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Background: Due to a myriad of risk factors, epistaxis is a very frequent presentation to the emergency room (ER). This study aims to ascertain the prevalence of epistaxis in our population, risk factors, effectiveness of ER treatment, complications, and ER outcome. Materials and Methods: This was a prospective observational study performed in the ER of a referral tertiary care center in south India. Data were categorized, coded, and analyzed to determine the objective of the study. Results: During the study's six-month duration, 188 (0.6%) patients presented with epistaxis. The mean age was 42.9 (SD: 16.49) years, with a male preponderance of 143 (76.1%). A majority of these patients (n: 156; 82.9%) were triaged as priority II, with hypertension (n: 53, 28.2%) as the commonest comorbidities. Trauma-related epistaxis (n: 107, 56.9%) was the most frequent cause. Anterior nasal packing was carried out for 85 (45.2%) patients, posterior nasal packing was carried out for one (0.5%) patient, and bleeding had spontaneously resolved in the majority (n: 102; 54.3%) patients. Seven (3.7%; p-value: 0.001) patients had recurrent epistaxis, and of those, three (1.6%) required urgent resuscitation with crystalloid fluid and blood products. Two of these patients had bleeding dyscrasias, four had history of trauma, and one patient presented with uncontrolled hypertension. Two (1.1%) patients came back to us with recurrent bleeding within 12 h of discharge. Majority (69.2%; 130) were discharged stable, (23.9%; 45) were admitted for observation and (6.9%; 13) were discharged against medical advice. There was no mortality among these study populations. Conclusion: Middle-young, aged males most commonly presented with epistaxis. Most of them were secondary to trauma. Anterior nasal bleeding was the most common source and hemostasis could be obtained by anterior nasal packing. Majority could be discharged stable from the ER. However, this cohort had seen patients in life-threatening conditions, so the severity cannot be overlooked.

The rodent cancer bioassays are conducted for agrochemical safety assessment yet they often do not inform regulatory decision-making. As part of a collaborative effort, the Rethinking Carcinogenicity Assessment for Agrochemicals Project (ReCAAP) developed a reporting framework to guide a weight of evidence (WOE)-based carcinogenicity assessment that demonstrates how to fulfill the regulatory requirements for chronic risk estimation without the need to conduct lifetime rodent bioassays. The framework is the result of a multi-stakeholder collaboration that worked through an iterative process of writing case studies (in the form of waivers), technical peer reviews of waivers, and an incorporation of key learnings back into the framework to be tested in subsequent case study development. The example waivers used to develop the framework were written retrospectively for registered agrochemical active substances for which the necessary data and information could be obtained through risk assessment documents or data evaluation records from the US EPA. This exercise was critical to the development of a framework, but it lacked authenticity in that the stakeholders reviewing the waiver already knew the outcome of the rodent cancer bioassay(s). Syngenta expanded the evaluation of the ReCAAP reporting framework by writing waivers for three prospective case studies for new active substances where the data packages had not yet been submitted for registration. The prospective waivers followed the established framework considering ADME, potential exposure, subchronic toxicity, genotoxicity, immunosuppression, hormone perturbation, mode of action (MOA), and all relevant information available for read-across using a WOE assessment. The point of departure was estimated from the available data, excluding the cancer bioassay results, with a proposed use for the chronic dietary risk assessment. The read-across assessments compared data from reliable registered chemical analogues to strengthen the prediction of chronic toxicity and/or tumorigenic potential. The prospective case studies represent a range of scenarios, from a new molecule in a well-established chemical class with a known MOA to a molecule with a new pesticidal MOA (pMOA) and limited read-across to related molecules. This effort represents an important step in establishing criteria for a WOE-based carcinogenicity assessment without the rodent cancer bioassay(s) while ensuring a health protective chronic dietary risk assessment.

