Happiness Maximization Is a WEIRD Way of Living.

Psychological science tends to treat subjective well-being and happiness synonymously. We start from the assumption that subjective well-being is more than being happy to ask the fundamental question: What is the ideal level of happiness? From a cross-cultural perspective, we propose that the idealization of attaining maximum levels of happiness may be especially characteristic of Western, educated, industrial, rich, and democratic (WEIRD) societies but less so for others. Searching for an explanation for why "happiness maximization" might have emerged in these societies, we turn to studies linking cultures to their eco-environmental habitat. We discuss the premise that WEIRD cultures emerged in an exceptionally benign ecological habitat (i.e., faced relatively light existential pressures compared with other regions). We review the influence of the Gulf Stream on the Northwestern European climate as a source of these comparatively benign geographical conditions. We propose that the ecological conditions in which WEIRD societies emerged afforded them a basis to endorse happiness as a value and to idealize attaining its maximum level. To provide a nomological network for happiness maximization, we also studied some of its potential side effects, namely alcohol and drug consumption and abuse and the prevalence of mania. To evaluate our hypothesis, we reanalyze data from two large-scale studies on ideal levels of personal life satisfaction-the most common operationalization of happiness in psychology-involving respondents from 61 countries. We conclude that societies whose members seek to maximize happiness tend to be characterized as WEIRD, and generalizing this across societies can prove problematic if adopted at the ideological and policy level.

Shared Decision Making in Hallux Valgus Surgery: A Prospective Observational Study.

Patient-physician communication has the potential to improve outcomes and satisfaction through the shared decision-making process (SDM). This study aims to assess the relationship between perception of SDM and demographic, clinical, and patient-reported outcomes in patients undergoing Hallux Valgus (HV) correction. A prospective analysis of 306 patients scheduled for HV surgery was completed. The CollaboRATE score was used to measure SDM. Multivariable linear regression model was used to assess whether SDM scores were associated with preoperative characteristics or postoperative outcome scores. The mean CollaboRATE score was 2.9 (SD 0.9) and did not differ by age, socioeconomic status, or sex. Lower CollaboRATE scores were associated with more symptoms of depression, lower socioeconomic status, and lower general health scores (p-value < 0.05). There was no association between SDM scores and postoperative outcome scores. In this study, patients with depressive symptoms and lower socioeconomic status had worse perceptions of SDM. There was no difference in postoperative outcomes among participants based on SDM scores. Level of Evidence: Level III, prospective observational study.

Diabetic Ketoacidosis.

This article reviews the most current literature on diabetic ketoacidosis, including how to make the diagnosis and management. It discusses euglycemic diabetic ketoacidosis and the risk factors for this rare but dangerous disease process. Pertinent pearls and pitfalls encountered by the emergency physician when managing these patients are included. Because these patients often stay in the emergency department for prolonged periods, recommendations on transitioning to subcutaneous insulin are included, along with dosing recommendations. Finally, the article reviews how to disposition patients with diabetic ketoacidosis and examines important factors that lead to a successful discharge home.

Identification of novel p-cresol inhibitors that reduce Clostridioides difficile's ability to compete with species of the gut microbiome.

Treatment of Clostridioides difficile infection (CDI) is expensive and complex, with a high proportion of patients suffering infection relapse (20-35%), and some having multiple relapses. A healthy, unperturbed gut microbiome provides colonisation resistance against CDI through competition for nutrients and space. However, antibiotic consumption can disturb the gut microbiota (dysbiosis) resulting in the loss of colonisation resistance allowing C. difficile to colonise and establish infection. A unique feature of C. difficile is the production of high concentrations of the antimicrobial compound para-cresol, which provides the bacterium with a competitive advantage over other bacteria found in the gut. p-cresol is produced by the conversion of para-Hydroxyphenylacetic acid (p-HPA) by the HpdBCA enzyme complex. In this study, we have identified several promising inhibitors of HpdBCA decarboxylase, which reduce p-cresol production and render C. difficile less able to compete with a gut dwelling Escherichia coli strain. We demonstrate that the lead compound, 4-Hydroxyphenylacetonitrile, reduced p-cresol production by 99.0 ± 0.4%, whereas 4-Hydroxyphenylacetamide, a previously identified inhibitor of HpdBCA decarboxylase, only reduced p-cresol production by 54.9 ± 13.5%. To interpret efficacy of these first-generation inhibitors, we undertook molecular docking studies that predict the binding mode for these compounds. Notably, the predicted binding energy correlated well with the experimentally determined level of inhibition, providing a molecular basis for the differences in efficacy between the compounds. This study has identified promising p-cresol production inhibitors whose development could lead to beneficial therapeutics that help to restore colonisation resistance and therefore reduce the likelihood of CDI relapse.

