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Oral medications for chronic conditions often involve a variety of instructions, including time of day/dosing, drug interactions, and food intake restrictions. However, the extent to which patients follow these instructions is unclear. We surveyed patients from the US and Europe (UK, France, Germany, Italy, Spain) who were prescribed sulfonylureas (SU: glimepiride, glipizide, or gliclazide) for diabetes or levothyroxine for hypothyroidism. Patients kept a daily diary for 3–5 days documenting their adherence to three criteria: dosing regimen including time of day, warning labels including drug interactions, and food restrictions. A total of 421 US and 493 European patients took the study medications; 546 patients took SU and 368 took levothyroxine. Overall, 48% of patients were males; 46% were age 65 years or older. Despite most patients having received instructions on medication requirements (US 71%, EU 75%), most patients reported being only somewhat knowledgeable (US 69%; EU 71%). Adherence, measured by the proportion of the days a participant was adherent to each category out of the observational period (ranging from 3–5 days), varied by type of instruction, with the poorest adherence observed for food restriction requirements (US 34% of the observation days, EU 26%) compared to warning labels (US 77%, EU 67%) and dosing regimen (US 85%, EU 87%). Patients adhered to dosing and cautionary instructions across the majority of the study period but were largely non-adherent to food intake restrictions. Improved communication and increased emphasis on food intake restrictions is needed when advising patients on their medications.

OBJECTIVE The aim of this study is to elucidate the unique challenges faced by pediatric emergency medicine (PEM) physicians from racial/ethnic groups underrepresented in medicine (URiM). METHODS This study is a subanalysis of data from 18 URiM faculty from a sample of 51 semistructured key informant interviews with PEM faculty in the top NIH-funded pediatric departments and highest-volume pediatric EDs in the country. Faculty are from eight hospitals representing a spectrum of geographic locations including the northeastern, midwestern, western, and southern regions of the country. RESULTS Of 18 study participants, the majority were Black (72.2%) and female (83.3%). Three main thematic categories were identified: challenges related to race, support systems, and suggested strategies to improve diversity and inclusion in PEM. A common race-related experience was microaggressions from colleagues and patients. Additionally, when attempting to lead and assert themselves, URiM women in particular were perceived as "angry" and "intimidating" in a way that non-URiM peers were not. As a result of these negative experiences, participants described the need to go above and beyond to prove themselves. Such pressure produced stress and feelings of isolation. Participants combatted these stressors through resilience strategies such as formal mentorship and peer and family support. Participants indicated the need to increase diversity and create more inclusive work environments, which would benefit both URiM physician wellness and the diverse patients they serve. CONCLUSION Those URiM in PEM face subtle racial discrimination at an institutional, peer, and patient level. The stress caused by this discrimination may further contribute to physician burnout in PEM. While URiMs adopt individual resilience strategies, their unique challenges suggest the need for departmental and institutional efforts to promote greater diversity and inclusion for physician wellness, retention, and quality patient care.

The sarcomere is the functional unit of cardiac muscle, essential for normal heart function. To date, it has not been possible to study, in real time, thin filament-based activation dynamics in live cardiac muscle. We report here results from a cardiac troponin C (TnC) FRET-based biosensor integrated into the cardiac sarcomere via stoichiometric replacement of endogenous TnC. The TnC biosensor provides, for the first time, evidence of multiple thin filament activating ligands, including troponin I interfacing with TnC and cycling myosin, during a cardiac twitch. Results show that the TnC FRET biosensor transient significantly precedes that of peak twitch force. Using small molecules and genetic modifiers known to alter sarcomere activation, independently of the intracellular Ca(2+) transient, the data show that the TnC biosensor detects significant effects of the troponin I switch domain as a sarcomere-activating ligand. Interestingly, the TnC biosensor also detected the effects of load-dependent altered myosin cycling, as shown by a significant delay in TnC biosensor transient inactivation during the isometric twitch. In addition, the TnC biosensor detected the effects of myosin as an activating ligand during the twitch by using a small molecule that directly alters cross-bridge cycling, independently of the intracellular Ca(2+) transient. Collectively, these results aid in illuminating the basis of cardiac muscle contractile activation with implications for gene, protein, and small molecule-based strategies designed to target the sarcomere in regulating beat-to-beat heart performance in health and disease.

