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The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms.

Quantity of citation is often used as a surrogate measurement of an article's importance or relevance in a given field. To date, there has been no study on citation quantity or density in pediatric orthopedics. We present such an analysis. We reviewed all articles in the ISI web of science under the subheading 'orthopedics' to find articles of relevance to pediatric orthopedic surgeons. We subsequently analyzed the characteristics of the most cited articles in terms of the level of evidence, journal of publication, and subcategory of pediatric orthopedics. The majority of the top 50 articles in pediatric orthopedics were from the 1970s and 1980s. All the articles were in English. Uncontrolled case series comprised the largest single level of evidence (level IV). We describe the top 50 articles in pediatric orthopedics by citation and citation density. The level of evidence for highly cited papers was low. Although many of these articles were written by the great thinkers of our field, a need exists for more rigorous methodology.

NA Laryngoscope, 2018.

Preterm, low-birth-weight neonates are predisposed to metabolic bone disease (MBD). This survey aimed to assess screening, diagnostic, and treatment practices in U.S. level IIIB/IIIC neonatal intensive care units (NICUs). A 29-question anonymous online survey was e-mailed to American Academy of Pediatrics Perinatal Section members. 338 neonatologists, representing 246 IIIB/IIIC NICUs, responded. 86% reported MBD screening. Screening was primarily based on gestational age (71%), with thresholds <26 to <36 weeks. Other criteria included birth weight (64%), total parenteral nutrition duration (48%), X-ray findings (56%), diuretic use (41%), and exclusive breast-feeding (9.6%). Almost universally, diagnosis was based on elevated alkaline phosphatase, most commonly >500 U/L (58.6%). 52% used X-ray for diagnosis. Treatment included human milk fortification (83%), vitamin D (67%), calcium (65%), and phosphorus (65%) supplementation. Our survey confirms widespread awareness of MBD but highlights lack of consensus regarding definition, screening, and treatment. Further research is needed to develop and optimize strategies to prevent, recognize, and manage MBD.

IMPORTANCE An increasing number of surgeries are being performed for differentiated thyroid cancer (DTC). Long-term voice abnormalities are a known risk of thyroid surgery; however, few studies have used validated scales to quantify voice outcomes after surgery.OBJECTIVE To identify the prevalence, severity, and factors associated with poor voice outcomes following surgery for DTC. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional, population-based survey was distributed via a modified Dillman method to 4185 eligible patients and linked to Surveillance, Epidemiology and End Results (SEER) data from SEER sites in Georgia and Los Angeles, California, from February 1, 2017, to October 31, 2018. Multivariable logistic regression and zero-inflated negative binomial analysis were performed to determine factors associated with abnormal voice. Participants included patients undergoing surgery for DTC between January 1, 2014, and December 31, 2015, excluding those with voice abnormalities before surgery. MAIN OUTCOMES AND MEASURESAbnormal Voice Handicap Index (VHI-10) score, defined as greater than 11. The VHI-10 is designed to quantify 10 psychosocial consequences of voice disorders on a Likert scale (0, never; to 4, always).RESULTS A total of 2632 patients (63%) responded to the survey and 2325 met the inclusion criteria. With data reported as unweighted number and weighted percentage, 1792 were women (77.4%); weighted mean (SD) age was 49.4 (14.4) years. Of these, 599 patients (25.8%) reported voice changes lasting more than 3 months following surgery, 272 patients (12.7%) were identified as having an abnormal VHI-10 score, and 105 patients (4.7%) reported vocal fold motion impairment diagnosed by laryngoscopy. In multivariable analysis, factors associated with an abnormal VHI-10 score included age 45 to 54 years (reference, Յ44 years; odds ratio [OR], 1.49; 95% CI, 1.05-2.11), black race (OR, 1.73; 95% CI, 1.14-2.62), Asian race (OR, 1.66; 95% CI, 1.08-2.54), gastroesophageal reflux disease (OR, 1.67; 95% CI, 1.15-2.43), and lateral neck dissection (OR, 1.99; 95% CI, 1.11-3.56). CONCLUSIONS AND RELEVANCEA high prevalence of abnormal voice per validation with the VHI-10 emphasizes the need for heightened awareness of voice abnormalities following surgery and warrants consideration in the preoperative risk-benefit discussion, planned extent of surgery, and postoperative rehabilitation.

Background The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population. Methods A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive. Results Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were “supertasters,” experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and non-tasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables. Conclusion This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals.

Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.