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Intravascular large B-cell lymphoma (IVLBCL) typically involves nonspecific symptoms that complicate diagnosis. This report discusses the case of a 70-year-old man, who presented with dyspnea, fatigue, and weight loss that evolved into severe respiratory failure, diagnosed with IVLBCL via random skin biopsy. The initial improvement in respiratory symptoms was followed by coronavirus disease. Response to steroid therapy and elevated lactate dehydrogenase levels suggested IVLBCL, confirmed by a random skin biopsy. The combination chemotherapy of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone improved the respiratory condition. This case highlights the diagnostic challenges associated with IVLBCL and the crucial role of random skin biopsy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Triple-stranded helical lanthanide MOFs with CO 2 adsorption properties were investigated. Lanthanide MOFs ([Eu 0.1 Tb 0.9 (hfa) 3 (dpa)] n ) are composed of lanthanide luminophores (Eu(III) and/or Tb(III) ions), fluorinated antenna ligands (hfa: hexafluoroacetylacetonate), and polyamide-type linker ligands (dpa: 4-(diphenylphosphoryl)-N-(4-(diphenylphosphoryl)phenyl)benzamide). The cylindrical structure was characterized by single-crystal X-ray analysis, thermogravimetric analysis, and gas adsorption measurements. The inner surfaces of the cylindrical channels were covered with the fluorine atoms of the hfa ligands. The emission intensity ratio (I Eu /I Tb ) in [Eu 0.1 Tb 0.9 (hfa) 3 (dpa)] n is affected by the CO 2 gas adsorption behavior. The change in I Eu /I Tb value was caused by the intermolecular interactions between the CO 2 gas molecules and the fluorinated ligands, resulting in an electronic structural change of the lowest triplet excited state in the photosensitized hfa ligands., (© 2024 Wiley-VCH GmbH.)

Appropriate symmetry breaking generates an anomalous Hall (AH) effect, even in antiferromagnetic (AFM) materials. Itinerant magnets with d electrons are typical examples that show a significant response. By contrast, the process by which a response emerges from f-electron AFM structures remains unclear. In this Letter, we show that an AFM material, Ce_{2}CuGe_{6}, yields a large AH conductivity (AHC) of 550  Ω^{-1} cm^{-1}, which exceeds the values previously reported in d-electron AFM materials. Observed features, including the scaling relation against electrical conductivity, suggest that this AH transport is induced cooperatively by both intrinsic and extrinsic mechanisms derived from the AFM structure.

Objective: During total arch replacement (TAR) using frozen elephant trunk (FET) technique with Frozenix for true thoracic aortic aneurysm (tTAA), oversized FET tends to be chosen similar to the endovascular devise selection. However, the oversized FET is considered a risk factor for intimal injury. The appropriate size selection of FET remains insufficiently understood., Methods: Between October 2014 and March 2022, a total of 49 patients underwent TAR using Frozenix for tTAA. Out of 49 patients, four patients planned to staged surgery were excluded, 19 patients were operated on with an undersized Frozenix compared with the descending aorta (undersized FET group) and in 26 patients an equal or oversized Frozenix was used (oversized FET group). Clinical outcomes and postoperative diameter changes were investigated., Results: In-hospital mortality was 0%. The mean diameter of Frozenix and the descending aorta was 30.7 mm and 28.8 mm, respectively, in the oversized FET group, and 26.7 mm and 30.1 mm in the undersized FET group. Postoperative computed tomography (CT) demonstrated no endoleaks not only in the oversized FET group but also in the undersized FET group. CT also revealed that undersized FET had expanded more than the original diameter in all cases except for two, with an average of 2.47 ± 1.53 mm. Additionally, the descending aorta covered with Frozenix shrank in 10 patients (53%). Postoperative adverse aortic events were not observed., Conclusions: Undersized Frozenix tightly fit the descending aorta and resulted in complete sealing without endoleaks. Oversized FET is not strictly necessary considering the size-related adverse complications., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

