A Decade of Melt Electrowriting.

Over the past decade, melt electrowriting (MEW) has established the fundamental understanding of processing (and printer) requirements. Iterative work on parametric development and dissemination of this recent additive manufacturing technology has been performed across many systems and polymers (mainly poly-(ε-caprolactone)), showing similarities and trends. However, the software and hardware ecosystems of MEW are not mature. Further, due to its multi-parametric nature, MEW can be challenging for laboratories to master. This review intends to provide a unique perspective on the dynamic relationship between MEW processing parameters. Such parameters can be divided into 1) those that affect the polymer flow rate to or 2) from the nozzle, and 3) environmental conditions. The most influential parameters for high-quality printing are applied voltage, applied pressure, collector speed, polymer temperature, nozzle diameter, and the conditions that lead to charge buildup (e.g., relative humidity). Other factors such as ambient temperature, nozzle size, and protrusion, collector temperature and conductivity, and collector distance can all affect the process. Success for MEW printing means fibers fall onto the collector according to their pre-programmed path with predicted fiber diameter. Here, the authors elucidate how the dynamic relationship between these parameters can converge into ideal printing conditions to produce scaffolds.

Mass spectrometry imaging discriminates glioblastoma tumor cell subpopulations and different microvascular formations based on their lipid profiles.

Glioblastoma is a prevalent malignant brain tumor and despite clinical intervention, tumor recurrence is frequent and usually fatal. Genomic investigations have provided a greater understanding of molecular heterogeneity in glioblastoma, yet there are still no curative treatments, and the prognosis has remained unchanged. The aggressive nature of glioblastoma is attributed to the heterogeneity in tumor cell subpopulations and aberrant microvascular proliferation. Ganglioside-directed immunotherapy and membrane lipid therapy have shown efficacy in the treatment of glioblastoma. To truly harness these novel therapeutics and develop a regimen that improves clinical outcome, a greater understanding of the altered lipidomic profiles within the glioblastoma tumor microenvironment is urgently needed. In this work, high resolution mass spectrometry imaging was utilized to investigate lipid heterogeneity in human glioblastoma samples. Data presented offers the first insight into the histology-specific accumulation of lipids involved in cell metabolism and signaling. Cardiolipins, phosphatidylinositol, ceramide-1-phosphate, and gangliosides, including the glioblastoma stem cell marker, GD3, were shown to differentially accumulate in tumor and endothelial cell subpopulations. Conversely, a reduction in sphingomyelins and sulfatides were detected in tumor cell regions. Cellular accumulation for each lipid class was dependent upon their fatty acid residue composition, highlighting the importance of understanding lipid structure-function relationships. Discriminating ions were identified and correlated to histopathology and Ki67 proliferation index. These results identified multiple lipids within the glioblastoma microenvironment that warrant further investigation for the development of predictive biomarkers and lipid-based therapeutics.

INTERPROFESSIONAL ROLES AND COLLABORATIONS TO ADDRESS COVID-19 PANDEMIC CHALLENGES IN NURSING HOMES.

Nursing home experts and informatics nurses collaborated to develop guidelines for nursing homes that revealed partnership principles in action during the COVID-19 pandemic. This article describes efforts to define interprofessional nursing home staff roles within the partnership-based COVID-19 Response Guideline, and to examine changes in nursing practice compared to the pre-pandemic practice of nurses. The qualitative process of identification of nursing home staff roles revealed the extensive scope of interprofessional partnership needed to respond to the pandemic. Using the Omaha System structure, we compared these collective COVID-19 response interventions of Nursing Service roles with nursing interventions of RNs and LPN/LVNs defined in previous nursing home studies. This comparison showed the necessary transformation and collaboration among nurses needed for the pandemic response in nursing homes. The Omaha System Pandemic Guideline is available online and in the Omaha System Guidelines app for immediate use as COVID-19 response practice guidelines and references for interprofessional roles in nursing homes, as well as for multidisciplinary roles across diverse care settings. The guideline is an exemplar of how informatics can facilitate interprofessional and multidisciplinary partnership for nursing homes and other care settings. Future use of the guidelines for decision making and documentation related to infection prevention and control in nursing homes may improve care quality and health outcomes of residents and population.

