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The cerebral cortex undergoes rapid microstructural changes throughout the third trimester. Recently, there has been growing interest on imaging features that represent cyto/myeloarchitecture underlying intracortical myelination, cortical gray matter (GM), and its adjacent superficial whitematter (sWM). Using 92 magnetic resonance imaging scans from 78 preterm neonates, the current study used combined T1-weighted/T2-weighted (T1w/T2w) intensity ratio and diffusion tensor imaging (DTI) measurements, including fractional anisotropy (FA) and mean diffusivity (MD), to characterize the developing cyto/myeloarchitectural architecture. DTI metrics showed a linear trajectory: FA decreased in GM but increased in sWM with time; and MD decreased in both GM and sWM. Conversely, T1w/T2w measurements showed a distinctive parabolic trajectory, revealing additional cyto/myeloarchitectural signature inferred. Furthermore, the spatiotemporal courses were regionally heterogeneous: central, ventral, and temporal regions of GM and sWM exhibited faster T1w/T2w changes; anterior sWM areas exhibited faster FA increases; and central and cingulate areas in GM and sWM exhibited faster MD decreases. These results may explain cyto/myeloarchitectural processes, including dendritic arborization, synaptogenesis, glial proliferation, and radial glial cell organization and apoptosis. Finally, T1w/T2w values were significantly associated with 1-year language and cognitive outcome scores, while MD significantly decreased with intraventricular hemorrhage.

Introduction The impact of modifications in curriculum and clinical rotations made secondary to the COVID-19 pandemic on medical education has yet to be fully investigated. We observed differences in the types of patients seen by medical students that may have resulted from clinical disruptions due to the COVID-19 pandemic. We then evaluated what impact these disruptions had on the students' clinical competency. Methods We obtained patient logbooks of third-year medical students (M3) and fourth-year sub-interns (M4) from the first three emergency medicine (EM) rotation blocks of the 2019-2020 (Y19) and 2020-2021 (Y20) academic years. We then reviewed and categorized the chief complaints seen and procedures in which they participated. A robust t-test was used to detect differences in chief complaints and procedures. Finally, we looked for objective differences using the chi-square test in clinical performance between the class of 2021 (Class21) and the class of 2022 (Class22), as assessed by performance on our institution's clinical competency examination. Results Overall, students saw a 25.3% decrease in average number of patient encounters. Statistically significant decreased average numbers of infectious (-28.3%, p=0.013); musculoskeletal (-22.2%, p=0.018); gastrointestinal (GI) (-24.6%, p0.01); genitourinary (GU) (-33.2%, p0.01); head, eyes, ears, nose, throat (HEENT) (-31.1%, p0.01); trauma (-33.0%, p0.01); and respiratory (-45.4%, p0.001) complaints were observed. Both M3s and M4s encountered significantly less GU (-25.6%, p=0.048; -41.7%, p=0.016) and trauma (-29.1%, p=0.023; -33.2%, p=0.032) complaints in Y20. M4s saw significantly less GI complaints (-42.6%, p0.001) in Y20, whereas M3s encountered significantly less psychiatric and HEENT complaints (-30.3%, p=0.046; -34.6%, p=0.013). Both classes saw significantly less respiratory complaints in Y20 but more so for M4s (-65.3%, p0.001) than for M3s (-27.9%, p=0.033). There were no significant differences in average number of procedures between years. We did not observe any differences in overall clinical performance between the two selected classes. While class of 2021 scored a significantly higher average on a case of fatigue (p=0.0004) and class of 2022 on a case of abdominal pain (p0.0001), there were no significant differences in the primary chief complaints that would be attributed to COVID-19, such as dyspnea. Conclusion Modifications made to curricula and clinical rotations due to the COVID-19 pandemic led to students encountering less patients overall, with significant decreases in multiple chief complaint types compared to Y19 but no significant change in procedure numbers. Notably, there was no major impact seen on clinical competency providing a positive argument for considering innovative teaching and learning methods.

BACKGROUND AND OBJECTIVE: Cancer is a major public health problem in the world, and it dramatically affects the life expectancy of patients and their quality of life. Natural products from botanicals could be beneficial in the prevention or treatment of a variety of cancers. Saffron (the extract of Crocus sativus) includes its major constituent, crocin, have been used as a folk medicine for a long time, and they have shown obvious cancer chemoprevention potential. The objectives of this review are to present the progress of research on the effects of saffron and crocin in cancer management and the underlying mechanisms of action. METHODS: We searched publications in the English language, published between January 1, 1980 and September 30, 2022, of saffron and crocin on cancer through several search engines, i.e., PubMed, SciFinder and Web of Science. KEY CONTENT AND FINDINGS: In this article, we first summarize the phytochemical studies of this botanical. Then, we present the anticancer effects of saffron and crocin on different human cancer cells. Saffron and crocin showed obvious antiproliferative effects on human cancer cell lines, including colorectal cancer, breast cancer, lung cancer, prostate cancer, cervical cancer, leukemia, glioblastoma and rhabdomyosarcoma. Finally, the anticancer-related mechanisms of action are summarized, including cell cycle arrest at G0/G1 or G2/M phases, induction of caspase-dependent apoptosis, signaling pathway-linked tumor metabolism regulation, and adaptive immunity regulated inflammation of host immune responses. CONCLUSIONS: Previous studies related to saffron and crocin in cancer management have been reviewed and reported results have been analyzed. Clinical data suggest that saffron and crocin have beneficial effects to improve quality of life in cancer patients. Thus, saffron and crocin can be considered promising candidates for future clinical cancer studies.

