Systematic analysis of ocular features and responses of cultured spotted wolffish (Anarhichas minor).

A better understanding of unique anatomical and functional features of the visual systems of teleost fish could provide key knowledge on how these systems influence the health and survival of these animals in both wild and culture environments. We took a systematic approach to assess some of the visual systems of spotted wolffish (Anarhichas minor), a species of increasing importance in North Atlantic aquaculture initiatives. The lumpfish (Cyclopterus lumpus) was included in these studies in a comparative manner to provide reference. Histology, light and electron microscopy were used to study the spatial distribution and occurrence of cone photoreceptor cells and the nature of the retinal tissues, while immunohistochemistry was used to explore the expression patterns of two photoreceptor markers, XAP-1 and XAP-2, in both species. A marine bacterial infection paradigm in lumpfish was used to assess how host-pathogen responses might impact the expression of these photoreceptor markers in these animals. We define a basic photoreceptor mosaic and present an ultrastructural to macroscopic geographical configuration of the retinal pigment tissues in both animals. Photoreceptor markers XAP-1 and XAP-2 have novel distribution patterns in spotted wolffish and lumpfish retinas, and exogenous pathogenic influences can affect the normal expression pattern of XAP-1 in lumpfish. Live tank-side ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT) revealed that normal cultured spotted wolffish display novel variations in the shape of the retinal tissue. These two complementary imaging findings suggest that spotted wolffish harbour unique ocular features not yet described in marine teleosts and that visual function might involve specific retinal tissue shape dynamics in these animals. Finally, extensive endogenous biofluorescence is present in the retinal tissues of both animals, which raises questions about how these animals might use retinal tissue in novel ways for visual perception and/or communication. This work advances fundamental knowledge on the visual systems of two economically important but now threatened North Atlantic teleosts and provides a basic foundation for further research on the visual systems of these animals in health versus disease settings. This work could also be useful for understanding and optimizing the health and welfare of lumpfish and spotted wolffish in aquaculture towards a one health or integrative perspective.

Treatment of Anticholinergic Delirium with Oral Rivastigmine: A Case Report.

BACKGROUND: Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment in these patients. CASE REPORT: A 33-year-old man presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic and delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5 mg to reverse his anticholinergic delirium. Although a repeat dose was required, his delirium resolved without recurrence. Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been applied successfully here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5-6 mg, if encountering anticholinergic delirium when physostigmine is not available.

A Decade in Review: Trends in Female Authorship in Peer-Reviewed Toxicology Journals.

BACKGROUND: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. RESEARCH QUESTIONS: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? METHODS: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). RESULTS: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. CONCLUSIONS: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts.

Residential Mobility and Reasons for Moving Among People Living With Spinal Cord Injury: Results of a Multisite Survey Study.

Background: Residential mobility after spinal cord injury (SCI) has not been extensively examined despite a growing interest in investigating the relationship between neighborhood exposures and community living outcomes. Objectives: This study explores residential mobility patterns, the annual move rate, and reasons for moving among a community-living sample of adults with SCI. Methods: A survey was conducted with 690 people at six SCI Model Systems centers in the United States between July 2017 and October 2020. The outcomes included move status in the past 12 months, move distance, and the primary reason for moving. A sample from the 2019 American Community Survey (ACS) 5-year pooled estimates was obtained for comparative analysis. Descriptive statistics were used to summarize the distributions of the outcomes and differences between the samples. Results: The annual move rate for adults with SCI was 16.4%, and most moves were within the same county (56.6%). Recent movers were more likely to be young adults, be newly injured, and have low socioeconomic status. Housing quality, accessibility, and family were more frequently reported motivations for moving compared to employment. Young adults more commonly moved for family and accessibility, whereas middle-aged adults more commonly moved for housing quality. No notable difference was observed in the annual move rate between the SCI and the general population samples. Conclusion: These findings suggest an age-related pattern of residential relocation after SCI, which may be indicative an extended search for optimal living conditions that meet the housing and accessibility needs of this population.

A pilot randomized control trial of topical capsaicin as adjunctive therapy for nausea and vomiting of pregnancy.

