The importance of including Long COVID outcomes when developing novel treatments for acute COVID-19.

The ongoing COVID-19 pandemic continues to present surges in infections demonstrating the persistent threat posed by COVID-19. Amidst efforts to develop effective treatments for acute COVID-19, there is a growing recognition of the need to address Long COVID. This manuscript reviews the current landscape of acute COVID-19 treatments and highlights the opportunity to incorporate Long COVID as a key outcome measure in clinical trials. Our analysis includes a review of current US clinical trials investigating acute COVID-19 treatments. Of the 19 studies that met our inclusion criteria, only one study currently incorporates Long COVID measurements. In our review, we argue there are 7 compelling reasons to include Long Covid measurements, including: (1) Long COVID is not rare (2) Long COVID is debilitating to individuals and has a high societal cost (3) Those at high risk of severe COVID-19 are also at higher risk of developing Long COVID if they are infected with COVID-19 (4) Treatments for acute COVID-19 may reduce the risk of Long COVID (5) Measures exist to track Long COVID (6) Long COVID considerations are potentially important for acute COVID-19 treatment decision-making (7) Deaths and hospitalizations due to COVID-19 are increasingly rare, creating an opportunity for other important clinical endpoints to be considered In conclusion, while not every trial needs to include assessments of Long COVID, it is worth the research burden to include assessments where possible as this could facilitate the uptake of acute COVID-19 treatments that lessen the societal burden of Long COVID.

Knockout of syntaxin-4 in 3T3-L1 adipocytes reveals new insight into GLUT4 trafficking and adiponectin secretion.

Adipocytes are key to metabolic regulation, exhibiting insulin-stimulated glucose transport that is underpinned by the insulin-stimulated delivery of glucose transporter type 4 (SLC2A4, also known and hereafter referred to as GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, and increase cell surface GLUT4 levels. Adipocytokines, such as adiponectin, are secreted via a similar mechanism. We used genome editing to knock out syntaxin-4, a protein reported to mediate fusion between GLUT4-containing vesicles and the plasma membrane in 3T3-L1 adipocytes. Syntaxin-4 knockout reduced insulin-stimulated glucose transport and adiponectin secretion by ∼50% and reduced GLUT4 levels. Ectopic expression of haemagglutinin (HA)-tagged GLUT4 conjugated to GFP showed that syntaxin-4-knockout cells retain significant GLUT4 translocation capacity, demonstrating that syntaxin-4 is dispensable for insulin-stimulated GLUT4 translocation. Analysis of recycling kinetics revealed only a modest reduction in the exocytic rate of GLUT4 in knockout cells, and little effect on endocytosis. These analyses demonstrate that syntaxin-4 is not always rate limiting for GLUT4 delivery to the cell surface. In sum, we show that syntaxin-4 knockout results in reduced insulin-stimulated glucose transport, depletion of cellular GLUT4 levels and inhibition of adiponectin secretion but has only modest effects on the translocation capacity of the cells. This article has an associated First Person interview with Hannah L. Black and Rachel Livingstone, joint first authors of the paper.

Systemic Caryospora-like coccidiosis in a clutch of hatchling red-eared slider turtles (Trachemys scripta elegans).

Caryospora-like organisms (CLOs) form a clade of at least 11 genotypes of related coccidia that can cause epizootic mortality in marine turtles. The biology, transmission, host species range, and host cell tropism of these organisms are still largely unknown. The goal of this study was to characterize the host cell tropism, pathologic and ultrastructural features, and phylogeny associated with the first report of a mortality event due to CLO in the freshwater red-eared slider turtle (Trachemys scripta elegans). Sudden mortalities within a clutch of captive-raised red-eared slider hatchlings (n = 8) were recorded, and deceased animals had severe segmental to diffuse, transmural, fibrinonecrotic enterocolitis and multifocal to coalescing hepatic necrosis, among other lesions associated with numerous intracytoplasmic developing stages of intralesional coccidia. Among the different developmental stages, merozoites were ultrastructurally characterized by an apical complex. A pan-apicomplexan polymerase chain reaction (PCR) yielded a 347 bp-amplicon matching the Schellackia/Caryospora-like clade with 99.1% identity to the US3 strain from green sea turtles (Chelonia mydas) and 99.1% identity to Schellackia sp. Isolate OC116. Surviving hatchlings were treated with toltrazuril sulfone (ponazuril) but were subsequently euthanized due to the risk of spreading the parasite to other chelonids in the collection. The ponazuril-treated hatchlings (n = 4) had mild proliferative anterior enteritis, with few intraepithelial coccidia in one hatchling confirmed as CLO by PCR. This is the first report of Caryospora-like coccidiosis in non-cheloniid turtles, highlighting the relevance of this disease as an emerging highly pathogenic intestinal and extra-intestinal form of coccidiosis of turtles with potential cross-species infectivity.

