Effect of the COVID-19 pandemic on emergency department utilization of computed tomography scans of appendicitis and diverticulitis.

PURPOSE: Investigating the effect of the COVID-19 lockdown on adult patient visits, computed tomography (CT) abdominal scans, and presentations of appendicitis and diverticulitis, to emergency departments (ED) in St. John's NL. METHODS: A retrospective quantitative analysis was applied, using ED visits and Canadian Triage and Acuity Scale (CTAS) scores. mPower (Nuance Communications, UK) identified CT abdominal scan reports, which were categorized into (1) normal/other, (2) appendicitis, or (3) diverticulitis. Time intervals included pre-lockdown (January-February), lockdown (March-June), and post-lockdown (July-August). Data from 2018 to 2019 (January-August) were used to generate expected patient volumes for 2020, and pre- and post-lockdown were included to control for other variables outside the lockdown. RESULTS: Chi-squared goodness of fit tested for deviations from predicted means for 2018-2019. Compared to expectations, daily ED visits from January to August 2020 showed a significant (p < 0.001) decrease in patient volumes independent of gender, age, and CTAS scores. During and post-lockdown, CT abdominal scans did not drop in proportion to patient volume. Appendicitis presentations remained indifferent to lockdown, while diverticulitis presentations appeared to wane, with no difference in combined complicated cases in comparison to what was expected. CONCLUSION: During lockdown, significantly fewer patients presented to the ED. The proportion of ordered CT abdominal scans increased significantly per person seen, without change in CTAS scores. Considering combined pathology cases increased during the lockdown, ED physicians were warranted in increasing abdominal imaging as patients did not avoid the ED. This may have resulted from a change in clinical practice where the uncertainty of COVID-19 increased CT scan usage.

Optimizing cecal views during colonoscopy using patient position change.

BACKGROUND: Patient positioning has been found to be a simple technique to improve luminal distention and visualization during colonoscopy. This study examined which position provided the cleanest image of the cecum using the Boston Bowel Prep Scale (BBPS) and the best view of the cecum overall as ranked by blinded assessors. METHODS: A sample of 90 sets of cecal images were obtained from patients undergoing a non-urgent colonoscopy. Each set included cecal images of patients while lying in three positions-right lateral decubitus, left lateral decubitus, and supine. Two authors reviewed these sets of images and excluded those that were unclear. A third author, blinded to the position, selected the final 33 sets of images. Two experienced endoscopists completed a blinded survey of each image set. They used the BBPS to assess and score each image as the primary outcome measure. The endoscopists also ranked each image set in terms of the best overall view of the cecum. Data were collected using Qualtrics software. Nonparametric tests were used to analyze the data using SPSS software (v.25). A p-value of ≤ 0.05 was considered significant. RESULTS: The BBPS showed a significant difference between patient positions when tested by Kruskal-Wallis. Subsequent Mann Whitney U tests indicated that the right lateral decubitus position was ranked higher than left lateral decubitus or supine positions. There was no significant difference in the left and supine positions. Cohen's Kappa suggested moderate agreement between raters. The raters also favored the right lateral position over the other positions when assessing overall image preference displaying the cecum. CONCLUSION: These results indicate that positioning patients in the right lateral decubitus position provides the best view of the cecum during colonoscopy.

Cecr2 mutant mice as a model for human cat eye syndrome.

Cat eye syndrome (CES), a human genetic disorder caused by the inverted duplication of a region on chromosome 22, has been known since the late 1890s. Despite the significant impact this disorder has on affected individuals, models for CES have not been produced due to the difficulty of effectively duplicating the corresponding chromosome region in an animal model. However, the study of phenotypes associated with individual genes in this region such as CECR2 may shed light on the etiology of CES. In this study we have shown that deleterious loss of function mutations in mouse Cecr2 effectively demonstrate many of the abnormal features present in human patients with CES, including coloboma and specific skeletal, kidney and heart defects. Beyond phenotypic analyses we have demonstrated the importance of utilizing multiple genetic backgrounds to study disease models, as we see major differences in penetrance of Cecr2-related abnormal phenotype between mouse strains, reminiscent of the variability in the human syndrome. These findings suggest that Cecr2 is involved in the abnormal features of CES and that Cecr2 mice can be used as a model system to study the wide range of phenotypes present in CES.