BACKGROUND: Nausea and vomiting is one of the most common complications of pregnancy, affecting 50% to 80% of pregnant persons. Moreover, despite its prevalence, it remains a challenging condition to treat. Treatment often involves oral and intravenous medications with potential side effects, particularly when taken in combination. Capsaicin cream is proven to decrease nausea and vomiting in cyclic vomiting syndrome; however, its use has not been well studied among pregnant patients. OBJECTIVE: This study aimed to test the feasibility of the off-label use of capsaicin for the treatment of nausea and vomiting in pregnancy. STUDY DESIGN: This was a double-blinded randomized controlled trial of pregnant individuals in their first trimester of pregnancy seeking care at a tertiary care hospital for nausea and vomiting. Consenting participants were randomized to abdominal application of topical capsaicin vs placebo. All participants received intravenous hydration and metoclopramide. The primary outcome, total treatment time, was recorded for all participants. In addition, symptom severity was assessed every 30 minutes using a visual analog scale. Data were analyzed using the Wilcoxon rank-sum test for continuous variables and the Fisher exact test for binary variables. RESULTS: Of the 38 eligible individuals approached, 30 were randomized. There was a trend toward decreased mean treatment time in the capsaicin group compared with the placebo group (79.9 vs 97.3 minutes; P=.1). There was no significant difference in visual analog scale scores at any time point between groups. Furthermore, capsaicin was well tolerated, with only 1 individual requesting the medication be removed. CONCLUSION: This study demonstrated that capsaicin is an acceptable treatment of nausea and vomiting in pregnancy and additional explorations of its use as treatment are feasible. A larger randomized controlled trial is needed to determine the efficacy of capsaicin in this population.

Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies.

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow-stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFß stimulation and engraftment with myelofibrosis but not healthy donor-derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow-like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. SIGNIFICANCE: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics. See related commentary by Derecka and Crispino, p. 263. This article is highlighted in the In This Issue feature, p. 247.

Firefighter Well-Being Defined and Operationalized at the Organizational and Worker Level: A Qualitative Study.

OBJECTIVE: The aim of the study is to define and explore organizational- and worker-level factors of firefighter well-being. METHODS: Qualitative data were collected using interviews and focus group sessions among 17 career firefighters across 4 fire departments. Interviews were recorded and transcribed, and a general inductive approach was used to code similar concepts into themes. RESULTS: Firefighters defined well-being as being content with oneself and being able to balance ones' emotional, mental, and physical health. Themes contributing to firefighter well-being include the nature of the job, the influence of others, and physical health. Subthemes mapping to themes include dealing with trauma, compartmentalizing work and home life, coworkers and station culture, the role of superiors on attitudes and practices, being a reliable firefighter, and lack of sleep. CONCLUSIONS: Career firefighters describe well-being as a holistic approach to balancing emotional, mental, and physical health.

Medical, dental, and optical care utilization among community-living people with spinal cord injury in the United States.

CONTEXT/OBJECTIVE: Information about patterns of healthcare utilization for people living with spinal cord injury (SCI) is currently limited, and this is needed to understand independent community living after SCI. This study investigates self-reported healthcare utilization among community-living people with SCI and assesses disparities across demographic, socioeconomic, and injury-related subgroups. DESIGN: Secondary analysis of cross-sectional survey data administered via telephone interview. SETTING: 6 SCI Model Systems centers in the United States (California, Colorado, New Jersey, New York, Ohio, and Pennsylvania). PARTICIPANTS: Adults with chronic, traumatic SCI who were community-living for at least one year after the completion of an inpatient rehabilitation program (N = 617). INTERVENTIONS: Not applicable. OUTCOME MEASURES: Utilization of a usual source of 4 types of health care in the past 12 months: primary, SCI, dental, and optical. RESULTS: 84% of participants reported utilizing primary care in the past year. More than half reported utilizing SCI (54%) and dental (57%) care, and 36% reported utilizing optical care. There were no significant differences across key subgroups in the utilization of primary care. Participants who had been injured for 5 years or less and participants with greater educational attainment were more likely to report utilizing SCI care. Participants with higher household income levels were more likely to report using dental care. Female participants and older age groups were more likely to report using optical care. CONCLUSION: Rates of healthcare utilization among people with SCI are below recommended rates and vary across demographic, socioeconomic, and injury-related subgroups. This information can inform future research to target barriers to using healthcare services among community-living people with SCI.

Association Between Low-Dose Aspirin and Development of Gestational Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the association between the use of low-dose aspirin for preeclampsia prophylaxis and risks of gestational diabetes (primary outcome), neonatal hypoglycemia, macrosomia, large for gestational age, birth trauma, and shoulder dystocia (secondary outcomes). DATA SOURCES: We searched Ovid MEDLINE, Embase, CINAHL, and Cochrane/CENTRAL for studies published between January 1, 1989, and April 24, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies of any size conducted in any setting were included. DATA EXTRACTION AND SYNTHESIS: We assessed risk of bias using the Cochrane Risk of Bias tool 2.0 (for RCTs) and the Newcastle-Ottawa Scale (for cohort studies). We meta-analyzed relative risks (RRs) using random-effects models. CONCLUSIONS: Our search retrieved 4441 records, of which 9 studies (6 RCTs with 1932 patients and 3 cohort studies with 313 837 patients) met inclusion criteria. We rated only 4 of the 6 RCTs and 1 of the 3 cohort studies at low risk of bias. Low-dose aspirin in pregnancy for preeclampsia prophylaxis was not associated with a greater risk of gestational diabetes (RR 1.18; 95% confidence interval 0.80-1.74). No studies reported data for the secondary outcomes. In summary, the use of low-dose aspirin does not appear associated with risk of gestational diabetes. The poor quality and small number of studies limit the interpretation of these results.

