Consultation-Liaison Case Conference: Overcoming Bias in the Differential Diagnosis of Psychosis.

We present the case of a 34-year-old Black patient with no significant psychiatric history who presented with catatonia and psychotic symptoms following a recent severe acute respiratory syndrome coronavirus-2 infection, whose diagnosis of coronavirus disease 2019 encephalitis was delayed by premature attribution of his symptoms to a primary psychiatric etiology. Top experts in the consultation-liaison field provide guidance for this commonly encountered clinical case based on their experience and a review of the available literature. Key teaching topics include the diagnosis and management of coronavirus disease 2019 encephalitis, cognitive bias, and racial bias. Specifically, this case illustrates the role of the consultation-liaison psychiatrist in identifying medical conditions that may overlap with psychiatric presentations and in advocating for marginalized patients.

Cell density, alignment, and orientation correlate with C-signal-dependent gene expression during Myxococcus xanthus development.

Starving Myxococcus xanthus bacteria use short-range C-signaling to coordinate their movements and construct multicellular mounds, which mature into fruiting bodies as rods differentiate into spherical spores. Differentiation requires efficient C-signaling to drive the expression of developmental genes, but how the arrangement of cells within nascent fruiting bodies (NFBs) affects C-signaling is not fully understood. Here, we used confocal microscopy and cell segmentation to visualize and quantify the arrangement, morphology, and gene expression of cells near the bottom of NFBs at much higher resolution than previously achieved. We discovered that "transitioning cells" (TCs), intermediate in morphology between rods and spores, comprised 10 to 15% of the total population. Spores appeared midway between the center and the edge of NFBs early in their development and near the center as maturation progressed. The developmental pattern, as well as C-signal-dependent gene expression in TCs and spores, were correlated with cell density, the alignment of neighboring rods, and the tangential orientation of rods early in the development of NFBs. These dynamic radial patterns support a model in which the arrangement of cells within the NFBs affects C-signaling efficiency to regulate precisely the expression of developmental genes and cellular differentiation in space and time. Developmental patterns in other bacterial biofilms may likewise rely on short-range signaling to communicate multiple aspects of cellular arrangement, analogous to juxtacrine and paracrine signaling during animal development.

A scoping review of the use of ethnographic approaches in implementation research and recommendations for reporting.

BACKGROUND: Researchers have argued for the value of ethnographic approaches to implementation science (IS). The contested meanings of ethnography pose challenges and possibilities to its use in IS. The goal of this study was to identify sources of commonality and variation, and to distill a set of recommendations for reporting ethnographic approaches in IS. METHODS: We included in our scoping review English-language academic journal articles meeting two criteria: (1) IS articles in the healthcare field and (2) articles that described their approach as ethnographic. In March 2019, we implemented our search criteria in four academic databases and one academic journal. Abstracts were screened for inclusion by at least two authors. We iteratively develop a codebook for full-text analysis and double-coded included articles. We summarized the findings and developed reporting recommendations through discussion. RESULTS: Of the 210 articles whose abstracts were screened, 73 were included in full-text analysis. The number of articles increased in recent years. Ethnographic approaches were used within a wide variety of theoretical approaches and research designs. Articles primarily described using interviews and observational methods as part of their ethnographic approaches, though numerous other methods were also employed. The most cited rationales for using ethnographic approaches were to capture context-specific phenomena, understand insiders' perspective, and study complex interactions. In reporting on ethnographic approaches, we recommend that researchers provide information on researcher training and position, reflect on researchers' positionality, describe observational methods in detail, and report results from all the methods used. CONCLUSION: The number of IS studies using ethnography has increased in recent years. Ethnography holds great potential for contributing further to IS, particularly to studying implementation strategy mechanisms and understanding complex adaptive systems.

Changes in Cell Size and Shape during 50,000 Generations of Experimental Evolution with Escherichia coli.

