Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease.

Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well conserved from zebrafish to humans in both development and disease. This makes the zebrafish a natural model for further interrogation into the functions of RA and RA-associated maladies for the sake of basic research, as well as human health. In this review, we explore both foundational and recent studies using zebrafish as a translational model for investigating RA from the molecular to the organismal scale.

Elf3 deficiency during zebrafish development alters extracellular matrix organization and disrupts tissue morphogenesis.

E26 transformation specific (ETS) family transcription factors are expressed during embryogenesis and are involved in various cellular processes such as proliferation, migration, differentiation, angiogenesis, apoptosis, and survival of cellular lineages to ensure appropriate development. Dysregulated expression of many of the ETS family members is detected in different cancers. The human ELF3, a member of the ETS family of transcription factors, plays a role in the induction and progression of human cancers is well studied. However, little is known about the role of ELF3 in early development. Here, the zebrafish elf3 was cloned, and its expression was analyzed during zebrafish development. Zebrafish elf3 is maternally deposited. At different developmental stages, elf3 expression was detected in different tissue, mainly neural tissues, endoderm-derived tissues, cartilage, heart, pronephric duct, blood vessels, and notochord. The expression levels were high at the tissue boundaries. Elf3 loss-of-function consequences were examined by using translation blocking antisense morpholino oligonucleotides, and effects were validated using CRISPR/Cas9 knockdown. Elf3-knockdown produced short and bent larvae with notochord, craniofacial cartilage, and fin defects. The extracellular matrix (ECM) in the fin and notochord was disorganized. Neural defects were also observed. Optic nerve fasciculation (bundling) and arborization in the optic tectum were defective in Elf3-morphants, and fragmentation of spinal motor neurons were evident. Dysregulation of genes encoding ECM proteins and matrix metalloprotease (MMP) and disorganization of ECM may play a role in the observed defects in Elf3 morphants. We conclude that zebrafish Elf3 is required for epidermal, mesenchymal, and neural tissue development.

Where are the female experts? Perceptions about the absence of female presenters at a Digital Health Conference in Bolivia.

BACKGROUND: Gender disparities exist worldwide related to female representation in digital health initiatives especially in low and middle income countries (LMICs). Upstream approaches and policy implementation has been effective in some countries to reduce the gender gap in the areas of political and sector leadership. At an international digital health conference in Bolivia, all-male expert panels presented their research and innovations to audiences from the Bolivian national and regional health departments and private and non-governmental organization heath leaders. METHODS: An in-depth qualitative analysis of participant perspectives related to the absence of female presenters at this digital health conference in Bolivia was performed. Using a cross-sectional research design, the questionnaire rated the respondents' satisfaction using Likert scales and their perspectives using open-ended questions. A multidisciplinary team of coders reviewed the respondents' responses in detail and developed general themes. RESULTS: The sample consisted of 80 respondents who completed the questionnaire from the 115 people attending the conference, giving a 70% response rate (80/115). Respondents were broadly represented in terms of gender, age, occupation and experience using digital health tools. The code structure contained five primary codes each reflecting sets of ideas and possible solutions for gender equality in science and health technology in Bolivia. The five recurrent themes, ranked from the most common mentioned to the least common, were: (I) opportunities and incentives (38%); (II) indifference (23%); (III) role models (18%); (IV) capacity strengthening and empowerment (15%); (V) norms and policies (7%). CONCLUSIONS: The results of this study can be useful for preparing a more representative digital health field in Bolivia overtime. Conference respondents provide key recommendations to reduce gender inequality at digital health conferences and in the field. This study provides evidence from Bolivian health workers and officials on their perspectives related to the absence of female presenters at an international digital health conference and their suggestions for optimizing female participation and leadership at conferences and in the digital health field going forward.

Hepatic Venous Pressure Gradient Measurements in Children: Correlation With Hepatic Histology and Clinical Indicators of Portal Hypertension.

