A Case Report of Acute Compartment Syndrome.

Acute compartment syndrome (ACS) is a surgical emergency which requires prompt identification and intervention to prevent irreversible tissue damage. Here we present the case of a 64-year-old male with lower extremity tenderness following a crush injury. This patient presented to the emergency department (ED) more than 12 hours after the initial incident occurred and was found to have a firm right calf with decreased sensation and absent distal pulses on his right leg. The patient's outer compartment pressure measured 32 mmHg. Because these findings were concerning for acute compartment syndrome, emergent fasciotomies of the four compartments of the lower right leg were performed with improvement in neuromuscular compromise. Early identification of the condition permitted a prompt recovery for the patient who was discharged home on day five. This case report reviews the clinical presentation and interventional modalities and aims to provide new images to help visualize a diagnosis of ACS. Topics: Acute compartment syndrome, fasciotomy, intramuscular pressure.

Germline intergenic duplications at Xq26.1 underlie Bazex-Dupré-Christol basal cell carcinoma susceptibility syndrome.

BACKGROUND: Bazex-Dupré-Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11·4-Mb interval on chromosome Xq25-q27.1. However, the genetic mechanism of BDCS remains an open question. OBJECTIVES: To investigate the genetic aetiology and molecular mechanisms underlying BDCS. METHODS: We ascertained multiple individuals from eight unrelated families affected with BDCS (F1-F8). Whole-exome (F1 and F2) and genome sequencing (F3) were performed to identify putative disease-causing variants within the linkage region. Array comparative genomic hybridization and quantitative polymerase chain reaction (PCR) were used to explore copy number variations, followed by long-range gap PCR and Sanger sequencing to amplify the duplication junctions and to define the head-tail junctions. Hi-C was performed on dermal fibroblasts from two affected individuals with BDCS and one control. Public datasets and tools were used to identify regulatory elements and transcription factor binding sites within the minimal duplicated region. Immunofluorescence was performed in hair follicles, BCCs and trichoepitheliomas from patients with BDCS and sporadic BCCs. The ACTRT1 variant c.547dup (p.Met183Asnfs*17), previously proposed to cause BDCS, was evaluated with t allele frequency calculator. RESULTS: In eight families with BDCS, we identified overlapping 18-135-kb duplications (six inherited and two de novo) at Xq26.1, flanked by ARHGAP36 and IGSF1. Hi-C showed that the duplications did not affect the topologically associated domain, but may alter the interactions between flanking genes and putative enhancers located in the minimal duplicated region. We detected ARHGAP36 expression near the control hair follicular stem cell compartment, and found increased ARHGAP36 levels in hair follicles in telogen, in BCCs and in trichoepitheliomas from patients with BDCS. ARHGAP36 was also detected in sporadic BCCs from individuals without BDCS. Our modelling showed the predicted maximum tolerated minor allele frequency of ACTRT1 variants in control populations to be orders of magnitude higher than expected for a high-penetrant ultra-rare disorder, suggesting loss of function of ACTRT1 variants to be an unlikely cause for BDCS. CONCLUSIONS: Noncoding Xq26.1 duplications cause BDCS. The BDCS duplications most likely lead to dysregulation of ARHGAP36. ARHGAP36 is a potential therapeutic target for both inherited and sporadic BCCs. What is already known about this topic? Bazex-Dupré-Christol syndrome (BDCS) is a rare X-linked basal cell carcinoma susceptibility syndrome linked to an 11·4-Mb interval on chromosome Xq25-q27.1. Loss-of-function variants in ACTRT1 and its regulatory elements were suggested to cause BDCS. What does this study add? BDCS is caused by small tandem noncoding intergenic duplications at chromosome Xq26.1. The Xq26.1 BDCS duplications likely dysregulate ARHGAP36, the flanking centromeric gene. ACTRT1 loss-of-function variants are unlikely to cause BDCS. What is the translational message? This study provides the basis for accurate genetic testing for BDCS, which will aid precise diagnosis and appropriate surveillance and clinical management. ARHGAP36 may be a novel therapeutic target for all forms of sporadic basal cell carcinomas.

