Adult Type Research Articles

Anomalous origin of the left coronary artery from the pulmonary artery: A rare congenital cardiac anomaly masquerading as dilated cardiomyopathy

ABSTRACT Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a cardiac anomaly which is quite complex and very rarely diagnosed. It can, however, have serious consequences for the patient. It has been divided into two types based on the age of presentation: the infant type and the adult type with different presentations and prognoses. The infant type usually presents with congestive heart failure or sometimes as myocardial infarction. Many of these patients do not make it beyond 1st year of life. The rare adult variant of ALCAPA syndrome may manifest as recurrent chest infections in the pediatric age group, dyspnea on exertion, or sometimes, even as sudden cardiac death. We report the case of a 7-year-old girl who presented with recurrent chest infections and echocardiography (ECG) was suggestive of dilated cardiomyopathy. The definitive diagnosis of ALCAPA was reached only by ECG-gated cardiac computed tomography.

P02-045-23 Association Between Bread Types and Blood Glucose Biomarkers of Adults in the United States: The National Health and Nutrition Examination Survey (NHANES) 2017–2018

P02-045-23 Association Between Bread Types and Blood Glucose Biomarkers of Adults in the United States: The National Health and Nutrition Examination Survey (NHANES) 2017–2018

Türkiye’de Genç Yetişkinlerin Sosyal Medya Kullanımları ve Paylaşım Türlerinin İncelenmesi

Bu çalışma, Türkiye’deki 18-29 yaş aralığındaki gençlerin hangi sosyal medya platformlarını kullandıklarına, ne kadar sıklıkla kullandıklarına ve bu platformlarda ne tarz içerikler paylaştıklarını incelemektedir. Literatüre katkı olarak, gençlerin sosyal medya kullanım pratiklerinin, paylaşım türlerinin ve motivasyonlarının sosyodemografik özelliklerle (cinsel kimlik, yaş, yaşanılan yer, sosyoekonomik statü, eğitim seviyesi ve dinî kimlik) ilişkisini araştırmaktadır. Türkiye’nin 12 ilinde yaşayan gençlerle gerçekleştirilen yüz yüze anket çalışmamızın (N=1537) bulgularına göre, en çok kullanılan sosyal medya platformları sırasıyla Instagram, YouTube ve Twitter’dır. Bulgular, bir zamanlar gençlerin yoğunlukla kullandığı Facebook’un popülerliğini yitirmeye başladığını ortaya koymaktadır. Gençlerin öğrencilik durumları, sosyoekonomik statüleri, yaşadıkları il ve cinsel kimlikleri ile sosyal medya tercihleri arasında anlamlı bir ilişki gözlemlenmektedir. Ayrıca cinsel kimlik, dinî görüş, sosyoekonomik statü, öğrencilik durumu ve yaşanılan il ile sosyal medyaya paylaşılan içerik türleri arasında anlamlı bir ilişki bulunmaktadır. Çalışmamız, ulusal ve uluslararası çalışmaların bulgularını kısmen doğrulamakta ve önemli farklılıklar ortaya koymaktadır. Türkiye’deki genç yetişkinlerin sosyal medya pratiklerine dair güncel bir veri sunmaktadır.

Mindfulness facets differentially relate to self-reported negative and positive emotional eating types in treatment-seeking adults with overweight/obesity

BackgroundMindfulness is a meaningful therapeutic target in the treatment of emotional eating in adults with overweight/obesity. Descriptive research mapping relations between mindfulness facets and emotional eating types in treatment-seeking adults with overweight/obesity is needed.MethodsCross-sectional relations between mindfulness facets (i.e., acting with awareness, describe, non-judgment, non-reactive, and observe; Five Facet Mindfulness Questionnaire-Short Form) and emotional eating types (i.e., self-reported negative and positive emotional eating; Emotional Eating Scale-Revised, Emotional Appetite Questionnaire) were examined in a treatment-seeking sample of adults with overweight/obesity (N = 63).ResultsSignificant bivariate correlations revealed negative relations between mindfulness facets and emotional eating types. Multiple regressions revealed that higher describe (β = − 0.42, p = 0.004) mindfulness was associated with lower self-reported emotional eating–anger/anxiety; higher non-reactive (β = − 0.31, p = 0.01) and non-judgment (β = − 0.28, p = 0.02) mindfulness were associated with lower self-reported emotional eating-depression; and higher non-judgment (β = 0.26, p = 0.04) mindfulness was associated with higher self-reported emotional eating-positive.ConclusionsDescribe, non-judgment, and non-reactive mindfulness were uniquely and significantly associated with eating in response to negative and positive emotions. Results suggest the potential need for intervention programs to be sensitive to the multidimensional nature of mindfulness in the treatment of distinct types of emotional eating in adults with overweight/obesity.Level of evidenceV, cross-sectional descriptive study.

