in male but not female rats without a considerable effect on total fluid intake and body weight change in either sex. The average nicotine intake in male rats was 0.5 ± 0.05 and 1.4 ± 0.12 mg/kg/day for nicotine and menthol-nicotine combination (p < .05), respectively. The average nicotine intake in female rats was 0.6 ± 0.05 and 0.6 ± 0.03 mg/kg/day for nicotine and menthol-nicotine combination (p > .05), respectively. Plasma nicotine levels were not significantly different between the groups in either male (nicotine group: 20.8 ± 4.9, mentholated nicotine group: 31.9 ± 3.2 ng/mL) or female (nicotine group: 24.0 ± 3.3, mentholated nicotine group: 17.8 ± 2.9 ng/mL) rats (p > .05). CONCLUSIONS: Menthol increases oral nicotine consumption in male, but not female, rats. IMPLICATIONS: This study may provide data on the co-use of menthol and nicotine in smokeless tobacco, particularly oral dissolvable tobacco products.

Common, nonsexual masochistic preferences are positively associated with antisocial personality traits.

OBJECTIVE: Based on prior research linking masochism and antisocial behavior to sensation seeking, we hypothesized that masochistic and antisocial preferences are positively correlated. Besides sensation seeking, we tested whether disgust sensitivity (due to its inhibitory function) and shared social values (e.g., stimulation) accounted for the masochistic-antisocial link. We additionally examined the link in relation to broad personality factors. METHOD: Six online and laboratory studies (N = 2,999) with US-American and European samples. RESULTS: We consistently found positive correlations between masochistic enjoyment (e.g., enjoying the burn of spicy food, disgusting jokes, pounding heart, painful massage) and antisocial traits such as subclinical psychopathy, everyday sadism, and low Honesty-Humility. We observed behavioral correlations in that experienced pleasure of a painful event was positively related to causing another person to feel pain. Shared sensation seeking, low disgust sensitivity, and endorsement of social values such as social power, hedonism, and a stimulating life partially accounted for the masochistic-antisocial link. CONCLUSION: The extent to which a person enjoys threatening stimuli on the self is reliably related to how much a person enjoys and evokes others' suffering. Future research could explore the common core that underlies common masochistic and antisocial preferences beyond the mediators tested here.