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.

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.

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.

Thermokarst rates intensify due to climate change and forest fragmentation in an Alaskan boreal forest lowland.

Lowland boreal forest ecosystems in Alaska are dominated by wetlands comprised of a complex mosaic of fens, collapse-scar bogs, low shrub/scrub, and forests growing on elevated ice-rich permafrost soils. Thermokarst has affected the lowlands of the Tanana Flats in central Alaska for centuries, as thawing permafrost collapses forests that transition to wetlands. Located within the discontinuous permafrost zone, this region has significantly warmed over the past half-century, and much of these carbon-rich permafrost soils are now within ~0.5 °C of thawing. Increased permafrost thaw in lowland boreal forests in response to warming may have consequences for the climate system. This study evaluates the trajectories and potential drivers of 60 years of forest change in a landscape subjected to permafrost thaw in unburned dominant forest types (paper birch and black spruce) associated with location on elevated permafrost plateau and across multiple time periods (1949, 1978, 1986, 1998, and 2009) using historical and contemporary aerial and satellite images for change detection. We developed (i) a deterministic statistical model to evaluate the potential climatic controls on forest change using gradient boosting and regression tree analysis, and (ii) a 30 × 30 m land cover map of the Tanana Flats to estimate the potential landscape-level losses of forest area due to thermokarst from 1949 to 2009. Over the 60-year period, we observed a nonlinear loss of birch forests and a relatively continuous gain of spruce forest associated with thermokarst and forest succession, while gradient boosting/regression tree models identify precipitation and forest fragmentation as the primary factors controlling birch and spruce forest change, respectively. Between 1950 and 2009, landscape-level analysis estimates a transition of ~15 km² or ~7% of birch forests to wetlands, where the greatest change followed warm periods. This work highlights that the vulnerability and resilience of lowland ice-rich permafrost ecosystems to climate changes depend on forest type.

Multiple Translations in Bilingual Memory: Processing Differences Across Concrete, Abstract, and Emotion Words.

Historically, the manner in which translation ambiguity and emotional content are represented in bilingual memory have often been ignored in many theoretical and empirical investigations, resulting in these linguistic factors related to bilingualism being absent from even the most promising models of bilingual memory representation. However, in recent years it was reported that the number of translations a word has across languages influences the speed with which bilinguals translate concrete and abstract words from one language into another (Tokowicz and Kroll in Lang Cogn Process 22:727-779, 2007). The current work examines how the number of translations that characterize a word influences bilingual lexical organization and the processing of concrete, abstract, and emotional stimuli. In Experiment 1, Spanish-English bilinguals translated concrete and abstract words with one and more than one translation. As reported by Tokowicz and Kroll, concreteness effects emerged only when words had more than one translation across languages. In Experiment 2, bilinguals translated emotion words with more than one translation. Concreteness effects emerged in both language directions for words with more than one translation, and in the L1-L2 language direction for words with a single translation across languages. These findings are discussed in terms of how multiple translations, specifically for emotion words, might be incorporated into current models of bilingual memory representation.

Evidence-based strategies to reduce intravenous immunoglobulin-induced headaches.

OBJECTIVE: To review the literature evaluating pharmacotherapeutic and nonpharmacotherapeutic options available to reduce migraines or headaches associated with intravenous immunoglobulin (IVIG) treatment. DATA SOURCES: A search of MEDLINE (1946 to February 2015) and other secondary resources was performed using the terms immunoglobulin, immune globulin, intravenous immunoglobulins, migraine, and headache. Other relevant articles referenced from the MEDLINE search were also utilized. STUDY SELECTION AND DATA EXTRACTION: Data sources were limited to English language clinical trials and case studies. In all, 6 clinical studies and 2 case reports met the criteria. DATA SYNTHESIS: Headaches or migraines are common adverse effects associated with the administration of IVIG. We evaluated 6 clinical studies and 2 case reports discussing this adverse event in patients treated with IVIG. Strategies used were hydration, switching to an alternate IVIG product, decreased infusion rates, or treating with oral analgesics, opioids, propranolol, sumatriptan, or dihydroergotamines before, during, or after the IVIG infusion. Overall, the majority of patients experienced improvement in headache symptoms, suggesting benefit, after using the various strategies discussed. However, the evidence is limited to case reports and clinical studies with small sample sizes that do not directly measure cause and effect of headache resolution and therapy given in those treated with IVIG. CONCLUSIONS: An individualized treatment plan consisting of a pharmacotherapy or nonpharmacotherapy strategy used in the literature should be recommended after careful consideration of the patient's condition, specific IVIG product used, history of migraine, and previously failed and successful therapies.