Introduction: Many patients seen in the emergency department (ED) have central venous access placed or previously established placement. Catheters inadvertently placed in the arterial circulation may lead to complications or adverse events. Case Report: We present a case of hemiplegia in a 63-year-old man following intravenous fluid administration through a malpositioned catheter that was initially unrecognized. The patient initially presented to the ED for stroke-like symptoms and was discharged following workup. On a subsequent visit for similar symptoms, intra-arterial placement of the catheter was diagnosed. Conclusion: It is important for emergency physicians to be aware of this potential complication of central venous cannulation and that arterial malposition of a previously placed central line may go unrecognized with the potential to cause cerebral ischemia when cerebral blood flow is reduced by the infusion of intravenous fluids or medications.

Introduction: Patients commonly present with neck masses to the Emergency Department. The acute presentation of such a mass can be alarming to patients and their families. In this report we discuss a rare etiology of an acutely presenting neck mass in an adult. Case Report: We present a 19-year-old patient with an acute neck mass. The mass developed abruptly soon after initiation of a new upper body strength-training regimen. The patient’s history was unremarkable for any trauma or constitutional symptoms. Physical examination revealed the mass, which was diagnosed as a lymphatic malformation by imaging. Surgical removal was successful with pathology confirming the diagnosis. Conclusion: Lymphatic malformations, although rare, may present in adulthood. The acute presentation of a new mass, coupled with a lack of concerning constitutional symptoms, should increase the diagnostic suspicion of a lymphatic malformation.

The coronavirus disease 2019 (COVID-19) pandemic provided our institution a unique opportunity to develop a new procedural curriculum for our fourth-year, emergency medicine-bound medical students. A significant portion of our ED’s fourth-year elective has traditionally been centered in our simulation center, using high-fidelity simulation models to practice important emergency medicine procedures. Due to the pandemic, the simulation center was unavailable for our use, and this new curriculum was created in an effort to fill this gap in procedural education.

We present the HybridSynchAADL modeling language and formal analysis tool for virtually synchronous cyber-physical systems with complex control programs, continuous behaviors, and bounded clock skews, network delays, and execution times. We leverage the Hybrid PALS equivalence, so that it is sufficient to model and verify the simpler underlying synchronous designs. We define the HybridSynchAADL language as a sublanguage of the avionics modeling standard AADL for modeling such designs in AADL, and demonstrate the effectiveness of HybridSynchAADL on a number of applications., Official Website: https://hybridsynchaadl.github.io/

We present the$$\textsc {Hybrid}\textsc {Synch}\textsc {AADL}$$HYBRIDSYNCHAADLmodeling language and formal analysis tool for virtually synchronous cyber-physical systems with complex control programs, continuous behaviors, bounded clock skews, network delays, and execution times. We leverage the Hybrid PALS equivalence, so that it is sufficient to model and verify the simpler underlying synchronous designs. We define the$$\textsc {Hybrid}\textsc {Synch}\textsc {AADL}$$HYBRIDSYNCHAADLlanguage as a sublanguage of the avionics modeling standard AADL for modeling such designs in AADL, and demonstrate the effectiveness of$$\textsc {Hybrid}\textsc {Synch}\textsc {AADL}$$HYBRIDSYNCHAADLon a number of applications.

BACKGROUND Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P

MCom (Taxation), North-West University, Potchefstroom Campus, 2020 Since the announcement of the change in the foreign employment exemption in the National Budget in 2017, and the increase in the global networking, as well as political uncertainty in South Africa, many South Africans have left the country, either on a temporary or permanent basis, to start a new life somewhere else. The implications of leaving South Africa permanently, is a decision that will affect a person, both practically, and from a tax and exchange control perspective. The facts and circumstances for each person exiting South Africa need to be addressed on a case by case basis to determine how he will be affected from a tax and exchange control point of view. SARS has a comprehensive set of residency rules that need to be applied from a tax perspective and there is international case law and double tax agreements that need to be examined in order to determine a person’s tax position. From an exchange control perspective further rules and regulations exist where a person wish to exit from South Africa permanently and extract their remaining assets from South Africa in the most productive way possible. Emigrating from an exchange control perspective will also affect any future transactions taking place when that person wishes to transact with South Africa in the case of investment and receiving an inheritance. In comparing the tax legislation and exchange control restrictions in South Africa to that of India and Russia sought to determine the similarities the three countries may exhibit. All three countries being regarding as developing nations with large numbers of persons exiting their country of origin to relocate to other parts of the world. In making the comparison between South Africa, Russia and India it can be seen that South Africa has a more advanced set of rules surrounding the breaking of tax residency that can be used as guide by Russia and India in protecting the extent of their tax revenue leaving their shores on emigration. From a domestic perspective, it could be recommended that SARS implement a practical system in order to monitor the change of taxpayer’s residency to help align the legislation with the practical implementation and the interaction between SARS and the SARB. South Africa has a firm set of legal guidelines and interpretation surrounding the ceasing to be resident. The practical application of the law, however, does not always align with the legislation. Masters