BackgroundMitigation of climate change requires that new routes for the production of fuels and chemicals be as oil-independent as possible. The microbial conversion of lignocellulosic feedstocks into terpene-based biofuels and bioproducts represents one such route. This work builds upon previous demonstrations that the single-celled carotenogenic basidiomycete, Rhodosporidium toruloides, is a promising host for the production of terpenes from lignocellulosic hydrolysates.ResultsThis study focuses on the optimization of production of the monoterpene 1,8-cineole and the sesquiterpene α-bisabolene in R. toruloides. The α-bisabolene titer attained in R. toruloides was found to be proportional to the copy number of the bisabolene synthase (BIS) expression cassette, which in turn influenced the expression level of several native mevalonate pathway genes. The addition of more copies of BIS under a stronger promoter resulted in production of α-bisabolene at 2.2 g/L from lignocellulosic hydrolysate in a 2-L fermenter. Production of 1,8-cineole was found to be limited by availability of the precursor geranylgeranyl pyrophosphate (GPP) and expression of an appropriate GPP synthase increased the monoterpene titer fourfold to 143 mg/L at bench scale. Targeted mevalonate pathway metabolite analysis suggested that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), mevalonate kinase (MK) and phosphomevalonate kinase (PMK) may be pathway bottlenecks are were therefore selected as targets for overexpression. Expression of HMGR, MK, and PMK orthologs and growth in an optimized lignocellulosic hydrolysate medium increased the 1,8-cineole titer an additional tenfold to 1.4 g/L. Expression of the same mevalonate pathway genes did not have as large an impact on α-bisabolene production, although the final titer was higher at 2.6 g/L. Furthermore, mevalonate pathway intermediates accumulated in the mevalonate-engineered strains, suggesting room for further improvement.ConclusionsThis work brings R. toruloides closer to being able to make industrially relevant quantities of terpene from lignocellulosic biomass.

The SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.

Aims/hypothesisHypothalamic inflammation and sympathetic nervous system hyperactivity are hallmark features of the metabolic syndrome and type 2 diabetes. Hypothalamic inflammation may aggravate metabolic and immunological pathologies due to extensive sympathetic activation of peripheral tissues. Loss of somatostatinergic (SST) neurons may contribute to enhanced hypothalamic inflammation.MethodsThe present data show that leptin receptor-deficient (db/db) mice exhibit reduced hypothalamic SST neurons, particularly in the periventricular nucleus. We model this finding, using adeno-associated virus delivery of diphtheria toxin subunit A (DTA) driven by an SST-cre system to deplete these neurons in Sstcre/gfp mice (SST-DTA).ResultsSST-DTA mice exhibit enhanced hypothalamic c-Fos expression and brain inflammation as demonstrated by microglial and astrocytic activation. Bone marrow from SST-DTA mice undergoes skewed haematopoiesis, generating excess granulocyte-monocyte progenitors and increased proinflammatory (C-C chemokine receptor type 2; CCR2hi) monocytes. SST-DTA mice exhibited a 'diabetic retinopathy-like' phenotype: reduced visual function by optokinetic response (0.4 vs 0.25 cycles/degree; SST-DTA vs control mice); delayed electroretinogram oscillatory potentials; and increased percentages of retinal monocytes. Finally, mesenteric visceral adipose tissue from SST-DTA mice was resistant to catecholamine-induced lipolysis, displaying 50% reduction in isoprenaline (isoproterenol)-induced lipolysis compared with control littermates. Importantly, hyperglycaemia was not observed in SST-DTA mice.Conclusions/interpretationThe isolated reduction in hypothalamic SST neurons was able to recapitulate several hallmark features of type 2 diabetes in disease-relevant tissues.

Stigma in health care settings can have negative consequences on women living with HIV, such as increasing the likelihood of missed visits and reducing trust in their clinical providers. Informed by prior stigma research and considering knowledge gaps related to the effect of patient-provider race concordance, we conducted this study to assess if patient-provider race concordance moderates the expected association between HIV-related stigma in health care settings and patients' trust in their providers. Moderation analyses were conducted using Women's Interagency HIV Study data (N = 931). We found significant main effects for patient-provider race concordance. Higher experienced stigma was associated with lower trust in providers in all patient-provider race combinations [White-White: B = -0.89, standard error (SE) = 0.14, p = 0.000, 95% confidence interval, CI (-1.161 to -0.624); Black patient-White provider: B = -0.19, SE = 0.06, p = 0.003, 95% CI (-0.309 to -0.062); and Black-Black: B = -0.30, SE = 0.14, p = 0.037, 95% CI (-0.575 to -0.017)]. Higher anticipated stigma was also associated with lower trust in providers [White-White: B = -0.42, SE = 0.07, p = 0.000, 95% CI (-0.552 to -0.289); Black patient-White provider: B = -0.17, SE = 0.03, p = 0.000, 95% CI (-0.232 to -0.106); and Black-Black: B = -0.18, SE = 0.06, p = 0.002, 95% CI (-0.293 to -0.066)]. Significant interaction effects indicated that the negative associations between experienced and anticipated HIV-related stigma and trust in providers were stronger for the White-White combination compared with the others. Thus, we found that significant relationships between HIV-related experienced and anticipated stigma in health care settings and trust in providers exist and that these associations vary across different patient-provider race combinations. Given that reduced trust in providers is associated with antiretroviral medication nonadherence and higher rates of missed clinical visits, interventions to address HIV-related stigma in health care settings may improve continuum of care outcomes.