β-Aspartyl compounds, such as β-aspartyl hydroxamate (serine racemase inhibitor), β-aspartyl-l-lysine (moisture retention), and β-aspartyl-l-tryptophan (immunomodulator) are physiologically active compounds. There is limited literature on the development of effective methods of production of β-aspartyl compounds. In this study, we describe the biochemical characterization of asparagine synthetase (AS) from Streptococcus thermophilus NBRC 13957 (StAS) and the enzymatic synthesis of β-aspartyl compounds using StAS. Recombinant StAS was expressed in Escherichia coli BL21(DE3) and it displayed activity towards hydroxylamine, methylamine, ethylamine, and ammonia, as acceptors of the β-aspartyl moiety. StAS exhibited higher activity toward hydroxylamine and ethylamine as acceptor substrates compared with the enzymes from Lactobacillus delbrueckii NBRC 13953, Lactobacillus reuteri NBRC 15892, and E. coli. The coupling of the synthesis of β-aspartyl compounds by StAS with an ATP-regeneration system using polyphosphate kinase from Deinococcus proteoliticus NBRC 101906 displayed an approximately 2.5-fold increase in the production of β-aspartylhydroxamate from 1.06 mM to 2.53 mM after a 76-h reaction., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

For small-molecule drugs, lipidation via a cleavable linkage can extend half-life in circulation through interaction with albumin. Here we modified the cysteinylprolyl ester (CPE) system used in peptide thioester synthesis, which normally requires basic conditions, for use as an self-immolative linker and release device for a lipid-gemcitabine conjugate. To improve release under physiological conditions for medical application, a methyl group at the α-position of cysteine on the CPE unit was incorporated in anticipation of the Thorpe-Ingold effect. As a result, Ac-Gly-(α-Me)Cys(SH)-Pro-gemcitabine 11 drastically promoted the release of gemcitabine in comparison with Ac-Gly-Cys(SH)-Pro-gemcitabine 10. Furthermore, in the presence of bovine serum albumin and/or 2-mercaptoethanesulfonic acid, the gentle and continuous release of gemcitabine from the lipid-gemcitabine conjugate 16 was achieved. In addition to gemcitabine, this method could allow high clearance drugs, including nucleic acid and prostacyclin derivatives, to maintain their biological activity long enough to become effective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In recent years, the use of immune checkpoint inhibitors (ICI) has increased and there have been case reports of anti- aminoacyl tRNA synthetase (ARS) antibody syndrome during ICI treatment. However, these cases are limited, and their clinical characteristics are not fully understood. We report the first case of anti ARS antibody syndrome with KS antibody during ICI therapy. This report presents our case, along with a literature review of other anti ARS antibody syndrome cases that developed after ICI use, discussing their clinical characteristics and possible mechanisms of onset. Considering the widespread use of ICI in cancer therapy, we should aware of anti ARS antibody syndrome that develops during use of ICI ., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Aims: Excessive occlusal force with periodontitis leads to rapid alveolar bone resorption. However, the molecular mechanism by which inflammation and mechanical stress cause bone resorption remains unclear. We examined the role of Piezo1, a mechanosensitive ion channel expressed on osteoblasts, in the changes in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio in mouse MC3T3-E1 osteoblast-like cells under Porphyromonas gingivalis lipopolysaccharide (P.g.-LPS) and mechanical stress., Methods: To investigate the effect of P.g.-LPS and mechanical stress on the RANKL/OPG ratio and Piezo1 expression, we stimulated MC3T3-E1 cells with P.g.-LPS. After 3 days in culture, shear stress, a form of mechanical stress, was applied to the cells using an orbital shaker. Subsequently, to investigate the role of Piezo1 in the change of RANKL/OPG ratio, we inhibited Piezo1 function by knockdown via Piezo1 siRNA transfection or by adding GsMTx4, a Piezo1 antagonist., Results: The RANKL/OPG ratio significantly increased in MC3T3-E1 cells cultured in a medium containing P.g.-LPS and undergoing mechanical stress compared to cells treated with P.g.-LPS or mechanical stress alone. However, the expression of Piezo1 was not increased by P.g.-LPS and mechanical stress. In addition, phosphorylation of MEK/ERK was induced in the cells under P.g.-LPS and mechanical stress. MC3T3-E1 cells treated with P.g.-LPS and mechanical stress when cocultured with RAW264.7 cells induced their differentiation into osteoclast-like cells. The increased RANKL/OPG ratio was suppressed by either Piezo1 knockdown or the addition of GsMTx4. Furthermore, GsMTx4 inhibited the phosphorylation of MEK/ERK., Conclusion: These findings suggest that P.g.-LPS and Piezo1-mediated mechanical stress induce MEK/ERK phosphorylation and increase RANKL expression in osteoblasts. Consequently, this leads to the differentiation of osteoclast precursor cells into osteoclasts., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein associated with metastatic characteristics of certain cancer types. However, it remains poorly characterized and its direct function in cancer remains unclear. The study presented here aims to further examine whether PTGFRN expression affects a cancer cell's phenotype, as well as metastatic-like characteristics. We used stable shRNA and cDNA transfections to respectively knockdown and overexpress PTGFRN in three different cancer cell lines, two of which are representative of rare and aggressive cancers (Mesothelioma and Pediatric Medulloblastoma). We then examined the characteristics of the resulting clones and showed a decrease in proliferation, migration, colony formation, and spheroid growth capabilities in cells where PTGFRN expression had been inhibited, while cells overexpressing PTGFRN showed the opposite. In addition, we showed that PTGFRN displayed direct binding to two protein partners, Integrin β1 and E. Cadherin, the latter of which is a novel direct binding partner to PTGFRN. Furthermore, silencing PTGFRN expression impacted the cellular process of autophagy, thereby providing another avenue by which PTGFRN potentially contributes to a cancer cell phenotype. Our findings demonstrate the potential role of PTGFRN in cancer metastasis and suggest PTGFRN as a future target for drug development in the treatment of metastatic cancers., (© 2024 Wiley Periodicals LLC.)

