Search

The lung surfactant proteins are recognized as critical not only for their role in lowering lung surface tension but also in innate host defense. Reports have shown that some asthmatic patients have decreased levels of one member of this protein family in particular, surfactant protein-A (SP-A). Our studies set out to determine the contribution of SP-A to the response of a key effector cytokine in asthma, IL-13. Our studies employ both animal models sufficient and deficient in SP-A challenged with IL-13 and primary epithelial cells from participants with asthma that are exogenously treated with SP-A in the context of IL-13 challenge. The inflammatory response and mucin production were assessed in both model systems. As compared with WT mice, we show that the activity of IL-13 is dramatically augmented in SP-A−/− mice, which have significantly increased neutrophil and eosinophil recruitment, mucin production and asthma-associated cytokines in the bronchoalveolar lavage fluid. In parallel, we show asthma-associated factors are attenuated in human cells from asthma subjects when exogenous SP-A is added during IL-13 challenge. Although many of these phenotypes have previously been associated with STAT6 signaling, SP-A inhibited IL-13-induced STAT3 phosphorylation in mice and in human epithelial cells while having little effect on STAT6 phosphorylation. In addition, when either STAT3 or IL-6 were inhibited in mice, the phenotypes observed in SP-A−/− mice were significantly attenuated. These studies suggest a novel mechanism for SP-A in asthma as a modulator of IL-13-induced inflammation via mediating downstream IL-6/STAT3 signaling.

The implementation of Enhanced Recovery After Surgery (ERAS) guidelines has been widely studied among various surgical specialties. We aimed at comparing the perioperative outcomes and compliance with ERAS protocol in bariatric surgery at our center. An observational review of a prospectively maintained database was performed. Patients who underwent primary bariatric surgery (gastric bypass or sleeve gastrectomy) between January 2011 and June 2018 were included. Patients were divided into pre- and post-ERAS groups. Data including basic demographic information, length of hospital stay, 30-day perioperative complications, and readmission rates were collected. Compliance with elements of ERAS was assessed using a combination of chart review and a prospectively implemented checklist. P

Hearing loss is one of the most common human sensory disabilities, adversely affecting communication, socialization, mood, physical functioning, and quality of life. In addition to age and noise-induced damage, ototoxicity is a common cause of sensorineural hearing loss with chemotherapeutic agents, for example, cisplatin, being a major contributor. Zebrafish (Danio rerio) are an excellent model to study hearing loss as they have neurosensory hair cells on their body surface that are structurally similar to those within the human inner ear. Anatomic assays of toxin-mediated hair cell damage in zebrafish have been established; however, using fish swimming behavior--rheotaxis--as a biomarker for this anatomic damage was only recently described. We hypothesized that, in parallel, multilane measurements of rheotaxis could be used to create a high-throughput platform for drug development assessing both ototoxic and potentially otoprotective compounds in real time. Such a device was created, and results demonstrated a clear dose response between cisplatin exposure, progressive hair cell damage, and reduced rheotaxis in zebrafish. Furthermore, pre-exposure to the otoprotective medication dexamethasone, before cisplatin exposure, partially rescued rheotaxis swimming behavior and hair cell integrity. These results provide the first evidence that rescued swimming behavior can serve as a biomarker for rescued hair cell function. Developing a drug against hearing loss represents an unmet clinical need with global implications. Because hearing loss from diverse etiologies may result from common end-effects at the hair cell level, lessons learned from the present study may be broadly used.

Objective The aim of our study is to determine if a fresh cadaver model (FCM) for the instruction of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules is a practical method for instruction. Study Design Pre- and postinstruction assessment of medical students' ability to perform US-guided FNA of artificially created thyroid nodules placed adjacent to the thyroid gland of a fresh cadaver. Setting University-based fresh cadaver laboratory. Subjects and Methods Study participants included a total of 17 first- and second-year medical students with minimal US training. Technical skills were assessed using a 10-item checklist. In addition, a cognitive assessment regarding the indications, contraindications, and complications of the procedure was completed. A postinstruction assessment was provided for participants 5 weeks after their initial assessment. Differences between pre- and postinstruction assessment scores of technical skills were analyzed using McNemar's test. The mean cognitive knowledge gain was analyzed using a paired 2-sample t test. Results Eight of 10 items on the skills checklist were statistically significant between pre- and postinstruction skills assessment ( P < .05). There was a statistically significant change in cognitive knowledge gain regarding the contraindications of the procedure ( P = .001), but not for indications or complications ( P = .104 and P = .111, respectively). Conclusion US-guided FNA continues to be an important diagnostic procedure in the workup of thyroid nodules, making it an essential skill to integrate into surgical skills lab. Our FCM for the instruction of US-guided FNA is the first of its kind, and this pilot study shows this is a viable method for instruction.

Objectives:Develop a functional assay of zebrafish (Danio rerio) swimming behavior correlated with anatomic studies of hair cells along the lateral line as a platform for high-throughput drug devel...

Single nucleotide polymorphisms (SNPs) are abundant in genomes of all species and biologically informative markers extensively used across broad scientific disciplines. Newly identified SNP markers are publicly available at an ever-increasing rate due to advancements in sequencing technologies. Efficient, cost-effective SNP genotyping methods to screen sample populations are in great demand in well-equipped laboratories, but also in developing world situations. Dual Probe TaqMan assays are robust but can be cost-prohibitive and require specialized equipment. The Mismatch Amplification Mutation Assay, coupled with melt analysis (Melt-MAMA), is flexible, efficient and cost-effective. However, Melt-MAMA traditionally suffers from high rates of assay design failures and knowledge gaps on assay robustness and sensitivity. In this study, we identified strategies that improved the success of Melt-MAMA. We examined the performance of 185 Melt-MAMAs across eight different pathogens using various optimization parameters. We evaluated the effects of genome size and %GC content on assay development. When used collectively, specific strategies markedly improved the rate of successful assays at the first design attempt from ~50% to ~80%. We observed that Melt-MAMA accurately genotypes across a broad DNA range (~100 ng to ~0.1 pg). Genomic size and %GC content influence the rate of successful assay design in an independent manner. Finally, we demonstrated the versatility of these assays by the creation of a duplex Melt-MAMA real-time PCR (two SNPs) and conversion to a size-based genotyping system, which uses agarose gel electrophoresis. Melt-MAMA is comparable to Dual Probe TaqMan assays in terms of design success rate and accuracy. Although sensitivity is less robust than Dual Probe TaqMan assays, Melt-MAMA is superior in terms of cost-effectiveness, speed of development and versatility. We detail the parameters most important for the successful application of Melt-MAMA, which should prove useful to the wider scientific community.