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948-2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.

We investigated patterns of volatile organic compound (VOC) contamination in drinking water systems affected by the California 2018 Camp Fire. We performed spatial analysis of over 5000 water samples collected over a 17 month period by a local water utility, sampled tap water for VOCs in approximately 10% (N = 136) of standing homes, and conducted additional nontargeted chemical analysis of 10 samples. Benzene contamination was present in 29% of service connections to destroyed structures and 2% of service connections to standing homes. A spatial pattern was apparent. Tap water in standing homes 11 months after the fire contained low concentrations of benzene in 1% of samples, but methylene chloride was present in 19% of samples, including several above regulatory limits. Elevated methylene chloride was associated with greater distance from the water meter to the tap, longer stagnation time, and the presence of a destroyed structure on the service connection; it was inversely associated with certain trihalomethanes. Nontargeted analysis identified multiple combustion byproducts in the water at 2/10 homes. Our findings support the hypothesis that pyrolysis and smoke intrusion from depressurization contributed to the benzene contamination. Further research is needed to test the hypothesis that methylene chloride may be generated from the dehalogenation of disinfection byproducts stagnating in galvanized iron pipes.

BackgroundChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.MethodsData from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.ResultsIn a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P

Objective: To determine whether a postdischarge video visit with patients, conducted by hospital medicine advanced practice providers, improves adherence to hospital discharge recommendations. Patients and Methods: We conducted a single-institution 2-site randomized clinical trial with 1:1 assignment to intervention vs control, with enrollment from August 10, 2020, to June 23, 2022. Hospital medicine patients discharged home or to an assisted living facility were randomized to a video visit 2-5 days postdischarge in addition to usual care (intervention) vs usual care (control). During the video visit, advanced practice providers reviewed discharge recommendations. Both intervention and control groups received telephone follow-up 3-6 days postdischarge to ascertain the primary outcome of adherence to all discharge recommendations for new and chronic medication management, self-management and action plan, and home support. Results: Among 1190 participants (594 intervention; 596 control), the primary outcome was ascertained in 768 participants (314 intervention; 454 control). In intervention vs control, there was no difference in the proportion of participants with the primary outcome (76.7% vs 72.5%; P=.19) or in the individual domains of the primary outcome: new and chronic medication management (94.1% vs 92.8%; P=.50), self-management and action plan (76.5% vs 71.5%; P=.18), and home support (94.1% vs 94.3%; P=.94). Women receiving intervention vs control had higher adherence to recommendations (odds ratio, 1.77; 95% CI, 1.08-2.91). Conclusion: In hospital medicine patients, a postdischarge video visit did not improve adherence to discharge recommendations. Potential gender differences in adherence require further investigation.Clinicaltrials.gov number, NCT04547803.

Abstract Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p

Abstract Efficient conversion of pentose sugars remains a significant barrier to the replacement of petroleum-derived chemicals with plant biomass-derived bioproducts. While the oleaginous yeast Rhodosporidium toruloides (also known as Rhodotorula toruloides) has a relatively robust native metabolism of pentose sugars compared to other wild yeasts, faster assimilation of those sugars will be required for industrial utilization of pentoses. To increase the rate of pentose assimilation in R. toruloides, we leveraged previously reported high-throughput fitness data to identify potential regulators of pentose catabolism. Two genes were selected for further investigation, a putative transcription factor (RTO4_12978, Pnt1) and a homolog of a glucose transceptor involved in carbon catabolite repression (RTO4_11990). Overexpression of Pnt1 increased the specific growth rate approximately twofold early in cultures on xylose and increased the maximum specific growth by 18% while decreasing accumulation of arabitol and xylitol in fast-growing cultures. Improved growth dynamics on xylose translated to a 120% increase in the overall rate of xylose conversion to fatty alcohols in batch culture. Proteomic analysis confirmed that Pnt1 is a major regulator of pentose catabolism in R. toruloides. Deletion of RTO4_11990 increased the growth rate on xylose, but did not relieve carbon catabolite repression in the presence of glucose. Carbon catabolite repression signaling networks remain poorly characterized in R. toruloides and likely comprise a different set of proteins than those mainly characterized in ascomycete fungi.