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6., Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021., Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12., Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%)., Competing Interests: FJ: Speaker fees: Gilead Sciences, MSD, and Ascletis. Consultancy: Gilead Sciences, MSD. FJ has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2023. YJW: Speaker fees: Gilead Science, AbbVie. Research Grant: Medicine Academic Clinical Program, SingHealth, Singapore. YJW has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2020. HT: Speaker fees: Gilead Science, AbbVie, Eisai, Fujifilm WAKO, Takeda, Kowa, Terumo, Astra Zeneca. VWSW: Consultancy: AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna. Speaker fees: Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab. Research grants: Gilead Sciences. Stock: Co-founder of Illuminatio Medical Technology Limited. MA: Speakers’ fees: AbbVie, Gilead Sciences. SD: Speakers fees: Gilead Sciences. MFY: Speakers’ fees: Fujirebio Incorporation, Gilead Sciences, Roche, Sysmex Corporation. Consulting or advisory board: AbbVie, Abbott Diagnostics, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Precision BioSciences, Roche, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology and Visirna Therapeutics. Research grant: AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, Fujirebio Incorporation, Gilead Sciences, Immunocore, Sysmex Corporation and Roche. MFY has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2021. CW: Research grant: Gilead Sciences. MLYu: Research support (grant) from Abbvie, BMS, Gilead, Merck, and Roche diagnostics. Consultant of Abbvie, BMS, Gilead, Roche, and Roche diagnostics. Speaker of Abbvie, BMS, Eisai, Gilead, Roche, and Roche diagnostics. MLYu has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2023. MHN: Research grants via institution: Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest. Consulting/Advisory board: Intercept, Exact Science, Gilead, GSK. JL, MLYe, WLC and JFH have been Editorial Board Members of Journal of Clinical and Translational Hepatology since 2022. HR has been an Editor-in-Chief of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

An advanced insulin synthesis is presented that utilizes one-pot/stepwise disulfide bond formation enabled by acid-activated S-protected cysteine sulfoxides in the presence of chloride anion. S-chlorocysteine generated from cysteine sulfoxides reacts with an S-protected cysteine to afford S-sulfenylsulfonium cation, which then furnishes the disulfide or reversely returns to the starting materials depending on the S-protection employed and the reaction conditions. Use of S-acetamidomethyl cysteine (Cys(Acm)) and its sulfoxide (Cys(Acm)(O)) selectively give the disulfide under weak acid conditions in the presence of MgCl 2 even if S-p-methoxybenzyl cysteine (Cys(MBzl)) and its sulfoxide (Cys(MBzl)(O)) are also present. In contrast, the S-MBzl pair yields the disulfide under more acidic conditions in the presence of a chloride anion source. These reaction conditions allowed a one-pot insulin synthesis. Additionally, lipidated insulin was prepared by a one-pot disulfide-bonding/lipidation sequence., (© 2024 Wiley-VCH GmbH.)