Bacteria adopt a wide variety of sizes and shapes, with many species exhibiting stereotypical morphologies. How morphology changes, and over what timescales, is less clear. Previous work examining cell morphology in an experiment with Escherichia coli showed that populations evolved larger cells and, in some cases, cells that were less rod-like. That experiment has now run for over two more decades. Meanwhile, genome sequence data are available for these populations, and new computational methods enable high-throughput microscopic analyses. In this study, we measured stationary-phase cell volumes for the ancestor and 12 populations at 2,000, 10,000, and 50,000 generations, including measurements during exponential growth at the last time point. We measured the distribution of cell volumes for each sample using a Coulter counter and microscopy, the latter of which also provided data on cell shape. Our data confirm the trend toward larger cells while also revealing substantial variation in size and shape across replicate populations. Most populations first evolved wider cells but later reverted to the ancestral length-to-width ratio. All but one population evolved mutations in rod shape maintenance genes. We also observed many ghost-like cells in the only population that evolved the novel ability to grow on citrate, supporting the hypothesis that this lineage struggles with maintaining balanced growth. Lastly, we show that cell size and fitness remain correlated across 50,000 generations. Our results suggest that larger cells are beneficial in the experimental environment, while the reversion toward ancestral length-to-width ratios suggests partial compensation for the less favorable surface area-to-volume ratios of the evolved cells.IMPORTANCE Bacteria exhibit great morphological diversity, yet we have only a limited understanding of how their cell sizes and shapes evolve and of how these features affect organismal fitness. This knowledge gap reflects, in part, the paucity of the fossil record for bacteria. In this study, we revived and analyzed samples extending over 50,000 generations from 12 populations of experimentally evolving Escherichia coli to investigate the relation between cell size, shape, and fitness. Using this "frozen fossil record," we show that all 12 populations evolved larger cells concomitant with increased fitness, with substantial heterogeneity in cell size and shape across the replicate lines. Our work demonstrates that cell morphology can readily evolve and diversify, even among populations living in identical environments.

Vibrio cholerae adapts to sessile and motile lifestyles by cyclic di-GMP regulation of cell shape.

The cell morphology of rod-shaped bacteria is determined by the rigid net of peptidoglycan forming the cell wall. Alterations to the rod shape, such as the curved rod, occur through manipulating the process of cell wall synthesis. The human pathogen Vibrio cholerae typically exists as a curved rod, but straight rods have been observed under certain conditions. While this appears to be a regulated process, the regulatory pathways controlling cell shape transitions in V. cholerae and the benefits of switching between rod and curved shape have not been determined. We demonstrate that cell shape in V. cholerae is regulated by the bacterial second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) by posttranscriptionally repressing expression of crvA, a gene encoding an intermediate filament-like protein necessary for curvature formation in V. cholerae. This regulation is mediated by the transcriptional cascade that also induces production of biofilm matrix components, indicating that cell shape is coregulated with V. cholerae's induction of sessility. During microcolony formation, wild-type V. cholerae cells tended to exist as straight rods, while genetically engineering cells to maintain high curvature reduced microcolony formation and biofilm density. Conversely, straight V. cholerae mutants have reduced swimming speed when using flagellar motility in liquid. Our results demonstrate regulation of cell shape in bacteria is a mechanism to increase fitness in planktonic and biofilm lifestyles.

Social Support Networks Among Young Men and Transgender Women of Color Receiving HIV Pre-Exposure Prophylaxis.

PURPOSE: The aim of the study was to characterize perceived social support for young men and transgender women who have sex with men (YM/TWSM) taking HIV pre-exposure prophylaxis (PrEP). METHODS: Mixed-methods study of HIV-negative YM/TWSM of color prescribed oral PrEP. Participants completed egocentric network inventories characterizing their social support networks and identifying PrEP adherence support figures. A subset (n = 31) completed semistructured interviews exploring adherence support and qualities of PrEP support figures. We calculated proportions of role types (e.g., family), individuals disclosed to regarding PrEP use, and PrEP-supportive individuals within each participant network. Interviews were analyzed using an inductive approach. RESULTS: Participants (n = 50) were predominately African American men who have sex with men. Median age was 22 years (interquartile range: 20-23). Biologic family were the most common support figures, reported by 75% of participants (mean family proportion .37 [standard deviation (SD): .31]), followed by 67% reporting friends (mean friend proportion .38 [SD: .36]). Most network members were aware (mean disclosed proportion .74 [SD: .31]) and supportive (mean supportive proportion .87 [SD: .28]) of the participants' PrEP use. Nearly all (98%) participants identified ≥1 figure who provided adherence support; more often friends (48%) than family (36%). Participants characterized support as instrumental (e.g., transportation); emotional (e.g., affection); and social interaction (e.g., taking medication together). Key characteristics of PrEP support figures included closeness, dependability, and homophily (alikeness) with respect to sexual orientation. CONCLUSIONS: Although most YM/TWSM identified family in their support networks, friends were most often cited as PrEP adherence support figures. Interventions to increase PrEP adherence should consider integrated social network and family-based approaches.