Enhancing Metabolite Coverage for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Through Multiple On-Tissue Chemical Derivatizations.

The ability to study and visualize metabolites on a cellular and sub-cellular level is important for gaining insights into biological pathways and metabolism of multicellular organisms. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a powerful analytical tool for metabolomics experiments due to its high sensitivity and small sampling size. The spatial resolution in MALDI-MSI is mainly limited by the number of molecules available in a small sampling size. When the sampling size is low enough to achieve cellular or subcellular spatial resolution, signal intensity is sacrificed making poorly ionized metabolites difficult to detect. To overcome this limitation, on-tissue chemical derivatization reactions have been used to enhance the desorption/ionization efficiency of selected classes of compounds by adding a functional group with a permanent positive charge or one that can be easily ionized. By utilizing several chemical derivatizations in parallel, metabolite coverage can be drastically improved. This chapter outlines methodology for sample preparation and data analysis for on-tissue chemical derivatization using various derivatization reagents.

In Vitro Miniaturized Tuberculosis Spheroid Model.

Tuberculosis (TB) is a public health concern that impacts 10 million people around the world. Current in vitro models are low throughput and/or lack caseation, which impairs drug effectiveness in humans. Here, we report the generation of THP-1 human monocyte/macrophage spheroids housing mycobacteria (TB spheroids). These TB spheroids have a central core of dead cells co-localized with mycobacteria and are hypoxic. TB spheroids exhibit higher levels of pro-inflammatory factor TNFα and growth factors G-CSF and VEGF when compared to non-infected control. TB spheroids show high levels of lipid deposition, characterized by MALDI mass spectrometry imaging. TB spheroids infected with strains of differential virulence, Mycobacterium tuberculosis (Mtb) HN878 and CDC1551 vary in response to Isoniazid and Rifampicin. Finally, we adapt the spheroid model to form peripheral blood mononuclear cells (PBMCs) and lung fibroblasts (NHLF) 3D co-cultures. These results pave the way for the development of new strategies for disease modeling and therapeutic discovery.

Importance of Shared Treatment Goal Discussions in Rheumatoid Arthritis-A Cross-Sectional Survey: Patients Report Providers Seldom Discuss Treatment Goals and Outcomes Improve When Goals Are Discussed.

OBJECTIVE: Treat-to-target (T2T) and shared decision-making are valued features of current guidelines for rheumatoid arthritis (RA) management. Although T2T has demonstrated value for improving RA outcomes, implementation remains inconsistent and lacks standardization and procedures for including patient input. We sought to better understand the impact of shared decisions on T2T and how treatment goal discussions between patients and providers impact RA treatment improvement and satisfaction. METHODS: An anonymous, web-based questionnaire was presented to United States residents aged 18 years or older with a self-reported diagnosis of RA by a medical professional with 28 questions regarding socio-demographics, RA disease activity (DA), diagnosis, treatments, outcomes, and goals. Analyses included descriptive statistics with χ2 and rank sum tests for comparisons. RESULTS: The questionnaire was completed by 907 people (mean age of 58 years; mean 11 years since diagnosis; 90% female). The majority (571; 63%) did not discuss RA treatment goals with providers. Patients engaging in treatment goal discussions with their providers were three times more likely to be satisfied with their treatment plans. Patients discussing treatment goals with their providers were more likely to have improved DA levels and 68% more likely to reach remission. CONCLUSION: A majority of patients with RA report having no treatment goal discussion with their providers; however, these discussions are associated with greater DA improvement and treatment satisfaction. Further research should seek understanding of how shared treatment goal discussions relate to successful RA management and explore the development of practical tools to implement them in regular clinic practice as part of a T2T regimen.

Visualizing Genotypic and Developmental Differences of Free Amino Acids in Maize Roots With Mass Spectrometry Imaging.