Introduction: A clonal shift from staphylococcal cassette chromosome mec (SCCmec) type II/ST5 methicillin-resistant Staphylococcus aureus (MRSA) to SCCmec type IV/clonal complex (CC)1 MRSA has occurred rapidly in Japan. Our previous research in a geriatric hospital found SCCmec type IV/CC1 MRSA prevalence in long-term care wards. Due to intensive personal care requirements, frequent contact with healthcare providers can potentially cause unintentional nosocomial MRSA transmission. We performed polymerase chain reaction-based open reading frame typing (POT) and core genome multilocus sequence typing (cgMLST) to investigate the occurrence of nosocomial transmission and to compare the results of these methods., Methods: POT and whole genome sequencing were performed in 83 MRSA isolates. Commercial automated software (Ridom SeqSphere+) was used to perform cgMLST. MRSA isolates with 0-8 allelic differences were considered related, and medical records were consulted in these cases., Results: SCCmec type IV/CC1 MRSA was the most frequently detected clone (n = 56, 67.5 %), which was divided into 14 POT types, followed by SCCmec type I/ST8 (n = 9) and SCCmec type IV/ST8 (n = 8). Identical POT types were found across 7 of 11 wards. However, cgMLST analysis identified only three cases (six strains) of high genetic similarity, indicating nosocomial transmission; only one involved SCCmec type IV/CC1 (two strains). The mean allelic difference in the core genomes between strains with identical POT types in the same ward was 55.3 ± 22.0., Conclusions: The cgMLST method proved more effective for identifying nosocomial transmissions compared to POT, highlighting its utility in tracking MRSA spread in healthcare settings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Although non-accidental trauma continues to be a leading cause of morbidity and mortality among children in the United States, the underlying factors leading to NAT are not well characterized. We aim to review reporting practices, clinical outcomes, and associated disparities among pediatric trauma patients experiencing NAT., Methods: A literature search utilizing PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane was conducted from database inception until April 6, 2023. This review includes studies that assessed pediatric (age <18) trauma patients treated for NAT in the United States emergency departments. The evaluated outcome was in-hospital mortality rates stratified by race, age, sex, insurance status, and socioeconomic advantage., Results: The literature search yielded 2641 initial articles, and after screening and applying inclusion and exclusion criteria, 15 articles remained. African American pediatric trauma patients diagnosed with NAT had higher mortality odds than white patients, even when adjusting for comparable injury severity. Children older than 12 mo experienced higher mortality rates compared to those younger than 12 mo, although some studies did not find a significant association between age and mortality. Uninsured insurance status was associated with the highest mortality rate, followed by Medicaid and private insurance. No significant association between sex and mortality or socioeconomic advantage and mortality was observed., Conclusions: Findings showed higher in-hospital mortality among African American pediatric trauma patients experiencing child abuse, and in patients 12 mo or older. Medicaid and uninsured pediatric patients faced higher mortality odds from their abuse compared to privately insured patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Late-stage formation of a sactionine thioether bond connecting a Gly α-carbon and Cys thiol was achieved by Lossen rearrangement of a glycyl hydroxamic acid (GlyHA) residue in a peptide. Lossen rearrangement allowed conversion of GlyHA within a peptide to an N -acyl iminium equivalent, which subsequently reacted with S -acetamidomethyl Cys (Cys(Acm)) in TFA in the presence of guanidine hydrochloride (Gn·HCl) to yield the desired thioether linkage in the final stage.

Pt-containing meta - and para -linked poly(phenyleneethynylene)s were synthesized by the dehydrochlorination coupling polymerization of PtCl 2 (PBu 3 ) 2 with m - and p -diethynylbenzenes. The formed polymers were sintered at 900 °C to obtain Pt-graphene hybrids, whose structures were examined by Raman scattering spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) measurements. Shapes─facets, terraces, and steps─with average diameters of 2.0-3.4 μm were observed by field emission scanning electron microscopy (FE-SEM). The Pt-graphene hybrids moderately adsorbed CO 2 and O 2 and slightly adsorbed ethylene and methane. Epoxidation of stilbene was carried out using Pt-graphene hybrids as catalysts to obtain stilbene oxide.