In recent years, there has been an increase in the demand for and supply of early childhood education (ECE) in low- and middle-income countries. There is also growing awareness that unless ECE is of high quality, children may attend school but not learn. There is a large literature on the conceptualization and measurement of ECE quality in the United States that focuses on the nature of teacher-child interactions. Efforts to expand access to high quality ECE in low- and middle-income countries will require similar measurement efforts that are theoretically-grounded and culturally-adapted. This paper assesses the factor structure and concurrent validity of an observational classroom quality tool to assess teacher-child interactions—the Teacher Instructional Practices and Processes System© (TIPPS; Seidman et al., 2013)—in Ghanaian pre-primary classrooms. We find evidence of three conceptually distinct but empirically correlated domains of quality: Facilitating Deeper Learning (FDL), Supporting Student Expression (SSE), and Emotional Support and Behavior Management (ESBM). Teachers’ schooling level, training in early childhood development, and professional well-being positively predict the three quality domains in different ways. SSE and ESBM predict classroom end-of-the-school-year academic outcomes, and SSE predicts classroom end-of-the-school-year social-emotional outcomes. Implications for the field of international education and global ECE policy and research are discussed.

Children in Sub-Saharan Africa (SSA) are burdened by significant unmet mental health needs. Despite the successes of numerous school-based interventions for promoting child mental health, most evidence-based interventions (EBIs) are not available in SSA. This study investigated the implementation quality and effectiveness of one component of an EBI from a developed country (United States) to a SSA country (Uganda). The EBI component, Professional Development, was provided by trained Ugandan mental health workers to Ugandan primary school teachers. It included large group experiential training and small group coaching to introduce and support a range of evidence-based practices (EBPs) to create nurturing and predictable classroom experiences. The study was guided by the Consolidated Framework for Implementation Research, the Teacher Training Implementation Model and the RE-AIM evaluation framework. Effectiveness outcomes were studied using a cluster randomized design, in which 10 schools were randomized to intervention and wait-list control conditions. A total of 79 early childhood teachers participated. Teacher knowledge and use of evidence-based practices (EBPs) were assessed at baseline and immediately post-intervention (4–5 months later). A sample of 154 parents was randomly selected to report on child behavior at baseline and post-intervention. Linear mixed effect modeling was applied to examine effectiveness outcomes. Findings support the feasibility of training Ugandan mental health professionals to provide Professional Development for Ugandan teachers. Professional Development was delivered with high levels of fidelity and resulted in improved teacher EBP knowledge and use of EBPs in the classroom, and child social competence.

F. Scott Fitzgerald identified Allan Dwan's parties as a source for chapter 3 of The Great Gatsby, but who was Dwan and how did he influence Fitzgerald's work? An inventive and prolific director, Allan Dwan (1885–1981) was one of the most successful filmmakers of the silent era, combining the skills of an engineer, an artist, and a businessman. Fitzgerald met him in 1923, during a visit to the set of Dwan's movie The Glimpses of the Moon. That summer, he went to Dwan's parties, mingling with Gloria Swanson and the movie crowd, while Dwan accompanied the Fitzgeralds to the opening night of Fitzgerald's play, The Vegetable. By the end of 1924, however, the two parted ways. The reasons why are unclear. Nonetheless, Fitzgerald drew upon Dwan more frequently for his fiction than any other director, in part as the quintessence of all he found gorgeously wrong with Hollywood, in part as a secret double for himself. Dwan was Lois Moran's close friend at the time Fitzgerald met her, and Dwan left his imprint not only on The Great Gatsby but also on “Jacob's Ladder,” “Magnetism,” “Crazy Sunday,” Tender Is the Night, “Two Old Timers,” and possibly The Love of the Last Tycoon.