State Policymaking and Stated Reasons: Prenatal Care for Undocumented Immigrants in an Era of Abortion Restriction.

Policy Points States can create policies that provide access to publicly funded prenatal care for undocumented immigrants that garner support from diverse political coalitions. Policymakers have used a wide range of moral and practical reasons to support the expansion of care to this population, which can be tailored to frame prenatal policies for different stakeholder groups. CONTEXT: Even though nearly 6% of citizen babies born in the United States have at least one undocumented parent, undocumented immigrants are ineligible for most public health insurance. Prenatal care is a recommended health service that improves birth outcomes, and some states, including both traditionally "blue" and "red" states, have opted to provide publicly funded coverage for prenatal services for people who are otherwise ineligible due to immigration status. This article explores how courts and legislatures in three states have approached the question of publicly funded prenatal care for undocumented immigrants and its relationship to the abortion debate, with a particular focus on the moral and practical justifications that policymakers employ. METHODS: We employed a review and qualitative analysis of the documents that comprise the legislative histories of prenatal policies in three case states: California, New York, and Nebraska. FINDINGS: This review and analysis of policy documents identified moral reasons based on appeals to different conceptions of moral status, respect for autonomy, and justice, as well as prudential reasons that appealed to the health and economic benefits of prenatal care for US citizens and legal residents. We found that much of the variation in reasons supporting policies by state can be traced to the state's position on the protection of reproductive rights and whether the policymakers in each state supported or opposed access to abortion. Interestingly, despite these differences, the states arrived at similar prenatal policies for immigrants. CONCLUSIONS: There may be areas where policymakers with different political orientations can converge on health policies affecting access to care for undocumented immigrants. Future research should explore the reception of various message frames for expanding public health insurance coverage to immigrants in other contexts.

Randomized comparison of two interventions to enhance understanding during the informed consent process for research.

BACKGROUND/AIMS: Many investigators have tested interventions to improve research participant understanding of information shared during the informed consent process, using a variety of methods and with mixed results. A valid criticism of most consent research is that studies are often conducted in simulated research settings rather than ongoing clinical studies. The present study rigorously tested two simple and easily adoptable strategies for presenting key consent information to participants eligible to enroll in six actual clinical trials (i.e. six parent studies). METHODS: In collaboration with the study team from each parent study, we developed two consent interventions: a fact sheet and an interview-style video. The content of each of the intervention was based on the information shared in the consent form approved for each parent study. Participants were randomized to the standard consent process, or to one of the two interventions. Once exposed to the assigned consent mode, participants were asked to complete an assessment of understanding. The study was powered to determine whether those exposed to the fact sheet or video performed better on the consent assessment compared to those exposed to the standard consent. We also assessed participant satisfaction with the consent process. RESULTS: A total of 284 participants were randomized to one of the three consent arms. Assessments of understanding were completed with a total of 273 participants from July 2017 to April 2019. Participants exposed to the video had better understanding scores compared to those exposed to the standard consent form process (p value = 0.020). Participants were more satisfied with the video when compared to the standard consent. Participants who received the fact sheet did not achieve higher overall understanding or satisfaction scores when compared to the standard consent process. CONCLUSION: This randomized study of two novel consent interventions across six different clinical trials demonstrated a statistically significant difference in participant understanding based on overall scores among those exposed to the video intervention compared to those exposed to the standard consent.

Action compatibility in spatial knowledge developed through virtual navigation.