What does it mean to be (seen as) human? Ten studies explore this age-old question and show that gender is a critical feature of perceiving humanness, being more central to conceptions of humanness than other social categories (race, age, sexual orientation, religion, disability). Our first six studies induce humanization (i.e., anthropomorphism) and measure social-category ascription. Across different manipulations (e.g., having participants recall experiences, observe moving shapes, imagine nonhuman entities as people, and create a human form), we find that gender is the most strongly ascribed social category and the one that uniquely predicts humanization. To provide further evidence that gender is central to conceptions of personhood, and to examine the consequences of withholding it, we then demonstrate that removing gender from virtual humans (Study 5), human groups (Study 6), alien species (Study 7), and individuals (Study 8) leads them to be seen as less human. The diminished humanness ascribed to nongendered and genderless targets is due, at least in part, to the lack of a gender schema to guide facile and efficient sensemaking. The relative difficulty perceivers had in making sense of nongendered targets predicted diminished humanness ratings. Finally, we demonstrate downstream consequences of stripping a target of gender: Perceivers consider them less relatable and more socially distant (Study 8). These results have theoretical implications for research on gender, (de)humanization, anthropomorphism, and social cognition, more broadly. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Women continue to be underrepresented in STEM (science, technology, engineering, math) fields. As such, there has been an increased interest in interventions to reduce bias against, and increase inclusion of, women in STEM. In this paper, we compare and contrast two commonly used strategies: awareness and blindness. We demonstrate that gender-blindness—a diversity ideology that advocates for downplaying gender differences, rather than embracing them—has the potential to diminish stereotyping of women in STEM fields. In six total studies, we show that men who believe, or are primed with, gender-blindness (compared to gender-awareness) are less likely to endorse gender stereotypes around women's STEM competencies. By measuring (Study 1) and manipulating ( Studies 2 –5) gender-blindness, we show that gender-blindness (compared to awareness) minimizes the gender gap on explicit stereotyping measures, as well as diminishes STEM stereotyping in target evaluations. Across six studies, we show the influence of diversity ideologies on stereotyping of women in STEM.

Effectively delegating work to others is considered critical to managerial success, as it frees up managers’ time and develops subordinates’ skills. We propose that female leaders are less likely t...

Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances. Taking advantage of the genetic tractability of the soil nematode Caenorhabditis elegans, a forward genetic screen was performed to isolate regulators of the vertebrate α7 nAChR homologue ACR-16. From this screen a novel regulator of the ACR-16 receptor was identified, the sarco(endo)plasmic reticulum calcium ATPase sca-1. The sca-1 mutant affects ACR-16 receptor level at the NMJ, receptor functionality, and synaptic transmission. Responses to pressure-ejected nicotine in sca-1 mutants are indistinguishable from wild type, which implies the ACR-16 receptors are mislocalized at the NMJ. Changes in cytosolic baseline calcium levels in sca-1 and other mutants indicates a calcium-driven regulation mechanism of the α7-like NAChR ACR-16.

BACKGROUND Numerous studies have shown that there are links between obesity, liver fat and the gut microbiome. However, there are mixed results on whether probiotics could impact the gut microbiome and/or help to decrease liver fat and obesity outcomes. OBJECTIVE This study aimed to determine whether a probiotic supplement (VSL#3® ) intervention altered gut microbiota and/or gut hormones associated with appetite regulation. The secondary aim of this study was to determine whether VSL#3® altered body composition and liver fat and fibrosis. METHODS We conducted a double-blind, randomized placebo-controlled trial in 19 obese Latino adolescents. The intervention consisted of three packets per day of VSL#3® or a matched placebo for 16 weeks. Pre-intervention and post-intervention measures included gut microbial abundance, gut appetite regulating hormones, anthropometrics, body composition, liver fat and liver fibrosis. We conducted linear models to determine whether there were any significant differences in the changes in these outcomes following VSL#3® intervention. RESULTS Compared with placebo, adolescents that received VSL#3 had significant increases in total adiposity (%) (+1.7 ± 0.6 vs. -1.3 ± 0.5, p