Using mobile technology in assessment of entrustable professional activities in undergraduate medical education.

BACKGROUND: The adoption of competency-based medical education requires objective assessments of a learner's capability to carry out clinical tasks within workplace-based learning settings. This study involved an evaluation of the use of mobile technology to record entrustable professional activity assessments in an undergraduate clerkship curriculum. APPROACH: A paper-based form was adapted to a mobile platform called eClinic Card. Students documented workplace-based assessments throughout core clerkship and preceptors confirmed accuracy via mobile phones. Assessment scores for the 2017-2018 academic year were collated and analyzed for all core rotations, and preceptors and students were surveyed regarding the mobile assessment experience. EVALUATION: The mobile system enabled 80 students and 624 preceptors to document 6850 assessment submissions across 47 clinical sites over a 48-week core clerkship curriculum. Students' scores demonstrated progressive improvement across all entrustable professional activities with stage-appropriate levels of independence reported by end of core clerkship. Preceptors and students were satisfied with ease of use and dependability of the mobile assessment platform; however, students felt quality of formative coaching feedback could be improved. REFLECTION: Our preliminary evaluation suggests the use of mobile technology to assess entrustable professional activity achievement across a core clerkship curriculum is a feasible and acceptable modality for workplace-based assessment. The use of mobile technology supported a programmatic assessment approach. However, meaningful coaching feedback, as well as faculty development and support, emerged as key factors influencing successful adoption and usage of entrustable professional activities within an undergraduate medical curriculum.

Peer assessment of professionalism in undergraduate medical education.

BACKGROUND: Fostering professional behaviour has become increasingly important in medical education and non-traditional approaches to assessment of professionalism may offer a more holistic representation of students' professional behaviour development. Emerging evidence suggests peer assessment may offer potential as an alternative method of professionalism assessment. We introduced peer assessment of professionalism in pre-clerkship phases of undergraduate medical education curriculum at our institution and evaluated suitability of adopting a professional behaviour scale for longitudinal tracking of student development, and student comfort and acceptance of peer assessment. METHODS: Peer assessment was introduced using a validated professional behaviours scale. Students conducted repeated, longitudinal assessments of their peers from small-group, clinical skills learning activities. An electronic assessment system was used to collect peer assessments, collate and provide reports to students. Student opinions of peer assessment were initially surveyed before introducing the process, confirmatory analyses were conducted of the adopted scale, and students were surveyed to explore satisfaction with the peer assessment process. RESULTS: Students across all phases of the curriculum were initially supportive of anonymous peer assessment using small-group learning sessions. Peer scores showed improvement over time, however the magnitude of increase was limited by ceiling effects attributed to the adopted scale. Students agreed that the professional behaviours scale was easy to use and understand, however a majority disagreed that peer assessment improved their understanding of professionalism or was a useful learning experience. CONCLUSIONS: Peer assessment of professional behaviours does expose students to the process of assessing one's peers, however the value of such processes at early stages of medical education may not be fully recognized nor appreciated by students. Electronic means for administering peer assessment is feasible for collecting and reporting peer feedback. Improvement in peer assessed scores was observed over time, however student opinions of the educational value were mixed and indeterminate.

YouTube as an Educational Resource in Medical Education: a Scoping Review.

YouTube has emerged as a growing educational resource for medical learners and educators; yet, its broad implementation may lack guidance from evidence-based evaluations. This article presents a scoping review of the utility, effectiveness, and validity of YouTube video resources in medical education. Of the 113 articles identified, 31 articles met inclusion criteria that focused on use of YouTube in medical education. Only 19.4% of the articles (n = 6) reported evaluative outcomes related to the use of YouTube for instructional purposes. Recommendations are offered for improving the usefulness and quality of YouTube videos as an educational resource in medical education.

FGF23 Is Not Required to Regulate Fetal Phosphorus Metabolism but Exerts Effects Within 12 Hours After Birth.

