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Clostridioides difficile infections (CDIs) are responsible for a significant number of antibiotic-associated diarrheal cases. The standard-of-care antibiotics for C. difficile are limited to fidaxomicin and vancomycin, with the recently obsolete metronidazole recommended if both are unavailable. No new antimicrobials have been approved for CDI since fidaxomicin in 2011, despite varying rates of treatment failure among all standard-of-care drugs. Drug repurposing is a rational strategy to generate new antimicrobials out of existing therapeutics approved for other indications. Auranofin is a gold-containing anti-rheumatic drug with antimicrobial activity against C. difficile and other microbes. In a previous report, our group hypothesized that inhibition of selenoprotein biosynthesis was auranofin's primary mechanism of action against C. difficile. However, in this study, we discovered that C. difficile mutants lacking selenoproteins are still just as sensitive to auranofin as their respective wild-type strains. Moreover, we found that selenite supplementation dampens the activity of auranofin against C. difficile regardless of the presence of selenoproteins, suggesting that selenite's neutralization of auranofin is not because of compensation for a chemically induced selenium deficiency. Our results clarify the findings of our original study and may aid drug repurposing efforts in discovering the compound's true mechanism of action against C. difficile., (© 2023. Springer Nature Limited.)

Huntington disease (HD) is a progressive neurodegenerative disorder. Presymptomatic genetic testing allows at-risk individuals to clarify their risk status. Understanding the characteristics and motivations of individuals seeking HD presymptomatic genetic testing better equips genetic counselors and other healthcare professionals to provide comprehensive and personalized care. The aims of this study were to (1) determine whether the average age when individuals seek presymptomatic HD genetic testing has decreased over time, (2) assess motivations for seeking testing, (3) explore whether there is a relationship between age and motivations, and (4) explore genetic counselors' perceptions of the shift in age. Data from the US HD testing centers (N = 4) were analyzed. A small but statistically significant decrease in age of individuals seeking presymptomatic testing was observed (p = 0.045). HD community members (N = 77) were surveyed regarding presymptomatic testing motivations. Younger individuals were more likely than older individuals to cite "To learn whether or not you would develop HD" and "To make choices about further education or a career" compared to older individuals (p < 0.05). Conversely, older individuals more frequently cited "To give children a better idea of their risk" (p < 0.002). Sixteen percent of genetic counselors surveyed (6/37) perceived a change in age of testing. All of these respondents had provided HD testing for ten or more years and anecdotally believed the age at testing has decreased over time. Study results help providers personalize counseling based on patient's age and serve as a starting point for more research into the relationship between age at testing and motivations for testing.

Background/aims: The study aimed to characterize the use of genetic testing after abnormal screening ultrasound., Methods: We performed a retrospective review of patients undergoing genetic testing after abnormal ultrasound. Genetic evaluation consisted of noninvasive prenatal screening (NIPS) or amniocentesis. Classification of ultrasound findings, type of genetic testing, and results were collected., Results: A total of 139 subjects underwent genetic evaluation after abnormal screening ultrasound. Screening via NIPS was pursued by 61 (44%) patients while 78 (56%) proceeded directly to amniocentesis. Patients electing for amniocentesis had more cardiac, neurologic, and gastrointestinal malformations while soft markers for aneuploidy prompted more NIPS screening. Results were negative in 85% of the NIPS group compared to 60% of the amniocentesis group. Only 8% of patients who underwent NIPS proceeded to diagnostic testing., Conclusion: Patients pursuing NIPS after abnormal ultrasound had more soft markers of aneuploidy. Patients pursuing diagnostic testing were more likely to have major structural malformations and more total abnormalities identified. Patients who proceeded directly to amniocentesis were more likely to have abnormal genetic testing., (© 2017 S. Karger AG, Basel.)

