Structural maturation of myofilaments in engineered 3D cardiac microtissues characterized using small angle x-ray scattering.

Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, and designing therapies. Here we use a method not commonly applied to biological materials, small angle x-ray scattering, to characterize the structural development of hiPSC-CMs within three-dimensional engineered tissues during their preliminary stages of maturation. An x-ray scattering experimental method enables the reliable characterization of the cardiomyocyte myofilament spacing with maturation time. The myofilament lattice spacing monotonically decreases as the tissue matures from its initial post-seeding state over the span of 10 days. Visualization of the spacing at a grid of positions in the tissue provides an approach to characterizing the maturation and organization of cardiomyocyte myofilaments and has the potential to help elucidate mechanisms of pathophysiology, and disease progression, thereby stimulating new biological hypotheses in stem cell engineering.

Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Changes in social norms during the early stages of the COVID-19 pandemic across 43 countries.

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat.

Overdue Assignment: A Case Study on Academic Writing Development for Postgraduate Health Professional Trainees in Kenya.

OBJECTIVES: Though essential for research capacity building, development of authorial identity for thesis projects and publications has been overlooked in African postgraduate residency programs. This study aims to explore authorial identity among postgraduate health professional trainees at two universities in Kenya. It also evaluated the effect of Age of Acquisition of English on confidence in writing. METHODS: This exploratory case study utilized quantitative and qualitative data. Pre- and post-workshop surveys were generated from learning objectives and evaluated confidence in writing and plagiarism awareness, both important attributes of authorial identity. As confidence in writing might be influenced by the English Age of Acquisition, the questionnaire also included items from the Language Experience and Proficiency Questionnaire. Pre- and post-workshop responses were analyzed using planned comparisons. Focus group discussions further explored authorial identity among participants and were analyzed thematically. RESULTS: A total of 57 postgraduate trainees from nine medical specialties participated in the study. Both confidence in writing and plagiarism awareness improved significantly after the workshop: confidence in writing pre-test (M = 3.20, SD = 0.59) and post-test (M = 3.97, SD = 0.61), t(56) = 6.93, P < .001, d = 0.9; plagiarism awareness pre-test (M = 3.01, SD 0.72) and post-test (M = 3.92, SD 0.65), t(56) = 6,8, P < .001, d = 0.9. The average English Age of Acquisition was 4.98 years and showed no correlation with confidence in writing. Participants recognized that authentic authorship requires hard work and suggested plagiarism is driven by inadequate writing instruction. They proposed that changing perceptions of research and writing could overcome a graduation requirement mindset among trainees. CONCLUSIONS: Interactive workshops using procedural and enculturation approaches may be useful to develop authorial identity among postgraduate health professionals in Kenya. Further research is needed on evaluating workshop effectiveness using direct indicators of learning and other curricular reforms to promote authorship.

Exploration of human cognitive universals and human cognitive diversity.

In this editorial, the editors briefly introduce the aims of the Special Issue. If the goal of the scientific field of Cognitive Psychology is to improve our understanding of human cognition, then research needs to be conducted on a much broader slice of humanity than it has mostly been doing. The first aim of this Special Issue was to examine cognitive processes in populations that are different from the typical Western young adult samples often used in previously published studies. Studies in this issue therefore included both non-WEIRD participants as well as WEIRD participants who process information using different sensory experiences (e.g., individuals who are deaf). The second aim was to amplify - where possible - the research of scholars from less well-represented regions. The authors of the studies were affiliated with a diverse range of academic institutes and frequently included partnerships between Western and non-Western investigators.

Fact or artifact? Demand characteristics and participants' beliefs can moderate, but do not fully account for, the effects of facial feedback on emotional experience.

The facial feedback hypothesis suggests that an individual's facial expressions can influence their emotional experience (e.g., that smiling can make one feel happier). However, a reoccurring concern is that supposed facial feedback effects are merely methodological artifacts. Six experiments conducted across 29 countries (N = 995) examined the extent to which the effects of posed facial expressions on emotion reports were moderated by (a) the hypothesis communicated to participants (i.e., demand characteristics) and (b) participants' beliefs about facial feedback effects. Results indicated that these methodological artifacts moderated, but did not fully account for, the effects of posed facial expressions on emotion reports. Even when participants were explicitly told or personally believed that facial poses do not influence emotions, they still exhibited facial feedback effects. These results indicate that facial feedback effects are not solely driven by demand or placebo effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Benefits, Barriers, and Risks of Big-Team Science.

