"Covering provider": an effort to streamline clinical communication chaos.

Objective: This report describes a root cause analysis of incorrect provider assignments and a standardized workflow developed to improve the clarity and accuracy of provider assignments. Materials and Methods: A multidisciplinary working group involving housestaff was assembled. Key drivers were identified using value stream mapping and fishbone analysis. A report was developed to allow for the analysis of correct provider assignments. A standardized workflow was created and piloted with a single service line. Pre- and post-pilot surveys were administered to nursing staff and participating housestaff on the unit. Results: Four key drivers were identified. A standardized workflow was created with an exclusive treatment team role in Epic held by a single provider at any given time, with a corresponding patient list column displaying provider information for each patient. Pre- and post-survey responses report decreased confusion, decreased provider identification errors, and increased user satisfaction among RNs and residents with sustained uptake over time. Conclusion: This work demonstrates structured root cause analysis, notably engaging housestaff, to develop a standardized workflow for an understudied and growing problem. The development of tools and strategies to address the widespread burdens resulting from clinical communication failures is needed.

A novel HSPB1S139F mouse model of Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth Disease (CMT) is a commonly inherited peripheral polyneuropathy. Clinical manifestations for this disease include symmetrical distal polyneuropathy, altered deep tendon reflexes, distal sensory loss, foot deformities, and gait abnormalities. Genetic mutations in heat shock proteins have been linked to CMT2. Specifically, mutations in the heat shock protein B1 (HSPB1) gene encoding for heat shock protein 27 (Hsp27) have been linked to CMT2F and distal hereditary motor and sensory neuropathy type 2B (dHMSN2B) subtype. The goal of the study was to examine the role of an endogenous mutation in HSPB1 in vivo and to define the effects of this mutation on motor function and pathology in a novel animal model. As sphingolipids have been implicated in hereditary and sensory neuropathies, we examined sphingolipid metabolism in central and peripheral nervous tissues in 3-month-old HspS139F mice. Though sphingolipid levels were not altered in sciatic nerves from HspS139F mice, ceramides and deoxyceramides, as well as sphingomyelins (SMs) were elevated in brain tissues from HspS139F mice. Histology was utilized to further characterize HspS139F mice. HspS139F mice exhibited no alterations to the expression and phosphorylation of neurofilaments, or in the expression of acetylated α-tubulin in the brain or sciatic nerve. Interestingly, HspS139F mice demonstrated cerebellar demyelination. Locomotor function, grip strength and gait were examined to define the role of HspS139F in the clinical phenotypes associated with CMT2F. Gait analysis revealed no differences between HspWT and HspS139F mice. However, both coordination and grip strength were decreased in 3-month-old HspS139F mice. Together these data suggest that the endogenous S139F mutation in HSPB1 may serve as a mouse model for hereditary and sensory neuropathies such as CMT2F.

Effects of Electrode Support Structure on Electrode Microstructure, Transport Properties, and Gas Diffusion within the Gas Diffusion Layer.

The effects of gas diffusion layer (GDL) and electrode microstructure, which influence the catalyst layer and catalyst-membrane interface on the performance of a membrane electrode assembly (MEA) for gas-phase electrolysis and the separation of CO2 were experimentally characterized. Several types of GDL materials, with and without a microporous layer (MPL), were characterized using scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) surface area analysis. The diffusion of reactants through the GDL materials was measured to determine the effects on the microstructure and chemical properties on mass transport. The effects on the GDL structure and chemistry were determined through evaluation of Pt-IrO2 MEAs with different GDL materials using constant-current measurements. Increasing the thickness of the MPL and hydrophobicity within the GDL assist with retaining water within the membrane and catalyst layers, which results in greater performance at high current densities.

A rare neuromyelitis optica mimic: Primary CNS histiocytic sarcoma.