Mapping the Peaks: Fitness Landscapes of the Fittest and the Flattest.

Populations exposed to a high mutation rate harbor abundant deleterious genetic variation, leading to depressed mean fitness. This reduction in mean fitness presents an opportunity for selection to restore fitness through the evolution of mutational robustness. In extreme cases, selection for mutational robustness can lead to flat genotypes (with low fitness but high robustness) outcompeting fit genotypes (with high fitness but low robustness)-a phenomenon known as survival of the flattest. While this effect was previously explored using the digital evolution system Avida, a complete analysis of the local fitness landscapes of fit and flat genotypes has been lacking, leading to uncertainty about the genetic basis of the survival-of-the-flattest effect. Here, we repeated the survival-of-the-flattest study and analyzed the mutational neighborhoods of fit and flat genotypes. We found that the flat genotypes, compared to the fit genotypes, had a reduced likelihood of deleterious mutations as well as an increased likelihood of neutral and, surprisingly, of lethal mutations. This trend holds for mutants one to four substitutions away from the wild-type sequence. We also found that flat genotypes have, on average, no epistasis between mutations, while fit genotypes have, on average, positive epistasis. Our results demonstrate that the genetic causes of mutational robustness on complex fitness landscapes are multifaceted. While the traditional idea of the survival of the flattest emphasized the evolution of increased neutrality, others have argued for increased mutational sensitivity in response to strong mutational loads. Our results show that both increased neutrality and increased lethality can lead to the evolution of mutational robustness. Furthermore, strong negative epistasis is not required for mutational sensitivity to lead to mutational robustness. Overall, these results suggest that mutational robustness is achieved by minimizing heritable deleterious variation.

Handedness, Grip Strength, and Memory Function: Considerations by Biological Sex.

Background and Objective: The objective of this study was to evaluate the potential independent and interactive effects of handedness and grip strength on episodic memory function, and whether biological sex moderated these relationships. Materials and Methods: 162 young adults (Mage = 20.7 years) completed a series of memory assessments including a subjective memory complaint evaluation and several objective measures of memory. Handedness (i.e., left-hand dominant, inconsistent handedness (ICH), and right-hand dominant) was evaluated using the Edinburgh Handedness Inventory. Handgrip strength was determined from a handgrip dynamometer. Results: When compared to ICH individuals, retrospective memory scores were statistically significantly worse for left-handed (p = 0.02) and right-handed (p = 0.03) individuals. Higher grip strength was statistically significantly associated with fewer retrospective memory complaints (b = 0.10, 95% CI: 0.01, 0.19, p = 0.04). Conclusions: The present study provides some suggestive evidence that ICH (inconsistent handedness) and greater grip strength are associated with fewer retrospective memory complaints. However, we did not observe any evidence of an interaction effect of handedness and grip strength on memory, and similarly, biological sex did not interact with these parameters to influence memory.

Barriers and Facilitators of PrEP Adherence for Young Men and Transgender Women of Color.

We aimed to discover barriers and facilitators of HIV pre-exposure prophylaxis (PrEP) adherence in young men and transgender women of color who have sex with men (YMSM/TW). Short-term and sustained adherence were measured by urine tenofovir concentration and pharmacy refills, respectively. Optimal adherence was defined as having both urine tenofovir concentration consistent with dose ingestion within 48 h and pharmacy refills consistent with ≥ 4 doses per week use. Participants completed semi-structured interviews exploring adherence barriers and facilitators. Participants (n = 31) were primarily African-American (68%), mean age 22 years (SD: 1.8), and 48% had optimal adherence. Adherence barriers included stigma, health systems inaccessibility, side effects, competing stressors, and low HIV risk perception. Facilitators included social support, health system accessibility, reminders/routines, high HIV risk perception, and personal agency. Our findings identify targets for intervention to improve PrEP adherence in these populations, including augmenting health activation and improving accuracy of HIV risk perception.