Aneuploidy—or an unbalanced karyotype in which whole chromosomes are gained or lost—causes reduced fitness at both the cellular and organismal levels but is also a hallmark of human cancers. Aneuploidy causes a variety of cellular stresses, including genomic instability, proteotoxic and oxidative stresses, and impaired protein trafficking. The deubiquitinase Ubp3, which was identified by a genome-wide screen for gene deletions that impair the fitness of aneuploid yeast, is a key regulator of aneuploid cell homeostasis. We show that deletion of UBP3 exacerbates both karyotype-specific phenotypes and global stresses of aneuploid cells, including oxidative and proteotoxic stress. Indeed, Ubp3 is essential for proper proteasome function in euploid cells, and deletion of this deubiquitinase leads to further proteasome-mediated proteotoxicity in aneuploid yeast. Notably, the importance of UBP3 in aneuploid cells is conserved. Depletion of the human homolog of UBP3, USP10, is detrimental to the fitness of human cells upon chromosome missegregation, and this fitness defect is accompanied by autophagy inhibition. We thus used a genome-wide screen in yeast to identify a guardian of aneuploid cell fitness conserved across species. We propose that interfering with Ubp3/USP10 function could be a productive avenue in the development of novel cancer therapeutics.

OBJECTIVES: Epidemiological studies have shown that consumption of fruits and vegetables (F&V) is inversely associated with incidence of cardiovascular disease (CVD). However, the evidence for causality and underlying mechanisms is lacking. Our objective was to determine if increased consumption of F&V could prevent atherosclerosis and its underlying mechanisms. METHODS: A unique blend of the most commonly consumed 24 F&V was freeze-dried into a powder and mixed into diets. Thirty six 4-week old male LDL receptor knockout mice were randomly assigned to one of 3 diet groups (12/group): low fat (LF, 10 kcal% fat), high-fat (27 kcal% fat) with 0% F&V (HF), and HF plus 15% F&V diet (HF + FV, equivalent to 8–9 servings for humans). After 20 weeks, mice were euthanized and blood, aorta, and liver tissue were collected. Aortic atherosclerotic lesion, hepatic steatosis, plasma lipid profile and pro-inflammatory cytokine levels were measured. RESULTS: No significant differences were found in body weight among the 3 groups. Mice fed HF diet had larger aortic atherosclerotic lesion and hepatic steatosis area than mice fed LF diet by 6.5 and 1.9 fold, respectively (p

Author(s): dela Cruz, Jonathan; Fulks, Tyler; Baker, Mark; Kegg, Jason; Austin, Richard; Jain, Jimmy; Boehler, Michael; Kim, Sharon; Jaeger, Cassie

BACKGROUND Commonly consumed mushrooms, portobello (PBM) and shiitake (SHM), are abundant in nutrients, soluble dietary fibers, and bioactive compounds that have been implicated as beneficial in reducing inflammation, improving lipid profiles, and ameliorating heart disease and atherosclerosis, an inflammatory disease of the arteries. OBJECTIVE The aim of this study was to determine effects of PBM and SHM in preventing atherosclerosis and associated inflammation in an animal model. METHODS Four-week-old Ldlr-/- male mice were divided into 5 dietary groups for 16 wk: a low-fat control (LF-C, 11 kcal% fat), high-fat control (HF-C, 18.9 kcal% fat), HF + 10% (wt:wt) PBM (HF-PBM, 19.5 kcal% fat) or SHM (HF-SHM, 19.7 kcal% fat) powder, and HF + mushroom control mix (MIX-C, 19.6 kcal% fat), a diet best matched to the average macronutrient content of both mushrooms. Body composition was measured using MRI. Aortic tricuspid valves and aortas were collected and stained to quantify plaque formation. Adhesion molecule expression was quantified by immunohistochemistry. Plasma lipid and cytokine concentrations were measured. RESULTS We found that mice fed a HF-SHM diet had ∼86% smaller aortic lesion area than mice in both HF-C (P

The conserved chromatin remodeling and assembly factor CHD1 (chromodomains, helicase, DNA-binding domain) is present at active genes where it participates in histone turnover and recycling during transcription. In order to gain a more complete understanding of the mechanism of action of CHD1 during development, we created a novel genetic assay in Drosophila melanogaster to evaluate potential functional interactions between CHD1 and other chromatin factors. We found that overexpression of CHD1 results in defects in wing development and utilized this fully penetrant and reliable phenotype to conduct a small-scale RNAi-based candidate screen to identify genes that functionally interact with chd1 in vivo. Our results indicate that CHD1 may act in opposition to other remodeling factors, including INO80, and that the recruitment of CHD1 to active genes by RTF1 is conserved in flies.

Objectives Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period. Methods This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality. Results A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease. Conclusions Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.

Background Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur’s bioavailability and efficacy, may be candidate agents for controlling body fat, metabolism and low grade inflammation. Methods 47 eight-week-old male C57BL/6 mice were fed a high fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip or none of these. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1β, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured. Results Compared to the other groups, obese mice who underwent CR and received Cur + Pip in their diet lost more fat and had significantly lower IL-1β and KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no difference in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1β levels were inversely correlated with curcumin glucuronide. Minor modulation of telomere length were observed. Conclusions It is plausible that supplementing the high fat diet of CR mice with Cur + Pip may increase loss of body fat and suppresses HFD induced inflammation. Combination of Cur and Pip has potential to enhance CR effects for the prevention of metabolic syndrome.