Comparing the Psychological Effects of Manikin-Based and Augmented Reality-Based Simulation Training: Within-Subjects Crossover Study.

BACKGROUND: Patient simulators are an increasingly important part of medical training. They have been shown to be effective in teaching procedural skills, medical knowledge, and clinical decision-making. Recently, virtual and augmented reality simulators are being produced, but there is no research on whether these more realistic experiences cause problematic and greater stress responses as compared to standard manikin simulators. OBJECTIVE: The purpose of this research is to examine the psychological and physiological effects of augmented reality (AR) in medical simulation training as compared to traditional manikin simulations. METHODS: A within-subjects experimental design was used to assess the responses of medical students (N=89) as they completed simulated (using either manikin or AR) pediatric resuscitations. Baseline measures of psychological well-being, salivary cortisol, and galvanic skin response (GSR) were taken before the simulations began. Continuous GSR assessments throughout and after the simulations were captured along with follow-up measures of emotion and cortisol. Participants also wrote freely about their experience with each simulation, and narratives were coded for emotional word use. RESULTS: Of the total 86 medical students who participated, 37 (43%) were male and 49 (57%) were female, with a mean age of 25.2 (SD 2.09, range 22-30) years and 24.7 (SD 2.08, range 23-36) years, respectively. GSR was higher in the manikin group adjusted for day, sex, and medications taken by the participants (AR-manikin: -0.11, 95% CI -0.18 to -0.03; P=.009). The difference in negative affect between simulation types was not statistically significant (AR-manikin: 0.41, 95% CI -0.72 to 1.53; P=.48). There was no statistically significant difference between simulation types in self-reported stress (AR-manikin: 0.53, 95% CI -2.35 to 3.42; P=.71) or simulation stress (AR-manikin: -2.17, 95% CI -6.94 to 2.59; P=.37). The difference in percentage of positive emotion words used to describe the experience was not statistically significant between simulation types, which were adjusted for day of experiment, sex of the participants, and total number of words used (AR-manikin: -4.0, 95% CI -0.91 to 0.10; P=.12). There was no statistically significant difference between simulation types in terms of the percentage of negative emotion words used to describe the experience (AR-manikin: -0.33, 95% CI -1.12 to 0.46; P=.41), simulation sickness (AR-manikin: 0.17, 95% CI -0.29 to 0.62; P=.47), or salivary cortisol (AR-manikin: 0.04, 95% CI -0.05 to 0.13; P=.41). Finally, preexisting levels of posttraumatic stress disorder, perceived stress, and reported depression were not tied to physiological responses to AR. CONCLUSIONS: AR simulators elicited similar stress responses to currently used manikin-based simulators, and we did not find any evidence of AR simulators causing excessive stress to participants. Therefore, AR simulators are a promising tool to be used in medical training, which can provide more emotionally realistic scenarios without the risk of additional harm.

Influence of Factors Relating to Sex and Gender on Rank List Decisions and Perceptions of Residency Training: Survey Study.

