Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

The Margaret Sloss Women\u27s Center at Iowa State University: A Model

Presents the Margaret Sloss Women\u27s Center as a model to assist in the continued development of campus-based women\u27s centers. Discusses the purpose and mission of the center and describes areas of advocacy, information and referrals, programming, and organizational structure

Mucoadhesive chitosan derivatives as novel drug carriers

Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles.Scopu

THE IMPACT OF STRUCTURE ON PHYSICAL ACTIVITY OF PRESCHOOL-AGED CHILDREN

Hannah Parker, Sarah Burkart, Layton Reesor-Oyer, Michal T. Smith, Lauren von Klinggraeff, Roddrick Dugger, James W. White III, Olivia Finnegan, Meghan Bastyr, Christopher D. Pfledderer, Elizabeth L. Adams, R. Glenn Weaver, Michael W. Beets, Bridget Armstrong. University of South Carolina, Columbia, SC. BACKGROUND: Higher levels of physical activity (PA), are associated with positive health outcomes among children. Structured environments, such as daycare/preschool, may be a potential mechanism for promoting healthy behaviors and limiting discretionary time when children may engage in unhealthy behaviors; however, the literature examining the relationship between daycare/preschool and children engaging in PA has been mixed and limited in examination at the day-level. Understanding the potential role structure may have as a mechanism to improve movement behaviors of preschool-aged children may guide the development of effective intervention strategies. The current study used intensive longitudinal data to examine the within- and between-person effects of hours spent in daycare/preschool (i.e., structure) on children’s physical activity. METHODS: Children (N=67, 4.5±0.8 yrs, 49.3% female, 65.7% White) wore an Axivity AX3 accelerometer on their wrist 24 hours/day for 14 days. Data were processed with GGIR (v2.6-4) with the Roscoe et al. (2017) intensity thresholds for preschoolers. Caregivers reported the number of hours their child attended daycare/preschool each day. We ran linear mixed-effects models predicting day-level moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA) from hours spent in daycare. We included child age, sex, and wear-time as covariates. Weekends were excluded from analysis. RESULTS: Children wore accelerometers for an average of 9.3±1.2 (range = 1-11) days and 59 children attended daycare/preschool on at least one day. Children spent an average of 4.6±3.9 hrs/day in daycare/preschool and had an average of 120.7±30.0 min of MVPA/day and an average of 118.0±33.8 min of LPA/day. Mixed models indicated that for every 1-hour extra children spent in daycare/preschool above their own average daycare/preschool time, children had 1.1 min (95%CI = 0.25, 1.93) more MVPA/day and 1.4 min (95%CI = 0.65, 2.19) more LPA/day. CONCLUSION: On days when children attend more hours of daycare/preschool, beyond their typical daycare/preschool time, they have more minutes of MVPA and LPA. Daycare/preschool, as a source of structure, may be a day-level contextual factor to help improve movement behaviors in children. Future studies should examine the impact of structure from daycare/preschool on other movement behaviors such as sleep and sedentary behavior