OBJECTIVES: In adults, elevated hepatic venous pressure gradients (HVPGs) are correlated with the degree of liver fibrosis on histopathology and predict worse outcomes including variceal bleeding and death. We aimed to examine the association between HVPG measurements, histopathologic findings, and clinical indicators of portal hypertension in children. METHODS: Utilizing retrospective data from 2 pediatric centers between 2006 and 2015, we identified children who underwent simultaneous HVPG measurement and transjugular liver biopsy. Medical charts were reviewed for histopathology, imaging, endoscopic, and clinical data. RESULTS: Forty-one children (median age 11 years) were included in the analysis with diagnoses of acute hepatitis (n = 15), chronic liver disease (n = 12), hepatic noncirrhotic portal hypertension (n = 4), acute liver failure (n = 3), and nonhepatic causes of portal hypertension (n = 7). Elevated mean HVPG measurements were found in children with acute liver failure (10 mmHg, range 4-12) and chronic liver disease (7 mmHg, range 1-12). HVPG measurements did not correlate with the histological severity of fibrosis (ρ = 0.23, P = 0.14) or portal inflammation (ρ = 0.24, P = 0.29), and no difference was found in HVPG when comparing children with and without a history of variceal bleeding (P = 0.43). CONCLUSIONS: HVPG measurements do not correlate significantly with the degree of hepatic fibrosis on biopsy. Furthermore, HVPG measurements are not associated with the presence of varices or history of variceal bleeding, suggesting the possibility of intrahepatic shunting in children with advanced liver disease. Therefore, unlike in adults, HVPG measurements may not accurately predict children who are at risk of complications from portal hypertension.

Developing cellulosic waste products as platform chemicals: protecting group chemistry of α-glucoisosaccharinic acid.

Alpha and beta-glucoisosaccharinic acids ((2S,4S)-2,4,5-trihydroxy-2-(hydroxymethyl)pentanoic acid and (2R,4S)-2,4,5-trihydroxy-2-(hydroxymethyl)pentanoic acid) which are produced when cellulosic materials are treated with aqueous alkali are potentially valuable platform chemicals. Their highly functionalised carbon skeleton, with fixed chirality at C-2 and C-4, makes them ideal starting materials for use in synthesis. In order to assess the potential of these saccharinic acids as platform chemicals we have explored the protecting group chemistry of the lactone form of alpha-glucoisosaccharinic acid (α-GISAL). We report here the use of single and multiple step reaction pathways leading to the regioselective protection of the three different hydroxyl groups of α-GISAL. We report strategies for protecting the three different hydroxyl groups individually or in pairs. We also report the synthesis of a range of tri-O-protected α-GISAL derivatives where a number of the products contain orthogonal protecting groups.

A study of regulatory policies and relevant issues concerning electronic cigarette use in Taiwan.

Recent technological innovations have increased the amount of tobacco products available to smokers. In particular, electronic cigarettes, sometimes call e-cigarettes, have received substantial attention as their sales have rapidly increased. Electronic cigarettes were invented in China and now have become prevalent worldwide. Electronic cigarettes can be considered fashionable and come in numerous flavors; accordingly, many young adults and students have begun to use e-cigarettes. However, like traditional tobacco products, e-cigarettes have negative influences on human health. After e-cigarettes were introduced into Taiwan, they have not been effectively managed and regulated because of insufficient supporting measures. Related legislation in developed countries can serve as a reference for Taiwan. For this study, the development of e-cigarettes is described and a theoretical analysis was performed from the administration and legal perspectives. In addition to clarifying related problems and offering measures to prevent students from using e-cigarettes, we propose suggestions to help governments improve their strategies to protect students' health.

Perceiver as polar planimeter: Direct perception of jumping, reaching, and jump-reaching affordances for the self and others.

Runeson (Scandanavian Journal of Psychology 18:172-179, 1977) suggested that the polar planimeter might serve as an informative model system of perceptual mechanism. The key aspect of the polar planimeter is that it registers a higher order property of the environment without computational mediation on the basis of lower order properties, detecting task-specific information only. This aspect was posited as a hypothesis for the perception of jumping and reaching affordances for the self and another person. The findings supported this hypothesis. The perception of reaching while jumping significantly differed from an additive combination of jump-without-reaching and reach-without-jumping perception. The results are consistent with Gibson's (The senses considered as perceptual systems, Houghton Mifflin, Boston, MA; Gibson, The senses considered as perceptual systems, Houghton Mifflin, Boston, MA, 1966; The ecological approach to visual perception, Houghton Mifflin, Boston, MA; Gibson, The ecological approach to visual perception, Houghton Mifflin, Boston, MA, 1979) theory of information-that aspects of the environment are specified by patterns in energetic media.