Loss of fibroblast growth factor-23 (FGF23) causes hyperphosphatemia, extraskeletal calcifications, and early mortality; excess FGF23 causes hypophosphatemia with rickets or osteomalacia. However, FGF23 may not be important during fetal development. FGF23 deficiency (Fgf23 null) and FGF23 excess (Phex null) did not alter fetal phosphorus or skeletal parameters. In this study, we further tested our hypothesis that FGF23 is not essential for fetal phosphorus regulation but becomes important after birth. Although coreceptor Klotho null adults have extremely high FGF23 concentrations, intact FGF23 was normal in Klotho null fetuses, as were fetal phosphorus and skeletal parameters and placental and renal expression of FGF23 target genes. Pth/Fgf23 double mutants had the same elevation in serum phosphorus as Pth null fetuses, as compared with normal serum phosphorus in Fgf23 nulls. We examined the postnatal time courses of Fgf23 null, Klotho null, and Phex null mice. Fgf23 nulls and Klotho nulls were normal at birth, but developed hyperphosphatemia, increased renal expression of NaPi2a and NaPi2c, and reduced renal phosphorus excretion between 5 and 7 days after birth. Parathyroid hormone remained normal. In contrast, excess FGF23 exerted effects in Phex null males within 12 hours after birth, with the development of hypophosphatemia, reduced renal expression of NaPi2a and NaPi2c, and increased renal phosphorus excretion. In conclusion, although FGF23 is present in the fetal circulation at levels that may equal adult values, and there is robust expression of FGF23 target genes in placenta and fetal kidneys, FGF23 itself is not an important regulator of fetal phosphorous metabolism.

Analysis of the structure, evolution, and expression of CD24, an important regulator of cell fate.

BACKGROUND: CD24 is a small, glycophosphatidylinositol-anchored cell surface receptor, expressed in a variety of cells types and tissues. CD24 gene and protein expression is highly dynamic in response to cellular differentiation and stimulation in a cell-specific manner. Furthermore, CD24 interacts with a diverse collection of ligands, including cell adhesion molecules such as P-selectin, and the immune-associated siglec family of transmembrane proteins. While much is known regarding the biological roles of CD24 in regulating cell survival, death and differentiation, little is known about the evolution and organization of CD24 across species or the relationship between CD24 expression and its known ligands. RESULTS: We analyzed the organization and evolution of the CD24 gene from 56 mammalian, avian and reptilian species. We further examined the mRNA expression of CD24 and its known ligands in Mus musculus in immune cells, immunologically privileged tissues, developing brain, and developing and regenerating liver. CD24 arose prior to the reptilian-avian divergence and is conserved across many mammalian species, although we were unable to identify CD24 in marsupials or monotremes. The CD24 genomic structure is diverse between and within species, with varying numbers of exons, introns, and the presence of untranslated regions. Of note, we found no obvious criteria distinguishing CD24 genes from those annotated as CD24-like. The expression of CD24 is similarly complex, with immune cells showing dynamic changes in mRNA levels during development, while immunologically privileged and developing tissues show a high, static expression level that decreases in mature tissues. Furthermore, the expression of CD24 correlated with some but not all of its known ligands in a tissues-specific manner, suggesting that novel ligands have yet to be identified and that cell-specific ligand expression can influence CD24 function. CONCLUSIONS: We find that CD24 arose prior to the divergence of reptiles, birds and mammals. Furthermore, the most highly conserved areas of the protein are the amino acids which can be glycosylated. We also find that CD24 expression is highly tissue-specific and in many cases, not well conserved with known CD24 ligands, suggesting yet-unknown CD24-ligand interactions. Together, these data are a valuable resource for furthering studies in CD24 biology.

Loss of CD24 in Mice Leads to Metabolic Dysfunctions and a Reduction in White Adipocyte Tissue.