Progress in psychology has been frustrated by challenges concerning replicability, generalizability, strategy selection, inferential reproducibility, and computational reproducibility. Although often discussed separately, these five challenges may share a common cause: insufficient investment of intellectual and nonintellectual resources into the typical psychology study. We suggest that the emerging emphasis on big-team science can help address these challenges by allowing researchers to pool their resources together to increase the amount available for a single study. However, the current incentives, infrastructure, and institutions in academic science have all developed under the assumption that science is conducted by solo principal investigators and their dependent trainees, an assumption that creates barriers to sustainable big-team science. We also anticipate that big-team science carries unique risks, such as the potential for big-team-science organizations to be co-opted by unaccountable leaders, become overly conservative, and make mistakes at a grand scale. Big-team-science organizations must also acquire personnel who are properly compensated and have clear roles. Not doing so raises risks related to mismanagement and a lack of financial sustainability. If researchers can manage its unique barriers and risks, big-team science has the potential to spur great progress in psychology and beyond.

A multi-lab test of the facial feedback hypothesis by the Many Smiles Collaboration.

Following theories of emotional embodiment, the facial feedback hypothesis suggests that individuals' subjective experiences of emotion are influenced by their facial expressions. However, evidence for this hypothesis has been mixed. We thus formed a global adversarial collaboration and carried out a preregistered, multicentre study designed to specify and test the conditions that should most reliably produce facial feedback effects. Data from n = 3,878 participants spanning 19 countries indicated that a facial mimicry and voluntary facial action task could both amplify and initiate feelings of happiness. However, evidence of facial feedback effects was less conclusive when facial feedback was manipulated unobtrusively via a pen-in-mouth task.

The influence of pesticides on the corrosion of a Roman bowl excavated in Kent, UK.

We analysed corrosion from a copper bowl dating from the Roman period (43-410 AD) found in a farm in Kent, UK. Despite its relatively good condition, the interior and exterior surface of the object had areas of deterioration containing green and brown-coloured corrosion which were sampled for characterization by a multi-analytical protocol. Basic copper chlorides atacamite and paratacamite were identified in the context of mineral phases along with chlorobenzenes in the green corrosion. Chlorobenzenes are common soil contaminants in rural areas from the use of pesticides, many of which were banned more than 50 years ago. Here we show that their presence is associated with accelerated corrosion, and this provides a threat to the preservation of archaeological metal objects in the ground.

Pathogenic variants in SMARCA5, a chromatin remodeler, cause a range of syndromic neurodevelopmental features.

Intellectual disability encompasses a wide spectrum of neurodevelopmental disorders, with many linked genetic loci. However, the underlying molecular mechanism for more than 50% of the patients remains elusive. We describe pathogenic variants in SMARCA5, encoding the ATPase motor of the ISWI chromatin remodeler, as a cause of a previously unidentified neurodevelopmental disorder, identifying 12 individuals with de novo or dominantly segregating rare heterozygous variants. Accompanying phenotypes include mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Loss of function of the SMARCA5 Drosophila ortholog Iswi led to smaller body size, reduced sensory dendrite complexity, and tiling defects in larvae. In adult flies, Iswi neural knockdown caused decreased brain size, aberrant mushroom body morphology, and abnormal locomotor function. Iswi loss of function was rescued by wild-type but not mutant SMARCA5. Our results demonstrate that SMARCA5 pathogenic variants cause a neurodevelopmental syndrome with mild facial dysmorphia.

Perceptions of the appropriate response to norm violation in 57 societies.

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate.

Nitric oxide inhibits interleukin-1-mediated protection against Escherichia coli K1-induced sepsis and meningitis in a neonatal murine model.

Neonatal meningitis-associated Escherichia coli (NMEC) is a leading cause of sepsis and meningitis in newborn infants. Neonates are known to have impaired inflammasome activation and interleukin (IL)-1 production. However, it is unknown what role this plays in the context of NMEC infection. Here we investigated the role of IL-1 signaling in the pathogenesis of NMEC infection. We found both IL-1ß and IL-1α were secreted from macrophages and microglial cells in response to NMEC in a Toll-like receptor 4- and NLR family pyrin domain containing 3 (NPLR3)-dependent manner. Intracerebral infection of adult mice indicated a protective role of IL-1 signaling during NMEC infection. However, IL-1 receptor blockade in wild-type neonatal mice did not significantly alter bacterial loads in the blood or brain, and we, therefore, investigated whether protection conferred by IL-1 was age dependent. Neonates are known to have increased nitric oxide (NO) levels compared with adults, and we found NO inhibited the secretion of IL-1 by macrophages in response to NMEC. In contrast to our results in wild-type neonates, blockade of IL-1 receptor in neonates lacking inducible nitric oxide synthase (iNOS) led to significantly increased bacterial loads in the blood and brain. These data indicate IL-1 signaling is protective during NMEC infection in neonates only when iNOS is absent. Collectively, our findings suggest that increased NO production by neonates inhibits IL-1 production, and that this suppresses the protective role of IL-1 signaling in response to NMEC infection. This may indicate a general mechanism for increased susceptibility of neonates to infection and could lead to new therapeutic strategies in the future.