Routine prenatal care in the United States includes screening for asymptomatic bacteriuria (ASB), which occurs in 2 to 7 percent of pregnant women and can cause urinary tract infection and pyelonephritis. We present the case of a pregnant woman affected by multidrug resistant Klebsiella induced ASB during her prenatal screen, which was untreated due to a repeat urine culture showing mixed flora; subsequently, the patient’s postpartum course was complicated by pyelonephritis and perinephric abscess, concluding in a radical nephrectomy. Current recommendations are to treat ASB after two consecutive voided urine cultures showing the same bacterial strain in quantitative counts of =/> 10(5) colony forming units (cfu)/mL or a single-catheterized specimen with quantitative count of =/> 10(2) cfu/mL. For women with ASB in their prenatal screen or other high risk factors, consideration should be given to testing urine cultures every trimester until the completion of pregnancy to prevent the complications of persistent bacteriuria.

Highlights • Inflammatory myofibroblastic tumor (IMT) tends to locally recur but rarely metastasizes. • IMT tends to locally recur but rarely metastasizes. • IMTs that do not express anaplastic lymphoma kinase (ALK) have worse prognosis. • Current trials for ALK targeted therapies show promise in treating this neoplasm.

For centuries, mushrooms have been used as medicinal plants, and, more recently, have been a growing component of a healthy diet. Mushrooms are low in sodium and are good sources of fiber, bioactiv...

Twist transcription factors, members of the basic helix-loop-helix family, play crucial roles in mesoderm development in all animals. Humans have two paralogous genes, TWIST1 and TWIST2, and mutations in each gene have been identified in specific craniofacial disorders. Here, we describe a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions (p.Glu117Val and p.Glu117Gly) at a highly conserved glutamic acid residue located in the basic DNA binding domain of TWIST1, in two subjects with frontonasal dysplasia and additional malformations. Although about one hundred different TWIST1 mutations have been reported in patients with the dominant haploinsufficiency Saethre-Chotzen syndrome (typically associated with craniosynostosis), substitutions uniquely affecting the Glu117 codon were not observed previously. Recently, subjects with Barber-Say and Ablepharon-Macrostomia syndromes were found to harbor heterozygous missense substitutions in the paralogous glutamic acid residue in TWIST2 (p.Glu75Ala, p.Glu75Gln and p.Glu75Lys). To study systematically the effects of these substitutions in individual cells of the developing mesoderm, we engineered all five disease-associated alleles into the equivalent Glu29 residue encoded by hlh-8, the single Twist homolog present in Caenorhabditis elegans. This allelic series revealed that different substitutions exhibit graded severity, in terms of both gene expression and cellular phenotype, which we incorporate into a model explaining the various human disease phenotypes. The genetic analysis favors a predominantly dominant-negative mechanism for the action of amino acid substitutions at this highly conserved glutamic acid residue and illustrates the value of systematic mutagenesis of C. elegans for focused investigation of human disease processes.

We have previously shown that curcumin (CUR) may increase lipid accumulation in cultured human acute monocytic leukaemia cell line THP-1 monocytes/macrophages, but that tetrahydrocurcumin (THC), an in vivo metabolite of CUR, has no such effect. In the present study, we hypothesised that the different cellular uptake and/or metabolism of CUR and THC might be a possible explanation for the previously observed differences in their effects on lipid accumulation in THP-1 monocytes/macrophages. Chromatography with tandem MS revealed that CUR was readily taken up by THP-1 monocytes/macrophages and slowly metabolised to hexahydrocurcumin sulphate. By contrast, the uptake of THC was low. In parallel with CUR uptake, increased lipid uptake was observed in THP-1 macrophages but not with the uptake of THC or another CUR metabolite and structurally related compounds. From these results, it is possible to deduce that CUR and THC are taken up and metabolised differently in THP-1 cells, which determine their biological activity. The remarkable differential cellular uptake of CUR, relative to THC and other similar molecules, may imply that the CUR uptake into cells may occur via a transporter.

