A dry polymer nanocomposite transcutaneous electrode for functional electrical stimulation.

BACKGROUND: Functional electrical stimulation (FES) can be used in rehabilitation to aid or improve function in people with paralysis. In clinical settings, it is common practice to use transcutaneous electrodes to apply the electrical stimulation, since they are non-invasive, and can be easily applied and repositioned as necessary. However, the current electrode options available for transcutaneous FES are limited and can have practical disadvantages, such as the need for a wet interface with the skin for better comfort and performance. Hence, we were motivated to develop a dry stimulation electrode which could perform equivalently or better than existing commercially available options. METHODS: We manufactured a thin-film dry polymer nanocomposite electrode, characterized it, and tested its performance for stimulation purposes with thirteen healthy individuals. We compared its functionality in terms of stimulation-induced muscle torque and comfort level against two other types of transcutaneous electrodes: self-adhesive hydrogel and carbon rubber. Each electrode type was also tested using three different stimulators and different intensity levels of stimulation. RESULTS: We found the proposed dry polymer nanocomposite electrode to be functional for stimulation, as there was no statistically significant difference between its performance to the other standard electrodes. Namely, the proposed dry electrode had comparable muscle torque generated and comfort level as the self-adhesive hydrogel and carbon rubber electrodes. From all combinations of electrode type and stimulators tested, the dry polymer nanocomposite electrode with the MyndSearch stimulator had the most comfortable average rating. CONCLUSIONS: The dry polymer nanocomposite electrode is a durable and flexible alternative to existing self-adhesive hydrogel and carbon rubber electrodes, which can be used without the addition of a wet interfacing agent (i.e., water or gel) to perform as well as the current electrodes used for stimulation purposes.

A novel functional electrical stimulation sleeve based on textile-embedded dry electrodes.

BACKGROUND: Functional electrical stimulation (FES) is a rehabilitation technique that enables functional improvements in patients with motor control impairments. This study presents an original design and prototyping method for a smart sleeve for FES applications. The article explains how to integrate a carbon-based dry electrode into a textile structure and ensure an electrical connection between the electrodes and the stimulator for effective delivery of the FES. It also describes the materials and the step-by-step manufacturing processes. RESULTS: The carbon-based dry electrode is integrated into the textile substrate by a thermal compression molding process on an embroidered conductive matrix. This matrix is composed of textile silver-plated conductive yarns and is linked to the stimulator. Besides ensuring the electrical connection, the matrix improves the fixation between the textile substrate and the electrode. The stimulation intensity, the perceived comfort and the muscle torque generated by the smart FES sleeve were compared to hydrogel electrodes. The results show a better average comfort and a higher average stimulation intensity with the smart FES sleeve, while there were no significant differences for the muscle torque generated. CONCLUSIONS: The integration of the proposed dry electrodes into a textile is a viable solution. The wearable FES system does not negatively impact the electrodes' performance, and tends to improve it. Additionally, the proposed prototyping method is applicable to an entire garment in order to target all muscles. Moreover, the process is feasible for industrial production and commercialization since all materials and processes used are already available on the market.

"A whole other competence story": exploring faculty perspectives on the process of workplace-based assessment of entrustable professional activities.

The centrality of entrustable professional activities (EPAs) in competency-based medical education (CBME) is predicated on the assumption that low-stakes, high-frequency workplace-based assessments used in a programmatic approach will result in accurate and defensible judgments of competence. While there have been conversations in the literature regarding the potential of this approach, only recently has the conversation begun to explore the actual experiences of clinical faculty in this process. The purpose of this qualitative study was to explore the process of EPA assessment for faculty in everyday practice. We conducted 18 semi-structured interviews with Anesthesia faculty at a Canadian academic center. Participants were asked to describe how they engage in EPA assessment in daily practice and the factors they considered. Interviews were audio-recorded, transcribed, and analysed using the constant comparative method of grounded theory. Participants in this study perceived two sources of tension in the EPA assessment process that influenced their scoring on official forms: the potential constraints of the assessment forms and the potential consequences of their assessment outcome. This was particularly salient in circumstances of uncertainty regarding the learner's level of competence. Ultimately, EPA assessment in CBME may be experienced as higher-stakes by faculty than officially recognized due to these tensions, suggesting a layer of discomfort and burden in the process that may potentially interfere with the goal of assessment for learning. Acknowledging and understanding the nature of this burden and identifying strategies to mitigate it are critical to achieving the assessment goals of CBME.