BACKGROUND: Females make up more than half of medical school matriculants but only one-third of emergency medicine (EM) residents. Various factors may contribute to why fewer females choose the field of EM, such as the existing presence of females in the specialty. OBJECTIVE: This study is a follow-up to previous work, and a survey is used to assess current residents' attitudes and perceptions on various factors, including those relating to sex and gender on creating rank lists as medical students and in perceived effects on residency education. METHODS: A web-based survey consisting of Likert scale questions regarding a variety of factors influencing a student's decision to create a rank list and in perceived effects on residency education was sent to current EM residents in 2020. RESULTS: Residents from 17 programs participated in the survey with an 18.2% (138/758) response rate. The most important factors in creating a rank list were the personality of residents in the program, location, and facility type. For factors specifically related to gender, respondents who answered affirmatively to whether the gender composition of residents affected the selection of a program in making a rank list were more likely to also answer affirmatively to subsequent questions related to the gender of program leadership (P<.001) and gender composition of attending physicians (P<.001). The personality of residents was also the most important factor perceived to affect residency education. For factors influencing rank list and residency education, female respondents placed higher importance on subcategories related to gender (ie, gender composition of the residents, of the program leadership, and of the attending physicians) to a significant degree compared with their male counterparts. CONCLUSIONS: Although factors such as location and resident personality show the most importance in influencing residency selection, when stratifying based on respondent sex, females tend to indicate that factors relating to gender have more influence on rank list and residency education compared with males.

A Virtual Escape Room versus Lecture on Infectious Disease Content: Effect on Resident Knowledge and Motivation.

INTRODUCTION: Medical educators are constantly seeking methods to increase engagement in the era of coronavirus disease 2019 (COVID-19) where virtual and blended learning formats are increasingly common. Educational escape rooms have previously been used to motivate learners, enhance communication skills, and cultivate teamwork. However, it is not known whether escape rooms increase learner knowledge as compared to a lecture format. METHODS: This quasi-experimental study included 30 emergency medicine residents at two programs who participated in both a virtual escape room and a lecture on infectious disease content. Learners completed a pre- and post-quiz and a tool to gauge resident motivation for each activity (the Intrinsic Motivation Inventory [IMI]). The primary objective was to determine a change in knowledge as a result of the activities, and a secondary objective was to determine resident motivation for each format. RESULTS: At both programs learners demonstrated a significant improvement in their pre- vs. post-quiz scores for the escape rooms (University of California Irvine [UCI]: 77.8% to 88.9%, p = 0.028, Prisma: 73.81% to 89.68%, p = 0.002), whereas the lectures did not impact a statistical improvement (UCI: 73.8% to 78.6%, p = 0.460, Prisma: 85.71% to 91.27%, p = 0.236). Learners at UCI noted equivalent results on the IMI for both formats, while residents at Prisma noted they were more motivated by the escape room. CONCLUSION: Emergency medicine residents at two programs participating in a virtual escape room demonstrated a statistical increase in knowledge on infectious disease content as compared to a lecture format and reported positive motivation ratings for both formats, with one program preferring the escape room.

A Case Report of Fournier's Gangrene.

Early identification and intervention of Fournier's gangrene in the Emergency Department (ED) requires a high index of suspicion and is critical in improved patient outcomes. We present a case of a 64-year-old male with two months of progressively worsening buttock and rectal pain found to have extensive black eschar and ecchymosis on exam. In addition, this patient displayed marked leukocytosis, lactic acidosis, and elevated inflammatory markers. A preoperative computed tomography (CT) scan of the abdomen and pelvis revealed multiple perirectal abscesses and subcutaneous fluid and gas in the perineum and scrotum concerning for Fournier's Gangrene. He was started on broad spectrum antibiotics while in the ED and taken to the operating room for urgent surgical debridement with clinical improvement and was discharged home on day nine. This case report reviews the clinical presentation and interventional modalities, and aims to provide new images to better help visualize a diagnosis of Fournier's Gangrene. Topics: Fournier's gangrene, necrotizing soft tissue infection, necrotizing fasciitis.

Zombie Cruise Ship Virtual Escape Room for POCUS Pulmonary: Scan Your Way Out.