Objectives: To evaluate the risk of emergent cesarean delivery with the use of neuraxial anesthesia for external cephalic version in a single practice., Background: Randomized trials have shown increased external cephalic version success when neuraxial anesthesia is used, without additional risk. We hypothesized that in our actual clinical practice, outside the confines of randomized trials, neuraxial anesthesia could be associated with an increased risk of emergent cesarean delivery., Methods: This retrospective cohort study included all women who underwent external cephalic version at a single institution with and without neuraxial anesthesia. The primary outcome was the incidence of emergent cesarean delivery (defined as delivery within 4hours of version). Secondary outcomes were version success and ultimate mode of delivery., Results: A total of 135 women underwent external cephalic version procedures; 58 with neuraxial anesthesia (43.0%) and 77 without (57.0%). Location of the procedure, tocolytic therapy, and gestational age were different between groups. An increased rate of emergent cesarean delivery was found in procedures with neuraxial anesthesia compared to procedures without (5/58 (8.6%) compared to 0/77 (0.0%); 95% CI for difference, 1.4 to 15.8%; P=0.013)., Conclusion: In this single hospital's practice, patients who may be at higher risk of complications and have a lesser likelihood of success were provided NA for ECV. As a result, the use of neuraxial anesthesia for external cephalic version was associated with a higher rate of emergent cesarean delivery. Obstetric and anesthetic practices should evaluate their patient selection and procedure protocol for external cephalic version under neuraxial anesthesia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Emotional intelligence (EI) has been associated with increased academic achievement, but its impact on medical education is relatively unexplored. This study sought to evaluate change in EI, performance outcomes, and team cohesion within a team-based medical school anatomy course. Forty-two medical students completed a pre-course and post-course Schutte Self-Report Emotional Intelligence Test (SSEIT). Individual EI scores were then compared with composite course performance grade and team cohesion survey results. Mean pre-course EI score was 140.3 out of a possible 160. During the course, mean individual EI scores did not change significantly (P = 0.17) and no correlation between EI scores and academic performance was noted (P = 0.31). In addition, EI did not correlate with team cohesion (P = 0.16). While business has found significant utility for EI in increasing performance and productivity, its role in medical education is still uncertain., (© 2015 American Association of Anatomists.)

Cigarette smoke is a common environmental insult associated with increased risk of developing airway diseases such as wheezing and asthma in neonates and children. In adults, asthma involves airway remodeling characterized by increased airway smooth muscle (ASM) cell proliferation and increased extracellular matrix (ECM) deposition, as well as airway hyperreactivity. The effects of cigarette smoke on remodeling and contractility in the developing airway are not well-elucidated. In this study, we used canalicular-stage (18-20 wk gestational age) human fetal airway smooth muscle (fASM) cells as an in vitro model of the immature airway. fASM cells were exposed to cigarette smoke extract (CSE; 0.5-1.5% for 24-72 h), and cell proliferation, ECM deposition, and intracellular calcium ([Ca(2+)]i) responses to agonist (histamine 10 μM) were used to evaluate effects on remodeling and hyperreactivity. CSE significantly increased cell proliferation and deposition of ECM molecules collagen I, collagen III, and fibronectin. In contrast, [Ca(2+)]i responses were not significantly affected by CSE. Analysis of key signaling pathways demonstrated significant increase in extracellular signal-related kinase (ERK) and p38 activation with CSE. Inhibition of ERK or p38 signaling prevented CSE-mediated changes in proliferation, whereas only ERK inhibition attenuated the CSE-mediated increase in ECM deposition. Overall, these results demonstrate that cigarette smoke may enhance remodeling in developing human ASM through hyperplasia and ECM production, thus contributing to development of neonatal and pediatric airway disease., (Copyright © 2014 the American Physiological Society.)

Object: The aim in this study was to describe the clinical presentation, differential diagnosis, and risk for neurofibromatosis Type 2 (NF2) in pediatric patients presenting with cerebellopontine angle (CPA) and internal auditory canal (IAC) tumors., Methods: The authors conducted a retrospective study at a tertiary care academic referral center. All patients with an age ≤ 18 years who had presented with an extraaxial CPA or IAC tumor between 1987 and 2012 were included in the study cohort. Data regarding symptoms, diagnosis, tumor characteristics, and NF2 status were collected and analyzed., Results: Sixty patients (55% female, 45% male) harboring 87 tumors were identified. The mean age at diagnosis was 12.8 years (median 14.0 years, range 0.9-18.9 years). Schwannomas were the most commonly identified lesions (57 of 87 tumors, including 52 vestibular, 3 facial, and 2 trigeminal schwannomas), followed by meningiomas (5 of 87) and epidermoid cysts (4 of 87). Six malignant tumors were diagnosed, including small-cell sarcoma, squamous cell carcinoma, malignant meningioma, atypical rhabdoid-teratoid tumor, endolymphatic sac tumor, and malignant ganglioglioma. Headache, followed by hearing loss and imbalance, was the most common presenting symptom, whereas dysphagia, otalgia, and facial pain were uncommon. Neurofibromatosis Type 2 was diagnosed in 20 (61%) of 33 patients with vestibular schwannoma (VS), while the other 13 patients (39%) had sporadic tumors. Nineteen of the 20 patients with NF2 met the diagnostic criteria for that disorder on initial presentation, and 15 of them presented with bilateral VS. At the last follow-up, 19 of the 20 patients subsequently diagnosed with NF2 demonstrated bilateral VSs, whereas 1 patient with a unilateral VS and multiple other NF2-associated tumors has yet to demonstrate a contralateral VS to date. Only 1 patient presenting with an isolated unilateral VS and no family history of NF2 demonstrated a contralateral VS on subsequent radiological screening., Conclusions: Cerebellopontine angle and IAC tumors in the pediatric population are rare. There are several noteworthy differences between the adult and pediatric populations harboring these lesions. While VS is the most common pathology in both age groups, the lesion was found in only 60% of the pediatric patients in the present study. Unlike in adults, VSs in the pediatric population were associated with NF2 in over one-half of all cases. The majority of pediatric patients with NF2 fulfilled the diagnostic criteria at initial presentation; however, approximately 7% of patients presenting with a seemingly sporadic (no family history of NF2) unilateral VS will meet the criteria for NF2 later in life. Finally, malignancies account for a significantly higher percentage (10%) of cases among pediatric patients. These findings underscore the importance of early screening and close radiological follow-up and may be helpful in patient counseling.