Ascribing and denying humanity has profound consequences, often leading to devastating outcomes (e.g., violence, genocide). As such, understanding what, exactly, makes “someone human” becomes imperative. In this paper, we leverage the ubiquitous Big Two dimensions of social perception (agency and communality) to examine the process of humanization. In five studies (N = 1900), we find that the “Big Two” dimensions—agency (assertiveness, competence) and communality (warmth, kindness)—predict humanization, and critically, we show the primacy of communality in this process. We find that communality takes primacy in humanization when anthropomorphizing, describing an alien species, or ascribing humanness to real-world social targets (Studies 1–3); it is only for contexts where, or targets for whom, agency is particularly relevant that agency predicts humanization (Studies 4–5). We conclude with implications for research on (de)humanization, mind-perception, and social-perception.

The ways in which we discuss gender (embracing vs. downplaying difference) has implications for women’s workplace confidence and behavior, especially in male-dominated environments and positions of power. In five total studies (N = 1453), across a variety of samples, we found that gender-blindness—the belief that gender differences should be downplayed—is a more adaptive strategy for increasing female workplace confidence than gender-awareness—the belief that gender differences should be celebrated. In addition to increasing confidence, gender-blindness was related to actions necessary for reducing gender disparities (e.g., risk-taking, negotiation). We found that perceived gender differences in agency (i.e., assertiveness, independence) accounts for gender differences in workplace confidence, especially in male-dominated environments (e.g., business school) and positions of power (managerial positions). Finally, we found that gender-blindness either lessened or had no effect on men’s confidence, demonstrating the unique positive effect of gender-blindness on women’s confidence. Together, this research highlights the potential for downplaying differences, instead of emphasizing them, to combat the confidence gap.

Crotalidae envenomation has been managed successfully in emergency departments across the world with antivenom. Over the years, antivenom has evolved and newer agents have been studied with the possibility of eliminating maintenance antivenom therapy. Here we report a patient who had worsening platelet and fibrinogen concentrations, as well as complaints of swelling and pain at the site of a rattlesnake envenomation following an initial dose of F(ab')2AV (Crotalidae immune F(ab')2 (equine) [ANAVIP®]) Crotalidae antivenom. The patient was subsequently transferred to a tertiary children's hospital for a higher level of care and received FabAV (Crotalidae polyvalent immune Fab (ovine) [CroFab®]) Crotalidae antivenom. The details of this patient's treatment course highlight the possibility that patients who receive F(ab')2AV, may require additional antivenom treatment. Furthermore, it appears that based on our single patient experience, giving FabAV after F(ab')2AV is safe and effective.

There is a lack of knowledge regarding in-vehicle concentrations of nitrogen dioxide (NO2) during transit through road tunnels in urban environments. Furthermore, previous studies have tended to involve a single vehicle and the range of in-vehicle NO2 concentrations that vehicle occupants may be exposed to is not well defined. This study describes simultaneous measurements of in-vehicle and outside-vehicle NO2 concentrations on a route through Sydney, Australia that included several major tunnels, minor tunnels and busy surface roads. Tests were conducted on nine passenger vehicles to assess how vehicle characteristics and ventilation settings affected in-vehicle NO2 concentrations and the in-vehicle-to-outside vehicle (I/O) concentration ratio. NO2 was measured directly using a cavity attenuated phase shift (CAPS) technique that gave a high temporal and spatial resolution. In the major tunnels, transit-average in-vehicle NO2 concentrations were lower than outside-vehicle concentrations for all vehicles with cabin air recirculation either on or off. However, markedly lower I/O ratios were obtained with recirculation on (0.08–0.36), suggesting that vehicle occupants can significantly lower their exposure to NO2 in tunnels by switching recirculation on. The highest mean I/O ratios for NO2 were measured in older vehicles (0.35–0.36), which is attributed to older vehicles having higher air exchange rates. The results from this study can be used to inform the design and operation of future road tunnels and modelling of personal exposure to NO2.

