Faculty Combine for Publication in Journal of Cystic Fibrosis

Drs. Katie Larson Ode (Endo), Aliye Uc (GI), and Andy Norris (Endo) teamed up for a collaborative article published in the Journal of Cystic Fibrosis on “Incretin dysfunction and hyperglycemia in cystic fibrosis: Role of acyl-ghrelin.”

The research suggests a mechanism by which elevated AG (acyl-ghrelin) contributes to CF hyperglycemia through inhibition of insulin secretion, an effect magnified by low GLP-1 and GIP. Interventions that lower ghrelin, ghrelin action, and/or raise GLP-1 or GIP might improve glycemia in CF.

Dr. Uc Publishes in Gastroenterology on Pancreatitis

Dr. Aliye Uc, Division Director of the Division of Gastroenterolgy, Hepatology, Pancreatology, and Nutrition, published a review of Pancreatitis in Children in Gastroenterology. The review summarizes the definitions, epidemiology, risk factors, diagnosis and management of pediatric pancreatitis, identifies the features that are unique to the childhood-onset disease, identifies gaps and proposes recommendations for future opportunities.

Dr. Glykys Publishes in Neurobiology of Disease

The newest faculty member to the Department, Dr. Joseph Glykys in Neurology, just had an article published in Neurobiology of Disease titled “Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water“.

J. Glykys, E. Duquette, N. Rahmati, et al., Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water, Neurobiology of Disease, https://doi.org/10.1016/j.nbd.2019.01.024.

The paper concludes that that an increase in extracellular osmolarity by mannitol mediates the efflux of [Cl-]i and water through CCCs, which results in a decrease in epileptiform activity and enhances benzodiazepine actions in the developing neocortex in vitro. Congratulations, Dr. Glykys!

Dr. Strathearn Publishes on Autism and Unresolved Trauma

Dr. Lane Strathearn, Division Director of the Division of Developmental and Behavioral Pediatrics, recently had two articles published. One article looked at mother’s unresolved trauma and how it may interfere with her ability to sensitively respond to her infant, thus affecting the development of attachment in her own child, and potentially contributing to the intergenerational transmission of trauma.

Iyengar U, Rajhans P, Fonagy P, Strathearn L, & Kim S. Unresolved Trauma and Reorganization in Mothers: Attachment and Neuroscience Perspectives. Frontiers in Psychology, 2019 10(110), 1-9.

The second article sought to estimate the prevalence and treatment patterns of Autism Spectrum Disorder (ASD) among US children using nationally representative data. This study showed that the prevalence of ASD in the United States was relatively high, and it varied substantially across US states. Almost 30% of US children with ASD did not receive behavioral or medication treatment, which calls for a critical need to understand and address the barriers for those children to receive appropriate treatments.

Xu, G., Strathearn, L., Liu, B., O’Brien, M., Kopelman, T. G., Snetselaar, L. G., & Bao, W. (2018). Prevalence and Treatment Patterns of Autism Spectrum Disorder in the United States, 2016. JAMA Pediatrics.  2018 Dec 3. doi: 10.1001/jamapediatrics.2018.4208. [Epub ahead of print].

Congratulations to Dr. Strathearn and his team on their continued successes!

New Publications from the Lab of Dr. Bassuk

Dr. Alex Bassuk, Division Director for the Division of Neurology, recently had a series of publications come out of his lab. Congratulations to Dr. Bassuk and his team on their record of scholarly activity!

Kousa YA, Zhu H, Fakhouri WD, Lei Y, Kinoshita A, Roushangar RR, Patel NK, Agopian AJ, Yang W, Leslie EJ, Busch TD, Mansour TA, Li X, Smith AL, Li EB, Sharma DB, Williams TJ, Chai Y, Amendt BA, Liao EC, Mitchell LE, Bassuk AG, Gregory S, Ashley-Koch A, Shaw GM, Finnell RH, Schutte BC. The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation. Hum Mol Genet. 2019 Jan 25. doi: 10.1093/hmg/ddz010. [Epub ahead of print] PubMed PMID: 30689861.

Tang PH, Velez G, Tsang SH, Bassuk AG, Mahajan VB. VCAN Canonical Splice Site Mutation is Associated With Vitreoretinal Degeneration and Disrupts an MMP Proteolytic Site. Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):282-293. doi: 10.1167/iovs.18-25624. PubMed PMID: 30657523.

Machlab DA, Velez G, Bassuk AG, Mahajan VB. ProSave: an application for restoring quantitative data to manipulated subsets of protein lists. Source Code Biol Med. 2018 Nov 12;13:3. doi: 10.1186/s13029-018-0070-0. eCollection 2018. PubMed PMID: 30459825; PubMed Central PMCID: PMC6233572.

Brueggeman L, Sturgeon ML, Martin RM, Grossbach AJ, Nagahama Y, Zhang A, Howard MA III, Kawasaki H, Wu S, Cornell RA, Michaelson JJ, Bassuk AG. Drug repositioning in epilepsy reveals novel anti-seizure candidates. Annals of Clinical and Translational Neurology. First published: 11 December 2018. https://doi.org/10.1002/acn3.703.