956-P: Association between Glycemia Risk Index (GRI) and Diabetic Retinopathy in Type 2 Diabetes—A Prospective Cohort Study

Background: The glycemia risk index (GRI) is a new composite metric for assessing the quality of glycemia based on expert ranking by 330 clinicians of 14-day continuous glucose monitoring (CGM) tracings. Compared with time in range (TIR), GRI has been shown to correlate more closely with the clinicians’ opinions as to the overall quality of glycemia profiles. However, the relationship between GRI and diabetes-related outcomes remains unknown. We aimed to investigate the association between GRI and incident diabetic retinopathy (DR). Methods: A total of 1,204 adult type 2 diabetes without DR at baseline were included between 2005-2019 from a single center in Shanghai, China. GRI was obtained from 3-day CGM data at baseline. Cox proportional hazards regression models were used to estimate the association between GRI and incident DR. Results: During a median follow-up of 8.4 years, 301 patients developed DR. The multivariable-adjusted (age, sex, current smoking status, diabetes duration, BMI, systolic BP, TG, HDL-C, and LDL-C) hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15~28, 29~47 and >47) were 1.00, 1.05 (95% CI 0.74-1.48), 1.33 (95% CI 0.96-1.84) and 1.53 (95% CI 1.11-2.11), respectively. For per 1-SD increase in GRI, the risk of DR was increased by 20% (HR=1.20, 95% CI 1.07-1.33) after adjustment for confounders. With respect to TIR, per 1-SD decrease was associated with a 23% (HR=1.23, 95% CI 1.10-1.37) increased risk of DR. There was no statistically significant difference in risk discrimination for incident DR when using GRI and TIR, as measured by C statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) (all P>0.05), after adjustment for confounders. Conclusion: In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR, with a predictive value comparable to TIR. The potential value of GRI needs to be explored in future studies. Disclosure Y.Wang: None. R.A.Vigersky: Employee; Medtronic. W.Jia: None. J.Zhou: None. J.Lu: None. J.Ni: None. M.Wang: None. Y.Shen: None. W.Lu: None. W.Zhu: None. Y.Bao: None. D.Rodbard: Consultant; Lilly Diabetes.

1455-P: Developing Computable Phenotypes (CPs) for Identifying Children, Adolescents, and Young Adults with Diabetes Using Electronic Health Records in the DiCAYA Network

The DiCAYA Network, which is funded by the CDC and NIDDK, is working to create a nationwide electronic health record-based diabetes surveillance system. The feasibility and performance of existing diabetes computable phenotypes in this system were unknown, as they had only been tested in individual health systems. This study aimed to develop a DiCAYA-wide EHR-based computable phenotype (CP) to identify prevalent cases of diabetes by type. We conducted network-wide chart reviews for 1830 youth (age < 18y) and 1830 young adults (age 18 - <45y) among individuals with possible diabetes, identified as those with any potential indication of diabetes in the EHR (any diabetes-related diagnosis, medication, or abnormal lab test). We assessed the performance of the DiCAYA CP (two outpatient diagnoses or one inpatient diagnosis by type) for identifying diabetes and diabetes type in children and young adults in the reviewed sample, using chart review as the gold standard. (Table 1). We developed a highly accurate EHR-based CP for diabetes in children and young adults based on EHR data from the DiCAYA network. Our results support the feasibility of deploying a unified CP across a nationwide EHR network for diabetes surveillance, with consistently high accuracy across the participating sites. Disclosure H.Shao: Consultant; Lilly Diabetes. B.E.Dixon: Consultant; Merck & Co., Inc. E.Lustigova: None. M.Rosenman: None. V.W.Zhong: None. S.Conderino: None. J.Divers: None. L.Thorpe: None. A.D.Liese: None. C.Rudisill: Stock/Shareholder; Pfizer Inc., Viatris Inc., Teladoc Health, Catalent. J.S.Obeid: None. Y.Guo: None. M.E.Pavkov: None. G.Imperatore: None. J.A.Ewing: None. J.Bian: None. P.Li: None. D.Dabelea: None. R.B.Conway: None. T.L.Crume: None. B.S.Schwartz: None. A.G.Hirsch: None. Funding Centers for Disease Control and Prevention (U18DP006512)