Racial disparities in pain management: Historical maleficence and solutions for equity.

ABSTRACT: Medical journals from the 1800s described differences in disease susceptibility, skin thickness, and pain tolerance among races. These misconceptions about biologic differences, the historical exploitation of minorities in research, and implicit biases among healthcare workers have all affected patient care. Discrepancies still exist in pain assessment and management for minority patients compared with their White counterparts and lead to poor health outcomes. By implementing specific changes in policy and practice, including standardization, implicit bias training, and building a diverse workforce, clinicians can begin to provide care that more equitably manages pain for all patients, regardless of race.

Now we are 30: 10 more years of MASCC.

This paper chronicles the third decade of MASCC from 2010. There was a generational change in this decade, building on the solid foundation of the founders. It included the first female President, and a new Executive Director with a background in strategy and business development and operations as applied to healthcare. The headquarters moved from Copenhagen to Toronto. The first meeting to be held outside of Europe or North America was held in Adelaide, Australia, and the membership in the Asia Pacific region expanded. A program of international affiliates saw national supportive care organisations formally link with MASCC. In cancer supportive care, there was a raft of new toxicities to manage as immunotherapies were added to conventional cytotoxic treatment. There was also a greater emphasis on the psychosocial needs of patients and families. New MASCC groups were formed to respond to this evolution in cancer management. The MASCC journal, Supportive Care in Cancer, continued to grow in impact, and MASCC published two editions of a textbook of supportive care and survivorship. The decade ended with the challenge of the COVID-19 pandemic, but that served to highlight the importance of good supportive care to patients with cancer.

Expanding the Scope of Single- and Double-Noncanonical Amino Acid Mutagenesis in Mammalian Cells Using Orthogonal Polyspecific Leucyl-tRNA Synthetases.

Engineered aminoacyl-tRNA synthetase/tRNA pairs that enable site-specific incorporation of noncanonical amino acids (ncAAs) into proteins in living cells have emerged as powerful tools in chemical biology. The Escherichia coli-derived leucyl-tRNA synthetase (EcLeuRS)/tRNA pair is a promising candidate for ncAA mutagenesis in mammalian cells, but it has been engineered to charge only a limited set of ncAAs so far. Here we show that two highly polyspecific EcLeuRS mutants can efficiently charge a large array of useful ncAAs into proteins expressed in mammalian cells, while discriminating against the 20 canonical amino acids. When combined with an opal-suppressing pyrrolysyl pair, these EcLeuRS variants further enabled site-specific incorporation of different combinations of two distinct ncAAs into proteins expressed in mammalian cells.

Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.

Covalent modification of histones is a fundamental mechanism of regulated gene expression in eukaryotes, and interpretation of histone modifications is an essential feature of epigenetic control. Bromodomains are specialized binding modules that interact with acetylated histones, linking chromatin recognition to gene transcription. Because of their ability to function in a domain-specific fashion, selective disruption of bromodomain:acetylated histone interactions with chemical probes serves as a powerful means for understanding biological processes regulated by these chromatin adaptors. Here we describe the discovery and characterization of potent and selective small molecule inhibitors for the bromodomains of CREBBP/EP300 that engage their target in cellular assays. We use these tools to demonstrate a critical role for CREBBP/EP300 bromodomains in regulatory T cell biology. Because regulatory T cell recruitment to tumors is a major mechanism of immune evasion by cancer cells, our data highlight the importance of CREBBP/EP300 bromodomain inhibition as a novel, small molecule-based approach for cancer immunotherapy.

A Unique Genetically Encoded FRET Pair in Mammalian Cells.

Förster resonance energy transfer (FRET) between two suitable fluorophores is a powerful tool to monitor dynamic changes in protein structure in vitro and in vivo. The ability to genetically encode a FRET pair represents a convenient "labeling-free" strategy to incorporate them into target protein(s). Currently, the only genetically encoded FRET pairs available for use in mammalian cells use fluorescent proteins. However, their large size can lead to unfavorable perturbations, particularly when two are used at the same time. Additionally, fluorescent proteins are largely restricted to a terminal attachment to the target, which might not be optimal. Here, we report the development of an alternative genetically encoded FRET pair in mammalian cells that circumvents these challenges by taking advantage of a small genetically encoded fluorescent unnatural amino acid as the donor and enhanced green fluorescent protein (EGFP) as the acceptor. The small size of Anap relative to fluorescent proteins, and the ability to co-translationally incorporate it into internal sites on the target protein, endows this novel FRET pair with improved versatility over its counterparts that rely upon two fluorescent proteins.

