Clinical Images in Emergency Medicine: Cushing's Disease.

Case Presentation: A 22-year-old female presented to the emergency department with a two-month history of worsening fatigue, unintentional weight gain, and progressive facial swelling. Physical examination findings included hirsutism, moon facies, and abdominal striae. Subsequent brain magnetic resonance imaging revealed the presence of a 2.4-centimeter pituitary macroadenoma, confirming the diagnosis of Cushing's disease. The patient was then admitted for neurosurgical tumor resection. Discussion: Cushing's disease is exceedingly rare and often presents with symptoms resembling more prevalent disorders, contributing to delays in diagnosis. Therefore, maintaining a high index of suspicion for this disease is crucial for emergency physicians.

Human placental organoids as a model to probe early gestation maternal immune dynamics.

During pregnancy, the human placenta establishes tolerance toward fetal allogeneic tissue, where specialized trophoblast subtypes play a complex role in local and peripheral immunomodulation. However, due to inadequate models to study the early gestation of the human placenta, each trophoblast subtype's role in modulating the maternal immune response has remained elusive. Here, we derived human placental organoids from early gestation trophoblast stem cells to (1) identify patterns of immunomodulatory protein expression by trophoblast subtype and (2) evaluate the effects of the placental organoid secretome on immune cell activation and regulation. We show that the three primary trophoblast phenotypes had distinct influences on immune cell phenotype and activation and that three-dimensional culture significantly alters trophoblast immunomodulation relative to traditional two-dimensional trophoblast culture.

Engineered 3D Hydrogel Matrices to Modulate Trophoblast Stem Cell-Derived Placental Organoid Phenotype.

Placental organoid models are a promising platform to study human placental development and function. Organoid systems typically use naturally derived hydrogel extracellular matrices (ECM), resulting in batch-to-batch variability that limits experimental reproducibility. As an alternative, synthetic ECM-mimicking hydrogel matrices offer greater consistency and control over environmental cues. Here, we generated trophoblast stem cell-derived placental organoids using poly(ethylene glycol) (PEG) hydrogels with tunable degradability and placenta-derived ECM cues to evaluate trophoblast differentiation relative to Matrigel and two-dimensional (2D) culture controls. Our data demonstrate that PEG hydrogels support trophoblast viability and metabolic function comparable to gold standard Matrigel. Additionally, phenotypic characterization via proteomic analysis revealed that PEG and Matrigel matrices drive syncytiotrophoblast and extravillous trophoblast-dominant placental organoid phenotypes, respectively. Further, three-dimensional (3D) environments promoted greater integrin expression and ECM production than 2D culture. This study demonstrates that engineered 3D culture environments can be used to reliably generate placental organoids and guide trophoblast differentiation.

Association between Surgery, Anesthesia, and Obstetric Workforce and Emergent Surgical and Obstetric Mortality among United States Hospital Referral Regions.

OBJECTIVE: To determine the association between SAO workforce and mortality from emergent surgical and obstetric conditions within US HR Rs. BACKGROUND: SAO workforce per capita has been identified as a core metric of surgical capacity by the Lancet Commission on Global Surgery, but its utility has not been assessed at the subnational level for a high-income country. METHODS: The number of practicing surgeons, anesthesiologists, and obstetricians per capita was estimated for all HRRs using the US Health Resources & Services Administration Area Health Resource File Database. Deaths due to emergent general surgical and obstetric conditions were determined from the Center for Disease Control and Prevention WONDER database. We utilized B-spline quantile regression to model the relationship between SAO workforce and emergent surgical mortality at different quantiles of mortality and calculated the expected change in mortality associated with increases in SAO workforce. RESULTS: The median SAO workforce across all HRRs was 74.2 per 100,000 population (interquartile range 33.3-241.0). All HRRs met the Lancet Commission on Global Surgery lower target of 20 SAO per 100,000, and 97.7% met the upper target of 40 per 100,000. Nearly 2.8 million Americans lived in HRRs with fewer than 40 SAO per 100,000. Increases in SAO workforce were associated with decreases in surgical mortality in HRRs with high mortality, with minimal additional decreases in mortality above 60 to 80 SAO per 100,000. CONCLUSIONS: Increasing SAO workforce capacity may reduce emergent surgical and obstetric mortality in regions with high surgical mortality but diminishing returns may be seen above 60 to 80 SAO per 100,000. Trial Registration: N/A.