Table of contents A1 Point-of-care ultrasound examination of cervical spine in emergency department Yahya Acar, Onur Tezel, Necati Salman A2 A new technique in verifying the placement of a nasogastric tube: obtaining the longitudinal view of nasogastric tube in addition to transverse view with ultrasound Yahya Acar, Necati Salman, Onur Tezel, Erdem Cevik A3 Pseudoaneurysm of the femoral artery after cannulation of a central venous line. Should we always use ultrasound in these procedures? Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A4 Ultrasound-guided supraclavicular subclavian vein catheterization. A novel approach in emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A5 Clinical ultrasound in a septic and jaundice patient in the emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A6 Characterization of the eyes in preoperative cataract Saudi patients by using medical diagnostic ultrasound Mustafa Z. Mahmoud, Abdelmoneim Sulieman A7 High-frequency ultrasound in determining the causes of acute shoulder joint pain Mustafa Z. Mahmoud A8 Teaching WINFOCUS Ultrasound Life Support Basic Level 1 for Providers in resource-limited countries Abbas Ali, Alrayah Mustafa, Ihab Abdelrahman, Mustafa Bahar, Osama Ali, H. Lester Kirchner, Gregor Prosen A9 Changes of arterial stiffness and endothelial function during uncomplicated pregnancy Ajda Anzic, Paul Leeson A10 Cardiovascular haemodynamic properties before, during and after pregnancy Ajda Anzic, Paul Leeson A11 An old man with generalized weakness Maryam Bahreini, Fatemeh Rasooli A12 Ultrasonography for non-specific presentations of abdominal pain Maryam Bahreini, Houman Hosseinnejad A13 Introduction of a new imaging guideline for suspected renal colic in the emergency department: effect on CT Urogram utilisation Gabriel Blecher, Robert Meek, Diana Egerton-Warburton A14 Transabdominal ultrasound screening for pancreatic cancer in Croatian military veterans: a retrospective analysis from the first Croatian veteran’s hospital Edina Ćatić Ćuti, Stanko Belina, Tihomir Vančina, Idriz Kovačević A15 The challenge of AAA: unusual case of obstructive jaundice Edina Ćatić Ćuti, Nadan Rustemović A16 Educational effectiveness of easy-made new simulator model for ultrasound-guided procedures in pediatric patients: vascular access and foreign body management Ikwan Chang, Jin Hee Lee, Young Ho Kwak, Do Kyun Kim A17 Detection of uterine rupture by point-of-care ultrasound at emergency department: a case report Chi-Yung Cheng, Hsiu-Yung Pan, Chia-Te Kung A18 Abdominal probe in the hands of interns as a relevant diagnostic tool in revealing the cause of heart failure Ela Ćurčić, Ena Pritišanac, Ivo Planinc, Marijana Grgić Medić, Radovan Radonić A19 Needs assessment of the potential utility of point-of-care ultrasound within the Zanzibar health system Abiola Fasina, Anthony J. Dean, Nova L. Panebianco, Patricia S. Henwood A20 Ultrasonographic diagnosis of tracheal compression Oliviero Fochi, Moreno Favarato, Ezio Bonanomi A21 The role of ultrasound in the detection of lung infiltrates in critically ill patients: a pilot study Marijana Grgić Medić, Ivan Tomić, Radovan Radonić A22 The SAFER Lasso; a novel approach using point-of-care ultrasound to evaluate patients with abdominal complaints in the emergency department Youngrock Ha, Hongchuen Toh A23 Awareness and use of clinician-performed ultrasound among clinical clerkship faculty Elizabeth Harmon, Wilma Chan, Cameron Baston, Gail Morrison, Frances Shofer, Nova Panebianco, Anthony J. Dean A24 Clinical outcomes in the use of lung ultrasound for the diagnosis of pediatric pneumonias Angela Hua, Sharon Kim, James Tsung A25 Effectiveness of ultrasound in hypotensive patients Isa Gunaydin, Zeynep Kekec, Mehmet Oguzhan Ay A26 Moderate-to-severe left ventricular ejection fraction related to short-term mortality of patients with post-cardiac arrest syndrome after out-of-hospital cardiac arrest Jinjoo Kim, Jinhyun Kim, Gyoosung Choi, Dowon Shim A27 Usefulness of abdominal ultrasound for acute pyelonephritis diagnosis after kidney transplantation Ji-Han Lee A28 Lung ultrasound for assessing fluid tolerance in severe preeclampsia Jana Ambrozic, Katja Prokselj, Miha Lucovnik A29 Optic nerve sheath ultrasound in severe preeclampsia Gabrijela Brzan Simenc, Jana Ambrozic, Miha Lucovnik A30 Focused echocardiography monitoring in the postoperative period for non-cardiac patients Asta Mačiulienė, Almantas Maleckas, Algimantas Kriščiukaitis, Vytautas Mačiulis, Andrius Macas A31 POCUS-guided paediatric upper limb fracture reduction: algorithm, tricks, and tips Sharad Mohite A32 Point-of-care lung ultrasound: a good diagnostic tool for pneumonia in a septic patient Zoltan Narancsik, Hugon Možina A33 A case of undergraduate POCUS (r)evolution Sara Nikolić, Jan Hansel, Rok Petrovčič, Una Mršić, Gregor Prosen A34 The Graz Summer School for ultrasound: from first contact to bedside application: three-and-a-half-day undergraduate ultrasound training: résumé after two years of continuous development Simon Orlob, Markus Lerchbaumer, Niklas Schönegger, Reinhard Kaufmann A35 Usefulness of point-of-care ultrasound in the emergency room in a patient with acute abdominal pain Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A36 Use of bedside ultrasound in a critically ill patient. A case report Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A37 Diagnostic yield of clinical echocardiography for the emergency physician Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A38 Focused cardiac ultrasound in early diagnosis of type A aortic dissection with atypical presentation Chun-I Pan, Hsiu-Yung Pan, Chien-Hung Wu A39 Detection of imperforated hymen by point-of-care ultrasound Hsiu-yung Pan, Chia-Te Kung A40 Developing a point-of-care ultrasound curriculum for pediatric nurse practitioners practicing in the pediatric emergency department Sarah Pasquale, Stephanie J. Doniger, Sharon Yellin, Gerardo Chiricolo A41 Use of transthoracic echocardiography in emergency setting: patient with mitral valve abscess Maja Potisek, Borut Drnovšek, Boštjan Leskovar A42 A young man with syncope Fatemeh Rasooli, Maryam Bahreini A43 Work-related repetitive use injuries in ultrasound fellows Kristine Robinson, Clara Kraft, Benjamin Moser, Stephen Davis, Shelley Layman, Yusef Sayeed, Joseph Minardi A44 Lung ultrasonography in the evaluation of pneumonia in children Irmina Sefic Pasic, Amra Dzananovic, Anes Pasic, Sandra Vegar Zubovic A45 Central venous catheter placement with the ultrasound aid: two years’ experience of the Interventional unit, Division of Intensive Care Medicine, KBC Zagreb Ana Godan Hauptman, Marijana Grgic Medic, Ivan Tomic, Ana Vujaklija Brajkovic, Jaksa Babel, Marina Peklic, Radovan Radonic A46 Duplicitas casui: two patients admitted due to acute liver failure Vedran Radonic, Ivan Tomic, Luka Bielen, Marijana Grgic Medic A47 A pilot survey on an understanding of Bedside Point-of-Care Ultrasound (POCUS) among medical doctors in internal medicine: exposure, perceptions, interest, and barriers to training Peh Wee Ming A48 Unusual case of defecation syncope Nur hafiza Yezid, Fatahul Laham Mohammed A49 A case report of massive pulmonary embolism; a multidisciplinary approach Zainal Abidin Huda, Wan Nasarudin Wan Ismail, W.Yus Haniff W.Isa, Hashairi Fauzi, Praveena Seeva, Mohd Zulfakar Mazlan