In western and westernized societies, large portions of the population live in what are considered to be “obesogenic” environments. Among other things, obesogenic environments are characterized by a high prevalence of external cues that are associated with highly palatable, energy-dense foods. One prominent hypothesis suggests that these external cues become such powerful conditioned elicitors of appetitive and eating behavior that they overwhelm the internal, physiological mechanisms that serve to maintain energy balance. The present research investigated a learning mechanism that may underlie this loss of internal relative to external control. In Experiment 1, rats were provided with both auditory cues (external stimuli) and varying levels of food deprivation (internal stimuli) that they could use to solve a simple discrimination task. Despite having access to clearly discriminable external cues, we found that the deprivation cues gained substantial discriminative control over conditioned responding. Experiment 2 found that, compared to standard chow, maintenance on a “western-style” diet high in saturated fat and sugar weakened discriminative control by food deprivation cues, but did not impair learning when external cues were also trained as relevant discriminative signals for sucrose. Thus, eating a western-style diet contributed to a loss of internal control over appetitive behavior relative to external cues. We discuss how this relative loss of control by food deprivation signals may result from interference with hippocampal-dependent learning and memory processes, forming the basis of a vicious-cycle of excessive intake, body weight gain, and progressive cognitive decline that may begin very early in life.

Driving in fog is a potentially dangerous activity that has been investigated in a number of different ways; however, most have focused on identifying the underlying perceptual changes that result in an inability to perceive speed of vehicle motion. Although the previous research has identified the perceptual changes associated with driving in fog and shows that people are highly likely to perceive their speed to be higher than it actually is, these research studies have not investigated driving behavior when drivers are allowed to maintain speed as they feel appropriate and make use of the vehicle's speedometer. In addition, much of the existing research focuses on speed perception and presents a limited view of other driving performance metrics in terms of lane keeping and event detection. The current study addresses these issues utilizing a driving simulator-based method where fog is simulated as a distance dependent contrast reduction while having participants drive at speeds they feel are appropriate. A number of different instructions and speed feedback mechanisms were tested in order to determine how drivers react when driving in varying levels of fog. Results also include lane keeping measures in order to assess whether drivers are willing to drive at speeds where their lane keeping performance is degraded due to the reduced visibility. Results indicate that, in general, drivers do not tend to slow down significantly until visibility distance is drastically reduced by fog; however, lane keeping ability is maintained throughout most of the range of visibility distances. Lane keeping ability was reduced only when fog results in visibility distances

Previous studies show that high-intensity sweeteners can stimulate weight gain in rats. The present studies examined whether caffeine, a stimulant commonly added to beverages consumed by humans, influences intake of saccharin- or glucose-sweetened solutions or body weight gain in rats and whether the nature of the maintenance diet influences the effects of caffeine. In two experiments, rats received glucose or saccharin solution mixed with 0.125 mg/g caffeine or no caffeine. Rats consumed significantly more caffeinated than noncaffeinated solutions when they were maintained on a low-fat chow diet (Experiment 1) and when maintained on a sweet, high-fat, high calorie chow diet (Experiment 2). Consumption of saccharin resulted in higher body weight gain in both experiments. Caffeine reversed this effect in Experiment 1 (low-fat diet) but not Experiment 2 (sweet, high-fat diet). The findings extend what is known about the conditions under which consumption of high intensity sweeteners promote energy dysregulation.