An oxidant-free approach to the synthesis of N -glyoxylyl peptides has been developed that utilizes the Lossen rearrangement of the N-terminal glycyl hydroxamic acid residue. The synthesis proceeds via an intramolecular redox mechanism to yield the glyoxylyl peptides, which are then subjected to various peptide cyclization procedures. The reaction scheme is suitable for oxidation-sensitive moieties including amino acids.

This study investigated the diagnostic and surgical management of urachal abscessation involving the urinary bladder in three cattle aged >18 months. While the abdominal floor or paralumbar fossa are typically considered for accessing the urachus and bladder in calves and heifers, the distance is too great to perform the procedure under direct vision in adult cows. Therefore, a novel preinguinal approach was used for access in cows with urachal abscesses after 18 months. Access was successfully achieved in all the three cows through a preinguinal incision to the urachal abscess at the apex of the bladder. However, in cases wherein the abscess and adhesions are severe, removal may be challenging or may necessitate a combined median or paramedian approach.

Background: Despite increasing attention, disparities in outcomes for Black and Hispanic patients undergoing orthopedic surgery are widening. In other racial-ethnic minority groups, outcomes often go unreported. We sought to quantify disparities in surgical outcomes among Asian, American Indian or Alaskan Native, and Native Hawaiian or Pacific Islander patients across multiple orthopedic subspecialties., Materials and Methods: The National Surgical Quality Improvement Program was queried to identify all surgical procedures performed by an orthopedic surgeon from 2014 to 2020. Multivariable logistic regression models were used to investigate the impact of race and ethnicity on 30-day medical complications, readmission, reoperation, and mortality, while adjusting for orthopedic subspecialty and patient characteristics., Results: Across 1,512,480 orthopedic procedures, all patients who were not White were less likely to have arthroplasty-related procedures ( P <.001), and Hispanic, Asian, and American Indian or Alaskan Native patients were more likely to have trauma-related procedures ( P <.001). American Indian or Alaskan Native (adjusted odds ratio [AOR], 1.005; 95% CI, 1.001-1.009; P =.011) and Native Hawaiian or Pacific Islander (AOR, 1.009; 95% CI, 1.005-1.014; P <.001) patients had higher odds of major medical complications compared with White patients. American Indian or Alaskan Native patients had higher risk of reoperation (AOR, 1.005; 95% CI, 1.002-1.008; P =.002) and Native Hawaiian or Pacific Islander patients had higher odds of mortality (AOR, 1.003; 95% CI, 1.000-1.005; P =.019) compared with White patients., Conclusion: Disparities regarding surgical outcome and utilization rates persist across orthopedic surgery. American Indian or Alaskan Native and Native Hawaiian or Pacific Islander patients, who are under-represented in research, have lower rates of arthroplasty but higher odds of medical complication, reoperation, and mortality. This study highlights the importance of including these patients in orthopedic research to affect policy-related discussions. [ Orthopedics . 2024;47(3):e131-e138.].

Background: Humans continuously maintain and adjust posture during gait, standing, and sitting. The difficulty of postural control is reportedly increased during unstable stances, such as unipedal standing and with closed eyes. Although balance is slightly impaired in healthy young adults in such unstable stances, they rarely fall. The brain recognizes the change in sensory inputs and outputs motor commands to the musculoskeletal system. However, such changes in cortical activity associated with the maintenance of balance following periods of instability require further clarified., Methods: In this study, a total of 15 male participants performed two postural control tasks and the center of pressure displacement and electroencephalogram were simultaneously measured. In addition, the correlation between amplitude of center of pressure displacement and power spectral density of electroencephalogram was analyzed., Results: The movement of the center of pressure was larger in unipedal standing than in bipedal standing under both eye open and eye closed conditions. It was also larger under the eye closed condition compared with when the eyes were open in unipedal standing. The amplitude of high-frequency bandwidth (1-3 Hz) of the center of pressure displacement was larger during more difficult postural tasks than during easier ones, suggesting that the continuous maintenance of posture was required. The power spectral densities of the theta activity in the frontal area and the gamma activity in the parietal area were higher during more difficult postural tasks than during easier ones across two postural control tasks, and these correlate with the increase in amplitude of high-frequency bandwidth of the center of pressure displacement., Conclusions: Taken together, specific activation patterns of the neocortex are suggested to be important for the postural maintenance during unstable stances., Competing Interests: The authors declare that they have no competing interests., (© 2024 Ue et al.)