Body size overestimation and its association with body mass index, body dissatisfaction, and drive for thinness in anorexia nervosa.

BACKGROUND: Body size overestimation is a fundamental feature in anorexia nervosa (AN). There have been inconclusive findings about the extent to which this feature distinguishes psychopathology and some authors have argued that overestimation may be a function of lower body mass index (BMI). METHODS: We examine body size estimation accuracy and body dissatisfaction in 74 females with AN and 11 age-matched female controls using two well-established psychophysical procedures. RESULTS: Participants with AN overestimated their body size more and had greater body dissatisfaction than controls. Size accuracy was found to be independent of BMI and correlated with body dissatisfaction and drive for thinness in participants with AN. CONCLUSIONS: We conclude that overestimation of body size in AN is related to the psychopathology associated with the disorder and is not due to any perceptual tendency for people with lower BMI to overestimate their body size. We discuss the implications of these findings for treatment of AN.

The Food Addiction Clinical Treatment (FACT) Manual: A Harm Reduction Treatment Approach.

While the construct of food addiction has been controversial, there is growing evidence that certain foods can activate biobehavioral and neurological mechanisms consistent with addiction to other substances. Despite increased evidence and acceptance of certain foods as addictive substances amongst the scientific community, there is a paucity of interventions available that are uniquely suited for the treatment of this condition. Further, many of the addiction and disordered eating treatment models currently utilized for food addiction are seemingly at odds, with the former often recommending complete abstinence from trigger foods and the latter promoting intake of all foods in moderation. The Food Addiction Clinical Treatment (FACT) manual was created as an alternative using an empirically supported harm-reduction model specifically targeted to treat the addiction and disordered eating features of food addiction. The purpose of the current article is to expose readers to the key tenets of the FACT manual, demonstrate the feasibility of this intervention with a sample of participants with severe food addiction, and discuss future directions for the treatment of food addiction. Positive outcomes from this intervention provide preliminary evidence for the efficacy of FACT for the treatment of food addiction with minimal negative adverse effects. Future research using randomized control trials and longer follow-up is needed to validate the FACT manual as an empirically supported treatment for food addiction.

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.

Avanafil for erectile dysfunction.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of avanafil and evaluate relevant clinical trial data. DATA SOURCES: A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (1966 to July 2013) were conducted using the key words: avanafil, erectile dysfunction, and phosphodiesterase type 5 (PDE5) inhibitor. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating avanafil for erectile dysfunction (ED) published in English and using human subjects were selected. Five clinical trials were identified. References cited in identified articles were used for additional citations. DATA SYNTHESIS: Avanafil is a highly selective PDE5 inhibitor that is a competitive antagonist of cyclic guanosine monophosphate. Specifically, avanafil has a high ratio of inhibiting PDE5 as compared with other PDE subtypes allowing for the drug to be used for ED while minimizing adverse effects. Absorption occurs quickly following oral administration with a median Tmax of 30 to 45 minutes and a terminal elimination half-life of 5 hours. Additionally, it is predominantly metabolized by cytochrome P450 3A4. As such, avanafil should not be co-administered with strong cytochrome P450 3A4 inhibitors. Dosage adjustments are not warranted based on renal function, hepatic function, age or gender. Five clinical trials suggest that avanafil 100 and 200 mg doses are effective in improving the Sexual Encounter Profile and the Erectile Function Domain scores among men as part of the International Index of Erectile Function. A network meta-analysis comparing the PDE5 inhibitors revealed avanafil was less effective on Global Assessment Questionnaire question 1 while safety data indicated no major differences among the different PDE5 inhibitors. The most common adverse effects reported from the clinical trials associated with avanafil were headache, flushing, nasal congestion, nasopharyngitis, sinusitis, and dyspepsia. CONCLUSIONS: Avanafil is a potent PDE5 inhibitor and is an effective treatment option for ED.