National wealth, individualism, generalised trust, and religiosity as moderators of the relationship between helping strangers and life satisfaction in 137 societies.

We predicted that the relationship between helping strangers and life satisfaction would depend partially on the wealth of the country in which one lives. We argue that wealthy societies provide a wide range of welfare provisions for assisting their citizens. By contrast, people living in poorer countries with associated lower individualism, lower generalised trust, and higher religiosity have fewer financial and institutional supports for their daily welfare. They thus receive greater personal and interpersonal rewards for helping strangers in their societies and experience greater life satisfaction. Using a 137-country sample, we found that the relationship between helping strangers and life satisfaction was weaker in wealthier nations and in nations with more individualistic, more trusting, but less religious citizens. When all four moderators were used, only trust and religiosity remained significant moderators. In a supplementary mediated moderation model, we also found that trust and religiosity mediated the effect of national wealth on the relationship between kindness and life satisfaction. We conclude that the relationship between kindness and life satisfaction depends on various aspects of national culture that may reduce or increase people's dependence in their daily lives on the help of others as opposed to dependence on welfare institutions.

Individual uniqueness in trust profiles and well-being: Understanding the role of cultural tightness-looseness from a representation similarity perspective.

This paper provides a unique perspective for understanding cultural differences: representation similarity-a computational technique that uses pairwise comparisons of units to reveal their representation in higher-order space. By combining individual-level measures of trust across domains and well-being from 13,823 participants across 15 nations with a measure of society-level tightness-looseness, we found that any two countries with more similar tightness-looseness tendencies exhibit higher degrees of representation similarity in national interpersonal trust profiles. Although each individual's trust profile is generally similar to their nation's trust profile, the greater similarity between an individual's and their society's trust profile predicted a higher level of individual life satisfaction only in loose cultures but not in tight cultures. Using the framework of representation similarity to explore cross-cultural differences from a multidimensional, multi-national perspective provide a comprehensive picture of how culture is related to the human activities.

Emergency Considerations of Infective Endocarditis.

Although still a rare bacterial infection of the endocardium of the heart, the incidence of infective endocarditis continues to increase with the increased use of intracardiac devices, indwelling lines, and surgical procedures being done on patients. The diagnosis of infective endocarditis remains challenging and requires a high level of suspicion to initiate the appropriate investigation and treatment. Serious complications can still occur despite optimal care, so it is helpful that these patients be managed by a team that includes infectious disease, cardiology, and cardiac surgeons.

The weight of culture: Societal individualism and flexibility explain large global variations in obesity.

BACKGROUND: Obesity rates have been rising steeply across the globe in recent decades, posing a major threat to global human health. Despite this almost universal increase, differences between countries remain striking, even among equally developed societies. METHODS: We test if two cultural dimensions derived from a revised Hofstede model of culture from Minkov (2018), namely collectivism vs. individualism and monumentalism vs. flexibility, could help explain national variations in prevalence of obesity (BMI ≥ 30) among women and men around the world. We develop a theoretical framework that links these two cultural dimensions with obesity and then test their association empirically in analyses including 51 countries from all regions of the world as well as using imputed data for a total of 155 countries, representing 98% of the global population. RESULTS: In contrast to previous studies, we find that, adjusting for undernourishment and other potential confounds, individualism is associated with higher obesity prevalence in the male population, but not among the female population. We explain these findings by pointing to the different mechanisms through which individualism relates to health behavior, some of which are more gender-specific than others. A further novel finding is that flexibility, a national cultural trait that emphases humility, self-control, and restraint of desires, is a strong negative predictor of obesity in both genders beyond various potential confounds and is highly robust in specification curve analyses. CONCLUSIONS: Our findings suggest that taking national culture into account can enhance our understanding of the obesity pandemic and should thus be considered by policy-makers in their design of interventions.

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.

The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation. Considering this strong DcpS dependence in AML cell lines, we explored PROTAC-mediated degradation as an alternative strategy to modulate DcpS activity. Herein, we report the development of JCS-1, a PROTAC exhibiting effective degradation of DcpS at nanomolar concentrations. JCS-1 non-covalently binds DcpS with a RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sustained DcpS degradation in several AML cell lines. JCS-1 serves as a chemical biology tool to interrogate DcpS degradation and associated changes in RNA processes in different cellular contexts, which may be an attractive strategy for the treatment of AML and other DcpS-dependent genetic disorders.