Assessment of competence: developing trends and ethical considerations.

PURPOSE OF REVIEW: This review explores new concepts in competency assessment in anesthesiology, the associated ethical challenges, and directions for new research. RECENT FINDINGS: Many new tools for the assessment of competence are currently in development to address changes in medical education curricula. The assessment of competence currently focuses on technical skills, nontechnical skills, and the interaction of both through the use of simulation, with increasing emphasis on validity and reliability testing. SUMMARY: The search for objective measures of competence is well underway. Current methods require substantial investment of resources, and further research into more efficient and financially feasible tools of assessment is needed. As these assessments become more common in use, the ethical challenges raised by defining competency in high-stakes clinical practice situations will need to be addressed.

Role of podocyte B7-1 in diabetic nephropathy.

Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted therapies to halt or prevent these complications are currently not available. Here, we show that the immune-related molecule B7-1/CD80 is a critical mediator of podocyte injury in type 2 diabetic nephropathy. We report the induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2 diabetes. Genetic and epidemiologic studies revealed the association of two single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy. Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28 correlated with the progression to ESRD in individuals with type 2 diabetes. In vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase-dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1 in podocytes increased apoptosis and induced disruption of the cytoskeleton that were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was also induced in vivo in two murine models of diabetic nephropathy, and treatment with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney pathology in these animals. Taken together, these results identify B7-1 inhibition as a potential therapeutic strategy for the prevention or treatment of diabetic nephropathy.

Supportive care 2030 movement: towards unifying ambitions for global excellence in supportive cancer care-an international Delphi study.

Background: Supportive care to ensure optimal quality of life is an essential component of cancer care and symptom control across the lifespan. Ongoing advances in cancer treatment, increasing toxicity from many novel treatment regimes, and variations in access to care and cancer outcomes across the globe and resource settings present significant challenges for supportive care delivery. To date, no overarching framework has been developed to guide supportive care development worldwide. As an initial step of the Multinational Association of Supportive Care in Cancer (MASCC) Supportive Care 2030 Movement, we developed a targeted, unifying set of ambition statements to envision the future of supportive cancer care. Methods: From September 2022 until June 2023, we used a modified Delphi methodology to develop and attain consensus about ambition statements related to supportive cancer care. Leaders of MASCC Study Groups were invited to participate in an Expert Panel for the first two Delphi rounds (and a preliminary round to suggest potential ambition statements). Patient Advocates then examined and provided input regarding the ambition statements. Findings: Twenty-seven Expert Panelists and 11 Patient Advocates participated. Consensus was attained on 13 ambition statements, with two sub-statements. The ambition statements addressed global standards for guideline development and implementation, coordinated and individualized care, dedicated supportive oncology services, self-management, needs for screening and actions, patient education, behavioral support, financial impact minimization, comprehensive survivorship care, and timely palliative care, reflecting collaboration, coordination and team-based approach across all levels. Interpretation: This study is the first to develop shared ambitions for the future of supportive cancer care on a global level. These ambition statements can facilitate a coordinated, resource-stratified, and person-centered approach and inform research, education, clinical services, and policy efforts. Funding: This project received funding support from Prof Raymond Chan's NHMRC Investigator Grant (APP1194051).

Development of an Aerogel-Based Wet Electrode for Functional Electrical Stimulation.

Functional electrical stimulation (FES) has been a useful therapeutic tool in rehabilitation, particularly for people with paralysis. To deliver stimulation in its most basic setup, a stimulator and at least a pair of electrodes are needed. The electrodes are an essential part of the system since they allow the transduction of the stimulator signals into the body. Their performance can influence the experience of both patient and therapist in terms of movement generation, comfort, and ease of use. For non-invasive surface stimulation, current electrode options have several limitations involving their interfacing with the skin, practical inconveniences, and short-term functionality. Standard hydrogel electrodes tend to lose their adhesion with the skin quickly, while dry or textile electrodes require constant wetting to be comfortable. In this paper, we present the fabrication, characterization, and FES testing of a new aerogel-based wet electrode for surface stimulation applications for long-term and reusable FES applications. We investigated its functionality by stimulating the biceps brachii of twelve healthy individuals and collected elbow joint torque and comfort ratings for three different intensity levels (low, moderate, and high) of FES. Comparing to standard hydrogel electrodes, no statistically significant difference was found for any intensity of stimulation in either torque or comfort. Overall, the new aerogel-based electrode has an appropriate impedance, is flexible and soft, is conformable to the skin, has a high water absorption and retention, and can be used for FES purposes.

How deep is deep enough for RNA-Seq profiling of bacterial transcriptomes?

BACKGROUND: High-throughput sequencing of cDNA libraries (RNA-Seq) has proven to be a highly effective approach for studying bacterial transcriptomes. A central challenge in designing RNA-Seq-based experiments is estimating a priori the number of reads per sample needed to detect and quantify thousands of individual transcripts with a large dynamic range of abundance. RESULTS: We have conducted a systematic examination of how changes in the number of RNA-Seq reads per sample influences both profiling of a single bacterial transcriptome and the comparison of gene expression among samples. Our findings suggest that the number of reads typically produced in a single lane of the Illumina HiSeq sequencer far exceeds the number needed to saturate the annotated transcriptomes of diverse bacteria growing in monoculture. Moreover, as sequencing depth increases, so too does the detection of cDNAs that likely correspond to spurious transcripts or genomic DNA contamination. Finally, even when dozens of barcoded individual cDNA libraries are sequenced in a single lane, the vast majority of transcripts in each sample can be detected and numerous genes differentially expressed between samples can be identified. CONCLUSIONS: Our analysis provides a guide for the many researchers seeking to determine the appropriate sequencing depth for RNA-Seq-based studies of diverse bacterial species.

Postoperative Pseudomonas aeruginosa endophthalmitis associated with asymptomatic bacteriuria.

An 86-year-old man with diabetes and a history of prostate cancer, indwelling urinary catheter and Pseudomonas aeruginosa bacteriuria presented on day 4 post left phacoemulsification cataract extraction and intraocular lens implant with signs and symptoms of postoperative endophthalmitis. Vitreous sample was positive for P. aeruginosa Prompt treatment with intravitreal antibiotics was initiated followed by anterior chamber washout with pars plana vitrectomy; however, the visual outcome was poor.

"The Most Crushing Thing": Understanding Resident Assessment Burden in a Competency-Based Curriculum.

Background: Competency-based medical education (CBME) was expected to increase the workload of assessment for graduate training programs to support the development of competence. Learning conditions were anticipated to improve through the provision of tailored learning experiences and more frequent, low-stakes assessments. Canada has adopted an approach to CBME called Competence by Design (CBD). However, in the process of implementation, learner anxiety and assessment burden have increased unexpectedly. To mitigate this unintended consequence, we need a stronger understanding of how resident assessment burdens emerge and function. Objective: This study investigates contextual factors leading to assessment burden on residents within the framework of CBD. Methods: Residents were interviewed about their experiences of assessment using constructivist grounded theory. Participants (n=21) were a purposive sample from operative and perioperative training programs, recruited from 6 Canadian medical schools between 2019 and 2020. Self-determination theory was used as a sensitizing concept to categorize findings on types of assessment burden. Results: Nine assessment burdens were identified and organized by threats to psychological needs for autonomy, relatedness, and competence. Burdens included: missed opportunities for self-regulated learning, lack of situational control, comparative assessment, lack of trust, constraints on time and resources, disconnects between teachers and learners, lack of clarity, unrealistic expectations, and limitations of assessment forms for providing meaningful feedback. Conclusions: This study contributes a contextual understanding of how assessment burdens emerged as unmet psychological needs for autonomy, relatedness, and competence, with unintended consequences for learner well-being and intrinsic motivation.

Flexible, Air Dryable, and Fiber Modified Aerogel-Based Wet Electrode for Electrophysiological Monitoring.

This study presents a novel type of wet electrode material for electrophysiological monitoring based on a conductive aerogel film. The electrode material incorporates cellulose nanocrystal and fiber as a biocompatible polymer and multi-walled carbon nanotube as a conductive filler. The fabricated electrode is fully characterized to explore the chemical, mechanical, electrical, and water absorption properties. The wet aerogel film presents suitable mechanical flexibility owing to the use of fiber enabling it to be conformal to curved surfaces like human body. The water absorption percentage of the fabricated aerogel film is extremely high (∼500%) due to the porosity of the film and hydrophilicity of the base polymer allowing it for effective wet electrode applications. The film is air dryable with a fast (∼10 min) and facile wetting process granting the electrode application for long-term, multiple use, and remote monitoring of patients. The electrical impedance range of the fabricated aerogel electrodes is relatively low (20 Ω/cm2-370 Ω/cm2) which is within the range of use for various electrophysiological monitoring purposes such as electrocardiography (ECG) and electroencephalography (EEG). Overall, the presented study introduces a novel wet electrode based on porous and electrically conductive aerogel film to be used for various biomedical applications.