1056-P: Impact of Individualized HbA1c Target Setting on Diabetes-Distress, Self-Efficacy, Well-Being, and HbA1c

American Diabetes Association guidelines emphasize the importance of individualized HbA1c target setting in glycemic management, but little is known of the impact of target-setting on patient well-being. We randomized 50 adults (type 1 or 2) to receive HbA1c targets 5 mmol/mol (0.5%) above or below current value and evaluated impact on health-related quality of life: EQ-5D-5L, EQ-VAS, diabetes distress: Problem Areas in Diabetes, PAID, self-efficacy: Diabetes Empowerment Scale Long Form, DES-LF, well-being: Wellbeing Questionnaire-12, W-BQ12 and HbA1c (%) at baseline and 3 months; with thematic analysis of semi-structured interviews in a subset of 14 people. Tabulated results for 33 completers: We hypothesized that individualized target-setting, especially stretch targets, might worsen diabetes distress and compromise wellbeing. Multiple validated questionnaires and thematic analysis of semi-structured interviews showed no evidence of any significant deterioration. Indeed, the process of explicit individualized target setting was associated with improvements in all wellbeing measures except EQ-5D-5L and there were significant improvements in diabetes distress and psychosocial efficacy in the relaxed target group. Our data suggest that the process of setting explicit individualized HbA1c targets is a positive one, regardless of whether the target is ‘relaxed’ or ‘stretch’. Disclosure S.J.Westall: None. S.Watmough: None. R.Narayanan: None. G.Irving: Research Support; Graphnet, Takeda Pharmaceutical Co., Ltd. N.J.Furlong: None. G.A.Lewis: None. K.J.Hardy: Other Relationship; Sanofi, Speaker's Bureau; Napp Pharmaceuticals Limited.

1452-P: Type 1 Diabetes Subphenotypes—A Cluster Analysis

Adult-onset type 1 diabetes (T1D) is a chronic disease with progressive beta-cell destruction. However, individuals with adult-onset T1D are metabolically dissimilar. We aimed to identify metabolically distinct groups in a comprehensively phenotyped cohort of individuals with recent-onset T1D. Participants with T1D (n=550) were split by presence of glutamic-acid decarboxylase antibody (GADA) into a GADA- (n=95) and GADA+ groups (n=455). GADA+ was clustered using partitioning around medoids based on fasting C-peptide, glucose, triglycerides and HDL resulting in 2 distinguished GADA+ clusters. All 3 clusters were compared at baseline (first year of diabetes diagnosis) and after five years of follow-up using ANOVA, chi-squared test and logistic regression adjusted for age and sex. The larger GADA+ cluster (n=285) with younger age, lower BMI and lower C-peptide was termed “classic T1D”. The other GADA+ cluster (n=170) combined features of type 1 and type 2 diabetes and was named “mixed T1D”. Patients of the “mixed T1D” cluster did not gain weight over 5 years (p=0.29), which was not the case for “classic T1D” cluster (p<0.001, increased BMI with an effect size 0.07) and GADA-cluster (p=0.01, effect size 0.04) participants. The “classic T1D” cluster had the highest insulin sensitivity at baseline (p<0.001) that sharply decreased during five years of follow-up. At five years, there was no difference in insulin sensitivity across the 3 clusters (p=0.78). There were no differences in HbA1c levels across clusters neither at baseline (p=0.48) nor after 5 years (p=0.64). Classic T1D participants reported a higher incidence of hypoglycemia (OR 4.92, 95% CI 1.9-13.5, p=0.001). The incidence of both distal peripheral sensory (OR 2.89, 95%CI1.05-8.29, p= 0.041) and cardiac autonomic neuropathy (OR 9.61, 95%CI 2.35-49.8, p= 0.003), was higher in “mixed T1D”. Based on rapidly available laboratory variables, individuals with recent-onset adult type 1 diabetes can be stratified into clusters with different clinical course and complication risk Disclosure K.Prystupa: Other Relationship; Berlin-Chemie AG. S.M.Meyhöfer: Speaker's Bureau; Novo Nordisk, AstraZeneca, Lilly, Amgen Inc., Boehringer-Ingelheim, Novartis. O.P.Zaharia: None. N.Saatmann: None. M.Huttasch: None. K.Strassburger: None. V.Burkart: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. G.J.Bönhof: None. A.Strom: None. M.Heni: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Boehringer Ingelheim Inc., Speaker's Bureau; Lilly, Bayer Inc., Sanofi, Boehringer-Ingelheim, Novo Nordisk, Amryt Pharma Plc. J.Seissler: None. J.Szendroedi: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.W.Stumvoll: None.