HIV Infection and Depression Among Opiate Users in a US Epicenter of the Opioid Epidemic.

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder. The prevalence of HIV infection (8.5%) was more than seven times that found in the general population of the city. Eight of the HIV-positive participants (67.0%) reported receiving antiretroviral treatment but almost all of them had unsuppressed virus (87.5%). The majority of participants (57.4%) reported symptoms consistent with major depressive disorder. Severe economic distress (60.3%) and homelessness were common (57%). Polysubstance use was nearly universal, 72.1% had experienced multiple overdoses and prior medication for opioid use disorder (MOUD) treatment episodes (79.9%), but few currently engaged in addiction care. The prevalence, multiplicity and severity of chronic health and socioeconomic problems highlight consequences of the current opioid epidemic and underscore the urgent need to develop integrated models of treatment.

RESUMEN: Utilizando un Centro de Investigación Móvil, inscribimos a 141 usuarios de opioides del vecindario de Filadelfia, un epicentro urbano de la epidemia de opioides. Casi todos (95,6%) cumplieron con los criterios del DSM-5 para el trastorno del uso severo del consumo de opioides. La prevalencia de la infección de VIH (8,5%) fue másﹶ de 7 veces superior a las encontrada en la población general de la ciudad. Ocho de los participantes con VIH positivo (67,0%) reportaron haber recibido tratamiento antirretroviral pero casi todos tuvieron virus no suprimido (87,5%). La mayoría de los participantes (57,4%) informaron síntomas compatibles con el Desorden Depresivo Mayor. La angustia severa por lo económico (60,3%) y las personas sin hogar fueron comunes (57%). El uso de múltiples sustancias fue casi universal, el 721% había experimentado múltiples sobredosis y previos medicamentos para el tratamiento del trastorno por consumo de opioides (MOUD) (79,9%), pero muy pocos estaban comprometidos con la atención a las adicciones. La prevalencia, la multiplicidad y la seriedad de los problemas de salud crónica y los problemas socioeconómicos destacan las consecuencias de la actual epidemia de opioides y subrayan la urgente necesidad de desarrollar nuevos modelos de tratamiento integrados.

Determination of Total Folates in Complex Nutritional Drinks and Supplements Using a Tri-Enzyme Microbiological Method and Michaelis-Menten Kinetics.

Background: Recent development of LC methods for the determination of total folates (vitamin B9) in complex matrixes have been hindered by vitamer interconversion and yield variability. The official microbiological method (AOAC Official Methods of Analysis 944.12 and 960.46) uses an end point turbidity reading to determine folate concentration. However, when measuring complex matrixes, shifts are observed in the growth curves of the microorganism and inaccuracies are introduced to this quantification method. Objective/Methods: In addition to the tri-enzyme digestion of the standard microbiological method, we have applied enzyme modeling of the initial velocity of bacterial growth using Michaelis-Menten kinetics to achieve more accurate and reproducible determinations of total folates. Results/Conclusions: Accuracy determined through spike recovery in Infant/Adult Nutritional Drink and a complex vitamin matrix gave values acceptable to AOAC standards of 85-110%. Repeatability of the low mass fraction analyte measured at micrograms per 100 g yielded relative standard deviations <15% for all matrixes tested, including three standard reference materials.

Emergency airway and ventilator procedures for community based home care staff validation of an educational program.