Amino acids are essential biological compounds in plants as they store nitrogen, an essential nutrient, and are the building blocks for proteins that drive biological activity. Amino acids have been studied using a wide variety of analytical techniques in different plant systems, however, mass spectrometry imaging (MSI) is a particularly useful technique as it allows for the simultaneous collection of both chemical and spatial information. In this work, matrix-assisted laser desorption/ionization (MALDI)-MSI is used to study the different localization of free amino acids in the roots of maize inbred lines B73 and Mo17 and their reciprocal hybrids. Because amino acids are difficult to detect in mass spectrometry, especially directly on tissues, a chemical derivatization protocol is utilized to increase the ionization efficiency and improve their detection. We report differences in both abundance and localization of amino acids in B73 and Mo17 maize roots and suggest the hybrids show evidence of inheriting characteristics from both parents. Most genotypic differences are found in the cross-sections near the seed (∼2 cm away) at a later stage of development (10-11 cm in length). Here, B73 has lower amino acid abundance localized primarily to the center of the roots for most amino acids, while Mo17 has much higher abundance localized mainly to the root cortex. This difference in localization is minimized when grown in ammonium ion rich conditions. Roots grown in the presence of 15N-ammonium ions provided additional insight about the amino acid synthesis. The localization of some amino acids, particularly leucine/isoleucine and glutamine, is not affected by the addition of nitrogen and is consistent regardless of the nitrogen source, either from the seeds (14N-labeled) or environment (15N-labeled). Nitrogen uptake from the environment is confined to glutamine, asparagine, and alanine, consistent with their roles in amino acid storage and transportation.

Study of the cyanoacrylate fuming mechanism by matrix-assisted laser desorption/ionization mass spectrometry.

Despite cyanoacrylate fuming being widely used in the forensic science field, its mechanism is not well understood. In this study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is used to study latent fingerprints that have been cyanoacrylate fumed in an attempt to gain insight into the fuming mechanism. In the negative mode mass spectrometry data, four compounds related to the polymerization of cyanoacrylate are identified and their structures are determined from accurate mass and MS/MS. A mechanism is proposed for the formation of these compounds that are regarded as intermediates in the polymerization reaction. In addition, based on the fuming of standard endogenous compounds, we suggest that fatty acids and amino acids are the major catalytic nucleophiles that initiate the polymerization reactions.

Revealing Individual Lifestyles through Mass Spectrometry Imaging of Chemical Compounds in Fingerprints.

Fingerprints, specifically the ridge details within the print, have long been used in forensic investigations for individual identification. Beyond the ridge detail, fingerprints contain useful chemical information. The study of fingerprint chemical information has become of interest, especially with mass spectrometry imaging technologies. Mass spectrometry imaging visualizes the spatial relationship of each compound detected, allowing ridge detail and chemical information in a single analysis. In this work, a range of exogenous fingerprint compounds that may reveal a personal lifestyle were studied using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Studied chemical compounds include various brands of bug sprays and sunscreens, as well as food oils, alcohols, and citrus fruits. Brand differentiation and source determination were possible based on the active ingredients or exclusive compounds left in fingerprints. Tandem mass spectrometry was performed for the key compounds, so that these compounds could be confidently identified in a single multiplex mass spectrometry imaging data acquisition.

Chemical Imaging of Cyanoacrylate-Fumed Fingerprints by Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

For new techniques to be incorporated into forensic science, they must be compatible with current practices. Here, cyanoacrylate fuming, a common development technique for latent fingerprints, is studied for its compatibility with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for chemical imaging of latent fingerprints. Half of a fingerprint was fumed while the other half was not; then, the changes in chemical composition and signal intensity were compared with MALDI-MS imaging. No evidence was found that fingerprint compounds are chemically altered by fuming or their signal intensities affected. The only exceptions were significant signal loss for quaternary ammonium compounds from hygiene products and moderate signal loss for tertiary amine compounds. This result is in striking contrast with the previous attempts by others, which is attributed to the difference in instrumentation.

Effect of Aging and Surface Interactions on the Diffusion of Endogenous Compounds in Latent Fingerprints Studied by Mass Spectrometry Imaging.