Synthetic siRNA molecules without chemical modifications are easily degraded in the body, and 2'-O-modifications are frequently introduced to enhance stability. However, such chemical modifications tend to impact the gene knockdown potency of siRNA negatively. To circumvent this problem, we previously developed a prodrug-type siRNA bearing 2'-O-methyldithiomethyl (MDTM) groups, which can be converted into unmodified siRNA under the reductive environment in cells. In this study, we developed a nuclease-resistant prodrug-type 2'-O-MDTM siRNA for deployment in future animal experiments. To rationally design siRNA modified with a minimal number of 2'-O-MDTM nucleotide residues, we identified the sites susceptible to nuclease digestion and tolerant to 2'-O-methyl (2'-OMe) modification in the antisense strand of apolipoprotein B-targeted siRNA. Subsequently, we optimized the positions where the 2'-OMe and 2'-O-MDTM groups should be incorporated. siRNA bearing the 2'-O-MDTM and 2'-OMe groups at their respective optimized positions exhibited efficient knockdown potency in vitro and enhanced stability in serum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein whose expression has been previously implicated in cancer metastasis. However, the exact molecular mechanisms by which PTGFRN influences cancer progression are still unknown. As such, our laboratory set out to investigate how PTGFRN knockdown affected the expression of other proteins. We also carried out coimmunoprecipitation experiments using a monoclonal anti-PTGFRN antibody. We employed mass spectrometry-based proteomics for both experiments to identify proteins that were associated with PTGFRN. Our data show that PTGFRN knockdown increased pathways related to innate immune responses and decreased pathways associated with the synthesis of metabolic precursors and protein processing, among others. Additionally, the coimmunoprecipitation experiments indicated that PTGFRN is associated with proteins involved in processing and metabolism, as well as VEGF signaling molecules. These results highlight the role of PTGFRN as a protein processing regulator, which may be influencing cancer progression., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Maeda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute's L1000 datasets results in more effective compound-target predictions than models based on gene identities alone. By integrating additional pharmacological activity data sources, FRoGS significantly increases the number of high-quality compound-target predictions relative to existing approaches, many of which are supported by in silico and/or experimental evidence. These results underscore the general utility of FRoGS in machine learning-based bioinformatics applications. Prediction networks pre-equipped with the knowledge of gene functions may help uncover new relationships among gene signatures acquired by large-scale OMICs studies on compounds, cell types, disease models, and patient cohorts., (© 2024. The Author(s).)