Health-related outcomes in patients enrolled on surgical and non-surgical routes in a weight management service.

BACKGROUND AND AIMS: This study evaluates a specialist weight management service and compares outcomes in participants referred to the service undergoing either surgery or non-surgical routes to support weight loss. METHODS: Four hundred and forty eight participants were assessed on various weight-related outcomes (body mass index [BMI], psychological distress, quality of life, nutrition, weight-related symptoms, physical activity) on referral to the service and on discharge. The effect of group (surgery or non-surgery) and time in the service were facilitated by doubly multivariate analyses of variance models. RESULTS: Between referral and discharge, participants improved significantly on a combination of outcomes (P < .001) and on each outcome assessed individually. The magnitude of overall improvement was moderate (partial-η2 = 0.141). Individual improvement components varied; including a moderate reduction of 3.2% in the BMI outcome measure and a substantive gain of 64.6% in quality of life. Participants on non-surgical routes performed significantly better than participants on surgical routes on a linear combination of outcomes (P < .001) and on all outcomes except nutrition; with an effect of route small-to-moderate in magnitude (partial-η2 = 0.090). CONCLUSIONS: Weight management services are successful in achieving weight management-related outcomes in the short- and long-term, with large overall improvements between referral and discharge averaged over all participants observed. Non-surgical routes appear to confer benefits between referral and discharge compared to surgical routes.

Dynamic morphometric changes in degenerative lumbar spondylolisthesis: A pilot study of upright magnetic resonance imaging.

The objectives of this study were to (a) develop a standing MRI imaging protocol, tolerable to symptomatic patients with degenerative spondylolisthesis (DLS), and (b) to evaluate the morphometric changes observed in DLS patients in both supine and standing postures. Patients with single level, Meyerding grade 1 DLS undergoing surgery at a single institution between November 2015 to May 2017 were consented. Patients were imaged in the supine and standing positions in a 0.5 T vertically open MRI scanner (MROpen, Paramed, Genoa, Italy) with sagittal and axial T2 images. The morphometric parameters measured were: cross-sectional area of the thecal sac (CSA), lateral recess height, disc height, degree of anterolisthesis, disc angle, lumbar lordosis, the presence of facet effusion and restabilization signs. Measures from both postures were compared using paired T-test. Associations of posture with the magnitude of change in the various measurements was determined using Pearson correlation or paired T-test when appropriate. All fourteen patients (mean age 64.4 years) included tolerated standing for the time required for image acquisition. All measurements with the exception of lumbar lordosis and disk height showed a statistically significant difference between the postures (p < 0.05). In the standing position, CSA and lateral recess height were reduced by 28% and 50%, respectively. There was no relationship between the change in CSA of the thecal sac and any measures. Standing images acquired in an upright MRI scanner demonstrated postural changes associated with Meyerding grade 1 DLS and images acquisition was tolerated in all patients.

Proteolysis targeting chimeras (PROTACs) come of age: entering the third decade of targeted protein degradation.

With the discovery of PROteolysis TArgeting Chimeras (PROTACs) twenty years ago, targeted protein degradation (TPD) has changed the landscape of drug development. PROTACs have evolved from cell-impermeable peptide-small molecule chimeras to orally bioavailable clinical candidate drugs that degrade oncogenic proteins in humans. As we move into the third decade of TPD, the pace of discovery will only accelerate. Improved technologies are enabling the development of ligands for "undruggable" proteins and the recruitment of new E3 ligases. Moreover, enhanced computing power will expedite identification of active degraders. Here we discuss the strides made in these areas and what advances we can look forward to as the next decade in this exciting field begins.

Chest imaging of hypersensitivity pneumonitis induced by heroin abuse.

Long-term abuse of nasally inhaled substances such as heroin can result in life-threatening hypersensitivity pneumonitis and respiratory distress. In the setting of hypoxia, a chest CTA is often necessary to see the extent of the lung involvement and to rule out pulmonary emboli.

Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization.

A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2H)-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.

Intravenous Fat Emulsion Does Not Significantly Alter Clotting Markers in Dabigatran-Treated Blood.