Audience: Targeted audience could be learners in medical field with basic knowledge of point-of-care ultrasound (POCUS), pulmonary and emergency medicine for example, medical students, emergency medicine residents (1st-3rd year), emergency physicians at all level of trainings, or emergency medicine physician's assistants. Introduction: Point-of-care ultrasound (POCUS) is rapidly becoming an essential part of emergency medicine and patient care .1,2 POCUS can provide more detailed clinical information when used in conjunction with a physical examination, overall aiding clinicians' decision-making capacity.3 POCUS also proves a cost-effective tool in reducing the number of advanced imaging studies ordered and unnecessary patient radiation exposure.3,4 Performing POCUS has also proved beneficial for patient satisfaction because it increases the amount of face-to-face time spent with the patient while also providing live imaging interpretation during the emergency department visits .3,5,6 POCUS-Pulmonary can also create a safer environment for both medical staff and patients during the COVID-19 pandemic.6 Performing POCUS-Pulmonary on suspected COVID-19 patients can limit the number of patients receiving thoracic CT studies to confirm COVID-19 related pneumonia.6,7 Performing POCUS-Pulmonary reduces the number of patients transferred between the radiology department and the emergency department, significantly reduces overall possible COVID-19 exposures, and reduces equipment cleaning time.6 Given the overall reduction of advanced imaging studies ordered, CT scanners would be more readily available for critical care patients, such as trauma or other hemodynamic instability.6 Emergency providers practicing in rural areas with limited resources may benefit from the use of POCUS -Pulmonary, facilitating better patient care at decreased exposure-rate, cleaning cost, and overall increase in patient satisfaction given more bedside patient-provider communication.6-8 POCUS-Pulmonary is a crucial clinical skill for emergency medicine providers everywhere.6,8 Clinicians should be able to perform POCUS-Pulmonary, interpret image findings, and develop a treatment plan promptly.9. Educational Objectives: By the end of performing the Zombie Cruise Ship Virtual Escape Room, learners will be able to: 1) recognize sonographic signs of A-line, B-line, Barcode sign, Bat sign, Seashore Sign, Plankton sign, Jellyfish Sign, Lung point, lung lockets, and Lung pulse; 2) differentiate sonographic findings of pneumothorax, hemothorax, pneumonia, COVID 19 pneumonia, pulmonary edema, and pleural effusion from normal lung findings; 3) distinguish pneumonia from atelectasis by recognizing dynamic air bronchogram; and 4) recognize indications for performing POCUS pulmonary such as dyspnea, blunt trauma, fall, cough and/or heart failure. Educational Methods: This group-based learning program was designed for use in virtual meetings, lectures, and in small-group learning activities, such as didactic and EM conferences. A Google form was used to create a virtual escape room for learners in which they had to take quizzes to advance to the next level. Learners may enact teamwork through discussion and group effort, or respond individually to ultrasound pulmonary questions. Research Methods: Learners will take pre and post-test assessment to compare the learners POCUS-Pulmonary knowledge before and after small group, virtual escape room learning. All participants in the virtual escape room game are given a pre and post-test assessment comprised of seventeen total questions: two questions asking the participant's training level, and fifteen POCUS-Pulmonary questions. Pre and Post-test questions are identical; however, the participants' answers to the pre-test assessment are not revealed to them on completion. Instead, participants receive a letter grade on completing the pre-test assessment. Participants complete the pre and post-test assessments over fifteen minutes allotted before and after the virtual escape room. Upon completing the post-test assessment, a letter grade and the correct answers were given to the participants. Results: Twenty-four emergency medicine resident physicians (PGY 1-3)) participated in the Zombie Cruise Ship Escape Room pre-test, while a total of twenty-three resident physicians participated in the post-test assessment. The pre-test data showed an average of 10.33 points, compared to post-test data, which showed 11.91 points. There was an improvement of two points on the median score with a median pre-test score of 10 vs. the post-test median of 12. Discussion: The virtual zombie cruise ship experience proved a practical and useful tool in increasing overall participants' interest in POCUS pulmonary during the COVID-19 pandemic. Participants had higher retention after actively discussing and researching the most up-to-date clinical information during the virtual and inperson small group meetings. The game encouraged participants to make decisions quickly. This pace created a fun competition between participants who genuinely enjoyed the learning experience even during the COVID-19 pandemic via Zoom/Google Meet virtual conferences. By creating a virtual escape learning tool, learners can experience teamwork-based learning without concern for group size limitations during the pandemic. Topics: Sonographic findings of pneumothorax, hemothorax, pneumonia, COVID-19 pneumonia, pulmonary edema, pleural effusion, normal lung, A-line, lack of A-line, presence of B-line, Lung sliding, M mode, dynamic air bronchogram, lung rockets, Bar code Sign, Bat Sign, lung pulse, lung point, hepatization, Seashore Sign, Plankton Sign, Jellyfish Sign, and subpleural pulmonary consolidation.