Primary central nervous system (CNS) histiocytic sarcoma is a rare hematolymphoid malignancy with features of mature histiocytes and carries a poor prognosis. We describe a unique case in which a 50-year-old woman presented with recurrent acute brainstem syndrome, area postrema syndrome, and myelitis with corresponding magnetic resonance imaging (MRI) lesions meeting diagnostic criteria for seronegative neuromyelitis optica spectrum disorder (NMOSD). Despite initial improvement with steroids and plasma exchange, she experienced recurrent symptoms over 10 months referable to new and persistently enhancing lesions. At autopsy, neuropathology revealed a diffusely infiltrative primary CNS histiocytic sarcoma. This case represents a rare clinicoradiologic mimic of NMOSD, underscoring the importance of evaluation for infiltrative diseases in cases of atypical seronegative NMOSD.

Charcot-Marie-Tooth 2F (Hsp27 mutations): A review.

Charcot-Marie-Tooth disease is a commonly inherited form of neuropathy. Although named over 100 years ago, identification of subtypes of Charcot-Marie-Tooth has rapidly expanded in the preceding decades with the advancement of genetic sequencing, including type 2F (CMT2F), due to mutations in heat shock protein 27 (Hsp27). However, despite CMT being one of the most common inherited neurological diseases, definitive mechanistic models of pathology and effective treatments for CMT2F are lacking. This review extensively profiles the published literature on CMT2F and distal hereditary motor neuropathy II (dHMN II), a similar neuropathy with exclusively motor symptoms that is also due to mutations in Hsp27. This includes a review of case reports and sequencing studies detailing disease course. Included are tables listing of all known published mutations of Hsp27 that cause symptoms of CMT2F and dHMN II. Furthermore, pathological mechanisms are assessed. While many groups have established pathologies relating to defective chaperone function, cellular neurofilament and microtubule structure and function, and mitochondrial and metabolic dysfunction, there are still discrepancies in results between different model systems. Moreover, initial mouse models have also produced promising results with similar phenotypes to humans, however discrepancies still exist. Both patient-focused and scientific studies have demonstrated variability in phenotypes even considering specific mutations. Given the clinical heterogeneity in presentation, CMT2F and dHMN II likely result from similar pathological mechanisms of the same general disease process that may present distinctly due to other genetic and environment influences. Determining how these influences exert their effects to produce pathology contributing to the disease phenotype will be a major future challenge ahead in the field.

Gaseous and Particulate Emissions from a Chimneyless Biomass Cookstove Equipped with a Potassium Catalyst.

Approximately three billion people cook with solid fuels, mostly wood, on open fires or rudimentary stoves. These traditional cooking methods produce particulate matter and carbon monoxide known to cause significant respiratory health problems, especially among women and children, who often have the highest exposure. In this work, an inexpensive potassium-based catalyst was incorporated in a chimneyless biomass cookstove to reduce harmful emissions through catalytic oxidation. Potassium titanate was identified as an effective and stable oxidation catalyst capable of oxidizing particulate matter and carbon monoxide. Using a cordierite monolith to incorporate potassium titanate within a bespoke, rocket-style, improved cookstove led to a 36% reduction in particulate matter emissions relative to a baseline stove with a blank monolith and a 26% reduction relative to a stove with no monolith. Additionally, the catalytic stove reduced particulate matter emissions by 82%, reduced carbon monoxide emissions by 70%, and improved efficiency by 100% compared to a carefully tended, three-stone fire. Potassium titanate was also shown to oxidize carbon monoxide at temperatures as low as 500 °C, or as low as 300 °C when doped with copper or cobalt.

Quantifying 1-deoxydihydroceramides and 1-deoxyceramides in mouse nervous system tissue.