Abstract We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.

The most common method for RNA detection involves reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR) analysis. Commercial one-step master mixes-which include both a reverse transcriptase and a thermostable polymerase and thus allow performing both the RT and qPCR steps consecutively in a sealed well-are key reagents for SARS-CoV-2 diagnostic testing; yet, these are typically expensive and have been affected by supply shortages in periods of high demand. As an alternative, we describe here how to express and purify Taq polymerase and M-MLV reverse transcriptase and assemble a homemade one-step RT-qPCR master mix. This mix can be easily assembled from scratch in any laboratory equipped for protein purification. We also describe two simple alternative methods to prepare clinical swab samples for SARS-CoV-2 RNA detection by RT-qPCR: heat-inactivation for direct addition, and concentration of RNA by isopropanol precipitation. Finally, we describe how to perform RT-qPCR using the homemade master mix, how to prepare in vitro-transcribed RNA standards, and how to use a fluorescence imager for endpoint detection of RT-PCR amplification in the absence of a qPCR machine In addition to being useful for diagnostics, these versatile protocols may be adapted for nucleic acid quantification in basic research. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of a one-step RT-qPCR master mix using homemade enzymes Basic Protocol 2: Preparation of swab samples for direct RT-PCR Alternate Protocol 1: Concentration of RNA from swab samples by isopropanol precipitation Basic Protocol 3: One-step RT-qPCR of RNA samples using a real-time thermocycler Support Protocol: Preparation of RNA concentration standards by in vitro transcription Alternate Protocol 2: One-step RT-PCR using endpoint fluorescence detection.

Background: Knowledge of the structure and function of the human heart is fundamental to accurately understanding human physiology. As a complex biological system, naïve conceptions abound regarding cardiac anatomy and physiology for K-12 learners and medical students alike. Objective: Textbooks and lectures, as well models and simulations, have had limited success in aiding learners in constructing accurate and cohesive knowledge of the human heart. Three dimensional (3D) modelling, haptic-enabled (HE) feedback, and interactive virtual reality (VR) experiences aid tertiary learners, yet it is unknown if secondary learners benefit from learning with these technologies. Methods: An exploratory study examined secondary student knowledge of cardiac anatomy and physiology after participation in an interactive lesson on cardiac structure and function using a 3D, HE, VR technology system. Students from sixth grade (11-12 years old; n = 75) and ninth grade (14-15 years old; n = 76) completed a pre- and post-assessment on cardiac knowledge, anatomy, and physiology punctuated by technology-delivered instruction on the human heart. Results and Conclusions: Significant gains were found in knowledge from both groups in cardiac anatomy and blood circulation within the chambers of the heart; however, only ninth grade students demonstrated significant knowledge gains in pulmonary circulation. Takeaways: Results suggest that 3D HE VR technologies provide learners robust representations of and student-driven interactions with complex biological systems that are innovative instructionally for strong conceptual and systematic learning. This study offers insight on technology-assisted science visualizations for the promotion of knowledge acquisition and systems thinking of the human heart among secondary science students.

Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), result from an impairment of bile flow that leads to the hepatic retention of bile acids, causing liver injury. Until recently, the only approved treatments for PBC were ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). While these therapies slow the progression of PBC in the early stage of the disease, approximately 40% of patients respond incompletely to UDCA, and advanced cases do not respond. UDCA does not improve survival in patients with PSC, and patients often have dose-limiting pruritus reactions to OCA. Left untreated, these diseases can progress to fibrosis and cirrhosis, resulting in liver failure and the need for transplantation. These shortcomings emphasize the urgent need for alternative treatment strategies. Recently, nuclear hormone receptors have been explored as pharmacological targets for adjunct therapy because they regulate enzymes involved in bile acid metabolism and detoxification. In particular, the peroxisome proliferator-activated receptor (PPAR) has emerged as a therapeutic target for patients with PBC or PSC who experience an incomplete response to UDCA. PPARα is predominantly expressed in the liver, and it plays an essential role in the regulation of cytochrome P450 (CYP) and uridine 5’-diphospho-glucuronosyltransferase (UGT) enzymes, both of which are critical enzyme families involved in the regulation of bile acid metabolism and glucuronidation, respectively. Importantly, PPARα agonists, e.g., fenofibrate, have shown therapeutic benefits in reducing elevated markers of cholestasis in patients with PBC and PSC, and elafibranor, the first PPAR (dual α, β/δ) agonist, has been FDA-approved for the second-line treatment of PBC. Additionally, newer PPAR agonists that target various PPAR isoforms (β/δ, γ) are under development as an adjunct therapy for PBC or PSC, although their impact on glucuronidation pathways are less characterized. This review will focus on PPAR-mediated bile acid glucuronidation as a therapeutic pathway to improve outcomes for patients with PBC and PSC.

This article provides a novel approach to the traditional constant market share (CMS) analysis recognizing the importance of global production networks and fragmentation that necessitate using trade in value added (TiVA) rather than gross trade. We discuss how the components of a CMS analysis need to be (re)interpreted and apply our Constant Value Added Share (CVAS) analysis to the Philippines in the years 1995–2020 using the latest TiVA 2023 dataset (released in November 2023) and compare CMS to CVAS in order to facilitate understanding the contribution of the novel approach. The CVAS analysis finds that while Philippine and world Value Added grew at par, the country lost competitiveness. Traditional CMS suggests a smaller loss of competitiveness. Our approach also identifies specific sectoral weaknesses (i.e., computer and electronics exports) and emerging strengths (technology-related business services) that are unclear in CMS analysis. We argue that Constant Value Added Share analysis is useful for assessing the global value chain performance of other developing countries as well.

Research links to positive student outcomes have highlighted the need to address disposition during teacher clinical practice using sound measures. Education preparation providers may use these indicators to create defensible measures of disposition by formatting the indicators into Likert scales or rubrics. Authors have extended the psychometric evaluation of validated indicators by calculating reliability estimates. Additional evidence of construct validity was also provided by aligning the nine dispositions with prominent teacher evaluation instruments and quality standards.

National guidelines such as the "Standards for the 21st Century Learner" (American Association of School Librarians, 2007) and the "Common Core State Standards" (Common Core State Standards, 2010) recognize the importance of using a wide range of informational texts, including comic books and graphic novels to teach content, in kindergarten through fifth grade (Gavigan, 2014). To reinforce this expectation, the Common Core State Standards website features a video clip, "Learn about the Common Core in 3 minutes" (http://www.corestandards.org/about-the-standards/), in the format of a comic informational text that introduces the reader to the CCSS standards. Comic books and graphic novels, as examples of sequential art, have gained a prominent place in education (Gavigan, 2014; Hammond, 2012; Mortimore, 2009). Weiner and Syma (2013) reported, "Teachers in secondary and elementary schools, professors in universities, and instructors of all kinds are using comics and graphic novels to illustrate points about gender, history, sociology, philosophy, mathematics, and even medicine" (p. 1). Thus they concluded, "It is no longer a question of whether sequential art should be used in educational settings, but rather how to use it and for what purpose" (p. 1). The study presented in this article examines the use of comic books, TOON comic books, during guided reading. The TOON book concept was created by Françoise Mouly, an art editor of "The New Yorker" magazine, and her husband, Art Spiegelman, a prizewinning comic book artist, and author of "Maus: A survivor's tale" (1986). On the official TOON comic book series website (http://www.toon-books.com/our-mission.html), Mouly and Spiegelman indicated that these books were designed to promote literacy skills development among elementary students at different reading levels. The instruction with this comic book series was provided to struggling readers, kindergarten through fifth grade, by the pre-service teachers enrolled in the "Early Literacy" and "Literacy Assessment and Applications" courses at a comprehensive university in southeastern United States. In this work, a struggling reader is defined as a student who reads below grade level and who lacks proficiency in decoding, fluency, and comprehension skills (Rasinski & Padak, 2005).

This paper focuses on advancing Social Emotional Learning into the final internship to help teacher candidates effectively deal with the stressors they face in their intern classes.