The ability to determine the age of fingerprints would be immeasurably beneficial in criminal investigations. We explore the possibility of determining the age of fingerprints by analyzing various compounds as they diffuse from the ridges to the valleys of fingerprints using matrix-assisted laser desorption/ionization mass spectrometry imaging. The diffusion of two classes of endogenous fingerprint compounds, fatty acids and triacylglycerols (TGs), was studied in fresh and aged fingerprints on four surfaces. We expected higher molecular weight TGs would diffuse slower than fatty acids and allow us to determine the age of older fingerprints. However, we found interactions between endogenous compounds and the surface have a much stronger impact on diffusion than molecular weight. For example, diffusion of TGs is faster on hydrophilic plain glass or partially hydrophilic stainless steel surfaces, than on a hydrophobic Rain-x treated surface. This result further complicates utilizing a diffusion model to age fingerprints.

Quality improvement regarding handoff.

BACKGROUND AND OBJECTIVES: Previous studies have emphasized the importance of effectual communication during patient handoffs. The objectives of this study were to (1) implement a resident-driven quality improvement project to improve handoffs by including key elements that are necessary for a safe and effective handoff. We chose to use the IPASS (illness severity, patient summary, action items, situation awareness and contingency planning, synthesis by receiver) mnemonic as our standardized handoff model; (2) Consider balancing measures in an effort to be aware of any negative effects of our interventions on resident satisfaction with the system. METHODS: A senior resident established a quality improvement team which developed an AIM statement (a written, measurable, and time-sensitive description of the goal of a quality improvement team) and key drivers. A survey was administered to residents regarding their opinions about the handoff process. Tracking of whether or not handoffs included the component IPASS elements was performed over an 11-month period. During this time frame, three Plan-Do-Study-Act cycles were conducted. The first was an educational series involving lecture and role playing. The second was printed cards listing appropriate handoff elements. Intervention three was development of a tool and method to decrease nurse interruptions during handoff. RESULTS: Inclusion of six key elements of handoffs improved as follows. Illness severity improved from 5% to 97%, diagnosis from 60% to 100%, patient summary from 71% to 100%, contingency planning from 10% to 100%, action list from 23% to 100%, and receiver synthesis from 0% to 97%. Balancing measures showed the residents were more satisfied with the new system and found it to be more effective at providing a safe transition of care. CONCLUSION: Implementation of a resident-driven multidisciplinary IPASS handoff system resulted in improved inclusion of key handoff elements and increased resident satisfaction.

Acute tracheal compression in a large breed dog due to a dorsal tracheal membrane abscess.

OBJECTIVE: To describe a case of acute tracheal compression due to a dorsal tracheal membrane abscess in a dog. CASE SUMMARY: A 3-year-old intact male Bluetick Coonhound presented for evaluation of 36 hours of marked inspiratory dyspnea and stridor. A radiographic diagnosis of tracheal collapse was made on thoracic radiographs, which was confirmed to be static compression by tracheoscopy. Dorsal extraluminal tracheal compression from a fluid filled structure adjacent to the trachea was suspected based on ultrasonography. Endoscopic-guided transtracheal fine needle aspiration yielded septic suppurative inflammation. At surgery an abscess in the dorsal tracheal membrane was identified, lanced, and lavaged, which resulted in restoration of normal tracheal diameter. The dog developed bilateral pneumothorax, which was treated medically by thoracostomy tube placement and manual evacuation of the accumulated air. Postoperative radiographs also revealed evidence of pneumomediastinum. Pneumothorax and pneumomediastinum likely occurred secondary to the surgical approach, worsened by positive pressure ventilation. Cultures of the abscess isolated a nonhemolytic Streptococcus species but with no evidence of anaerobic bacteria. The dog made a full functional recovery. NEW OR UNIQUE INFORMATION PROVIDED: Tracheal compression is a rare diagnosis in dogs. To the authors' knowledge, this represents the first report of an abscess in the dorsal tracheal membrane, diagnosed by endoscopic-guided transtracheal fine needle aspiration, causing clinically relevant acute tracheal obstruction.

A Quality Improvement Project to Improve Family Recognition of Medical Team Member Roles.