Action-compatibility effects (ACEs) arise due to incongruity between perceptuo-motor traces stored in memory and the perceptuo-motor demands of a retrieval task. Recent research has suggested that ACEs arising during spatial memory retrieval are additionally modulated by individual differences in how experienced participants are with a college campus environment. However, the extent and nature of experience with a real-world environment is difficult to assess and control, and characteristics of the retrieval task itself might modulate ACEs during spatial memory retrieval. The present study provides a more controlled and in-depth examination of how individual differences and task-based factors interact to shape ACEs when participants retrieve spatial memories. In two experiments, participants with varied video game experience learned a virtual environment and then used the computer mouse to verify spatial relationships from different perspectives. Mouse trajectories demonstrated ACEs, differing by retrieval perspective and video game experience. Videogame experts demonstrated the ACE based on learned spatial relationships during egocentric retrieval only, whereas videogame novices showed the ACE based on semantic processing of directional terms only. Specifically, gaming experts invoke perspective-specific perceptuo-motor associations to retrieve spatial knowledge, whereas non-experts are influenced by semantically based associations specific to the retrieval task. Results are discussed in the context of action-compatibility effects, the intentional weighting hypothesis, and the flexible encoding and retrieval of spatial information.

Cognitive focus affects spatial decisions under conditions of uncertainty.

Finding one's way to a destination is a common, everyday task that often relies on spatial information provided by humans and/or automatic devices. However, the information can be inaccurate. How we decide which route to take will depend on our thoughts about the available route information, including who or what provided it, and how these sources may be associated with differential accuracy and fallibility. In three experiments (previously reported in Brunyé et al. (Q J Exper Psychol 68(3):585-607, 2015)), we found that when route directions conflicted with the perceived environment, people trusted the landmark information other humans provided, but relied on the turn direction information from an automatic device. But what guides these behavioral results? Here we present a systematic linguistic analysis of retrospective reports that sheds some light on how information about the direction source affects cognitive focus. A focus on direction sources in the instruction triggered a cognitive focus on the direction source throughout. Participants who systematically switched strategies focused more on features of the scenario than those who did not. Non-switching strategies were associated with a higher focus on the participants' own reasoning processes, in particular when relying on turn information. These results highlight how cognitive focus is guided by scenario factors and individual preferences, triggering inferences that influence decisions.

Make-A-Dice Test: Assessing the intersection of mathematical and spatial thinking.

Individuals with better spatial thinking have increased interest and greater achievement in science, technology, engineering, and mathematics (STEM) disciplines (Wai, Lubinski, & Benbow in Journal of Educational Psychology, 101, 817-835, 2009). This relationship means that STEM education may benefit from leveraging spatial thinking, but measures of spatial thinking as they relate to specific STEM disciplines are needed. The present work presents an assessment of spatial and mathematical reasoning, called Make-A-Dice. In Make-A-Dice, individuals are presented with a cube net (i.e., a flattened cube) with numbers on two sides. Their goal is to "make a dice" by filling in the blank sides using two rules: opposite sides add to 7, and the numbers 1 through 6 should be used once each. Make-A-Dice was given to adults (Study 1) and elementary students (Studies 2 and 3) along with math, spatial, and other measures, across two sessions in all studies. Make-A-Dice had both internal and test-retest reliability, with items ordered by difficulty. Furthermore, performance was related to spatial and mathematical reasoning. In Study 1, adults reported a range of strategies used to complete Make-A-Dice, and one strategy predicted performance. Studies 2 and 3 showed that Make-A-Dice is age-appropriate for elementary students. Make-A-Dice shows promise as an individual-difference measure linking spatial and mathematical thinking and has the potential to identify elementary-aged children who may benefit from spatial training.

Systemic Factors and Barriers That Hamper Adequate Data Collection on the HIV Epidemic and Its Associated Inequalities in Countries With Long-Term Armed Conflicts: Lessons From Colombia.