Recent epidemiological evidence points to a link between a variety of negative health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease) and the consumption of both calorically sweetened beverages and beverages sweetened with high-intensity, non-caloric sweeteners. Research on the possibility that non-nutritive sweeteners promote food intake, body weight gain, and metabolic disorders has been hindered by the lack of a physiologically-relevant model that describes the mechanistic basis for these outcomes. We have suggested that based on Pavlovian conditioning principles, consumption of non-nutritive sweeteners could result in sweet tastes no longer serving as consistent predictors of nutritive postingestive consequences. This dissociation between the sweet taste cues and the caloric consequences could lead to a decrease in the ability of sweet tastes to evoke physiological responses that serve to regulate energy balance. Using a rodent model, we have found that intake of foods or fluids containing non-nutritive sweeteners was accompanied by increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensation, compared to consumption of foods and fluids containing glucose. Our research also provided evidence consistent with the hypothesis that these effects of consuming saccharin may be associated with a decrement in the ability of sweet taste to evoke thermic responses, and perhaps other physiological, cephalic phase, reflexes that are thought to help maintain energy balance.

Conjugation of the phenol derived from rivastigmine with amphetamines gave access to novel carbamate cholinesterase inhibitors. All compounds possessed increased affinity and selectivity for AChE compared to rivastigmine and were orally bioavailable. Compound 4a, incorporating d-amphetamine, caused significant inhibition of cholinesterase in vivo at doses that were well tolerated. Release of amphetamine from 4a was demonstrated following in vitro and in vivo inhibition of cholinesterase. Compound 4a was also effective in alleviating scopolamine induced amnesia in a rat passive avoidance model.

Eating slowly is associated with a lower body mass index. However, the underlying mechanism is poorly understood. Here, our objective was to determine whether eating a meal at a slow rate improves episodic memory for the meal and promotes satiety. Participants (N = 40) consumed a 400 ml portion of tomato soup at either a fast (1.97 ml/s) or a slow (0.50 ml/s) rate. Appetite ratings were elicited at baseline and at the end of the meal (satiation). Satiety was assessed using; i) an ad libitum biscuit ‘taste test’ (3 h after the meal) and ii) appetite ratings (collected 2 h after the meal and after the ad libitum snack). Finally, to evaluate episodic memory for the meal, participants self-served the volume of soup that they believed they had consumed earlier (portion size memory) and completed a rating of memory ‘vividness’. Participants who consumed the soup slowly reported a greater increase in fullness, both at the end of the meal and during the inter-meal interval. However, we found little effect of eating rate on subsequent ad libitum snack intake. Importantly, after 3 h, participants who ate the soup slowly remembered eating a larger portion. These findings show that eating slowly promotes self-reported satiation and satiety. For the first time, they also suggest that eating rate influences portion size memory. However, eating slowly did not affect ratings of memory vividness and we found little evidence for a relationship between episodic memory and satiety. Therefore, we are unable to conclude that episodic memory mediates effects of eating rate on satiety., Highlights • Eating lunch at a slower rate promotes greater satiation and satiety. • Participants remember eating a larger meal if they eat it slowly. • Eating lunch at a slower rate does not affect subsequent snack-food intake. • Effects of eating rate on satiety might not be mediated by episodic memory.

Recent results from both human epidemiological and experimental studies with animals suggest that intake of noncaloric sweeteners may promote, rather than protect against, weight gain and other disturbances of energy regulation. However, without a viable mechanism to explain how consumption of noncaloric sweeteners can increase energy intake and body weight, the persuasiveness of such results has been limited. Using a rat model, the present research showed that intake of noncaloric sweeteners reduces the effectiveness of learned associations between sweet tastes and postingestive caloric outcomes (Experiment 1) and that interfering with this association may impair the ability of rats to regulate their intake of sweet, but not nonsweet, high-fat and high-calorie food (Experiment 2). The results support the hypothesis that consuming noncaloric sweeteners may promote excessive intake and body weight gain by weakening a predictive relationship between sweet taste and the caloric consequences of eating.