Dabigatran etexilate is an oral direct thrombin (Factor IIa) inhibitor approved for patients with atrial fibrillation and for management of risk of deep vein thrombosis and pulmonary embolism. Dabigatran offers advantages over treatment with warfarin, including limited laboratory monitoring. It is equivalent in prevention of stroke and deep vein thrombosis with essentially equivalent complication rates. In contrast to warfarin, reversal of the anticoagulation is less well established. Idarucizumab is available for reversal, however supporting research is mixed; the agent also happens to be quite expensive making availability difficult. Hemodialysis has been proposed as a method of reversal, but this is difficult in patients with life threatening hemorrhage, and is not available at many hospitals. Intravenous fat emulsion (IFE) has been used for treatment of overdose of lipophilic drugs. Most toxicologists only recommend IFE for patients in extremis after ingestion of a lipid soluble substance. Dabigatran is lipid soluble, although the pro-drug more so than the active metabolite. The authors sought to see if dabigatran-induced coagulopathy of human in vitro blood samples could be reversed with IFE. Blood samples were spiked with dabigatran or dabigatran plus IFE. Values for Ecarin clot time (ECT-primary outcome), PT/INR, and aPTT, were compared across both study arms. A total of 18 healthy volunteers were included in our study. There were no significant differences in the ECT, PT/INR, and aPTT between the dabigatran arm and the dabigatran plus IFE arm. Based on these methods, IFE does not reverse dabigatran-induced coagulopathy.

Emergency Medicine Interest Groups.

Emergency Medicine Interest Groups (EMIGs) serve as a bountiful resource for students interested in pursuing a career in Emergency Medicine (EM). In this article we elaborate on how medical students can get involved as members in an EMIG, discuss opportunities for leadership through these groups, detail how to make the most out of the EMIG (including a listing of important lectures, workshops/labs and opportunities for growth and advancement), provide a framework for how to institute a new EMIG when one does not exist, and discuss considerations for international EMIG groups.

Association between aspirin use and cardiovascular outcomes in ALLHAT participants with and without chronic kidney disease: A post hoc analysis.

It is unclear whether aspirin is beneficial for prevention of CVD in patients with CKD. We performed a secondary analysis of the ALLHAT trial to assess the effect of baseline aspirin use on nonfatal myocardial infarction (MI) or fatal coronary heart disease (CHD), all-cause mortality, and stroke. Baseline characteristics of aspirin users and nonusers were used to generate propensity-matched cohorts. Using conditional Cox proportional hazard regression models, we examined the effect of aspirin on the outcomes in the cohort at large and across 3 levels of kidney function (eGFR ≥90, 60-89, and <60). 11 250 ALLHAT participants reported using aspirin at baseline. The propensity-matched dataset included 6894 nonusers matched with replacement to achieve a balanced analysis population (n = 22 500). Risk of fatal CHD or nonfatal MI (HR = 0.94, 95% CI 0.86-1.02) and stroke (HR = 1.01, 95% CI 0.89-1.15) was not significantly different between groups. Aspirin users were at significantly lower risk of all-cause mortality compared to nonusers (HR = 0.82, 95% CI 0.76-0.88). Aspirin use was not associated with incidence of fatal CAD or nonfatal MI in patients with CVD (HR = 0.93, CI 0.84-1.04) or without CVD at baseline (HR = 1.04, CI 0.82-1.32). Results were consistent across strata of GFR (interaction p value NS). In hypertensive patients at high cardiovascular risk, aspirin use is not associated with risk of nonfatal MI, fatal CHD, or stroke; however, aspirin use is associated with lower risk of all-cause mortality. These results are consistent across baseline eGFR.

A Financial Plot to Reduce the Burden of Medical School Tuition Fees.

Tuition fees for medical school are continuously and riotously increasing. This upsurge is amassing debts on the backs of students. In the class of 2018, 75% finished medical school with an outstanding balance of $196,520, on average-a $5826 increase from 2017. Tuition fees differ in terms of the ownership of the medical school (public vs. private) and according to the medical student residence status (in-state or out-of-state). It is critical that students arrange a long-term budget that shows them where they stand: in surplus or in deficit. Students may classify expenditures into two groups: "fixed" and "variable," where they can manipulate the variable expenses to fit into their budget. To pay for their tuition, medical students have four possibilities: cash, scholarships and grants, service-obligation scholarships, and loans. Loans are the most common alternatives, and so there are Traditional Repayment Plans and Income-Driven Repayment Plans. This article serves to provide medical students with attainable alternatives for funding their education and for repaying their debts.