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.

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.

Planning a pharmacy-led medical mission trip, part 3: development and implementation of an elective medical missions advanced pharmacy practice experience (APPE) rotation.

With an increasing number of new pharmacy schools/colleges and expansion of existing ones, pharmacy schools/colleges are often in need of elective rotation experiences as part of the final year advanced pharmacy practice experience (APPE) program. Offering a medical missions elective APPE in either a domestic or international setting is a unique opportunity to expose pharmacy students to direct patient care. APPE students can be involved in triaging patients, compounding and dispensing medications, and providing patient education. As part of this APPE, pharmacy students are expected to complete projects such as formulary development, case presentations, book club discussions, journal reflections, manuscript preparations, and trip logistics planning. An elective APPE focused on medical missions facilitates the learning process and promotes the emergence of team leaders and leadership skills in general.

Planning a pharmacy-led medical mission trip, part 1: focus on medication acquisition.

Pharmacists can be involved in many functions of the medical mission team. Particularly, they can play a large role in formulary development, acquisition of medications, and organization of medications before and during the mission trip. Important factors for consideration in formulary development and logistical planning include the group's budget; importation laws and regulations of the country being visited; transportation and storage of medications and supplies; disease states anticipated; whether controlled substances will be included; whether medical or surgical procedures will be provided; age distribution and languages of the population to be treated; whether sample medications will be used; handling of unused medications and supplies after the trip; and considerations of the population's cultural beliefs. Various organizations are available to provide medications for medical mission efforts at little to no cost, and knowledge of these organizations will help to facilitate the process of medication acquisition. Additionally, pharmacists can provide insight regarding the logistical set-up and workflow considerations during the mission experience.

Planning a pharmacy-led medical mission trip, part 2: servant leadership and team dynamics.

While pharmacy curricula can prepare students for the cognitive domains of pharmacy practice, mastery of the affective aspects can prove to be more challenging. At the Gregory School of Pharmacy, medical mission trips have been highly effective means of impacting student attitudes and beliefs. Specifically, these trips have led to transformational changes in student leadership capacity, turning an act of service into an act of influence. Additionally, building team unity is invaluable to the overall effectiveness of the trip. Pre-trip preparation for teams includes activities such as routine team meetings, team-building activities, and implementation of committees, as a means of promoting positive team dynamics. While in the field, team dynamics can be fostered through activities such as daily debriefing sessions, team disclosure times, and provision of medical services.

Planning a pharmacy-led medical mission trip, part 4: an exploratory study of student experiences.

BACKGROUND: At the Gregory School of Pharmacy (GSOP), pharmacy students routinely participate in domestic and international medical mission trips. Participation can be for academic credit as part of final-year Advanced Pharmacy Practice Experiences (APPEs) or as required community service hours. These mission experiences could potentially result in both professional and personal transformations for participating students. OBJECTIVE: To evaluate data collected from GSOP pharmacy students regarding their experiences on the medical mission field in 2011 and how that participation has impacted the students professionally and personally. METHODS: GSOP students participating in an international or domestic medical mission trip in the summer of 2011 were asked to voluntarily complete pre- and posttrip surveys. RESULTS: Of the 68 final-year APPE students and student volunteers who participated in a summer 2011 GSOP medical mission trip, 36 (53%) completed pre- and posttrip surveys. The mission trips significantly impacted students' beliefs regarding better preparation to care for the medical needs of patients, identification of others' needs, understanding team dynamics, perceptions about the value of patient care, and comfort level with the provision of medical and pharmaceutical care in a foreign country. However, there were no statistically significant improvements in students' perceptions of their ability to care for the emotional needs of patients, the importance of team unity, and their level of respect for team members; their ability to lead or participate in future trips; and their belief that participating preceptors and faculty serve as effective role models of servant leaders. CONCLUSIONS: Based on the findings from this exploratory study, participation in a domestic or international medical mission trip as a student volunteer or APPE student appears to have a positive impact on some of the beliefs and perceptions of GSOP students. By continuing to follow these particular students and similar cohorts of students in the future, further insight may be gained regarding the long-term impact of medical mission experiences during pharmacy school training.

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.