Frequency of Social Media and Digital Scholarship Keywords in U.S. Medical Schools' Promotion and Tenure Guidelines.

PURPOSE: Medical schools must have clear policies and procedures for promotion and tenure (P&T) of faculty. Social media and digital scholarship (SMDS) is an emerging form of scholarship capable of reaching audiences quickly, conveniently, and in a wide variety of formats. It is unclear how frequently SMDS is considered during P&T reviews. The authors sought to determine whether current P&T guidelines at medical schools consider SMDS. METHOD: The authors acquired P&T guidelines from any U.S. Liaison Committee on Medical Education-accredited medical school (or their governing university) that were available online between October and December 2020. Using an iterative process, they developed a bank of keywords that were specific to SMDS or that could include SMDS between October and December 2020. The authors searched each school's guidelines for each keyword and determined whether the word was being used in relation to crediting faculty for SMDS in the context of P&T procedures. The primary outcome measure was the dichotomous presence or absence of SMDS-specific keywords in each school's P&T guidelines. RESULTS: The authors acquired P&T guidelines from 145/154 (94%) medical schools. After removing duplicate documents, the authors considered 139 guidelines. The keyword bank included 59 terms, of which 49 were specific to SMDS and 10 were umbrella terms that could be inclusive of SMDS. Of the 139 guidelines, 121 (87%) contained at least 1 SMDS-specific keyword. Schools had a median of 3 SMDS-specific keywords in their P&T guidelines. CONCLUSIONS: As the presence and impact of SMDS increase, schools should provide guidance on its role in the P&T process. Faculty should receive clear guidance on how to document quality SMDS for their promotion file.

The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation.

Maintaining tissue homeostasis depends on a balance between cell proliferation, differentiation, and apoptosis. Within the epidermis, the levels of the polyamines putrescine, spermidine, and spermine are altered in many different skin conditions, yet their role in epidermal tissue homeostasis is poorly understood. We identify the polyamine regulator, Adenosylmethionine decarboxylase 1 (AMD1), as a crucial regulator of keratinocyte (KC) differentiation. AMD1 protein is upregulated on differentiation and is highly expressed in the suprabasal layers of the human epidermis. During KC differentiation, elevated AMD1 promotes decreased putrescine and increased spermine levels. Knockdown or inhibition of AMD1 results in reduced spermine levels and inhibition of KC differentiation. Supplementing AMD1-knockdown KCs with exogenous spermidine or spermine rescued aberrant differentiation. We show that the polyamine shift is critical for the regulation of key transcription factors and signaling proteins that drive KC differentiation, including KLF4 and ZNF750. These findings show that human KCs use controlled changes in polyamine levels to modulate gene expression to drive cellular behavior changes. Modulation of polyamine levels during epidermal differentiation could impact skin barrier formation or can be used in the treatment of hyperproliferative skin disorders.

Planning Engaging, Remote, Synchronous Didactics in the COVID-19 Pandemic Era.

