The K+ affinity of the Na,K-ATPase α2 isoform matches its activity to the range of extracellular K+ concentrations in the T-tubules at rest and during contraction, maintaining the excitability of active muscle.

Pancreatic acinar cells display a remarkable degree of plasticity and can dedifferentiate into ductal-like progenitor cells by a process known as acinar ductal metaplasia (ADM). ADM is believed to be one of the earliest precursor lesions toward the development of pancreatic ductal adenocarcinoma and maintaining the pancreatic acinar cell phenotype suppresses tumor formation. The effects of a novel pStat3 inhibitor (LLL12B) and the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) were investigated using 3-D cultures from p48Cre/+ and p48Cre/+LSL-KrasG12D/+ (KC) mice. LLL12B and TSA inhibited ADM in both KC and p48Cre/+ mouse pancreatic organoids. Furthermore, treatment with LLL12B or TSA on dedifferentiated acini from p48Cre/+ and KC mice that had undergone ADM produced morphologic and gene expression changes that suggest a reversal of ADM. Validation experiments using qRT-PCR (p48Cre/+ and KC) and RNA sequencing (KC) of the LLL12B and TSA treated cultures showed that the ADM reversal was more robust for the TSA treatments. Pathway analysis showed that TSA inhibited Spink1 and PI3K/AKT signaling during ADM reversal. The ability of TSA to reverse ADM was also observed in primary human acinar cultures. We report that pStat3 and HDAC inhibition can attenuate ADM in vitro and reverse ADM in the context of wild-type Kras. Our findings suggest that pharmacological inhibition or reversal of pancreatic ADM represents a potential therapeutic strategy for blocking aberrant ductal reprogramming of acinar cells.

PurposeThe purpose of this study is to evaluate the status of eight interoperability protocols within repositories of electronic theses and dissertations (ETDs) as an introduction to further studies on feasibility of deploying these protocols in upcoming areas of interoperability.Design/methodology/approachThree surveys of 266 ETD repositories, 15 common ETD management software solutions, and 136 ETD experts were conducted in order to appraise the protocols. These protocols were evaluated in four categories of aggregation, syndication, distributed search, and publishing protocols.FindingsThis study revealed that, despite its drawbacks, Protocol for Metadata Harvesting (PMH) is still the most utilized interoperability protocol within ETD providers, ETD software developers, and implementers, followed by ATOM and Object Reuse and Exchange (ORE) protocols. However, in all competitive areas related to performance and functionality, ORE surpasses other protocols. It was also found that the three protocols of ATOM, PMH, and ORE could be used interchangeably in the most used cases of interoperability protocols in repositories.Practical implicationsIn this research, a combination of methods was employed to evaluate the status of protocols, from the perspectives of data providers, software providers, and implementers. Practitioners may use these methods to assess other protocols in terms of effectiveness and efficiency.Originality/valueThe conduct of this study has involved three types of surveys, through which different aspects of interoperability protocols are evaluated. Prior to the conduct of this study, there has yet any study focusing on the same topic, which has adopted the multi‐method that has been adopted in this study.

Objectives: To identify effective facility design strategies to improve the performance of healthcare providers and patient flow during mass casualty incidents (MCIs) in emergency departments. Background: Emergency departments (EDs) are the first line of medical care in MCIs. While operational surge management plans are well described in literature, physical design strategies to improve performance and patient flow during disasters are discussed scarcely. Method: An online questionnaire was sent to EDs’ caregivers nationwide asking them to rate the effectiveness of nine physical design strategies, discussed in the literature, to improve caregivers’ performance and patient flow during MCIs. Assessed strategies were about providing expandable departments and care areas, alternate care facilities for the least sick to maximize care areas for critical patients, care areas from nonemergency units, increased number of decontamination units, dedicated isolation units, within-hospital and close emergency operation centers, and within-hospital media areas. Results: All suggested strategies were rated as effective. The most effective and agreed-upon solution was identified as maximizing the care area for critical patients by establishing an alternate care facility with separate entrance and exit doors from the emergency department for the least critical patients. The least effective and agreed-upon strategy was identified as locating a media unit within the hospital outside of the ED. Conclusions: Caregivers who work in EDs consider design strategies to be effective in surge management during disasters. Designers can consider implementing identified strategies in designing new emergency departments or expansion and renovation projects.

Objective: To address prolonged lengths of stay (LOS) in a Level 1 trauma center, we examined the impact of implementing two data-driven strategies with a focus on the physical environment. Background: Crowding in emergency departments (EDs) is a widely reported problem leading to increased service times and patients leaving without being seen. Methods: Using ED historical data and expert estimates, we created a discrete-event simulation model. We analyzed the likely impact of initiating care and boarding patients in the hallway (hallway care) instead of the exam rooms and adding a dedicated triage space for patients who arrive by emergency medical services (EMS triage) to decrease hallway congestion. The scenarios were compared in terms of LOS, time spent in exam rooms and hallway spaces, service time, blocked time, and utilization rate. Results: The hallway care scenario resulted in significantly lower LOS and exam room time only for EMS patients but when implemented along with the EMS triage scenario, a significantly lower LOS and exam room time was observed for all patients (EMS and walk-in). The combination of two simulated scenarios resulted in significant improvements in other flow metrics as well. Conclusions: Our findings discourage boarding of admitted patients in ED exam rooms. If space limitations require that admitted patients be placed in ED hallways, designers and planners should consider enabling hallway spaces with features recommended in this article. Alternative locations for boarding should be prioritized in or out of the ED. Our findings also encourage establishing a triage area dedicated to EMS patients in the ED.