Objective: To investigate surgical, anesthetic, and device-related complications as well as auditory and speech-language development outcomes associated with cochlear implantation (CI) in children 12 months of age and younger., Study Design: Retrospective chart review., Setting: Tertiary academic referral center., Patients: All children with severe-to-profound sensorineural hearing loss who underwent cochlear implantation at 12 months of age or younger and an audiometric control group implanted between 13 and 24 months of age., Main Outcome Measures: Anesthetic and surgical course; major and minor surgical, anesthetic and device-related complications; postoperative disposition; postoperative auditory receptive and expressive language development., Results: Twenty-six patients (41 ears) met criteria. The median duration of follow-up was 58 months. No major surgical or anesthetic complications occurred. One patient (4%) experienced device failure, which required revision surgery and implant exchange. Two other patients (8%) had individual electrode anomalies that were treated with map exclusion. At the last recorded follow-up, 73% of patients were performing at or above the level of normal-hearing age-matched peers. Patients that were implanted at 12 months of age or younger reached age-appropriate speech and language skills by 24 months of age compared with 40 months for the older pediatric control group., Conclusion: The current study demonstrates that CI provides substantial benefit among infant recipients. Furthermore, when performed by an experienced cochlear implant and pediatric anesthesia team, the surgical and anesthetic risks are similar to that expected with both older pediatric and adult patients., ((C) 2013 Otology & Neurotology, Inc.)

The detrimental effects of elevated intensities of mid-UV radiation (UVB), a result of stratospheric ozone depletion during the austral spring, on the primary producers of the Antarctic marine ecosystem have been well documented. Here we report that natural populations of Antarctic zooplankton also sustain significant DNA damage [measured as cyclobutane pyrimidine dimers (CPDs)] during periods of increased UVB flux. This is the first direct evidence that increased solar UVB may result in damage to marine organisms other than primary producers in Antarctica. The extent of DNA damage in pelagic icefish eggs correlated with daily incident UVB irradiance, reflecting the difference between acquisition and repair of CPDs. Patterns of DNA damage in fish larvae did not correlate with daily UVB flux, possibly due to different depth distributions and/or different capacities for DNA repair. Clearance of CPDs by Antarctic fish and krill was mediated primarily by the photoenzymatic repair system. Although repair rates were large for all species evaluated, they were apparently inadequate to prevent the transient accumulation of substantial CPD burdens. The capacity for DNA repair in Antarctic organisms was highest in those species whose early life history stages occupy the water column during periods of ozone depletion (austral spring) and lowest in fish species whose eggs and larvae are abundant during winter. Although the potential reduction in fitness of Antarctic zooplankton resulting from DNA damage is unknown, we suggest that increased solar UV may reduce recruitment and adversely affect trophic transfer of productivity by affecting heterotrophic species as well as primary producers.

Members of the phylum Cnidaria are the lowest extant organisms to possess a nervous system and are the first that are known to contain cells that produce action potentials carried exclusively by Na+ ions. They thus occupy an important position in the evolution of Na+ channels. A cDNA encoding a 198-kDa protein with high sequence identity to known Na+ channels was isolated from the scyphozoan jellyfish Cyanea capillata. The similarity between this and other Na+ channels is greatest in the transmembrane segments and the putative pore region and less so in the cytoplasmic loops that link the four domains of the protein. Phylogenetic analysis of the deduced protein reveals that it is closely related to known Na+ channels, particularly those of squid and Drosophila, and more distantly separated from Ca2+ channels. Scrutiny of the Cyanea channel in regions corresponding to those purported to form the tetrodotoxin receptor and selectivity filter of Na+ channels in higher animals reveals several anomalies that suggest that current models of the location of the tetrodotoxin binding site and Na+ channel selectivity filter are incomplete.

Two experiments investigated the release from PI following a shift in mode of presentation of the study words. In each experiment, the interpolated task required processing of both auditory (A) and visual (V) information. The results were the same with mixed lists (Experiment I) and with independent groups (Experiment II): A release from PI was obtained following an A to V shift but not following a V to A shift. It was concluded that the mixed-modality filler task has functional characteristics very similar to those of an A filler and that the filler task influences the memory code for study items.