CD24 is a glycophosphatidylinositol (GPI)-linked cell surface receptor that is involved in regulating the survival or differentiation of several different cell types. CD24 has been used to identify pre-adipocytes that are able to reconstitute white adipose tissue (WAT) in vivo. Moreover, we recently found that the dynamic upregulation of CD24 in vitro during early phases of adipogenesis is necessary for mature adipocyte development. To determine the role of CD24 in adipocyte development in vivo, we evaluated the development of the inguinal and interscapular subcutaneous WAT and the epididymal visceral WAT in mice with a homozygous deletion of CD24 (CD24KO). We observed a significant decrease in WAT mass of 40% to 74% in WAT mass from both visceral and subcutaneous depots in male mice, with no significant effect in female mice, compared to wild-type (WT) sex- and age-matched controls. We also found that CD24KO mice had increased fasting glucose and free fatty acids, decreased fasting insulin, and plasma leptin. No major differences were observed in the sensitivity to insulin or glucose, or in circulating triglycerides, total cholesterol, HDL-cholesterol, or LDL-cholesterol levels between WT and CD24KO mice. Challenging the CD24KO mice with either high sucrose (35%) or high fat (45%) diets that promote increased adiposity, increased WAT mass and fasting insulin, adiponectin and leptin levels, as well as reduced the sensitivity to insulin and glucose, to the levels of WT mice on the same diets. The CD24-mediated reduction in fat pad size was due to a reduction in adipocyte cell size in all depots with no significant reduction pre-adipocyte or adipocyte cell number. Thus, we have clearly demonstrated that the global absence of CD24 affects adipocyte cell size in vivo in a sex- and diet-dependent manner, as well as causing metabolic disturbances in glucose homeostasis and free fatty acid levels.

Dynamic upregulation of CD24 in pre-adipocytes promotes adipogenesis.

The development of mature adipocytes from pre-adipocytes is a highly regulated process. CD24 is a glycophosphatidylinositol-linked cell surface receptor that has been identified as a critical cell surface marker for identifying pre-adipocytes that are able to reconstitute white adipose tissue (WAT) in vivo. Here, we examined the role and regulation of CD24 during adipogenesis in vitro. We found that CD24 mRNA and protein expression is upregulated early during adipogenesis in the 3T3-L1 pre-adipocytes and in murine primary pre-adipocytes isolated from subcutaneous and visceral WAT, followed by downregulation in mature adipocytes. CD24 mRNA expression was found to be dependent on increased transcription due to increased promoter activity in response to activation of a pre-existing transcriptional regulator. Furthermore, either intracellular cAMP or dexamethasone were sufficient to increase expression in pre-adipocytes, while both additively increased CD24 expression. Preventing the increase in CD24 expression, by siRNA-mediated knock-down, resulted in fewer mature lipid-laden adipocytes and decreased expression of mature adipogenic genes. Therefore, conditions experienced during adipogenesis in vitro are sufficient to increase CD24 expression, which is necessary for differentiation. Overall, we conclude that the dynamic upregulation of CD24 actively promotes adipogenesis in vitro.

Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes.

Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain-specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because a large portion of this region is syntenic to human chromosome 10q25, the site of a human susceptibility locus.

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development.

The loss of Cecr2, which encodes a chromatin remodeling protein, has been associated with the neural tube defect (NTD) exencephaly and open eyelids in mice. Here, we show that two independent mutations of Cecr2 are also associated with specific inner ear defects. Homozygous mutant 18.5 days post coitus (dpc) fetuses exhibited smaller cochleae as well as rotational defects of sensory cells and extra cell rows in the inner ear reminiscent of planar cell polarity (PCP) mutants. Cecr2 was expressed in the neuroepithelium, head mesenchyme, and the cochlear floor. Although limited genetic interaction for NTDs was seen with Vangl2, a microarray analysis of PCP genes did not reveal a direct connection to this pathway. The mechanism of Cecr2 action in neurogenesis and inner ear development is likely complex.

Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors.

BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex. METHODS: Gene-trap mutation Cecr2(Gt45Bic) results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11-14 somites stage Cecr2(Gt45Bic)embryos. RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2(Gt45Bic) embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only approximately 7- to 14-fold from normal levels, suggesting the Cecr2(Gt45Bic) is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2 (tm1.1Hemc)). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2(Gt45Bic) in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2(tm1.1Hemc) line. Subsequent qRT-PCR using Cecr2 (tm1.1Hemc) mutant heads confirmed downregulation of transcription factors Alx1/Cart1, Dlx5, Eya1, and Six1. CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2.