Deciphering the underlying mechanisms of the pharyngeal pumping motions in Caenorhabditis elegans.

The pharynx of the nematode Caenorhabditis elegans is a neuromuscular organ that exhibits typical pumping motions, which result in the intake of food particles from the environment. In-depth inspection reveals slightly different dynamics at the various pharyngeal areas, rather than synchronous pumping motions of the whole organ, which are important for its effective functioning. While the different pumping dynamics are well characterized, the underlying mechanisms that generate them are not known. In this study, the C. elegans pharynx was modeled in a bottom-up fashion, including all of the underlying biological processes that lead to, and including, its end function, food intake. The mathematical modeling of all processes allowed performing comprehensive, quantitative analyses of the system as a whole. Our analyses provided detailed explanations for the various pumping dynamics generated at the different pharyngeal areas; a fine-resolution description of muscle dynamics, both between and within different pharyngeal areas; a quantitative assessment of the values of many parameters of the system that are unavailable in the literature; and support for a functional role of the marginal cells, which are currently assumed to mainly have a structural role in the pharynx. In addition, our model predicted that in tiny organisms such as C. elegans, the generation of long-lasting action potentials must involve ions other than calcium. Our study exemplifies the power of mathematical models, which allow a more accurate, higher-resolution inspection of the studied system, and an easier and faster execution of in silico experiments than feasible in the lab.

Promoting a culture of reciprocity to build social capital in advanced practice nursing students.

ABSTRACT: A virtual activity integrating the evidence-based Reciprocity Ring model was designed to enhance confidence and skills for building social capital for advanced practice registered nursing (APRN) students. The central objective of the activity was to reduce the stigma of asking for help by providing a framework for the balanced exchange of favors, thus supporting new connections and feelings of trust among APRN students. Students from two APRN practice tracks ( N = 44) participated in a virtual Reciprocity Ring activity where they could post and respond to requests for help. On average, students posted 2.5 requests and received three offers for assistance; 220 connections were made overall with the major theme requests related to stress management. A retrospective survey was administered at the conclusion of the activity. Questions inquired about student confidence before, and then after, the activity for identifying resources, providing help to others, finding personal support when needed, accessing resources related to academic success, and finding solutions to problems. Student mean confidence scores were significantly higher after the activity compared with mean confidence scores before the activity ( p = .01). Additionally, the effect size was large (Cohen d = 0.89). Therefore, we suggest that integrating Reciprocity Ring exercises into nursing curricula and practice can be a useful tool for promoting skills related to productive help-seeking that will support APRN students' academic and professional success.

A Comparison of SARS-COV-2 Neutralizing Antibody Therapies in High-Risk Patients with Mild to Moderate COVID-19 Disease at a Single Academic Hospital.

BACKGROUND: Bamlanivimab and casirivimab/imdevimab are recombinant neutralizing monoclonal antibodies that decrease viral load in patients with coronavirus disease 2019 (COVID-19) and can decrease hospitalizations. Few data exist comparing these two therapies. OBJECTIVE: Our aim was to compare the efficacy and safety of bamlanivimab and casirivimab/imdevimab in emergency department (ED) patients with COVID-19 who met criteria for monoclonal antibody therapy. METHODS: We performed a single-center, open-label, prospective study in adult ED patients with confirmed COVID-19 and high-risk features for hospitalization. Enrolled patients received bamlanivimab or casirivimab/imdevimab, depending on the day of the week that they arrived. We observed patients for post-infusion-related reactions and contacted them on days 5, 10, and 30. The primary outcome was the number of hospitalizations through day 30. In addition, we compared groups with regard to return visits to the ED, symptom improvement, antibody-induced adverse events, and deaths. RESULTS: Between December 17, 2020 and January 17, 2021, 321 patients completed the study. We found no statistically significant difference in the rate of subsequent hospitalization between groups (bamlanivimab: n = 18 of 201 [8.9%] and casirivimab/imdevimab: n = 13 of 120 [10.8%]; p = 0.57). In addition, we found no statistically significant differences between groups regarding return visits to the ED or symptom improvement. One patient had a possible adverse reaction to the treatment, and 1 patient died. Both of these events occurred in the bamlanivimab group. CONCLUSIONS: We found no statistically significant differences in rates of subsequent hospitalization or other outcomes for ED patients with COVID-19 when they received bamlanivimab as opposed to casirivimab/imdevimab. Adverse events were rare in both groups.

Attention Robustly Gates a Closed-Loop Touch Reflex.

Rats' large whiskers (macrovibrissae) are used to explore their nearby environment, typically using repetitive protraction-retraction "whisking" motions that are coordinated with head and body movements [1-8]. Once objects are detected, the rat can further explore the object tactually by using both the macrovibrissae and an array of shorter, stationary microvibrissae on the chin, as well as by using the lips [9-11]. When touch occurs during whisking, a fast reflexive response, termed a touch-induced pump (TIP), may be triggered. During a TIP, the whisker slightly retracts and protracts again, doubling the number of pressure onsets per contact. In head-fixed rats, TIPs occur in ∼25% of the contacts [12]. Here we report that the occurrence of TIPs depends strongly on attention, indicated by head-turning toward an object: when rats intended to explore an object, either after encountering it during free exploration or when expecting its existence, the probability of a TIP increased from <30% to >65% without an increase in TIP latency. TIP regulation was unilateral and specific to the attended object; when two objects were palpated bilaterally simultaneously, TIP probability increased to >65% and decreased to <20% for contacts with the apparently-attended and apparently-unattended object, respectively. A data-driven computational model indicates that attentional gating could not be triggered by object contact, due to temporal constraints; rather, it could be based on a normally enabled or whisking-triggered scheme. Taken together, our results suggest that object-related attention regulates contact dynamics by gating the operation of a brainstem motor-sensory-motor loop and that this regulation is optimized for fast reaction.

Tactile modulation of whisking via the brainstem loop: statechart modeling and experimental validation.

Rats repeatedly sweep their facial whiskers back and forth in order to explore their environment. Such explorative whisking appears to be driven by central pattern generators (CPGs) that operate independently of direct sensory feedback. Nevertheless, whisking can be modulated by sensory feedback, and it has been hypothesized that some of this modulation already occurs within the brainstem. However, the interaction between sensory feedback and CPG activity is poorly understood. Using the visual language of statecharts, a dynamic, bottom-up computerized model of the brainstem loop of the whisking system was built in order to investigate the interaction between sensory feedback and CPG activity during whisking behavior. As a benchmark, we used a previously quantified closed-loop phenomenon of the whisking system, touched-induced pump (TIP), which is thought to be mediated by the brainstem loop. First, we showed that TIPs depend on sensory feedback, by comparing TIP occurrence in intact rats with that in rats whose sensory nerve was experimentally cut. We then inspected several possible feedback mechanisms of TIPs using our model. The model ruled out all hypothesized mechanisms but one, which adequately simulated the corresponding motion observed in the rat. Results of the simulations suggest that TIPs are generated via sensory feedback that activates extrinsic retractor muscles in the mystacial pad. The model further predicted that in addition to the touching whisker, all whiskers found on the same side of the snout should exhibit a TIP. We present experimental results that confirm the predicted movements in behaving rats, establishing the validity of the hypothesized interaction between sensory feedback and CPG activity we suggest here for the generation of TIPs in the whisking system.