BACKGROUND: Children discharged home with tracheostomy and chronic mechanical ventilator support are at high risk for complications and adverse events. Private duty nursing and home respiratory care services are a critical support necessary for successful discharge. The literature suggests that there are opportunities for home care staff (HCS) to improve upon the skills necessary to assess and intervene in an emergency thereby increasing the likelihood of improving long-term outcomes. METHODS: HCS (RN, LPN, RRT) participated in a 4-h session comprised of lecture and simulation. Lecture content focused on tracheostomy safety, operation of the Trilogy and LTV home ventilators, and review of their common alarms. Simulation included two scenarios simulating tracheostomy decannulation and mucous plugging events. Participant comfort with tracheostomy and ventilator management skills were measured on a five item self-assessment tool and clinical knowledge was measured using an 11 item multiple choice skills test, both of which were completed before and after the session. We tested to see if there was a change in test scores from pre- to post-intervention. RESULTS: Fifty-four HCS participated in the program and provided complete data sets. The vast majority (68%) were registered nurses, followed by licensed practical nurses (19%) and respiratory therapists (12%). Participant self-reported comfort with emergency skills prior to intervention was 3.2/5 which increased to 4.1/5 after intervention (P > 0.0001). Average test score prior to intervention was 62%, post intervention score increased to 82% which represented significant improvement (P > 0.0001). DISCUSSION: HCS are generally unprepared to intervene in an acute airway or ventilator emergency. This short, manageable program provided education that resulted in a significant improvement in both skill level and confidence.

Twitter as a Potential Data Source for Cardiovascular Disease Research.

IMPORTANCE: As society is increasingly becoming more networked, researchers are beginning to explore how social media can be used to study person-to-person communication about health and health care use. Twitter is an online messaging platform used by more than 300 million people who have generated several billion Tweets, yet little work has focused on the potential applications of these data for studying public attitudes and behaviors associated with cardiovascular health. OBJECTIVE: To describe the volume and content of Tweets associated with cardiovascular disease as well as the characteristics of Twitter users. DESIGN, SETTING, AND PARTICIPANTS: We used Twitter to access a random sample of approximately 10 billion English-language Tweets originating from US counties from July 23, 2009, to February 5, 2015, associated with cardiovascular disease. We characterized each Tweet relative to estimated user demographics. A random subset of 2500 Tweets was hand-coded for content and modifiers. MAIN OUTCOMES AND MEASURES: The volume of Tweets about cardiovascular disease and the content of these Tweets. RESULTS: Of 550 338 Tweets associated with cardiovascular disease, the terms diabetes (n = 239 989) and myocardial infarction (n = 269 907) were used more frequently than heart failure (n = 9414). Users who Tweeted about cardiovascular disease were more likely to be older than the general population of Twitter users (mean age, 28.7 vs 25.4 years; P < .01) and less likely to be male (59 082 of 124 896 [47.3%] vs 8433 of 17 270 [48.8%]; P < .01). Most Tweets (2338 of 2500 [93.5%]) were associated with a health topic; common themes of Tweets included risk factors (1048 of 2500 [41.9%]), awareness (585 of 2500 [23.4%]), and management (541 of 2500 [21.6%]) of cardiovascular disease. CONCLUSIONS AND RELEVANCE: Twitter offers promise for studying public communication about cardiovascular disease.

Establishing Edoxaban's Role in Anticoagulation.

PURPOSE: This article serves as a review of the current literature regarding the role of edoxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of venous thromboembolism (VTE). SUMMARY: Until recent years, oral treatment options for both treatment and prevention of VTE and stroke were limited to warfarin. Dabigatran was the first new oral anticoagulant approved in over 50 years followed by rivaroxaban and apixaban. These new oral anticoagulants offer many benefits over warfarin. Edoxaban is the newest member among the oral anticoagulants and exerts its action by direct inhibition of factor Xa. It may offer some advantages in that it is the second Food and Drug Administration-approved once-daily anticoagulant available and does not interact with the cytochrome P450 (CYP450) system. However, there are concerns in patients with AF and preserved renal function (>95 mL/min), as these cohorts experienced a higher incidence of stroke in trials. CONCLUSION: Based on the 3 clinical trials, edoxaban appears to be a safe and effective factor Xa inhibitor in patients with a creatinine clearance of <95 mL/min. It will serve as an alternative anticoagulant for those with a preference for once-daily dosing and/or taking medications that interact with the CYP450 system.

Serving with Pharmacy Students: Reflections from a Medical Mission Team Leader and Preceptor.

The medical mission field is an innovative setting for training and evaluating health care professional students. The motivating factor of serving indigent populations as a means of a humanitarian, or oftentimes a spiritual act, makes medical missions an attractive option for student participation. At the Gregory School of Pharmacy, medical mission teams are an integral part of the pharmacy program, including the opportunity for students to earn elective credit during their fourth year. This commentary provides five key elements to consider when serving with, training and evaluating pharmacy students from the perspective of a team leader and preceptor.