As part of the Accreditation Council for Graduate Medical Education requirements, residents must participate in structured didactic activities. Traditional didactics include lectures, grand rounds, simulations, case discussions, and other forms of in-person synchronous learning. The COVID-19 pandemic has made in-person activities less feasible, as many programs have been forced to transition to remote didactics. Educators must still achieve the goals and objectives of their didactic curriculum despite the new limitations on instructional strategies. There are several strategies that may be useful for organizing and creating a remote residency didactic curriculum. Educators must master new technology, be flexible and creative, and set rules of engagement for instructors and learners. Establishing best practices for remote didactics will result in successful, remote, synchronous didactics; reduce the impact of transitioning to a remote learning environment; and keep educators and learners safe as shelter-at-home orders remain in place.

Modernising fish and shark growth curves with Bayesian length-at-age models.

Growth modelling is a fundamental component of fisheries assessments but is often hindered by poor quality data from biased sampling. Several methods have attempted to account for sample bias in growth analyses. However, in many cases this bias is not overcome, especially when large individuals are under-sampled. In growth models, two key parameters have a direct biological interpretation: L0, which should correspond to length-at-birth and L∞, which should approximate the average length of full-grown individuals. Here, we present an approach of fitting Bayesian growth models using Markov Chain Monte Carlo (MCMC), with informative priors on these parameters to improve the biological plausibility of growth estimates. A generalised framework is provided in an R package 'BayesGrowth', which removes the hurdle of programming an MCMC model for new users. Four case studies representing different sampling scenarios as well as three simulations with different selectivity functions were used to compare this Bayesian framework to standard frequentist growth models. The Bayesian models either outperformed or matched the results of frequentist growth models in all examples, demonstrating the broad benefits offered by this approach. This study highlights the impact that Bayesian models could provide in age and growth studies if applied more routinely rather than being limited to only complex or sophisticated applications.

CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway.

The AHR is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as a critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway downmodulates skin inflammatory responses in animal models and psoriasis clinical samples. In this study, we identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signaling in the context of skin inflammation. Mice constitutively expressing Cyp1a1 displayed increased CYP1A1 enzymatic activity in the skin, which resulted in exacerbated immune cell activation and skin pathology, mirroring that observed in Ahr-deficient mice. Inhibition of CYP1A1 enzymatic activity ameliorated the skin immunopathology by restoring beneficial AHR signaling. Importantly, patients with psoriasis displayed reduced activation of the AHR pathway and increased CYP1A1 enzymatic activity compared with healthy donors, suggesting that dysregulation of the AHR/CYP1A1 axis may play a role in inflammatory skin disease. Thus, modulation of CYP1A1 activity may represent a promising alternative strategy to harness the anti-inflammatory effect exerted by activation of the AHR pathway in the skin.

Case Report of Thrombotic Thrombocytopenic Purpura in a Previously Healthy Adult.

This case report details the presentation of a 24-year-old male presenting with headache, palpitations, gingival bleeding, and pallor. The ultimate diagnosis of thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening condition which is typically hallmarked by thrombotic microangiopathy (TMA) and dysfunctional ADAMTS13 enzymatic activity. This patient displayed classically described findings, including marked anemia, thrombocytopenia, and acutely elevated creatinine as well as a brief period of newly onset word-finding difficulty while in the emergency department. His diminished ADAMTS13 activity level (<5%) and the presence of autoantibodies against ADAMTS13 confirmed a diagnosis of TTP. Fortunately, the patient's outcome was favorable after treatment with plasmapheresis, prednisone, and rituximab. This case report provides a review of the clinical presentation, diagnostic criteria, potentially confounding differential diagnosis, and expected course of treatment for patients with TTP. Topics: Thrombotic thrombocytopenic purpura (TTP), ADAMTS13, anemia.

Vascular endothelial growth factor-A as a promising therapeutic target for the management of psoriasis.