Access to Medical and Mental Health Services Across the HIV Care Continuum Among Young Transgender Women: A Qualitative Study.

Purpose: (1) To describe psychosocial, medical, and mental health outcomes of young transgender women (YTW) living with or at risk for HIV infection and (2) to explore barriers and facilitators to medical and mental health services across the HIV care continuum. Methods: We conducted a cross-sectional observational study of YTW aged 16-24 years who were at risk for contracting or living with HIV. Participants were recruited from an adolescent HIV clinic and local community-based organizations that serve YTW. The single study visit included: a computer-assisted self-interview of demographics, medical and mental health measures, a qualitative semi-structured interview, optional rapid HIV testing for HIV-negative/status-unknown participants, and a chart review to determine rates of antiretroviral therapy (ART) prescription and viral suppression among HIV+ participants. Descriptive statistics were used for quantitative data, and a modified-grounded theory approach was used for qualitative analysis. Results: Participants (n=25) had a mean age of 21.2 years; the majority were non-white (76%), had less than a college education (76%), were unemployed (52%), and had an income <$12,000/year (80%). More than one-third were unstably housed (36%) and uninsured (36%), and 28% reported having transactional sex. A majority had taken gender-affirming hormones (72%), but 17% obtained them from a source other than their doctor. Among HIV+ participants (n=8), 50% were prescribed ART and all four participants achieved viral suppression. Qualitative themes included lack of respect for or misunderstanding of gender identity, mismatch of mental health needs with available provider skills, challenges in finding HIV prevention services during adolescence or when transitioning to adult care, and importance of workforce diversity, including representation of transgender women in care teams. Conclusion: This study identified significant unmet mental health needs and several barriers and facilitators to engaging in healthcare for YTW across the HIV care continuum. Our data suggest an urgent need for provider competency training in gender-affirming care and integration of appropriate mental health and gender-affirming treatment with HIV prevention and treatment services for this population.

A partnership approach for Electronic Data Capture in small-scale clinical trials.

Amid researchers' growing need for study data management, the CTSA-funded Institute for Translational Health Sciences developed an approach to combine technical and scientific resources with small-scale clinical trials researchers in order to make Electronic Data Capture more efficient. In a 2-year qualitative evaluation we found that the importance of ease of use and training materials outweighed number of features and functionality. EDC systems we evaluated were Catalyst Web Tools, OpenClinica and REDCap. We also found that two other systems, Caisis and LabKey, did not meet the specific user needs of the study group.

Distributed XQuery-Based Integration and Visualization of Multimodality Brain Mapping Data.

This paper addresses the need for relatively small groups of collaborating investigators to integrate distributed and heterogeneous data about the brain. Although various national efforts facilitate large-scale data sharing, these approaches are generally too "heavyweight" for individual or small groups of investigators, with the result that most data sharing among collaborators continues to be ad hoc. Our approach to this problem is to create a "lightweight" distributed query architecture, in which data sources are accessible via web services that accept arbitrary query languages but return XML results. A Distributed XQuery Processor (DXQP) accepts distributed XQueries in which subqueries are shipped to the remote data sources to be executed, with the resulting XML integrated by DXQP. A web-based application called DXBrain accesses DXQP, allowing a user to create, save and execute distributed XQueries, and to view the results in various formats including a 3-D brain visualization. Example results are presented using distributed brain mapping data sources obtained in studies of language organization in the brain, but any other XML source could be included. The advantage of this approach is that it is very easy to add and query a new source, the tradeoff being that the user needs to understand XQuery and the schemata of the underlying sources. For small numbers of known sources this burden is not onerous for a knowledgeable user, leading to the conclusion that the system helps to fill the gap between ad hoc local methods and large scale but complex national data sharing efforts.

Web service access to semantic web ontologies for data annotation.

Recent advances in semantic web technologies now provide the methodology for efficient and adaptable deployment of ontology support to biomedical applications for data annotation and integration.