OBJECTIVE: Previous studies have shown that inpatients and families in academic settings have a limited ability to recall either their medical team members or the roles of those members. This is an important issue for patient and family satisfaction as well as patient safety. The objective of this study was to increase families' recognition of medical team members' roles. METHODS: We established a multidisciplinary quality improvement leadership team, measured family recognition of medical team members and their roles, and conducted 2 PDSA (Plan-Do-Study-Act) cycles. The first intervention was standardization of the content and delivery of our verbal team introductions to ensure inclusion of essential elements and family engagement. The second intervention was addition of an informational white board in each patient room. The prospective study included 105 families in the preintervention phase, 103 post-PDSA cycle 1, and 92 post-PDSA cycle 2. RESULTS: After conduction of 2 PDSA cycles, the recognition of the attending role increased from 49% to 87% (P = .000), the resident role from 39% to 73% (P = .000), and the medical student from 75% to 89% (P = .038). CONCLUSIONS: The multidisciplinary quality improvement model was effective in improving family recognition of the roles of attending physicians, resident physicians, and medical students. Consistent attention to engaging the families and explaining our roles as well as providing informational white boards are effective interventions to facilitate this process.

Effects of pH mismatch between the two dimensions of reversed-phase×reversed-phase two-dimensional separations on second dimension separation quality for ionogenic compounds-I. Carboxylic acids.

Two persistent impediments to wider adoption of two-dimensional liquid chromatography (2D-LC) are the perceptions that 2D methods are generally less sensitive than 1D ones, and that coupling of certain separation modes in a 2D system is difficult because of the negative impact of the effluent of the first separation on the second separation. In this work we address these problems in the specific case where reversed-phase separations are used in both dimensions of a 2D-LC system, but the pH is varied such that the ionization state of carboxylic acid analytes is different (i.e., neutral or negatively charged, in eluents buffered at pH 2 or 7) in the two columns. We first demonstrate that the effect of first dimension ((1)D) effluent on the performance of second dimension ((2)D) separation of ionogenic solutes is much more serious than it is for neutral compounds where the pH of the eluent does not play a role in retention. We have systematically varied the properties of the sample solution injected into the (2)D column (i.e., the (1)D effluent), as well as the (2)D eluent, with the goal of establishing guidelines for conditions that yield acceptable (2)D performance. We find that the organic solvent content of the (1)D effluent and (2)D eluent is not as important as the buffer concentrations in these two solutions, and that the greater the ratio of buffer concentration in the (1)D effluent relative to the (2)D eluent, the smaller the volume one can inject into the (2)D column before dramatic peak splitting occurs. We have then used the information from these simple experiments to guide both 1D experiments that mimic the (2)D separation, and actual 2D separations, to demonstrate that online adjustment of the properties of the (1)D effluent by dilution with a buffered solvent prior to injection into the (2)D column is a very effective solution to the pH mismatch problem. We find that when the buffer capacity of the diluent is high enough to effectively titrate the (1)D effluent such that its pH approaches that of the (2)D eluent, excellent (2)D peak shape is obtained for the carboxylic acid analytes, even when the volume of injected sample solution exceeds the (2)D column volume.

Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis.

BACKGROUND: Treatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders. METHODS: We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death. FINDINGS: Including the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone. INTERPRETATION: Extended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy. FUNDING: None.

Development and pilot-testing of a work readiness assessment battery.

OBJECTIVE: To develop a work readiness assessment battery that can be used in the course of work rehabilitation and to pilot test the battery to determine its ability to measure the effectiveness of work rehabilitation treatment. PARTICIPANTS: All participants were recruited from the patient population at the Occupational Performance Center (OPC) at The Rehabilitation Institute of St. Louis (TRISL) (n = 7). METHODS: A work readiness assessment battery was constructed using the Readiness to Return to Work theory and then pilot-tested using a repeated-measures design. RESULTS: Participants showed significant improvement on all measures including in the battery with the exception of the depression measure. CONCLUSIONS: These results demonstrate that it is feasible to construct a work readiness battery of assessments using the Readiness to Return to Work theory and that the measures included capture the effect of work rehabilitation on the constructs identified in the literature to effect work performance. Further investigation is necessary to validate this form of assessment for use in a work rehabilitation setting.