The consumption of oatmeal and oat bran has been shown to reduce total and low density lipoprotein (LDL) cholesterol levels in plasma, which are major risk factors for coronary heart disease (CHD)....

Aneuploidy, an unbalanced karyotype in which one or more chromosomes are present in excess or reduced copy number, causes an array of known phenotypes including proteotoxicity, genomic instability, and slowed proliferation. However, the molecular consequences of aneuploidy are poorly understood and an unbiased investigation into aneuploid cell biology is lacking. We performed high-throughput screens for genes the deletion of which has a synthetic fitness cost in aneuploid Saccharomyces cerevisiae cells containing single extra chromosomes. This analysis identified genes that, when deleted, decrease the fitness of specific disomic strains as well as those that impair the proliferation of a broad range of aneuploidies. In one case, a chromosome-specific synthetic growth defect could be explained fully by the specific duplication of a single gene on the aneuploid chromosome, highlighting the ability of individual dosage imbalances to cause chromosome-specific phenotypes in aneuploid cells. Deletion of other genes, particularly those involved in protein transport, however, confers synthetic sickness on a broad array of aneuploid strains. Indeed, aneuploid cells, regardless of karyotype, exhibit protein secretion and cell-wall integrity defects. Thus, we were able to use this screen to identify novel cellular consequences of aneuploidy, dependent on both specific chromosome imbalances and caused by many different aneuploid karyotypes. Interestingly, the vast majority of cancer cells are highly aneuploid, so this approach could be of further use in identifying both karyotype-specific and nonspecific stresses exhibited by cancer cells as potential targets for the development of novel cancer therapeutics.

Congenital long QT syndrome (LQTS) is a potentially lethal but highly treatable channelopathy. Along with multiple risk reduction measures, a recommendation for left sympathetic cardiac denervation therapy and/or implantable cardioverter defibrillator is made for higher risk patients. Despite its relatively common incidence in paediatric patients, there are no formal recommendations regarding perioperative management and discharge criteria for LQTS patients undergoing ambulatory surgery. This report describes a 17-year-old girl, diagnosed with congenital LQTS at 9 years of age, who had an episode of ventricular fibrillation the day after elective ear, nose and throat surgery. Despite several risk factors, she had a same-day dismissal, was not adequately monitored postoperatively and her cardiologists were not notified of her procedure. For the high-risk LQTS patient, we recommend monitoring of perioperative electrolytes and rhythm, postoperative ECG, adequate β-blockade therapy, avoidance of particular pharmacological agents, consideration of overnight observation and communication with the patient's cardiologist prior to procedure, and at discharge.