The Independent Perceptual Calibration of Action-Neutral and -Referential Environmental Properties.

Two experiments were conducted to explore how the calibration of perception of environmental properties taken with reference to an animal and their action capabilities (e.g., affordances) and those that are independent of action capabilities (e.g., metric properties) relate. In both experiments, participants provided reports of the maximum height they could reach above their head with a number of different stick(s) (reach-with-stick height) and the length of those stick(s), a property that is a constituent of reach-with-stick height. In Experiment 1 reach-with-stick height reports improved over trials whereas stick length reports remained constant. In Experiment 2, feedback about maximum reach-with-stick height improved perception of this affordance, but such improvements did not transfer to perception of stick length in a pretest/practice task/posttest design. The results suggest that the perceptual calibration with practice perceiving or feedback about actual dimensions of action-referential and action-neutral properties do not necessarily depend on one another.

Ultrasound-Guided Liver Biopsy With Gelatin Sponge Pledget Tract Embolization in Infants Weighing Less Than 10 kg.

OBJECTIVES: The aim of the study was to describe and assess the technical success and safety of ultrasound-guided liver biopsy with gelatin sponge pledget tract embolization technique in infants <10 kg across 3 tertiary pediatric hospitals. MATERIALS AND METHODS: There were 67 pediatric patients weighing <10 kg (36 boys; 31 girls; average age 202 days; average weight 6 kg, range 1.5-9.9 kg) referred for liver biopsy performed with ultrasound guidance and gelatin sponge pledget tract embolization during a 2-year period. Patient history, procedural records, and clinical follow-up documents were retrospectively reviewed. RESULTS: A total of 67 procedures were included. There was 100% technical success rate and all samples obtained provided adequate tissue for histological assessment. Average number of 18 G biopsy passes was 3 (range 1-6). There were no procedure-related deaths. There was 1 complication (1%) in a 5-kg infant who was readmitted 36 hours after biopsy with a fever and fully recovered after antibiotics were administered. Biliary atresia was the most common underlying diagnosis (20%), whereas others included acute rejection (16%) and biliary obstruction (7%). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy with gelatin sponge pledget tract embolization technique in children weighing <10 kg is safe, effective, and use of this technique may lead to a reduction in rates of adverse events reported in other pediatric series.

Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata.

BACKGROUND: The low-risk human papillomavirus types 6 and 11 are responsible for approximately 90% of anogenital wart cases, with approximately 190,000 new and recurrent cases reported in the UK in 2010. The UK has recently selected the quadrivalent HPV vaccine, which conveys protection against both HPV6 and HPV 11, as part of its immunisation programme for 2012 and it is expected that this will reduce disease burden in the UK. The aims of the study were to evaluate current strategies used for the monitoring of HPV infection in genital warts and to assess the suitability of laser-capture microdissection (LCM) as a technique to improve the understanding of the natural history of HPV types associated with genital wart lesions. METHODS: DNA and RNA were extracted from whole wart, surface swabs and LCM sections from 23 patients. HPV types present were determined using the Linear Array HPV Genotyping Test (Roche), with HPV DNA viral load and mRNA expression investigated using qPCR and qRT-PCR, respectively. RESULTS: Results indicated that swabbing the surface of warts does not accurately reflect potential causative HPV types present within a wart lesion, multiple HPV types being present on the surface of the wart that are absent in the lower layers of tissue isolated by LCM. Although it was shown that HPV DNA viral load does not directly correlate with HPV mRNA load, the presence of both DNA and mRNA from a single HPV type suggested a causative role in lesion development in 8/12 (66.6%) of patients analysed, with dual infections seen in 4/12 (33.3%) cases. HPV 6 and HPV 11 were present in more than 90% of the lesions examined. CONCLUSIONS: Surface swabbing of warts does not necessarily reflect the causative HPV types. HPV type specific DNA and mRNA loads do not correlate. HPV 6 and 11 were likely to be causally involved in over 90% of the lesions. Dual infections were also found, and further studies are required to determine the biological and clinical nature of dual/multiple infections and to establish the relationship of multiple HPV types within a single lesion.