Prostate Specific Antigen Testing Behaviors for Prostate Cancer Screening Among U.S. Immigrants: A Cross-sectional Analysis Using the National Health Interview Survey.

PURPOSE: Immigrants constitute 14% of the U.S. population, and this group is especially vulnerable to poor health care access. Prior research demonstrates U.S. immigrants have low rates of guideline-concordant breast and colorectal screening, but prostate cancer screening has not previously been evaluated. We sought to characterize screening behaviors among U.S. immigrants and to consider possible mechanisms to enhance PSA-based screening for this population. MATERIALS AND METHODS: Data were obtained from the 2010, 2013, 2015, and 2018 National Health Interview Survey reports, which were the recent survey years that included questions about PSA testing. Complex samples logistic regression was performed to assess the relationship between immigrant-specific characteristics including region of birth, citizenship status, length of residence within the U.S., English language proficiency, and history of PSA testing. RESULTS: There were 22,997 survey respondents; 3,257 were foreign-born and 19,740 were U.S.-born. Rates of PSA testing were much lower among the foreign-born population compared to the U.S.-born population (43% vs 60%). Citizenship status, length of residence in the U.S. for more than 15 years, and English proficiency were directly linked to increased rates of PSA testing. There was significant variability in PSA testing among immigrant subgroups and Asian immigrants had the lowest rate of PSA testing. Annual physician visits and English language proficiency were associated with increased PSA testing among the U.S. immigrant population. CONCLUSIONS: Immigrants have relatively low rates of PSA testing. Improving health care utilization and language services may help to narrow the gap in guideline-concordant prostate cancer screening between immigrants and nonimmigrants.

A Case Report of the Rapid Evaluation of a High-Pressure Injection Injury of a Finger Leading to Positive Outcomes.

High-pressure injection injuries, though rare, carry high rates of morbidity and amputation despite a potentially benign initial presentation. Emergency physicians must have a high index of suspicion and be ready to act quickly when evaluating this presenting complaint. In this case report, a patient presented to the emergency department with a chief complaint of finger pain after a pressure washer came into contact with his right index finger. He subsequently developed pain, numbness and a white discoloration to his finger surrounding a small puncture wound. Key interventions in his care included rapid assessment, beginning broad spectrum antibiotics, and quickly consulting the hand surgery team. Despite the potential for significant morbidity with this injury, expedited evaluation and treatment in this case allowed for adequate retention of function in the affected digit, with only mildly decreased pincer function. In summary, the early mobilization of resources for patients with high-pressure injection injuries, especially early surgical consultation, is paramount to achieving positive outcomes. Topics: Finger injury, hand injury, high-pressure injection injury.

Exploring the impact of rural health system factors on physician burnout: a mixed-methods study in Northern Canada.