This study, based on 108 interviews and participant observation at 22 churches, examines the tension among newly formed second-generation Korean American churches in Los Angeles over its ethnic boundaries. Although all of the newly formed churches are open to non-Koreans, not all envision or desire a multiracial church. First, some pastors want their churches to remain predominately Korean American because they believe that the church is the main institution responsible for preserving the Korean culture and passing it down to subsequent generations. Others want to stretch their boundaries to include all Asian Americans. They argue that the similarities in life experiences and cultural orientation, largely derived by their shared status as children of immigrants and as racial minorities in the United States, among different Asian American groups serve as the common denominator. Finally, several pastors are determined to transform their churches into multiracial congregations. Documenting the current stage of experimentation and transition, this study of second-generation churches provides important insights on the role of religion and religious organizations in immigrant adaptation and identity formation.

Subcutaneous nodules occur in approximately 20–25% of rheumatoid factor (RF)-positive rheumatoid patients. In this paper, we present a unique case of a 47-year-old healthy RF-negative woman with a 3-year history of necrobiotic nodules over the dorsum of her hands, extensor forearms, and lower extremities. This may represent an atypical presentation or a new rheumatoid variant.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.

Although not typically associated with literary epiphany, Wharton was one of the first to recognize its significance to modernist fiction. In The Writing of Fiction, Wharton made epiphany central to her theory of fiction and used it to enter into a dialogue with the modernism she viewed from a critical distance. Wharton distinguishes between two different epiphanies: the moral epiphany and the modern epiphany, which stresses the materiality of aesthetic perception. Wharton links the discontinuity of modernist fiction with the ahistorical thrust of modern epiphany. She argues instead for continuity with the narrative patterns inherited from literary history, patterns that interpolated moral epiphanies. In Hudson River Bracketed and The Gods Arrive, Wharton develops a third form of epiphany, one that combines the aesthetics of modern epiphany with a subjective and historical continuity that has its roots in an older, perhaps more female, source of creative production.

Background: Most high-risk neuroblastoma patients succumb to lethal therapy resistant disease acquired during the course of intensive multimodality treatment. This acquired therapy resistance is largely attributed to insensitivity to drug-induced apoptosis, however the exact mechanisms remain unknown. Apart from integrating death signals, mitochondria (mito) interact with the endoplasmic reticulum (ER) at close contact sites known as mitochondria associated membranes (MAM) of the ER to regulate calcium and lipid transfer and apoptotic sensitivity, a process often derailed in therapy resistant cancers. ER-mito contact sites are juxtaposed by various tethering protein complexes that include MFN2 and PACS2. Pathologic deregulation of these contact sites has been implicated in the genesis of neurodegenerative and metabolic disorders. Here, we show that disruption of bona fide ER-mito tethering proteins in therapy sensitive neuroblastomas induces apoptotic insensitivity and a drastic shift towards a resistance-like phenotype. Methods and Results: Previously we showed that isolated mitochondria from tumors at relapse resist induction of mitochondrial apoptosis when primed with the terminal death effectors that are downstream of therapeutic stress (tBid and Bim-BH3 peptide). We isolated mitochondria from seven matched isogenic tumor pairs obtained at diagnosis (DX) and relapse (REL) and quantified their apoptotic response to tBid and Bim by measuring cytochrome C release by ELISA. Electron microscopy (EM) image analyses of ER-mito contact sites revealed that REL tumors contain up to 70% fewer ER-mito interactions than their matched DX tumors, as confirmed by IB for organelle-specific proteins. Here, we recapitulate the post-therapy resistance phenotype in DX therapy sensitive cells by shRNA silencing of MFN2 or PACS2 and confirm their apoptotic resistance by BH3 profiling and drug response in vitro. A 60% decrease in MFN2 protein in DX cells partially phenocopied the resistance profile of isogenic REL cells. The degree of apoptotic resistance correlated with the extent of protein knockdown for MFN2. Treatment of shMFN2 and shPACS2 DX cells with ABT-737, a BH3 mimetic, or carboplatin, increased their IC50s multiple-fold compared to control cells, paralleling their blunted mitochondrial apoptotic response. Conclusions: Our data implicate ER-mito contact sites as positive regulators of apoptosis, whose disruption may be necessary for apoptotic attenuation in therapy resistant cancer cells to enable apoptosis evasion and survival. We present a potential mechanism for broad therapy resistance arising under therapeutic stress that selects for reduced communication of ER with mitochondria. Citation Format: Jorida Coku, Madison C. Pedrotty, David M. Booth, Sharon Kim, Annette Vu, C. Patrick Reynolds, György Hajnóczky, Michael D. Hogarty. Disrupted endoplasmic reticulum-mitochondria contacts promote multidrug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1201. doi:10.1158/1538-7445.AM2017-1201