Grose and Bonthius Publish on Herpes Zoster

Drs. Chuck Grose (ID) and Dan Bonthius (Neurology) recently had an article published in the Journal of Child Neurology on Severe Herpes Zoster Following Varicella Vaccination in Immunocompetent Young Children. Congratulations Dr. Grose and Dr. Bonthius!

Abstract: Varicella vaccination is now virtually universal in North America, as well as in some European and Asian countries. Since varicella vaccine is a live attenuated virus, the virus replicates in the skin after administration and can travel via sensory nerves or viremia to become latent in the dorsal root ganglia. In some immunized children, virus reactivates within a few months to a few years to cause the dermatomal exanthem known as herpes zoster (shingles). Herpes zoster caused by vaccine virus often reactivates within the same dermatome as the site of the original varicella vaccine injection. We present evidence that occasional cases of herpes zoster following varicella vaccination in immunocompetent children can be as severe as herpes zoster following wild-type varicella. Analysis of the virus in one case disclosed that the vaccine virus causing herpes zoster was a wild-type variant with a mutation in ORF0. With regard to dermatomal localization of the viral eruption, we predict that herpes zoster of the lumbar dermatomes in children is likely to be caused by vaccine virus, because herpes zoster in those dermatomes is rare in children after wild-type varicella. One of the children with herpes zoster subsequently developed asthma, a known risk factor for herpes zoster, but none of the children had an autoimmune disease. Although postherpetic neuralgia is exceedingly rare, children who develop herpes zoster following varicella vaccination are at risk (albeit low) of developing meningoencephalitis and should be carefully observed for a few weeks.

Dr. Fischer Publishes in JCI Insight

Dr. Tony Fischer in Pulmonary Medicine, Allergy and Immunology recently published an article in JCI Insight titled “Mucus strands from submucosal glands initiate mucociliary transport of large particles”.

Abstract: Mucus produced by submucosal glands is a key component of respiratory mucociliary transport (MCT). When it emerges from submucosal gland ducts, mucus forms long strands on the airway surface. However, the function of those strands is uncertain. To test the hypothesis that mucus strands facilitate transport of large particles, we studied newborn pigs. In ex vivo experiments, interconnected mucus strands moved over the airway surface, attached to immobile spheres, and initiated their movement by pulling them. Stimulating submucosal gland secretion with methacholine increased the percentage of spheres that moved and shortened the delay until mucus strands began moving spheres. To disrupt mucus strands, we applied reducing agents tris-(2-carboxyethyl)phosphine and dithiothreitol. They decreased the fraction of moving spheres and delayed initiation of movement for spheres that did move. We obtained similar in vivo results with CT-based tracking of microdisks in spontaneously breathing pigs. Methacholine increased the percentage of microdisks moving and reduced the delay until they were propelled up airways. Aerosolized tris-(2-carboxyethyl)phosphine prevented those effects. Once particles started moving, reducing agents did not alter their speed either ex vivo or in vivo. These findings indicate that submucosal glands produce mucus in the form of strands and that the strands initiate movement of large particles, facilitating their removal from airways.

Dr. Davis Publishes in the Journal of Fungi

Dr. Davis recently had an article published on “The Zebrafish as a Model Hostfor Invasive Fungal Infections”. Congratulations, Dr. Davis!

Abstract: The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review is to provide a thorough introduction into the published studies of fungal infection in the zebrafish and the specific ways in which this model has benefited the field. In doing so, we hope to provide potential new zebrafish researchers with a snapshot of the current toolbox and prior results, while illustrating how the model has been used well and where the unfulfilled potential of this model can be found.

Dr. Widness Publishes in AAPS

Dr. Jack Widness continues his scholarly proficiency as Professor Emeritus with a recent publication in the journal of the American Association of Pharmaceutical Scientists (AAPS). The article, titled “Overlooked Issues on Pharmacokinetics Data Interpretation of Protein Drugs – a Case Example of Erythropoietin” reports on two frequently overlooked issues on pharmacokinetics data interpretation of recombinant human erythropoietin (rhEPO) and offers solutions to ensure reliable estimation of the pharmacokinetics parameters. Congratulations, Dr. Widness!

Giesinger and McNamara Publish in Journal of Paeditrics and Child Health

Congratulations to Drs. Giesinger and McNamara who recently published in the Journal of Paediatrics and Child Health titled “Clinical and Echocardiography Predictors of Response to Inhaled Nitric Oxide in Hypoxic Preterm Neonates“. “The aim of this study was to identify clinical and echocardiography predictors of response to iNO in premature infants with acute hypoxemia. We hypothesized a priori, based on anecdotal experience, that the presence of pulmonary hypertension on echocardiography may be associated with an increased likelihood of clinical inhaled nitric oxide response.”