BACKGROUND: Burnout among physicians is a consequence of chronic occupational stresses and emotionally intense work demands. However, much of the evidence exploring burnout is derived from urban settings and may not reflect the work and social contexts of physicians in Indigenous communities or in rural and resource-constrained areas. We sought to characterize health system factors that influence burnout among physicians practicing in the three northern territories of Canada. METHODS: We conducted a mixed-methods study that included an online survey and qualitative interviews with physicians practicing in Nunavut, Northwest Territories, or Yukon in 2019. The survey adapted content from the Maslach Burnout Inventory. Results were analyzed with logistic regression to assess the association between health system factors and burnout. We conducted in-depth interviews with 14 physicians. Qualitative data was coded and analyzed for themes using the ATLAS.ti software. RESULTS: Thirty-nine percent of survey respondents (n = 22/57) showed features associated with burnout. Factors associated with burnout included use of electronic medical records (ß = - 0.7, p < .05), inadequate financial remuneration (ß = - 1.0, p < .05), and cross-cultural issues (ß = - 1.1, p < .05). Qualitative analysis further identified physician perceptions of lack of influence over health system policies, systemic failures in cultural safety, discontinuity of care, administrative burden, and physician turnover as important drivers of burnout. CONCLUSIONS: Physicians practicing in northern regions in Canada experience stress and burnout related to health system factors and cross-cultural issues. The relationship between cross-cultural issues and burnout has not previously been reported. This work may have implications for physician wellbeing and workforce attrition in other resource-constrained or culturally diverse clinical settings.

Gender-Based Microaggressions in Surgery: A Scoping Review of the Global Literature.

BACKGROUND: In addition to systemic gender disparities, women in surgery encounter interpersonal microaggressions. The objective of this study is to describe the most common forms of microaggressions reported by women in surgery. METHODS: We conducted a scoping review using PubMed/MEDLINE, Ovid, and Web of Science to describe the international, indexed English-language literature on gender-based microaggressions experienced by female surgeons, surgical trainees, and medical students in surgery. After screening by title, abstract, and full-text, 37 articles were retained for data extraction and analysis. Microaggressions were analyzed using the Sexist Microaggression Experience and Stress Scale (MESS) framework and stratified by country of origin. RESULTS: Gender-based microaggression publications most commonly originated from the United States (n = 27 articles), Canada (n = 3), and India (n = 2). Gender-based microaggressions were classified into environmental invalidations (n = 20), being treated like a second-class citizen (n = 18), assumptions of traditional gender roles (n = 12), sexual objectification (n = 11), assumptions of inferiority (n = 10), being forced to leave gender at the door (n = 8), and experiencing sexist language (n = 6). Additionally, attendings were more frequently reported to experience microaggressions than surgical trainees and medical students, but more articles reported data on attendings (n = 16) than surgical trainees (n = 10) or students (n = 4). CONCLUSION: While recent advancements have opened the field of surgery to women, there is still a lack of female representation, and persistent microaggressions may perpetuate this gender disparity. Addressing microaggressions against female surgeons is essential to achieving gender equity in surgical practice.

Patient experience studies in the circumpolar region: a scoping review.

OBJECTIVES: Patient experiences with health systems constitute a crucial pillar of quality care. Across the Arctic, patients' interactions with the healthcare system are influenced by challenges of access, historical inequities and social determinants. This scoping review sought to describe the range and nature of peer-reviewed literature on patient experience studies conducted within the circumpolar region. DESIGN: In a partnership between Danish/Greenlandic, Canadian and American research teams, a scoping review of published research exploring patient experiences in circumpolar regions was undertaken. DATA SOURCES: Seven electronic databases were queried: MEDLINE, Embase, Scopus, 'Global Health 1910 to 2019 Week 11', CINAHL, PsycINFO and SveMed+. ELIGIBILITY CRITERIA: Articles were eligible for inclusion if they (a) took place in the circumpolar region, (b) reported patients' perspective and (c) were focussed primarily on patient experiences with care, rather than satisfaction with treatment outcome. DATA EXTRACTION AND SYNTHESIS: Title and abstract screening, full-text review and data extraction was conducted by four researchers. Bibliometric information such as publication date and country of origin was extracted, as was information regarding study design and whether or not the article contained results relevant to the themes of Indigenous values, rural and remote context, telehealth and climate change. Two researchers then synthesised and characterised results relevant to these themes. RESULTS: Of the 2824 articles initially found through systematic searches in seven databases, 96 articles were included for data extraction. Findings from the review included unique features related to Indigenous values, rural and remote health, telehealth and climate change. CONCLUSIONS: The review findings provide an overview of patient experiences measures used in circumpolar nations. These findings can be used to inform health system improvement based on patient needs in the circumpolar context, as well as in other regions that share common features. This work can be further contextualized through Indigenous methodologies such as sharing circles and community based participatory methods.

Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion.

The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species.

Metal nanofibers with highly tunable electrical and magnetic properties via highly loaded water-based electrospinning.

Nanofibers are synthesized by electrospinning highly loaded water-based precursor-polymer hybrid solutions followed by thermal treatment to control crystal structure. Electrical conductivity and magnetic coercivity, as shown, are tested displaying independent magnetic and electrical property control from coercive to superparamagnetic and resistive to near-bulk conductivity at room temperature.

Inorganic nanofibers with tailored placement of nanocatalysts for hydrogen production via alkaline hydrolysis of glucose.

Monoaxial silica nanofibers containing iron species as well as coaxial nanofibers with a pure silica core and a silica shell containing high concentrations of iron nanocrystals were fabricated via electrospinning precursor solutions, followed by thermal treatment. Tetraethyl-orthosilicate (TEOS) and iron nitrate (Fe(NO(3))(3)) were used as the precursors for the silica and iron phases, respectively. Thermal treatments of as-spun precursor fibers were applied to generate nanocrystals of iron with various oxidation states (pure iron and hematite). Scanning electron microscopy (SEM), x-ray diffraction (XRD), and transmission electron microscopy (TEM) were used to probe the fiber morphology and crystal structures. The results indicated that the size, phase, and placement of iron nanocrystals can be tuned by varying the precursor concentration, thermal treatment conditions, and processing scheme. The resulting nanofiber/metal systems obtained via both monoaxial and coaxial electrospinning were applied as catalysts to the alkaline hydrolysis of glucose for the production of fuel gas. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and bulk weight change in a furnace with residual gas analysis (RGA) were used to evaluate the performance of the catalysts for various ratios of both Fe to Si, and catalyst to glucose, and the oxidation state of the iron nanocrystals. The product gas is composed of mostly H(2) (>96 mol%) and CH(4) with very low concentrations of CO(2) and CO. Due to the clear separation of reaction temperature for H(2) and CH(4) production, pure hydrogen can be obtained at low reaction temperatures. Our coaxial approach demonstrates that placing the iron species selectively near the fiber surface can lead to two to three fold reduction in catalytic consumption compared to the monoaxial fibers with uniform distribution of catalysts.

Profiling DNA methylation by bisulfite genomic sequencing: problems and solutions.

The surge of interest in DNA methylation during the last two decades has triggered an urgent need for an effective method to detect the methylation status of the cytosines in the genome. Bisulfite genomic sequencing is the most attractive choice so far for many laboratories. Various protocols have been established, but difficulties are often encountered, particularly by individuals who have limited experience in this field. This analysis presents a simple protocol that has consistently worked well in our laboratory. Discussions of potential technical problems and corresponding solutions are also included to facilitate the reproducibility of this protocol.

Control mechanisms in the regulation of telomerase reverse transcriptase expression in differentiating human teratocarcinoma cells.

Telomerase is active in about 90% of cancers and contributes to the immortality of cancer cells by maintaining the lengths of the ends of chromosomes. Undifferentiated embryonic human teratocarcinoma (HT) cells were found to express high levels of hTERT, the catalytic subunit of telomerase, and the hTERT promoter was unmethylated in these cells. Retinoic acid (RA)-induced differentiation led to hTERT gene silencing and increased methylation of the hTERT promoter. Treatment with trichostatin A, a histone deacetylase inhibitor, resulted in hTERT reactivation only in very early differentiating HT cells. After methylation patterns had been established within the hTERT promoter region in late differentiating cells, 5-azacytidine, a common demethylating agent, activated the hTERT gene but trichostatin A had no effect on hTERT transcription. These studies suggest that histone deacetylation is involved in early hTERT gene down-regulation and that DNA methylation may maintain silencing of the hTERT gene in these cells.