Vascular endothelial growth factor-A (VEGF-A), the main angiogenic mediator, plays a critical role in the pathogenesis of several inflammatory immune-mediated diseases, including psoriasis. Even though anti-angiogenic therapies, such as VEGF inhibitors, are licensed for the treatment of various cancers and eye disease, VEGF-targeting interventions are not part of current psoriasis therapy. In this viewpoint essay, we argue that the existing preclinical research evidence on the role of VEGF-A in the pathogenesis of psoriasis as well as clinical observations in patients who have experienced psoriasis remission during oncological anti-VEGF-A therapy strongly suggests to systematically explore angiogenesis targeting also in the management of psoriasis. We also point out that some psoriasis therapies decrease circulating levels of VEGF-A and normalise the psoriasis-associated vascular pathology in the papillary dermis of plaques of psoriasis and that a subset of patients with constitutionally high levels of VEGF-A may benefit most from the anti-angiogenic therapy we advocate here. Given that novel, well-targeted personalised medicine therapies for the development of psoriasis need to be developed, we explore the hypothesis that VEGF-A and signalling through its receptors constitute a promising target for therapeutic intervention in the future management of psoriasis.

Vascular Endothelial Growth Factor Blockade Induces Dermal Endothelial Cell Apoptosis in a Clinically Relevant Skin Organ Culture Model.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, plays a key role in physiological processes and is a major contributor to several diseases including cancer and psoriasis. Anti-VEGF therapies are widely used as cancer and ophthalmological treatments. There is some evidence that VEGF blockade may have utility in the management of psoriasis, although their potential has been largely unexplored. We hypothesized that a human skin organ culture could provide a stable ex vivo model in which the cutaneous microvascular network could be studied and experimentally manipulated. METHODS: Punch biopsies (3 mm) of skin, donated by healthy individuals (39-72 years old, n = 5), were incubated with monoclonal antibody (mAb) to human VEGF (bevacizumab) at doses based on data from animal and clinical studies. After 3-day culture, cell death and proliferation as well as vascular endothelial cell changes were assessed using quantitative immunohistomorphometry. RESULTS: Anti-VEGF mAb at 0.8 mg/mL induced a significant increase in cleaved caspase-3 expression in CD31+ cells (p < 0.05). None of the doses tested increased TUNEL or decreased Ki-67 expression in the basal layer of the epidermis, confirming the model's viability. In addition, the lactate dehydrogenase (LDH) assay showed no increase in LDH activity in treated samples compared to untreated control. The highest anti-VEGF mAb dose (0.8 mg/mL) induced an increase in TUNEL expression in the upper epidermis, which did not correlate with caspase-3 immunoreactivity. Further investigation revealed that anti-VEGF mAb did not change the expression of markers of terminal differentiation such as keratin 10, filaggrin, and involucrin, suggesting that VEGF depletion does not affect keratinocyte terminal differentiation. In contrast to the control group, levels of VEGF protein were undetectable in the culture supernatant of samples treated with 0.8 mg/mL of anti-VEGF mAb, suggesting sufficient dose. CONCLUSION: Our pilot study provides the first evidence that anti-VEGF therapy promotes endothelial cell apoptosis in human skin ex vivo. Our pragmatic human skin organ culture assay offers a valuable tool for future preclinical endothelial cell and translational microvascular network/anti-angiogenesis research in human skin.

Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring.

Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treated dams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice.

Validating peer-led assessments of CPR performance.

