Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.

No abstract

Background The use of ultrasound (US) in emergency departments (ED) has become widespread. This includes both traditional US scans performed by radiology departments as well as point-of-care US (POCUS) performed by bedside clinicians. There has been significant interest in better understanding the appropriate use of imaging and where opportunities to enhance cost-effectiveness may exist. The purpose of this systematic review is to identify published evidence surrounding the cost-effectiveness of US in the ED and to grade the quality of that evidence. Methods We performed a systematic review of the literature following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies were considered for inclusion if they were: (1) economic evaluations, (2) studied the clinical use of ultrasound, and (3) took place in an emergency care setting. Included studies were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards checklist. Results We identified 631 potentially relevant articles. Of these, 35 studies met all inclusion criteria and were eligible for data abstraction. In general, studies were supportive of the use of US. In particular, 11 studies formed a strong consensus that US enhanced cost-effectiveness in the investigation of pediatric appendicitis and 6 studies supported enhancements in the evaluation of abdominal trauma. Across the studies, weaknesses in methodology and reporting were common, such as lack of sensitivity analyses and inconsistent reporting of incremental cost-effectiveness ratios. Conclusions The body of existing evidence, though limited, generally demonstrates that the inclusion of US in emergency care settings allows for more cost-effective care. The most definitive evidence for improvements in cost-effectiveness surround the evaluation of pediatric appendicitis, followed by the evaluation of abdominal trauma. POCUS outside of trauma has had mixed results.

Understanding the mechanisms that establish variation in growth and metabolism is 12 fundamental in evolutionary and physiological ecology. Although a genetic basis is frequently 13 invoked to explain variation in performance, it remains challenging to study such processes in 14 marine animals due to the lack of genetically-enabled "model" organisms. The Pacific oyster 15 Crassostrea gigas is a species for which pedigreed genetic lines have been established. In this 16 study, a series of larval families were produced by crossbreeding pedigreed lines to yield large-17 volume larval cultures to provide sufficient biomass for biochemical and physiological analyses. 18Major phenotypic contrasts in larval growth rate were evident. A primary goal of this study was 19 to investigate the physiological bases for this variation in growth and to identify biomarkers that 20 are predictive of growth potential. To that end, measurements were undertaken to define the 21 relationship between rates of growth, respiration, and ion transport by the sodium-potassium 22 pump (in vivo Na + ,K + -ATPase activity). The relationship of respiration and ion transport during 23 larval growth showed that, on average, 17% of total energy demand was allocated to support ion 24 transport. Further analyses of total Na + ,K + -ATPase activity (in vitro enzyme assay) revealed that 25 41% of the total metabolic rate could be accounted for by this single process if all of the enzyme 26 was physiologically active. Significant biological variation was evident, however, when size-27 specific comparisons were made across different larval families. These differences were up to (i) 28 2.2-fold in ion transport rates; (ii) 2.8-fold in the allocation of energy to support the metabolic 29 demand of ion transport; (iii) 3.5-fold in total enzyme activity; (iv) 3.9-fold in the 30 physiologically active fraction of total enzyme; and (v) 3.1-fold in gene expression. These 31 differences among families highlight the need to distinguish genetic from environmental causes 32 of biological variation. Notably, for inferences of physiological changes based upon molecular 33 biological analyses, the measured rates of ion transport were not predicted from concurrent 34 measurements of gene expression or enzyme activity. Size-corrected rates of ion transport were 35 predictive of variation in growth rates among different larval families, supporting the application 36 of physiological rates of ion transport as a predictor of growth differences. Evolutionary 37 variation in physiological performance has important implications for understanding the ecology 38 of larval forms. Developing physiological indices will be of value in predicting growth and 39 metabolism and corresponding survival of larval forms of different genotypes in response to 40 environmental change.

Despite recent strides in global EM research and a proliferation of scholarly output in the field, further work is required to advocate for and inform research priorities in global EM. The priorities outlined in this paper aim to guide future research in the field, with the goal of advancing the development of EM worldwide.

No abstract

No abstract

Introduction: Pain scales are often used in peripheral nerve block studies but are problematic due to their subjective nature. Ultrasound-measured diaphragmatic excursion is an easily learned technique that could provide a much-needed objective measure of pain control over time with serial measurements. Case Series: We describe three cases where diaphragmatic excursion was used as an objective measure of decreased pain and improved respiratory function after serratus anterior plane block in emergency department patients with anterior or lateral rib fractures. Conclusion: Diaphragmatic excursion may be an ideal alternative to pain scores to evaluate serratus anterior plane block efficacy. More data will be needed to determine whether this technique can be applied to other ultrasound-guided nerve blocks.