Characterizing the Health and Safety Concerns of U.S. Rideshare Drivers: A Qualitative Pilot Study.

BACKGROUND: Despite the growth and popularity of gig work, limited information exists about the occupational health and safety concerns faced by individuals who are employed through ridesharing online applications. In this qualitative study, we characterized the perceived health and safety concerns of drivers employed by rideshare companies. METHODS: During September-October 2019, we requested car rides, using digital rideshare platforms. During the ride, drivers responded verbally to a brief closed-end sociodemographic and work characteristics survey. A semi-structured interview script was used to collect rideshare driver perceptions on health and safety risks. FINDINGS: A total of 35 rideshare drivers of group mean age of 43.1 ± 11.2 years were interviewed, of whom 77.1% were male and 82.9% identified as Latino. Sixty percent of participants reported rideshare as their primary job, working an average of 47.9 ± 19.6 hours weekly (minimum = 6 hours, maximum = 84 hours). Drivers enjoyed job autonomy yet faced stressors such as passenger risky behavior, car accidents, and lack of policies that protect the driver. Rideshare drivers also raised concerns about their current health status, economic pressures, and worker safety. CONCLUSION/APPLICATION TO PRACTICE: Drivers are forced to extend work hours to support themselves financially, exacerbating their current health concerns and safety risks as it means more time spent working in their sedentary job, compromising their mental and physical health as well as their safety. Occupational health and safety programs geared toward workers in the gig economy are needed.

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials.

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

Greener on the other side? an analysis of the association between residential greenspace and psychological well-being among people living with spinal cord injury in the United States.

STUDY DESIGN: Secondary analysis of cross-sectional data from a multisite survey study. OBJECTIVES: To describe associations between residential greenspace and psychological well-being among adults living with chronic spinal cord injury (SCI). SETTING: Community. METHODS: Participants were from the Spinal Cord Injury-Quality of Life (SCI-QOL) Calibration Study (N = 313). Geographic Information Systems (GIS) analysis was used to define five- and half-mile buffer areas around participants' residential addresses to represent community and neighborhood environments, respectively, and to create measures of natural and developed open greenspace. Associations of greenspace measures with two SCI-QOL psychological well-being domains (positive affect and depressive symptoms) were modeled using ordinary least squares (OLS) regression, adjusted for demographic, injury-related, and community socioeconomic characteristics. RESULTS: People living in a community with a moderate amount of natural greenspace reported less positive affect and more depressive symptoms compared to people living in a community with low natural greenspace. At the neighborhood level, a moderate amount of developed open space was associated with less positive affect and more depressive symptoms than a low amount of developed open space. CONCLUSIONS: Contrary to expectations, residential greenspace had a negative relationship with psychological well-being in this sample of adults with SCI. Understanding how and why natural spaces are associated with quality of life for people with mobility disabilities can influence public policy and urban planning designs to ensure that residential greenspaces are accessible and beneficial to all.

A systematic review of screening for perinatal depression and anxiety in community-based settings.

Screening for perinatal depression and anxiety in community-based maternal and child health settings may help close the detection and treatment gap among women at higher risk for these conditions. We aim to review perinatal depression and anxiety screening tools, timing, and follow-up processes for positive screens in community-based settings. We conducted a systematic review of the literature to identify papers describing screening and interventions for perinatal depression and anxiety in community-based settings. We identified 49 papers describing 47 studies of perinatal depression or anxiety screening in community-based settings. The Edinburgh Postnatal Depression Scale (EPDS) was the most frequently used screening tool. Referral and referral tracking for those who screened positive for symptoms were inadequately described. Types of training and technical assistance provided for screening varied widely. It is feasible and acceptable to screen for perinatal depression in community settings, but there is a need for systematic research examining which screening tools to use, the ideal frequency of screening, and referral completion rates. There is a lack of information regarding perinatal anxiety screening and a lack of uniformity in training regarding screening in community-based settings. Future studies should compare the efficacy of screening in community-based settings to screening in healthcare settings.

Who Moves After SCI? Individual, Health, and Neighborhood Predictors of Residential Mobility Among Participants in the National Spinal Cord Injury Model Systems Database.