716-P: Improving Provider–Patient Relationships in Treatment of Young Adult Type 1 Diabetes

Aims: Type 1 diabetes mellitus (T1D) is a chronic illness that requires constant monitoring and management of one's blood glucose levels. This study focuses specifically on young adults aged 18-25 living with T1D in the United States and aims to identify strengths and areas of improvement for provider-patient relationships within young adult T1D care. Methods: An online 15-question Qualtrics survey was distributed across social media over one month, and responses were studied using descriptive, inferential, and causal statistical analysis. Results: Of the 48 responses, 56% strongly agreed that their provider listens to how they like to do things and conveys confidence in their ability to make changes, whereas 29% didn't feel trust and are unable to be open with their provider. Diabetes-specific stressors and diabetes burnout was the most selected topic that participants wanted their provider to address more often. 56.3% of participants have switched diabetes care providers due to dissatisfaction, and 47.9% have felt belittled or called a bad diabetic by a diabetes provider. Discussion: Strong provider-patient relationships that facilitate trust, comfort, and connection were related to lower HbA1C, improved diabetes control, and improved diabetes-related stress. Disclosure C.N.Diaz: None. A.Ong: None. C.Chen: None.

A role for P-selectin and complement in the pathological sequelae of germinal matrix hemorrhage

BackgroundGerminal matrix hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and subsequent neurocognitive deficits. We demonstrate vascular expression of the adhesion molecule P-selectin after GMH and investigate a strategy to specifically target complement inhibition to sites of P-selectin expression to mitigate the pathological sequelae of GMH.MethodsWe prepared two fusion proteins consisting of different anti-P-selectin single chain antibodies (scFv’s) linked to the complement inhibitor Crry. One scFv targeting vehicle (2.12scFv) blocked the binding of P-selectin to its PSGL-1 ligand expressed on leukocytes, whereas the other targeting vehicle (2.3scFv) bound P-selectin without blocking ligand binding. Post-natal C57BL/6 J mice on day 4 (P4) were subjected to collagenase induced-intraventricular hemorrhage and treated with 2.3Psel-Crry, 2.12Psel-Crry, or vehicle.ResultsCompared to vehicle treatment, 2.3Psel-Crry treatment after induction of GMH resulted in reduced lesion size and mortality, reduced hydrocephalus development, and improved neurological deficit measurements in adolescence. In contrast, 2.12Psel-Crry treatment resulted in worse outcomes compared to vehicle. Improved outcomes with 2.3Psel-Crry were accompanied by decreased P-selectin expression, and decreased complement activation and microgliosis. Microglia from 2.3Psel-Crry treated mice displayed a ramified morphology, similar to naïve mice, whereas microglia in vehicle treated animals displayed a more ameboid morphology that is associated with a more activated status. Consistent with these morphological characteristics, there was increased microglial internalization of complement deposits in vehicle compared to 2.3Psel-Crry treated animals, reminiscent of aberrant C3-dependent microglial phagocytosis that occurs in other (adult) types of brain injury. In addition, following systemic injection, 2.3Psel-Crry specifically targeted to the post-GMH brain. Likely accounting for the unexpected finding that 2.12Psel-Crry worsens outcome following GMH was the finding that this construct interfered with coagulation in this hemorrhagic condition, and specifically with heterotypic platelet–leukocyte aggregation, which express P-selectin and PSGL-1, respectively.ConclusionsGMH induces expression of P-selectin, the targeting of which with a complement inhibitor protects against pathogenic sequelae of GMH. A dual functioning construct with both P-selectin and complement blocking activity interferes with coagulation and worsens outcomes following GMH, but has potential for treatment of conditions that incorporate pathological thrombotic events, such as ischemic stroke.