Accumulation of deoxysphingolipids (deoxySLs) has been implicated in many neural diseases, although mechanisms remain unclear. A major obstacle limiting understanding of deoxySLs has been the lack of a method easily defining measurement of deoxydihydroceramide (deoxydhCer) and deoxyceramide (deoxyCer) in neural tissues. Furthermore, it is poorly understood if deoxySLs accumulate in the nervous system with aging. To facilitate investigation of deoxydhCer and deoxyCer in nervous system tissue, we developed a method to evaluate levels of these lipids in mouse brain, spinal cord, and sciatic nerve. Many deoxydhCers and brain C24-deoxyCer were present at 1, 3, and 6 months of age. Furthermore, while ceramide levels decreased with age, deoxydhCers increased in sciatic nerve and spinal cord, suggesting they may accumulate in peripheral nerves. C22-deoxydhCer was the highest deoxydhCer species in all tissues, suggesting it may be important physiologically. The development of this method will facilitate straightforward profiling of deoxydhCers and deoxyCers and the study of their metabolism and function. These results also reveal that deoxydhCers accumulate in peripheral nerves with normal aging.

Multiple actions of doxorubicin on the sphingolipid network revealed by flux analysis.

Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs through further metabolism, resulting in diverse cellular responses. Here we explore the effects of both lethal and sublethal doses of doxorubicin (Dox) in MCF-7 cells. The two concentrations of Dox resulted in the regulation of SLs, including accumulations in sphingosine, sphingosine-1-phosphate, dihydroceramide, and ceramide, as well as reduced levels of hexosylceramide. To further define the effects of Dox on SLs, metabolic flux experiments utilizing a d17 dihydrosphingosine probe were conducted. Results indicated the regulation of ceramidases and sphingomyelin synthase components specifically in response to the cytostatic dose. The results also unexpectedly demonstrated dose-dependent inhibition of dihydroceramide desaturase and glucosylceramide synthase in response to Dox. Taken together, this study uncovers novel targets in the SL network for the action of Dox, and the results reveal the significant complexity of SL response to even a single agent. This approach helps to define the role of specific SL enzymes, their metabolic products, and the resulting biologies in response to chemotherapeutics and other stimuli.

Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide. Given that Hsp27 is a chaperone protein, we examined its role in regulating ceramide synthases (CerSs), an enzyme family responsible for catalyzing generation of the sphingolipid ceramide. We determined that CerSs colocalized with Hsp27, and upon the presence of S135F mutants, CerS1 lost its colocalization with mitochondria suggesting that decreased mitochondrial ceramides result from reduced mitochondrial CerS localization rather than decreased CerS activity. Mitochondria in mutant cells appeared larger with increased interconnectivity. Furthermore, mutant cell lines demonstrated decreased mitochondrial respiratory function and increased autophagic flux. Mitochondrial structural and functional changes were recapitulated by blocking ceramide generation pharmacologically. These results suggest that mutant Hsp27 decreases mitochondrial ceramide levels, producing structural and functional changes in mitochondria leading to neuronal degeneration.-Schwartz, N. U., Linzer, R. W., Truman, J.-P., Gurevich, M., Hannun, Y. A., Senkal, C. E., Obeid, L. M. Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.

Egg laying decisions in Drosophila are consistent with foraging costs of larval progeny.

Decision-making is defined as selection amongst options based on their utility, in a flexible and context-dependent manner. Oviposition site selection by the female fly, Drosophila melanogaster, has been suggested to be a simple and genetically tractable model for understanding the biological mechanisms that implement decisions. Paradoxically, female Drosophila have been found to avoid oviposition on sugar which contrasts with known Drosophila feeding preferences. Here we demonstrate that female Drosophila prefer egg laying on sugar, but this preference is sensitive to the size of the egg laying substrate. With larger experimental substrates, females preferred to lay eggs directly on sugar containing media over other (plain, bitter or salty) media. This was in contrast to smaller substrates with closely spaced choices where females preferred non-sweetened media. We show that in small egg laying chambers newly hatched first instar larvae are able to migrate along a diffusion gradient to the sugar side. In contrast, in contexts where females preferred egg laying directly on sugar, larvae were unable to migrate to find the sucrose if released on the sugar free side of the chamber. Thus, where larval foraging costs are high, female Drosophila choose to lay their eggs directly upon the nutritious sugar substrate. Our results offer a powerful model for female decision-making.