OBJECTIVE: To investigate residential mobility among community-living adults with spinal cord injury (SCI) and the individual, health, and neighborhood factors associated with the propensity to relocate. DESIGN: Retrospective analysis of data from the National SCI Model Systems (SCIMS) Database collected between 2006 and 2018 and linked with the American Community Survey 5-year estimates. SETTING: Community. INTERVENTIONS: Not applicable. PARTICIPANTS: People with traumatic SCI (N=4599) who participated in 2 waves of follow-up and had residential geographic identifiers at the census tract level. MAIN OUTCOME MEASURES: Moving was a binary measure reflecting change in residential locations over a 5-year interval. Move distance distinguished nonmovers from local movers (different tracts within the same county) and long-distance movers (to different county or state). Move quality included 4 categories: stayed/low poverty tract, stayed/high poverty tract, moved/low poverty tract, and moved/high poverty tract. RESULTS: One in 4 people moved within a 5-year interval (n=1175). Of the movers, 55% relocated to a different census tract within the same county and 45% relocated to a different county or state. Thirty-five percent of all movers relocated to a high poverty census tract. Racial and ethnic minorities, people from low-income households, and younger adults were more likely to move, move locally, and relocate to a high poverty neighborhood. High poverty and racial/ethnic segregation in the origin neighborhood predicted an increased risk for remaining in or moving to a high poverty neighborhood. CONCLUSIONS: Although people with SCI relocated at a lower rate than has been reported in the general population, moving was a frequent occurrence postinjury. People from vulnerable groups were more likely to remain in or relocate to socioeconomically disadvantaged neighborhoods, thus increasing the risk for health disparities and poorer long-term outcomes among minorities and people from low-income households. These findings inform policy makers' considerations of housing, health care, and employment initiatives for individuals with SCI and other chronic disabilities.

Influence of genetic counselor medical history on specialty and psychosocial practice in North America.

A personal or family medical history is inherently part of a genetic counselor's life story. Yet, the degree to which this history influences counselors' clinical specialty choice and professional psychosocial practice is unexplored. A medical diagnosis may foster capacity for greater empathy, understanding, and rapport-building self-disclosure. Conversely, it could lead to disruptive countertransference, compassion fatigue, and eventually burnout. Research, however, has not specifically investigated this intersection. The aim of this study was to explore the impact of genetic counselors' personal and/or family medical history on choice of practice area and self-perceived impact on their psychosocial work within sessions. Members of the National Society of Genetic Counselors were recruited to complete an online screening survey. Of the 69 survey respondents that met inclusion criteria, 23 volunteered for and completed a telephone interview. Interview questions explored counselors' medical narratives and their consequent influence on specialty choice and clinical interaction with patients. Inductive analysis yielded nine domains within three major themes: Medical Story, Specialty Impact, and Psychosocial Influence. Participants were more likely to be attracted to a specialty possessing overlap with their medical history and attributed many of their psychosocial strengths to personal and/or family medical experiences, such as increased empathy or a more expansive scope in how they cared for patients. Many counselors, however, noted their medical history did not frequently influence their clinical practice, with most initially denying or downplaying use of self-disclosure about their history. Contradictory to their statements, the majority gave at least one example of self-disclosure, whether indirect, prompted, or direct. Importantly, almost all participants named or demonstrated countertransference. This study highlights that while medical history can be a valuable asset in providing care for patients, it requires a genetic counselor's diligent attentiveness and commitment to honest self-reflection.

Utility of expanded carrier screening in pregnancies with ultrasound abnormalities.

OBJECTIVE: Explore the utility of expanded carrier screening in evaluating heritable causes of congenital anomalies detected by prenatal ultrasound. METHOD: A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. These were used to determine if expanded carrier screening could have determined the etiology prior to delivery. Additionally, recessive and X-linked conditions on clinically available carrier screening panels were evaluated to determine the number of conditions associated with abnormal ultrasound findings. RESULTS: Our retrospective chart review found 222 patients with genetic etiologies, including eight unique autosomal recessive conditions and six X-linked conditions in the 23% who underwent exome sequencing. Of these 14 unique conditions detected, three were included on a list of 271 conditions for which screening was available in 2019 and five were included on a 500 condition panel available in 2020. A literature review was performed on the list of 271 conditions and 88 were reported to be associated with one or more ultrasound abnormalities. CONCLUSION: This study demonstrates limited but potential utility for expanded carrier screening to determine the underlying etiology of congenital anomalies.

Message in a platelet: decoding platelet transcriptomes in myeloproliferative neoplasms.

Platelets are anucleate but contain a rich repertoire of mRNAs. In this issue of Cell Reports Medicine, Shen and colleagues1 present platelet transcriptomes from patients with myeloproliferative neoplasms to study disease mechanisms and generate a predictive algorithm for fibrotic progression.