The implications of this are significant. This is The Matrix of knowledge translation. Crown All rights reserved.AIM OF STUDY Gastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado. METHODS A case-control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into 30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36-14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03). CONCLUSIONS Young maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis. TYPE OF STUDY Prognosis Study. LEVEL OF EVIDENCE Level III. BACKGROUND The effect of the consolidation of neonatal pediatric surgical cases to limited surgeons within a hospital is unknown. We elected to model the distribution of complex neonatal procedures using an economic measure of market concentration, the Herfindahl-Hirschmann Index (HHI), and study its effect on outcomes of index pediatric surgical operations. METHODS We used data from 49 US children's hospitals between 2007 and 2017 for the following procedures congenital diaphragmatic hernia repair (CDH), esophageal atresia and tracheoesophageal fistula repair (EA/TEF), and pull-through for Hirschsprung disease (HD). Mixed effects logistic regression modeling was used to adjust for salient patient characteristics to determine the effect of HHI on in-hospital mortality, condition-specific one-year re-operation, and one-year unplanned readmissions. RESULTS A total of 2270 infants were identified who underwent surgery for the three conditions of interest. On multivariable analysis, increasing HHI was not associated with differences in mortality or condition-specific re-operation within the first year. A decrease in the number of unplanned readmissions at highly concentrated centers was seen for HD (RR 0.8 CI (0.69-0.97), p = 0.02) and CDH (RR 0.4 CI (0.28-0.71), p  less then  0.001). CONCLUSIONS Pediatric surgical specialization did not affect mortality or condition-specific re-operation. However, it did decrease the number of unplanned readmissions following CDH repairs and pull-throughs for HD. STUDY DESIGN Retrospective Cohort Study. LEVEL OF EVIDENCE Level II. We sought to explore the current landscape of team composition in the provision of major head and neck ablative and reconstructive surgery in the UK. We conducted a survey of maxillofacial surgery units and compiled data on the operating model adopted at each institution. Our survey confirmed 54 active maxillofacial units undertaking microvascular free flap reconstructive surgery, with 44 (82%) hospitals adopting a two-team operative approach. We found no significant association between hospital type and volume of free flaps undertaken and prevailing operating team model. Our study provides an interesting snapshot of the current head and neck microvascular reconstructive practice in the UK. Steroid sulfatase (STS) has recently emerged as a drug target for management of hormone-dependent malignancies. In the present study, a new series of twenty-one aryl amido-linked sulfamate derivatives 1a-u was designed and synthesized, based upon a cyclohexyl lead compound. All members were evaluated as STS inhibitors in a cell-free assay. Adamantyl derivatives 1h and 1p-r were the most active with more than 90% inhibition at 10 µM concentration and, for those with the greatest inhibitory activity, IC50 values were determined. These compounds exhibited STS inhibition within the range of ca 25-110 nM. Amongst them, compound 1q possessing a o-chlorobenzene sulfamate moiety exhibited the most potent STS inhibitory activity with an IC50 of 26 nM. Furthermore, to assure capability to pass through the cell lipid bilayer, compounds with low IC50 values were tested against STS activity in JEG-3 whole-cell assays. Consequently, 1h and 1q demonstrated IC50 values of ca 14 and 150 nM, respectively. Thus, compound 1h is 31 times more potent than the corresponding cyclohexyl lead (IC50 value = 421 nM in a JEG-3 whole-cell assay). Furthermore, the most potent STS inhibitors (1h and 1p-r) were evaluated for their antiproliferative activity against the estrogen-dependent breast cancer cell line T-47D. They showed promising activity with single digit micromolar IC50 values (ca 1-6 µM) and their potency against T-47D cells was comparable to that against STS enzyme. In conclusion, this new class of adamantyl-containing aryl sulfamate inhibitor has potential for further development against hormone-dependent tumours. Disabling hearing loss is expected to affect over 900 million people worldwide by 2050. The World Health Organization estimates that the annual economic impact of hearing loss globally is US$ 750 billion. The inability to hear may complicate effective interpersonal communication and negatively impact personal and professional relationships. Recent advances in the genetic diagnosis of inner ear disease have keenly focused attention on strategies to restore hearing and balance in individuals with defined gene mutations. Mouse models of human hearing loss serve as the primary approach to test gene therapies and pharmacotherapies. The goal of this review is to articulate the rationale for fetal gene therapy and pharmacotherapy to treat congenital hearing loss and vestibular dysfunction. The differential onset of hearing in mice and humans suggests that a prenatal window of therapeutic efficacy in humans may be optimal to restore sensory function. Mouse studies demonstrating the utility of early fetal intervention in the inner ear show promise. We focus on the modulation of gene expression through two strategies that have successfully treated deafness in animal models and have had clinical success for other conditions in humans gene replacement and antisense oligonucleotide-mediated modulation of gene expression. https://www.selleckchem.com/products/eidd-2801.html The recent establishment of effective therapies targeting the juvenile and adult mouse provide informative counterexamples where intervention in the maturing and fully functional mouse inner ear may be effective. Distillation of the current literature leads to the conclusion that novel therapeutic strategies to treat genetic deafness and imbalance will soon translate to clinical trials.