BackgroundAngelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3am-/p+), as well as complete loss of Ube3a expression (Ube3am-/p-), have been reproduced in the mouse model used here.ResultsHere we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3am+/p+, Ube3am-/p+, Ube3am-/p-) were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.ConclusionsAlthough hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

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Introduction Early diagnosis of pediatric syndromes that are rare and involve multiple systems can be challenging. Rapid onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysregulation characterizes ROHHAD syndrome which, if undiagnosed, can lead to potentially harmful outcomes including deferring radiological workup for a neural crest tumor (which has an over 50% association) and cardiopulmonary arrest. Report of case(s) A 10-year-old female with a history of obesity, precocious puberty, recurrent hypothermia, recurrent sodium derangements, bilateral ptosis, seizure disorder, and GERD initially presented to sleep clinic as a 4-year-old in 2017 when she recently began snoring with excessive daytime sleepiness as a result of rapid onset of weight gain. BMI at that time was 99th percentile and Epworth was 11. An in-lab polysomnography revealed severe OSA with AHI 26.4 events/hour; nocturnal hypoxemia with TS90 27% and O2 nadir 70%; and sleep related hypoventilation based on elevated pCO2 on end-tidal capnometry. Patient underwent adenotonsillectomy, revision adenoidectomy, and was started on CPAP before transitioning to BiPAP over the span of the next several years with serial polysomnographies ultimately showing significant improvement of sleep apnea with AHI 5.4 events/hour. Sleep-related hypoventilation, however, remained persistent with blood gases showing pCO2 as high as 89. PHOX2B gene testing was negative and secondary causes of hypoventilation were ruled out. During this time, she was also followed by Endocrinology for suspected hypothalamic dysfunction resulting in precocious puberty, deceleration of growth rate, sodium derangements. Autonomic dysfunction was also suspected due to recurrent hypothermia including a recent admission for Temperature < 95F and ophthalmologic abnormalities including bilateral ptosis. At a multidisciplinary care conference, a working diagnosis of ROHHAD syndrome was made based on the rapid onset of obesity, hypoventilation on sleep studies and CBGs, hypothalamic dysfunction, and autonomic degeneration. Workup for neural crest tumor with MRI chest and abdomen unremarkable. Outside academic consultation was sought for management which recommended shared decision-making regarding steroids, immunosuppressive therapy (eg rituximab, cyclophosphamide), and IVIG. Conclusion For ROHHAD syndrome, there are very few documented cases in the United States and there is no known laboratory marker; diagnosis remains clinical and takes multidisciplinary collaboration, education, and a high degree of suspicion. Support (if any)

The most widely used language in research, business, politics and other areas of life in our twenty first century is the English language. The invasion of India by the British company and later by British government contributed immensely to the spreading of the language. The paper elaborates the effectiveness of English in our day today life and also how to study the same that is either as a language or a part of the curriculum. As English has come to us a result of invasion of British it is the foreign language nearest to our civilisation and we must learn it properly so that we can easily use it as our weapon against our opponents in this competitive world. The paper tells about the importance of English language and the methods which must be implied to learn the language properly so that it is not difficult for is to communicate with the people around the globe.

Introduction Obstructive Sleep Apnea (OSA) and Nonalcoholic Fatty Liver Disease (NAFLD) are two conditions that have increased in prevalence in the United States. NAFLD is a spectrum of liver disease ranging from steatosis to non-alcoholic steatohepatitis (NASH) to cirrhosis. The purpose of this project is to study the relationship between OSA, measured by apnea-hypopnea index and/or arterial oxygen saturation nadir (O2 nadir) during sleep (independent variable) vs. extent of NAFLD as measured by non-invasive scores such as NAFLD Fibrosis score, aminotransferase to platelet ratio index (APRI), BARD score and FIB-4 score (dependent variable). Methods A convenient sample of 91 haphazardly selected veterans with OSA and NAFLD from the Veterans Affairs (VA) Computerized Record System (CPRS) system were included in the study. NAFLD eligibility was determined by abdominal ultrasound, CT scan, MRI, or biopsy. Dependent variables were NAFLD scores of APRI, NAFLD Fibrosis, BARD, and FIB-4. OSA was determined by in-lab polysomnogram or home sleep study. Independent variables were AHI, O2 nadir, age and body mass index (BMI). Patients with a history of alcohol abuse or Hepatitis B or C were excluded from the study. A multiple regression analysis was used to describe the relationship between OSA and NAFLD scores. P< 0.05 was considered statistically significant. Results Age correlated with FIB-4 score, BARD score, and NAFLD fibrosis score (p = < 0.001, 0.003, < 0.001, respectively). BMI correlated with NAFLD fibrosis score (p < 0.001). When controlled for age and BMI, AHI and O2 nadir did not correlate with APRI, NAFLD fibrosis, BARD, or FIB-4 scores. Conclusion OSA measured by AHI and O2 nadir do not correlate with severity of fatty liver disease as measured by APRI, NAFLD fibrosis, BARD, or FIB-4 scores. Support (if any) None