BACKGROUND: A patient's survival from cardiac arrest is improved if they receive good quality chest compressions as soon as possible. During cardiopulmonary resuscitation (CPR) training subjective assessments of chest compression quality is still common. Recently manikins allowing objective assessment have demonstrated a degree of variance with Instructor assessment. The aim of this study was to compare peer-led subjective assessment of chest compressions in three groups of participants with objective data from a manikin. METHOD: This was a quantitative multi-center study using data from simulated CPR scenarios. Seventy-eight Instructors were recruited, from different backgrounds; lay persons, hospital staff and emergency services personnel. Each group consisted of 13 pairs and all performed 2 â€‹min of chest compressions contemporaneously by peers and manikin (Brayden PRO®). The primary hypothesis was subjective and objective assessment methods would produce different test outcomes. RESULTS: 13,227 chest compressions were assessed. The overall median score given by the manikin was 88.5% (interquartile range 71.75-95), versus 92% (interquartile range 86.75-98) by observers. There was poor correlation in scores between assessment methods (Kappa -0.051 - +0.07). Individual assessment of components within the manikin scores demonstrated good internal consistency (alpha â€‹= â€‹0.789) compared to observer scores (alpha â€‹= â€‹0.011). CONCLUSION: Observers from all backgrounds were consistently more generous in their assessment when compared to the manikin. Chest compressions quality influences outcome following cardiac arrest, the findings of this study support increased use of objective assessment at the earliest opportunity, irrespective of background.

Age, growth and maturity of the Australian sharpnose shark Rhizoprionodon taylori from the Gulf of Papua.

Coastal sharks with small body sizes may be among the most productive species of chondrichthyans. The Australian sharpnose shark (Rhizoprionodon taylori) is one of the most productive members of this group based on work in northern and eastern Australia. However, life history information throughout the remainder of its range is lacking. To address this knowledge gap, the age, growth and maturity of R. taylori caught in the Gulf of Papua prawn trawl fishery in Papua New Guinea, were studied. One hundred and eighty six individuals, comprising 131 females (31-66 cm TL) and 55 males (31-53 cm TL) were aged using vertebral analysis and growth was modelled using a multi-model approach. The lack of small individuals close to the size at birth made fitting of growth curves more difficult, two methods (fixed length at birth and additional zero aged individuals) accounting for this were trialled. The von Bertalanffy growth model provided the best fit to the data when used with a fixed length-at-birth (L0 = 26 cm TL). Males (L∞ = 46 cm TL, k = 3.69 yr-1, L50 = 41.7 cm TL and A50 = 0.5 years) grew at a faster rate and matured at smaller sizes and younger ages than females (L∞ = 58 cm TL, k = 1.98 yr-1, L5o = 47.0 cm TL and A50 = 0.93 years). However, none of the methods to account for the lack of small individuals fully accounted for this phenomenon, and hence the results remain uncertain. Despite this, the results reaffirm the rapid growth of this species and suggest that the Gulf of Papua population may grow at a faster rate than Australian populations. Rhizoprionodon taylori is possibly well placed to withstand current fishing pressure despite being a common bycatch species in the Gulf of Papua prawn trawl fishery. However, further research needs to be undertaken to estimate other key life history parameters to fully assess the population status of this exploited shark species and its vulnerability to fishing in the Gulf of Papua.

Refining mortality estimates in shark demographic analyses: a Bayesian inverse matrix approach.

Leslie matrix models are an important analysis tool in conservation biology that are applied to a diversity of taxa. The standard approach estimates the finite rate of population growth (λ) from a set of vital rates. In some instances, an estimate of λ is available, but the vital rates are poorly understood and can be solved for using an inverse matrix approach. However, these approaches are rarely attempted due to prerequisites of information on the structure of age or stage classes. This study addressed this issue by using a combination of Monte Carlo simulations and the sample-importance-resampling (SIR) algorithm to solve the inverse matrix problem without data on population structure. This approach was applied to the grey reef shark (Carcharhinus amblyrhynchos) from the Great Barrier Reef (GBR) in Australia to determine the demography of this population. Additionally, these outputs were applied to another heavily fished population from Papua New Guinea (PNG) that requires estimates of λ for fisheries management. The SIR analysis determined that natural mortality (M) and total mortality (Z) based on indirect methods have previously been overestimated for C. amblyrhynchos, leading to an underestimated λ. Updated distributions of Z and λ were produced for the GBR population and corrected obvious error in the demographic parameters for the PNG population. This approach provides opportunity for the inverse matrix approach to be applied more broadly to situations where information on population structure is lacking.