Prevalence of overweight and obesity and its risk factors in adults Type 1 Diabetic patients among Saudi general population

Prevalence of overweight and obesity and its risk factors in adults Type 1 Diabetic patients among Saudi general population

Glycated haemoglobin trajectories and one-year risk of potentially avoidable hospitalisations among adult patients with type 2 diabetes from specialist outpatient clinics of a tertiary hospital: A cohort study

AimTo evaluate the association between trajectories of glycated haemoglobin (HbA1c) and potentially avoidable hospitalisations (PAH). MethodsWe performed a cohort study in a tertiary hospital in Singapore among adult type 2 diabetes patients with ≥ 3 HbA1c tests over two years. Then, we followed up for one year after the last HbA1c reading to determine the PAH outcome. Glycaemic control was analysed by (1) HbA1c trajectories through group-based trajectory modelling, and (2) mean HbA1c. PAH was defined using the Agency of Healthcare Research and Quality criteria, categorising as overall, diabetes, acute, and chronic-composites. ResultsA total of 14,923 patients (mean age: 62.9 ± 12.8 years; 55.2% men) were included. Four HbA1c trajectories were observed; low-stable (n = 9854, 66.0%), moderate-stable (n = 3125, 20.9%), high-decrease (n = 1017, 6.8%) and high-persistent (n = 927, 6.2%). Compared to the low-stable trajectory, one-year risk ratio (RR) and 95% confidence interval (CI), respectively for moderate-stable, high-decrease and high-persistent trajectories were as follows: (1) overall PAH: 1.15 (1.00–1.31), 1.53 (1.31–1.80), 1.96 (1.58–2.43); (2) diabetes PAH: 1.30 (1.04–1.64), 1.98 (1.55–2.53), 2.24 (1.59–3.15); (3) acute PAH: 1.14 (0.90–1.44), 1.29 (0.95–1.77), 1.75 (1.17–2.62); and (4) chronic PAH: 1.21 (1.02–1.43), 1.62 (1.34–1.97), 2.14 (1.67–2.75). Mean HbA1c was significantly associated with overall and chronic-composites of PAH whilst evidence of a non-linear relationship with diabetes-composite of PAH was noted. ConclusionPatients with high-decrease trajectory had a risk lower than those with persistently-high HbA1c, highlighting that a greater risk of hospitalisation conferred by poor glycaemic control is potentially reversible. Determining HbA1c trajectories could help to identify the high-risk individuals for targeted and intensive management to improve care and reduce hospitalisations.

Association of Glycemic Index Using HbA1c and Sensorineural Hearing Loss in Diabetes Mellitus Type 2 Patients: A Systematic Review and Meta-Analysis

ABSTRACT
 Objective: To systematically review the available evidence on the association of HBA1c levels and development of sensorineural hearing loss and to quantitatively analyze the available data on HBA1c levels in patients with type 2 diabetes mellitus and sensorineural hearing loss to determine an HbA1c level that may be associated with the risk of having sensorineural hearing loss.
 Methods:
 Design: Systematic Review and Meta-analysis Eligibility Criteria: Cross-sectional studies, or cohort studies which were limited to English language that investigated the correlation of glycemic index using HBA1c and sensorineural hearing loss among adult type 2 diabetic patients which were done from January 2010 to December 2021. Studies with no published outcome, incomplete data or that were ongoing as of August 1, 2022 were also excluded.
 Information Sources: MEDLINE (through PubMed), Cochrane Library, Scopus, Embase (through OVID@journal), Directory of Open Access Journals (DOAJ), Google Scholar and HERDIN Plus
 Risk of Bias: Risk of Bias was assessed using the Guidelines for Cochrane Collaboration Synthesis of Results: Results were presented using forest plots for representation.Results: A total of 8 studies were reviewed with 2,103 participants in all. Six articles compared hearing loss incidence between diabetic and non-diabetic patients. Overall, there were a total of 881 diabetic patients and 1222 non-diabetic patients. There was a significantly lower incidence of sensorineural hearing loss in non-diabetic patients with a risk ratio of 1.89, 95% CI [1.65, 2.16]. Three articles compared the HbA1c levels of diabetic patients with or without sensorineural hearing loss. Diabetic patients without sensorineural hearing loss had significantly lower HbA1c levels compared to those with sensorineural hearing loss with mean difference of 1.04, 95%CI [0.82, 1.25].Conclusion: In conclusion, this meta-analysis showed a higher prevalence rate of sensorineural hearing loss among patients with diabetes mellitus compared to non-diabetic patients. Moreover, poor glycemic control among diabetic patients with a glycemic index based on HbA1c of more than 8.3 (6.97-9.6) is associated with sensorineural hearing loss.