Feasibility and significance of stimulating interscapular muscles using transcutaneous functional electrical stimulation in able-bodied individuals.

OBJECTIVE: The study objective was to assess the feasibility of stimulating the lower trapezius (LT), the upper trapezius (UT) and serratus anterior (SA) muscles along with anterior or middle deltoid, using surface functional electrical stimulation (FES). The secondary aim was to understand the effects of LT, UT, and SA stimulation on maximum arm reach achieved in shoulder flexion and abduction. DESIGN: Single arm interventional study. SETTING: Inpatient Rehabilitation Hospital. PARTICIPANTS: Ten healthy volunteers. INTERVENTION: Participants completed 10 trials for each of the 3 conditions in flexion and abduction, i.e. (1) Active voluntary flexion or abduction, (2) FES for anterior deltoid for flexion or middle deltoid for abduction, and (3) FES for LT, UT, and SA along with anterior deltoid for flexion or middle deltoid for abduction. OUTCOME MEASURES: Maximum arm reach and percent angle relative to the voluntary movement were computed from motion capture data for each condition. Wilcoxon signed-rank test was used to compare the maximum reach between two FES conditions. RESULTS: The study results showed that all three interscapular muscles can be stimulated using surface FES. Maximum reach in abduction was greater for FES of middle deltoid along with the interscapular muscles (51.77° ± 17.54°) compared to FES for middle deltoid alone (43.76° ± 15.32°; Z = -2.701, P = 0.007). Maximum reach in flexion for FES of anterior deltoid, along with interscapular muscles, was similar to that during FES of anterior deltoid alone. CONCLUSION: Interscapular muscles can be stimulated using surface FES devices and should be engaged during rehabilitation as appropriate.

Novel Electrode Designs for Neurostimulation in Regenerative Medicine: Activation of Stem Cells.

Neural stem and progenitor cells (i.e., neural precursors) are found within specific regions in the central nervous system and have great regenerative capacity. These cells are electrosensitive and their behavior can be regulated by the presence of electric fields (EFs). Electrical stimulation is currently used to treat neurological disorders in a clinical setting. Herein we propose that electrical stimulation can be used to enhance neural repair by regulating neural precursor cell (NPC) kinetics and promoting their migration to sites of injury or disease. We discuss how intrinsic and extrinsic factors can affect NPC migration in the presence of an EF and how this impacts electrode design with the goal of enhancing tissue regeneration. We conclude with an outlook on future clinical applications of electrical stimulation and highlight technological advances that would greatly support these applications.

Color Stability of a New Rice Husk Composite in Comparison with Conventional Composites after Exposure to Commonly Consumed Beverages in Malaysia.

OBJECTIVE: To evaluate the color stability of a new organic rice husk nanocomposite as compared to four conventional composites after exposure to commonly consumed beverages in Malaysia. METHODS: One hundred and twenty-five disk samples were prepared from a new rice husk-based composite and four other conventional methacrylate-based light-cured composites of shade A2. The samples were immersed in four commonly consumed beverages: coco-based drink, kopi, Chinese tea, and teh tarik for four weeks. The color measurements were carried out every week using the reflectance spectrophotometer according to the CIE L ∗ a ∗ b ∗ color system. Color changes of samples (ΔE) in each week were calculated. Statistical analysis was carried out by performing a mixed ANOVA and Tukey's post hoc test in order to analyse the differences in ΔE. RESULTS: The findings revealed a statistically significant difference of ΔE reading (p < 0.05) among all composites immersed in all four beverages after four weeks. Rice husk composites exhibited lesser color stability as compared to Ceram.X One Universal (p < 0.001) and G-aenial Universal Flo (p < 0.001) but showed higher color stability compared to Solare-X (p < 0.001) and Neofil (p < 0.001). Coffee and Chinese tea had the most significant impact on color changes (p < 0.05) observed in all composites over four weeks of study. CONCLUSION: Rice husk composite showed acceptable color stability. It can be considered as an alternative to conventional composites due to its eco-friendly properties.