Although advances in treatment and diagnosis have transformed HIV into a chronic disease in high-income countries, a spectrum of structural, political, sociocultural, and health system barriers hamper early diagnosis and timely treatment of HIV in many middle- and low-income countries. In most Latin American countries, in spite of the great improvement in access to antiretroviral therapy, a large proportion of individuals infected with HIV do not know their status. In Colombia, the Joint United Nations Programme on HIV/AIDS currently estimates a much larger number of HIV cases than the number reported by Colombian authorities. Potential reasons for underdiagnosis and underreporting include sociocultural factors such as social stigma, restrictions in access to health care, a lack of public health research and robust surveillance systems, and the particular recent history and social situation related to the armed conflict the country has suffered through for several decades. Lessons from Colombia may be helpful in monitoring, understanding, and tackling the HIV epidemic in countries with long-term armed conflicts.

Age-related differences in the use of spatial and categorical relationships in a visuo-spatial working memory task.

Research examining object identity and location processing in visuo-spatial working memory (VSWM) has yielded inconsistent results on whether age differences exist in VSWM. The present study investigated whether these inconsistencies may stem from age-related differences in VSWM sub-processes, and whether processing of component VSWM information can be facilitated. In two experiments, younger and older adults studied 5 × 5 grids containing five objects in separate locations. In a continuous recognition paradigm, participants were tested on memory for object identity, location, or identity and location information combined. Spatial and categorical relationships were manipulated within grids to provide trial-level facilitation. In Experiment 1, randomizing trial types (location, identity, combination) assured that participants could not predict the information that would be queried. In Experiment 2, blocking trials by type encouraged strategic processing. Thus, we manipulated the nature of the task through object categorical relationship and spatial organization, and trial blocking. Our findings support age-related declines in VSWM. Additionally, grid organizations (categorical and spatial relationships), and trial blocking differentially affected younger and older adults. Younger adults used spatial organizations more effectively whereas older adults demonstrated an association bias. Our finding also suggests that older adults may be less efficient than younger adults in strategically engaging information processing.

The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative.

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.

Responding to the Call to Meaningfully Assess Institutional Review Board Effectiveness.

This Viewpoint discusses the difficult task of creating a stakeholder-driven, evidence-based approach to assessing institutional review board effectiveness beyond regulatory compliance.

Action Guide for Addressing Ethical Challenges of Resource Allocation Within Community-Based Healthcare Organizations.

This article proposes an action guide to making decisions regarding the ethical allocation of resources that affect access to healthcare services offered by community-based healthcare organizations. Using the filter of empirical data from a study of decision making in two community-based healthcare organizations, we identify potentially relevant conceptual guidance from a review of frameworks and action guides in the public health, health policy, and organizational ethics literature. We describe the development of this action guide. We used data from a prior empirical study of the values that influence decision making about the allocation of resources in particular types of community-based healthcare organizations. We evaluated, organized, and specified the conceptual guidance we found in 14 frameworks for ethical decision making. The result is an action guide that includes four domains that are relevant to the context of the decision to be made, eight domains that are relevant to the process of the decision to be made, and 15 domains that are relevant to the criteria of the decision to be made. We demonstrate the potential use of this action guide by walking through an illustrative resource allocation decision. The action guide provides community-based healthcare organizations with a conceptually grounded, empirically informed framework for ethical decision making.

Cognitive strategies in the mental rotation task revealed by EEG spectral power.

The classic mental rotation task (MRT; Shepard & Metzler, 1971) is commonly thought to measure mental rotation, a cognitive process involving covert simulation of motor rotation. Yet much research suggests that the MRT recruits both motor simulation and other analytic cognitive strategies that depend on visuospatial representation and visual working memory (WM). In the present study, we investigated cognitive strategies in the MRT using time-frequency analysis of EEG and independent component analysis. We scrutinized sensorimotor mu (µ) power reduction, associated with motor simulation, parietal alpha (pα) power reduction, associated with visuospatial representation, and frontal midline theta (fmθ) power enhancement, associated with WM maintenance and manipulation. µ power increased concomitant with increasing task difficulty, suggesting reduced use of motor simulation, while pα decreased and fmθ power increased, suggesting heightened use of visuospatial representation processing and WM, respectively. These findings suggest that MRT performance involves flexibly trading off between cognitive strategies, namely a motor simulation-based mental rotation strategy and WM-intensive analytic strategies based on task difficulty. Flexible cognitive strategy use may be a domain-general cognitive principle that underlies aptitude and spatial intelligence in a variety of cognitive domains. We close with discussion of the present study's implications as well as future directions.

Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills.