Recent advances in unlinked total elbow arthroplasty in Japan.

Background: Total elbow arthroplasty (TEA) is a valuable therapeutic approach for improving function and relieving pain in severely deformed elbow joints. However, TEA is associated with a high incidence of complications. In Japan, the use of unlinked TEA has a long history, with the development of the Kudo prosthesis marking a significant milestone. Subsequently, various unlinked implant designs have been developed. Although favorable long-term clinical results have been reported, complications remain a concern. To further improve the outcome of unlinked TEA, attempts have been made in recent years to develop various surgical approaches and intraoperative support devices. This review focuses on the clinical outcomes and recent advances in unlinked TEA in Japan. Methods: A comprehensive review of clinical results and advancements in unlinked TEA in Japan was conducted. The analysis included trends in the number of TEA, medium-term and long-term results for unlinked TEA, surgical approaches, or preoperative planning techniques. Results: Several implant designs have been developed in Japan. Clinical studies have reported satisfactory long-term outcomes with these implants, but complications, such as infection, fractures, and dislocation, have been observed. In order to enhance the outcomes of unlinked TEA, various triceps-on approaches have been developed as alternatives to the triceps-detaching approach, which compromises the continuity between the triceps tendon and ulna, leading to inevitable complications related to the triceps tendon. Preservation or repair of the surrounding soft tissues is considered critical for preventing postoperative instability due to the absence of a radial head in the current unlinked TEA design. Computed tomography-based 3-dimensional preoperative planning has been pioneered in Japan, demonstrating its effectiveness in predicting implant size and achieving appropriate implant placement. Additionally, augmented reality-assisted surgery is being explored to accurately translate preoperative planning into the surgical procedure. Conclusion: Unlinked TEA for inflammatory arthritis has exhibited promising long-term results in Japan, with ongoing efforts to improve surgical techniques and preoperative planning. Further advancements are anticipated to prevent complications such as dislocation and peri-implant fractures.

Webplasty using an external fixator for complex syndactyly caused by Apert syndrome.

BACKGROUND: Webplasty can be conducted for complex syndactyly caused by Apert syndrome (also referred to as Apert hand) by extending the soft tissue in the lateral direction using an external fixator. This study aimed to verify the usefulness of webplasty without skin grafting. METHODS: Webplasty with lateral extension was conducted at a single institution from 2015 to 2023. The patients were four children with Apert hand aged 1-3 years. A custom-made small external fixator was used for all of the soft tissue extension. RESULTS: Webplasty without skin grafting was completed by the time all five patients were 5-6 years of age. CONCLUSION: Webplasty without skin grafting was possible with lateral extension of the soft tissue using a simple external fixator.

Global changes in gene expression during compatible and incompatible interactions of faba bean (Vicia faba L.) during Orobanche foetida parasitism.

Orobanche foetida Poiret is the main constraint facing faba bean crop in Tunisia. Indeed, in heavily infested fields with this parasitic plant, yield losses may reach 90%, and the recent estimation of the infested area is around 80,000 ha. Identifying genes involved in the Vicia faba/O. foetida interaction is crucial for the development of effective faba bean breeding programs. However, there is currently no available information on the transcriptome of faba bean responding to O. foetida parasitism. In this study, we employed RNA sequencing to explore the global gene expression changes associated with compatible and incompatible V. faba/O. foetida interactions. In this perspective, two faba bean varieties (susceptible and resistant) were examined at the root level across three stages of O. foetida development (Before Germination (BG), After Germination (AG) and Tubercule Stage (TS)). Our analyses presented an exploration of the transcriptomic profile, including comprehensive assessments of differential gene expression and Gene Ontology (GO) enrichment analyses. Specifically, we investigated key pathways revealing the complexity of molecular responses to O. foetida attack. In this study, we detected differential gene expression of pathways associated with secondary metabolites: flavonoids, auxin, thiamine, and jasmonic acid. To enhance our understanding of the global changes in V. faba response to O. foetida, we specifically examined WRKY genes known to play a role in plant host-parasitic plant interactions. Furthermore, considering the pivotal role of parasitic plant seed germination in this interaction, we investigated genes involved in the orobanchol biosynthesis pathway. Interestingly, we detected the gene expression of VuCYP722C homolog, coding for a key enzyme involved in orobanchol biosynthesis, exclusively in the susceptible host. Clearly, this study enriches our understanding of the V. faba/O. foetida interaction, shedding light on the main differences between susceptible and resistant faba bean varieties during O. foetida infestation at the gene expression level.

ICLAMP: a novel technique to explore adenosine deamination via inosine chemical labeling and affinity molecular purification.

Recent developments in sequencing and bioinformatics have advanced our understanding of adenosine-to-inosine (A-to-I) RNA editing. Surprisingly, recent analyses have revealed the capability of adenosine deaminase acting on RNA (ADAR) to edit DNA:RNA hybrid strands. However, edited inosines in DNA remain largely unexplored. A precise biochemical method could help uncover these potentially rare DNA editing sites. We explore maleimide as a scaffold for inosine labeling. With fluorophore-conjugated maleimide, we were able to label inosine in RNA or DNA. Moreover, with biotin-conjugated maleimide, we purified RNA and DNA containing inosine. Our novel technique of inosine chemical labeling and affinity molecular purification offers substantial advantages and provides a versatile platform for further discovery of A-to-I editing sites in RNA and DNA.

The process of reacquiring new vocalization in total laryngectomy patients with head and neck cancer: A qualitative study.

Objective: Speech rehabilitation significantly contributes to the enhanced quality of life for patients who have undergone laryngectomy due to head and neck cancer. The initiation of tracheoesophageal speech early in the rehabilitation process has been associated with improved speech quality. Despite this, voice changes can carry a stigma due to communication challenges, even after successful voice restoration, potentially limiting the overall improvement in quality of life. Thus, our aim was to gain a profound understanding of the transition process from the selection to the adaptation of tracheoesophageal speech in patients with head and neck cancer. Methods: Participants, who had undergone laryngectomy for head and neck cancer, were recruited from peer support groups in Japan, resulting in the identification of thirteen tracheoesophageal speakers. The data were analyzed using grounded theory methodology, incorporating open, axial, and selective coding. Semi-structured interviews delved into tracheoesophageal speakers' perceptions of their voices and the adaptive strategies employed for their preferred alternative communication methods. Results: During the adaptation process, participants underscored the importance of communicating with their own voices. However, they also experienced anxiety about losing their natural voice, confronted the reality of living without a voice, and coped with their new voice. Eventually, participants came to recognize the changed voice as their own. Conclusions: The personal conviction associated with the notion of "communicating with one's own voice" is integral to the adaptation process for patients with head and neck cancer who undergo laryngectomies and utilize tracheoesophageal speech. Some aspects of tracheoesophageal speech can evoke feelings of hopelessness, emphasizing the importance of comprehensive support for professional speech rehabilitation.

Visually assessing work performance using a smartwatch via day-to-day fluctuations in heart rate variability.

Objective: To optimize workplace health promotion, a simple method for quantifying allostatic load response is needed. This study examines the feasibility of optimizing objective anxiety and presenteeism monitoring using daily smartwatch-measured ultra-short heart rate variability (HRV). Methods: Office workers without diagnosed disease prospectively performed 30 s HRV self-measurement each morning for two months and responded to the State-Trait Anxiety Inventory (STAI) and Work Limitation Questionnaire (WLQ). Logistic regression analysis examined daily HRV parameters in the high-trait anxiety group (HTA, STAI ≥ 40) using mean and variance HRV, age, self-reported gender, and body mass index (BMI). The ideal cutoff value enabled comparison of WLQ using the Mann-Whitney U test. Heart rate variability data were collected for 279 participants (male ratio, 83.9%; age, 42 ± 10 years) who completed questionnaires and monitored HRV for 30+ days. Results: Compared to the low-trait anxiety group, HTA exhibited higher variance of the log-transformed coefficient of component variance of high-frequency component (LnccvHF) and low-frequency per HF (Lnccv L/H), in addition to differences in the means of these HRV parameters. In addition to BMI (odds ratio [OR] = 0.92, p = 0.02) and mean LnccvL/H (OR = 10.75, p < 0.01), the variance of Lnccv L/H was an independent predictor of HTA (OR = 2.39E + 8, p = 0.011). The daily Lnccv L/H dispersion group had a lower WLQ productivity loss score (p = 0.02, r = 0.17). Conclusions: By focusing on HRV dispersion status, this simple and instantly applicable daily HRV monitoring system enables optimized quantitative monitoring of anxiety and productivity.

Injury prevalence and associated factors among Japanese lacrosse collegiate athletes.

Context: Sports injuries have a substantial impact on athletes' performance and health. To reduce the risk of an injury occurring, the prevalence, localization, and severity need to be established. Objective: To examine the prevalence of sports injuries in collegiate lacrosse athletes. Design: Descriptive epidemiological study using online survey design. Setting: Japanese universities associated with UNIVAS. Participants: A total of 1,689 Japanese collegiate lacrosse athletes, 978 females and 701 males. Main outcome measures: Athletes were surveyed on the injuries within the previous year, their severity, localization, and onset characteristics. The support of an athletic trainer and its association with the odds of sustaining an injury was assessed. Factors related to injuries were explored. Results: One-year prevalence of injuries was 42%. Male sex, higher year at the university, and support from an athletic trainer were identified as factors related to higher odds of sustaining an injury and practicing at least 5 days per week was associated with lower odds of sustaining an injury. Conclusions: Male sex athletes, and athletes at the higher year at university are especially at risk of sustaining a lacrosse injury. The aspects of training (e.g., frequency, volume) should be investigated across the athlete development process to address these findings. Further investigation is needed to determine the extent to which the support of athletic trainers affects both the frequency and severity of injuries in lacrosse athletes.

Nursing-care for family caregivers of terminally ill cancer patients to enhance preparedness for death.

Family caregivers of terminally ill cancer patients prepare for a patient's death. Nursing-care for preparedness is effective for their psychological health. This study aims to structuralize nursing-care for preparedness and extract related factors while presenting the implications for improved quality of care. Data from a cross-sectional survey of general ward and palliative care unit nurses in designated cancer care hospitals (n=561) was analyzed with exploratory factor analysis and multiple regression analyses. The results of the analysis, the structure was classified into "Nurse-centered support" and "Support through inter-professional work." Both supports were practiced significantly more frequently in palliative care units than general wards. Related factors in general wards were; communication skills, cooperation with doctors, the existence of certified nurse/certified nurse specialists as consultants, attitudes toward care of the dying, frequency of death conferences, and cooperation with specialist cancer counselors. Therefore, the results can help improve the quality of family care in palliative care, especially in general wards.

Point of care ultrasound combined with CTS-6 to diagnose idiopathic carpal tunnel syndrome.

BACKGROUND: This study aimed to demonstrate the effectiveness of our new diagnostic chart using point of care ultrasound combined with CTS-6 for diagnosing idiopathic carpal tunnel syndrome. METHODS: We conducted a retrospective analysis of the data of patients who visited our department and received point of care ultrasound combined with CTS-6 from 2020 to 2023. Data regarding age, sex, initial and final diagnosis, cross-sectional area of the median nerve, CTS-6 score, and electrodiagnostic severity were obtained and statistically analyzed. RESULTS: Of the 177 wrists included in our study, 138 (78 %) were diagnosed with carpal tunnel syndrome, while 39 (22 %) were not (non-carpal tunnel syndrome). With our diagnostic method, 127 wrists (72 %) were diagnosed initially with carpal tunnel syndrome, 23 wrists (13 %) with non-carpal tunnel syndrome, and the rest 27 wrists (15 %) as borderline. Our initial diagnoses of carpal tunnel syndrome and non-carpal tunnel syndrome were maintained in all cases except for two. Cross-sectional area, CTS-6 score, and electrodiagnostic severity showed a positive correlation. A post hoc analysis showed that the new scoring system (CTS-6 score + 2 × cross-sectional area) with a cutoff value of 31.25 points showed a sensitivity as high as 95 % and a specificity of 100 %. CONCLUSIONS: Our findings suggest that most suspected idiopathic carpal tunnel syndrome cases can be diagnosed correctly using the diagnostic chart. Although additional tools, including electrodiagnostic studies, may be needed for borderline cases, the use of point of care ultrasound combined with CTS-6 may be a recommendable first-line confirmatory test because point of care ultrasound and CTS-6 could be complementary tools, and this chart may be especially beneficial for atypical or outlier cases. LEVEL OF EVIDENCE: Diagnostic III.

The Reality of a Head-Mounted Display (HMD) Environment Tested via Lightness Perception.

Head-mounted displays (HMDs) are becoming more and more popular as a device for displaying a virtual reality space, but how real are they? The present study attempted to quantitatively evaluate the degree of reality achieved with HMDs by using a perceptual phenomenon as a measure. Lightness constancy is an ability that is present in human visual perception, in which the perceived reflectance (i.e., the lightness) of objects appears to stay constant across illuminant changes. Studies on color/lightness constancy in humans have shown that the degree of constancy is high, in general, when real objects are used as stimuli. We asked participants to make lightness matches between two virtual environments with different illuminant intensities, as presented in an HMD. The participants' matches showed a high degree of lightness constancy in the HMD; our results marked no less than 74.2% (84.8% at the maximum) in terms of the constancy index, whereas the average score on the computer screen was around 65%. The effect of head-tracking ability was confirmed by disabling that function, and the result showed a significant drop in the constancy index but that it was equally effective when the virtual environment was generated by replay motions. HMDs yield a realistic environment, with the extension of the visual scene being accompanied by head motions.

Magnon thermal Hall effect via emergent SU(3) flux on the antiferromagnetic skyrmion lattice.

Complexity of quantum phases of matter is often understood theoretically by using gauge structures, as is recognized by the [Formula: see text] and U(1) gauge theory description of spin liquids in frustrated magnets. Anomalous Hall effect of conducting electrons can intrinsically arise from a U(1) gauge expressing the spatial modulation of ferromagnetic moments or from an SU(2) gauge representing the spin-orbit coupling effect. Similarly, in insulating ferro and antiferromagnets, the magnon contribution to anomalous transports is explained in terms of U(1) and SU(2) fluxes present in the ordered magnetic structure. Here, we report thermal Hall measurements of MnSc2S4 in an applied field up to 14 T, for which we consider an emergent higher rank SU(3) flux, controlling the magnon transport. The thermal Hall coefficient takes a substantial value when the material enters a three-sublattice antiferromagnetic skyrmion phase, which is in agreement with the linear spin-wave theory. In our description, magnons are dressed with SU(3) gauge field, which is a mixture of three species of U(1) gauge fields originating from the slowly varying magnetic moments on these sublattices.

Predictive Models for Palliative Care Needs of Advanced Cancer Patients Receiving Chemotherapy.

CONTEXT: Early palliative care is recommended within eight-week of diagnosing advanced cancer. Although guidelines suggest routine screening to identify cancer patients who could benefit from palliative care, implementing screening can be challenging due to understaffing and time constraints. OBJECTIVES: To develop and evaluate machine learning models for predicting specialist palliative care needs in advanced cancer patients undergoing chemotherapy, and to investigate if predictive models could substitute screening tools. METHODS: We conducted a retrospective cohort study using supervised machine learning. The study included patients aged 18 or older, diagnosed with metastatic or stage IV cancer, who underwent chemotherapy and distress screening at a designated cancer hospital in Japan from April 1, 2018, to March 31, 2023. Specialist palliative care needs were assessed based on distress screening scores and expert evaluations. Data sources were hospital's cancer registry, health claims database, and nursing admission records. The predictive model was developed using XGBoost, a machine learning algorithm. RESULTS: Out of the 1878 included patients, 561 were analyzed. Among them, 114 (20.3%) exhibited needs for specialist palliative care. After under-sampling to address data imbalance, the models achieved an Area Under the Curve (AUC) of 0.89 with 95.8% sensitivity and a specificity of 71.9%. After feature selection, the model retained five variables, including the patient-reported pain score, and showcased an 0.82 AUC. CONCLUSION: Our models could forecast specialist palliative care needs for advanced cancer patients on chemotherapy. Using five variables as predictors could replace screening tools and has the potential to contribute to earlier palliative care.

Alpha-synuclein promotes PRMT5-mediated H4R3me2s histone methylation by interacting with the BAF complex.

α-Synuclein (αS) is a key molecule in the pathomechanism of Parkinson's disease. Most studies on αS to date have focused on its function in the neuronal cytosol, but its action in the nucleus has also been postulated. Indeed, several lines of evidence indicate that overexpressed αS leads to epigenomic alterations. To clarify the functional role of αS in the nucleus and its pathological significance, HEK293 cells constitutively expressing αS were used to screen for nuclear proteins that interact with αS by nanoscale liquid chromatography/tandem mass spectrometry. Interactome analysis of the 229 identified nuclear proteins revealed that αS interacts with the BRG1-associated factor (BAF) complex, a family of multi-subunit chromatin remodelers important for neurodevelopment, and protein arginine methyltransferase 5 (PRMT5). Subsequent transcriptomic analysis also suggested a functional link between αS and the BAF complex. Based on these results, we analyzed the effect of αS overexpression on the BAF complex in neuronally differentiated SH-SY5Y cells and found that induction of αS disturbed the BAF maturation process, leading to a global increase in symmetric demethylation of histone H4 on arginine 3 (H4R3me2s) via enhanced BAF-PRMT5 interaction. Chromatin immunoprecipitation sequencing confirmed accumulated H4R3me2s methylation near the transcription start site of the neuronal cell adhesion molecule (NRCAM) gene, which has roles during neuronal differentiation. Transcriptional analyses confirmed the negative regulation of NRCAM by αS and PRMT5, which was reconfirmed by multiple datasets in the Gene Expression Omnibus (GEO) database. Taken together, these findings suggest that the enhanced binding of αS to the BAF complex and PRMT5 may cooperatively affect the neuronal differentiation process.

Detection of Modified Histones from Oral Mucosa of a Patient with DYT-KMT2B Dystonia.

Introduction: DYT-KMT2B is a rare childhood-onset, hereditary movement disorder typically characterized by lower-limb dystonia and subsequently spreads into the craniocervical and laryngeal muscles. Recently, KMT2B-encoding lysine (K)-specific histone methyltransferase 2B was identified as the causative gene for DYT-KMT2B, also known as DYT28. In addition to the fact that many physicians do not have sufficient experience or knowledge of hereditary dystonia, the clinical features of DYT-KMT2B overlap with those of other hereditary dystonia, and limited clinical biomarkers make the diagnosis difficult. Methods: Histone proteins were purified from the oral mucosa of patients with de novo KMT2B mutation causing premature stop codon, and then trimethylated fourth lysine residue of histone H3 (H3K4me3) which was catalyzed by KMT2B was analyzed by immunoblotting with specific antibody. We further analyzed the significance of H3K4me3 in patients with DYT-KMT2B using publicly available datasets. Results: H3K4me3 histone mark was markedly lower in the patient than in the control group. Additionally, a reanalysis of publicly available datasets concerning DNA methylation also demonstrated that KMT2B remained inactive in DYT-KMT2B. Discussion: Although only one case was studied due to the rarity of the disease, the reduction of H3K4me3 in the patient's biological sample supports the dysfunction of KMT2B in DYT-KMT2B. Together with informatics approaches, our results suggest that KMT2B haploinsufficiency contributes to the DYT-KMT2B pathogenic process.

Anaerobic threshold using sweat lactate sensor under hypoxia.

We aimed to investigate the reliability and validity of sweat lactate threshold (sLT) measurement based on the real-time monitoring of the transition in sweat lactate levels (sLA) under hypoxic exercise. In this cross-sectional study, 20 healthy participants who underwent exercise tests using respiratory gas analysis under hypoxia (fraction of inspired oxygen [FiO2], 15.4 ± 0.8%) in addition to normoxia (FiO2, 20.9%) were included; we simultaneously monitored sLA transition using a wearable lactate sensor. The initial significant elevation in sLA over the baseline was defined as sLT. Under hypoxia, real-time dynamic changes in sLA were successfully visualized, including a rapid, continual rise until volitionary exhaustion and a progressive reduction in the recovery phase. High intra- and inter-evaluator reliability was demonstrated for sLT's repeat determinations (0.782 [0.607-0.898] and 0.933 [0.841-0.973]) as intraclass correlation coefficients [95% confidence interval]. sLT correlated with ventilatory threshold (VT) (r = 0.70, p < 0.01). A strong agreement was found in the Bland-Altman plot (mean difference/mean average time: - 15.5/550.8 s) under hypoxia. Our wearable device enabled continuous and real-time lactate assessment in sweat under hypoxic conditions in healthy participants with high reliability and validity, providing additional information to detect anaerobic thresholds in hypoxic conditions.

Internucleotidic bond formation using H-phosphonamidate derivatives and acidic activators.

We previously developed a synthesis method for oligodeoxynucleotides using H-phosphonamidate derivatives as monomers. In this synthesis method, H-phosphonamidate monomers having a heterocyclic amino group as a leaving group reacts with an alcohol to form an internucleotidic H-phosphonate diester in pyridine without any additives upon heating. In this study, H-phosphonamidate reacted to form an internucleotidic linkage in the presence of acidic activators at room temperature. This finding is the first example of the activation of an amino group of an H-phosphonamidate derivative in the presence of acidic activators. In addition, the condensation reaction with acidic activators was accelerated with the use of pyridine as a solvent. Moreover, heterocyclic amino groups that have an electronegative atom, such as S and O, effectively served as a leaving group of the H-phosphonamidate monomer. From the results, we hypothesized that the tautomerization to the phosphite-form of the H-phosphonamidate monomer is an important step of the condensation reaction using acidic activators, and such process is accelerated when using pyridine as the solvent and heterocyclic amino groups as the leaving groups of the H-phosphonamidate monomer. Molecular orbital calculations also support our hypothesis. We optimized the condensation reaction conditions and synthesized dinucleoside phosphorothioate derivatives bearing all nucleobases.

Aggressive End-of-Life Treatments Among Inpatients With Cancer and Non-cancer Diseases Using a Japanese National Claims Database.

To describe aggressive treatments at end-of-life among inpatients with cancer and non-cancer diseases and to evaluate factors associated with these treatments using the Japanese national database (NDB). We conducted a retrospective cohort study among inpatients aged ≥ 20 years who died between 2012 and 2015 using a sampling dataset of NDB. The outcome was the proportion of aggressive treatments in the last 14 days of life. We considered the underlying causes of death as cancer, dementia/senility, and heart, cerebrovascular, renal, liver, respiratory, and neurodegenerative diseases. We analyzed 54,105 inpatients, with underlying cause of death distributed as follows: cancer, 24.9%; heart disease, 16.5%; respiratory disease, 12.3%; and cerebrovascular disease, 9.7%. The proportion of intensive care unit (ICU) admission was 9.7%, being the highest in heart disease (20.5%), followed by cerebrovascular diseases (12.6%), and least in dementia/senility (.6%). The proportion of cardiopulmonary resuscitation was 19.6%, being the highest in heart disease (38.1%), followed by renal diseases (19.5%), and least in cancer (6.2%). Multivariate logistic regression analysis revealed that having heart diseases, cerebrovascular diseases, younger age, less comorbidities, and shorter length of stay were associated with an increasing risk of aggressive treatments in the last 14 days of life. The proportion of aggressive treatments at the end-of-life varies depending on the disease; additionally, these treatments were associated with having heart diseases, younger age, less comorbidity, and shorter length of stay. Our findings may help develop and set benchmarks for quality indicators at the end-of-life for patients with non-cancer diseases.

High-precision rapid testing of omicron SARS-CoV-2 variants in clinical samples using AI-nanopore.

A digital platform that can rapidly and accurately diagnose pathogenic viral variants, including SARS-CoV-2, will minimize pandemics, public anxiety, and economic losses. We recently reported an artificial intelligence (AI)-nanopore platform that enables testing for Wuhan SARS-CoV-2 with high sensitivity and specificity within five minutes. However, which parts of the virus are recognized by the platform are unknown. Similarly, whether the platform can detect SARS-CoV-2 variants or the presence of the virus in clinical samples needs further study. Here, we demonstrated the platform can distinguish SARS-CoV-2 variants. Further, it identified mutated Wuhan SARS-CoV-2 expressing spike proteins of the delta and omicron variants, indicating it discriminates spike proteins. Finally, we used the platform to identify omicron variants with a sensitivity and specificity of 100% and 94%, respectively, in saliva specimens from COVID-19 patients. Thus, our results demonstrate the AI-nanopore platform is an effective diagnostic tool for SARS-CoV-2 variants.

MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion.

BACKGROUND: The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis. METHODS: In vivo fluctuations of both intra- and extracellular metabolite levels during IR were explored via microdialysis and tissue metabolome analysis. Oxidized phosphatidylcholines were assessed using liquid chromatography high-resolution mass spectrometry. The areas at risk following IR were assessed using triphenyl-tetrazolium chloride/Evans blue stain. RESULTS: Metabolomic analysis combined with microdialysis revealed a significant release of glutathione from the ischemic region into extracellular spaces during ischemia and after reperfusion. The release of glutathione into extracellular spaces and a concomitant decrease in intracellular glutathione concentrations were also observed during anoxia-reperfusion in an in vitro cardiomyocyte model. This extracellular glutathione release was prevented by chemical inhibition or genetic suppression of glutathione transporters, mainly MRP1 (multidrug resistance protein 1). Treatment with MRP1 inhibitor reduced the intracellular reactive oxygen species levels and lipid peroxidation, thereby inhibiting cell death. Subsequent in vivo evaluation of endogenously oxidized phospholipids following IR demonstrated the involvement of ferroptosis, as levels of multiple oxidized phosphatidylcholines were significantly elevated in the ischemic region 12 hours after reperfusion. Inhibition of the MRP1 transporter also alleviated intracellular glutathione depletion in vivo and significantly reduced the generation of oxidized phosphatidylcholines. Administration of MRP1 inhibitors significantly attenuated infarct size after IR injury. CONCLUSIONS: Glutathione was released continuously during IR, primarily in an MRP1-dependent manner, and induced ferroptosis. Suppression of glutathione release attenuated ferroptosis and reduced myocardial infarct size following IR.

AQUACEL® Ag Advantage reduces the stress of postoperative packing removal after endoscopic sinus surgery

Abstract Objective: After Endoscopic Sinus Surgery (ESS), packing plays an important role in wound healing and hemostasis. However, the effect of the packing removal procedure on physician stress has not been evaluated. The purpose of this study was to evaluate physician stress during packing removal for patients treated with AQUACEL® Ag Advantage versus KALTOSTAT®. Methods: This retrospective study included 15 patients who underwent packing with ESS for chronic rhinosinusitis performed at two centers; 9 were treated with AQUACEL® Ag Advantage and 6 were treated with KALTOSTAT®. Physician stress during packing removal was evaluated with the National Aeronautics and Space Administration-Task Load Index (NASA-TLX). The time required to remove the packing and the number of instruments used in the procedure were recorded. Postoperative bleeding (Boezaart bleeding score) and wound healing were graded. Patient symptoms on the day after surgery and pain during packing removal were assessed using a visual analog scale. Results: Computed tomography scores, asthma complications, and blood eosinophil counts were significantly higher in the AQUACEL® Ag Advantage group. Patient symptoms on the day after surgery were not significantly different between the two groups. Physician stress during the task of packing removal was significantly lower in the AQUACEL® Ag Advantage group than in the KALTOSTAT® group (35.5 vs. 81.0, p = 0.016) according to the NASA-TLX scores. The number of instruments used in the procedure was significantly lower in the AQUACEL® Ag Advantage group than in the KALTOSTAT® group (3.0 vs. 6.0, p = 0.015). There were no significant differences in procedure time for packing removal, postoperative bleeding, wound healing, or patient pain at the time of packing removal between the groups. Conclusion: Physicians feel stressed about packing removal. In addition, AQUACEL® Ag Advantage is useful for packing after ESS, requiring fewer instruments for the procedure than KALTOSTAT® and reducing physician stress about the procedure. Level of evidence: Level 3.