ЮВЕНИЛЬНАЯ ГРАНУЛЕЗОКЛЕТОЧНАЯ ОПУХОЛЬ ЯИЧНИКА У РЕБЕНКА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И ОБЗОР ЛИТЕРАТУРЫ

Juvenile granulosa cell tumor of the ovaries is a rare disease in pediatric oncology. Mostly seen in girls and young women in premenarchal age (median age 10 y/o) and is more aggressive than the adult type, but has a favorable prognosis, especially in its early stages. Large reviews and studies include patients with bot adult and juvenile types granulosa cell tumor. Due to the limited cohort of pediatric patients, there are no standards for the treatment of juvenile granulosa cell tumor in pediatric practice. Therefore, diagnosis, treatment, and long-term follow-up for this disease are based on recommendations for an adult cohort. Adjuvant chemotherapy as a curative option is used in advanced stages above the FIGO IC. For the IC stage, the issue of prescribing adjuvant chemotherapy remains debatable. Article represents analysis of the bibliographical data of the largest studies on the treatment of this disease as well as clinical case of a 15 y/o patient with juvenile granulosa cell tumor of the right ovary who had received complex treatment in the Oncological Department of the Morozov Children’s City Clinical Hospital (Moscow, Russia).

ЮВЕНИЛЬНАЯ ГРАНУЛЕЗОКЛЕТОЧНАЯ ОПУХОЛЬ ЯИЧНИКА У РЕБЕНКА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И ОБЗОР ЛИТЕРАТУРЫ

Juvenile granulosa cell tumor of the ovaries is a rare disease in pediatric oncology. Mostly seen in girls and young women in premenarchal age (median age 10 y/o) and is more aggressive than the adult type, but has a favorable prognosis, especially in its early stages. Large reviews and studies include patients with bot adult and juvenile types granulosa cell tumor. Due to the limited cohort of pediatric patients, there are no standards for the treatment of juvenile granulosa cell tumor in pediatric practice. Therefore, diagnosis, treatment, and long-term follow-up for this disease are based on recommendations for an adult cohort. Adjuvant chemotherapy as a curative option is used in advanced stages above the FIGO IC. For the IC stage, the issue of prescribing adjuvant chemotherapy remains debatable. Article represents analysis of the bibliographical data of the largest studies on the treatment of this disease as well as clinical case of a 15 y/o patient with juvenile granulosa cell tumor of the right ovary who had received complex treatment in the Oncological Department of the Morozov Children’s City Clinical Hospital (Moscow, Russia).

Types of work young adults perform to adjust to a cancer diagnosis and treatment.

e24179 Background: Patients and their caregivers perform work (i.e., demanding and arduous labor that takes resources and coordination to address) to manage their illness, relationships, and lives. A growing body of psychosocial research has investigated the communication work performed by young adults (18-39 years old at diagnosis; YAs) and their caregivers as they adjust to cancer treatment and survivorship. However, to our knowledge, no studies have examined how the four types of work identified through Theory of Illness Trajectories (i.e., everyday, illness-related, biographical, and communication) interact within cancer survivorship. Thus, the study purpose was to investigate how and why YAs describe their efforts to manage life along the cancer trajectory as work or labor. Methods: We conducted a qualitative secondary analysis leveraging three separate qualitative interview datasets that sought to describe and explain similar psychosocial aspects of the YA cancer experience. Two specific interview questions: 1) “What advice would you give to another person your age who received a similar diagnosis?” and 2) “What did you learn from your cancer experience that you wish you knew when you were diagnosed?” shaped our thematic analysis. We applied the Theory of Illness Trajectories in the open coding phase, where everyday-life work referred to recurring existing responsibilities (e.g., employment, childcare); illness work related to cancer-management tasks like taking medication and seeing physicians; biographical work involved one’s cognitive efforts to reconstruct their identity, and communication work involved the demanding use of communication to manage identities, share information, or solicit support. During axial coding, each author reviewed one-third of the data individually, making note of units that could be classified as themes related to each type of work. Results: A total of 112 participants completed qualitative interviews across the three studies. Most (71%) were female, and mean age was 26 years. Most received a diagnosis of lymphoma (33.0%), leukemia (17.9%), and breast cancer (11.6%). Data analyses are still ongoing; we are currently meeting regularly to reach consensus on our axial codes. Our final abstract will include findings from our selective coding phase, which will allow us to examine comparisons and interactions between types of work. Conclusions: Additional goals of our innovative qualitative secondary analysis are to a) to identify the most salient subtypes of biographical, illness-related, everyday, and communication work in the YA cancer context and b) to better understand how the four types of work described by theory of illness trajectories interact and whether they facilitate or hinder the performance of additional types of work.

Structured nutrition and advanced carbohydrate counting questionnaire for adult type 1 diabetes.

Structured nutrition and advanced carbohydrate counting questionnaire for adult type 1 diabetes.

The UHRF1 protein is a key regulator of retrotransposable elements and innate immune response to viral RNA in human cells

ABSTRACT While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.

Rhabdomyoma of the Oral Cavity Mimicking Reactive Lesions: A Case Report and Review of the Literature.

Extracardiac rhabdomyoma is a tumor that rarely occurs in head and neck region. Adult and fetal types of extracardiac rhabdomyoma are diagnosed only by histopathological examination. In the oral cavity, this lesion usually affects the mouth floor and tongue. Despite the low incidence, adult rhabdomyoma should be considered in the differential diagnosis of oral cavity lesions, and histopathological evaluation might be helpful for the final diagnosis. This study aims to report a rare case of rhabdomyoma mimicking reactive lesions and review the literature. A 34-year-old male was referred to the pathology department with a yellowish sessile lesion in the labial maxillary vestibule. During an excisional biopsy, a mass of unencapsulated soft tissue beneath the vestibular mucosa was observed. The yellowish color in clinical features has led to lipoma as the initial clinical diagnosis. The histological examination exhibited an encapsulated, well-circumscribed benign neoplasm composed of multiple lobules of large polygonal cells with prominent abundant granular eosinophilic cytoplasm. No cellular atypia was observed. Diagnosis of the adult type of rhabdomyoma was made by collective agreement. Rhabdomyoma can be mistaken for other reactive lesions and may resemble their appearance.

Systematic discovery of transcription factors that improve hPSC-derived cardiomyocyte maturation via temporal analysis of bioengineered cardiac tissues.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have the potential to become powerful tools for disease modeling, drug testing, and transplantation; however, their immaturity limits their applications. Transcription factor (TF) overexpression can improve hPSC-CM maturity, but identifying these TFs has been elusive. Toward this, we establish here an experimental framework for systematic identification of maturation enhancing factors. Specifically, we performed temporal transcriptome RNAseq analyses of progressively matured hPSC-derived cardiomyocytes across 2D and 3D differentiation systems and further compared these bioengineered tissues to native fetal and adult-derived tissues. These analyses revealed 22 TFs whose expression did not increase in 2D differentiation systems but progressively increased in 3D culture systems and adult mature cell types. Individually overexpressing each of these TFs in immature hPSC-CMs identified five TFs (KLF15, ZBTB20, ESRRA, HOPX, and CAMTA2) as regulators of calcium handling, metabolic function, and hypertrophy. Notably, the combinatorial overexpression of KLF15, ESRRA, and HOPX improved all three maturation parameters simultaneously. Taken together, we introduce a new TF cocktail that can be used in solo or in conjunction with other strategies to improve hPSC-CM maturation and anticipate that our generalizable methodology can also be implemented to identify maturation-associated TFs for other stem cell progenies.