Pavement ant extract is a chemotaxis repellent for C. elegans.

Ant behavior relies on a collection of natural products, from following trail pheromones during foraging to warding off potential predators. How nervous systems sense these compounds to initiate a behavioral response remains unclear. Here, we used Caenorhabditis elegans chemotaxis assays to investigate how ant compounds are detected by heterospecific nervous systems. We found that C. elegans avoid extracts of the pavement ant ( Tetramorium immigrans ) and either osm-9 or tax-4 ion channels are required for this response. These experiments were conducted in an undergraduate laboratory course, demonstrating that new insights into interspecies interactions can be generated through genuine research experiences in a classroom setting.

Positron emission tomography/computed tomography differentiates resectable thymoma from anterior mediastinal lymphoma.

OBJECTIVE: Discrete anterior mediastinal masses most often represent thymoma or lymphoma. Lymphoma treatment is nonsurgical and requires biopsy. Noninvasive thymoma is ideally resected without biopsy, which may potentiate pleural metastases. This study sought to determine if clinical criteria or positron emission tomography/computed tomography could accurately differentiate the 2, guiding a direct surgery versus biopsy decision. METHODS: A total of 48 subjects with resectable thymoma and 29 subjects with anterior mediastinal lymphoma treated from 2006 to 2019 were retrospectively examined. All had pretreatment positron emission tomography/computed tomography and appeared resectable (solitary, without clear invasion or metastasis). Reliability of clinical criteria (age and B symptoms) and positron emission tomography/computed tomography maximum standardized uptake value were assessed in differentiating thymoma and lymphoma using Wilcoxon rank-sum test, chi-square test, and logistic regression. Receiver operating characteristic analysis identified the maximum standardized uptake value threshold most associated with thymoma. RESULTS: There was no association between tumor type and age group (P = .183) between those with thymoma versus anterior mediastinal lymphoma. Patients with thymoma were less likely to report B symptoms (P < .001). The median maximum standardized uptake value of thymoma and lymphoma differed dramatically: 4.35 versus 18.00 (P < .001). Maximum standardized uptake value was independently associated with tumor type on multivariable regression. On receiver operating characteristic analysis, lower maximum standardized uptake value was associated with thymoma. Maximum standardized uptake value less than 12.85 was associated with thymoma with 100.00% sensitivity and 88.89% positive predictive value. Maximum standardized uptake value less than 7.50 demonstrated 100.00% positive predictive value for thymoma. CONCLUSIONS: Positron emission tomography/computed tomography maximum standardized uptake value of resectable anterior mediastinal masses may help guide a direct surgery versus biopsy decision. Tumors with maximum standardized uptake value less than 7.50 are likely thymoma and thus perhaps appropriately resected without biopsy. Tumors with maximum standardized uptake value greater than 7.50 should be biopsied to rule out lymphoma. Lymphoma is likely with maximum standardized uptake value greater than 12.85.

Rationale and design of a mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction.

INTRODUCTION: Ventilator-induced diaphragm dysfunction (VIDD) is an important phenomenon that has been repeatedly demonstrated in experimental and clinical models of mechanical ventilation. Even a few hours of MV initiates signaling cascades that result in, first, reduced specific force, and later, atrophy of diaphragm muscle fibers. This severe, progressive weakness of the critical ventilatory muscle results in increased duration of MV and thus increased MV-associated complications/deaths. A drug that could prevent VIDD would likely have a major positive impact on intensive care unit outcomes. We identified the JAK/STAT pathway as important in VIDD and then demonstrated that JAK inhibition prevents VIDD in rats. We subsequently developed a clinical model of VIDD demonstrating reduced contractile force of isolated diaphragm fibers harvested after ∼7 vs ∼1 h of MV during a thoracic surgical procedure. MATERIALS AND METHODS: The NIH-funded clinical trial that has been initiated is a prospective, placebo controlled trial: subjects undergoing esophagectomy are randomized to receive 6 preoperative doses of the FDA-approved JAK inhibitor Tofacitinib (commonly used for rheumatoid arthritis) vs. placebo. The primary outcome variable will be the difference in the reduction that occurs in force generation of diaphragm single muscle fibers (normalized to their cross-sectional area), in the Tofacitinib vs. placebo subjects, over 6 h of MV. DISCUSSION: This trial represents a first-in-human, mechanistic clinical trial of a drug to prevent VIDD. It will provide proof-of-concept in human subjects whether JAK inhibition prevents clinical VIDD, and if successful, will support an ICU-based clinical trial that would determine whether JAK inhibition impacts clinical outcome variables such as duration of MV and mortality.