Introduction: Over and under-triage represent a misallocation of resources that can affect patient outcomes. The purpose of this study is to evaluate over and under-triage rates in relation to risk factors and associated outcomes of trauma patients nationwide., Methods: A retrospective cohort study using the Trauma Quality Improvement Program from 2017 to 2020. Multivariable regression models were used to assess predictors of over-triage (activation when unnecessary) and under-triage (limited activation when full activation was necessary)., Results: 22.2 % (32,782) of the study population were over-triaged and 20.3 % (29,996) were under-triaged. Most over-triaged patients were Black, with Medicaid, or had a penetrating injury, whereas most under-triaged patients were White, with private/commercial insurance, or had a blunt injury. With covariates adjusted for, Pacific Islander (p = 0.024) and American Indian patients (p = 0.015) were associated with higher odds of over-triage, and Hispanic patients had higher odds of under-triage (p<0.001). Patients with Medicare (p<0.001) had higher odds of over-triage, and patients with private/commercial insurance (p<0.001) had higher odds of under-triage compared to Medicaid patients. Patients in level II (p<0.001) and level III (p<0.001) trauma hospitals were associated with higher odds of over-triage., Conclusion: Pacific Islander and American Indian patients, Medicare, and level II and III trauma centers are at increased risk of over-triage rates, while Hispanic and privately insured trauma patients had a higher risk for under-triage. Future studies should further investigate factors contributing to poor outcomes linked to under-triage practices and methods to improve consistency and standardization of triage tools across various levels of trauma centers., Competing Interests: Declaration of Competing Interest Authors declare no competing Interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Studies focusing on Emergency General Surgery (EGS) and Interhospital Transfer (IHT) and the association of race and sex and morbidity and mortality are yet to be conducted. We aim to investigate the association of race and sex and outcomes among IHT patients who underwent emergency general surgery., Methods: A retrospective review of adult patients who were transferred prior to EGS procedures using the National Surgery Quality Improvement Project from 2014 to 2020. Multivariable logistic regression models were used to compare outcomes (readmission, major and minor postoperative complications, and reoperation) between interhospital transfer and direct admit patients and to investigate the association of race and sex for adverse outcomes for all EGS procedures. A secondary analysis was performed for each individual EGS procedure., Results: Compared to patients transferred directly from home, IHT patients (n = 28,517) had higher odds of readmission [odds ratio (OR): 1.004, 95% confidence interval (CI) (1.002-1.006), P < 0.001], major complication [adjusted OR: 1.119, 95% CI (1.117-1.121), P < 0.001), minor complication [OR: 1.078, 95% CI (1.075-1.080), P < 0.001], and reoperation [OR: 1.014, 95% CI (1.013-1.015), P < 0.001]. In all EGS procedures, Black patients had greater odds of minor complication [OR 1.041, 95% CI (1.023-1.060), P < 0.001], Native Hawaiian and Pacific Islander patients had greater odds of readmission [OR 1.081, 95% CI (1.008-1.160), P = 0.030], while Asian and Hispanic patients had lower odds of adverse outcome, and female patients had greater odds of minor complication [OR 1.017, 95% CI (1.008-1.027), P < 0.001]., Conclusions: Procedure-specific racial and sex-related disparities exist in emergency general surgery patients who underwent interhospital transfer. Specific interventions should be implemented to address these disparities to improve the safety of emergency procedures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: B.J.J.V reported institutional research grant and speaker fees paid to his department by Medtronic. R.J.M.K. reported research support, consultation fees, and European Principal Investigator of the PERIGON Pivotal Trial for Medtronic. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

A convenient method for the determination of plant sphingolipids (glycosylinositol phosphoceramide, GIPC; glucosylceramide, GluCer; phytoceramide 1-phosphate, PC1P and phytoceramide, PCer) was developed. This method includes the extraction of lipids using 1-butanol, alkali hydrolysis with methylamine and separation by TLC. The amounts of sphingolipids in the sample were determined based on the relative intensities of standard sphingolipids visualized by primulin/UV on TLC. Using this method, we found that almost all GIPCs were degraded in response to tissue homogenization in cruciferous plants (cabbage, broccoli and Arabidopsis thaliana). The decrease in GIPCs was compensated for by increases in PC1P and PCer, indicating that GIPC was degraded by hydrolysis at the D and C positions of GIPC, respectively. In carrot roots and leaves, most of GIPC degradation was compensated for by an increase in PCer. In rice roots, the decrease in GIPCs was not fully explained by the increases in PC1P and PCer, indicating that enzymes other than phospholipase C and D activities operated. As the visualization of lipids on TLC is useful for detecting the appearance or disappearance of lipids, this method will be available for the characterization of metabolism of sphingolipids in plants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Various chemical modifications have been developed to create new antisense oligonucleotides (AONs) for clinical applications. Our previously designed prodrug-type phosphotriester-modified oligonucleotide with cyclic disulfides (cyclic SS PTE ON) can be converted into unmodified ON in an intracellular-mimetic reducing environment. However, the conversion rate of the cyclic SS PTE ON was very low, and the AON with cyclic SS PTE modifications showed much weaker antisense activity than corresponding to the fully phosphorothioate-modified AON. In this study, we synthesized several types of PTE ONs containing linear disulfides (linear SS PTE ONs) and evaluated their conversion rates under reducing conditions. From the results, the structural requirements for the conversion of the synthesized linear SS PTE ONs were elucidated. Linear SS PTE ON with promising promoieties showed a nuclease resistance up to 4.8-fold compared to unmodified ON and a cellular uptake by endocytosis without any transfection reagent. In addition, although the knockdown activity of the linear SS PTE gapmer AON is weaker than that of the fully phosphorothioate-modified gapmer AON, the knockdown activity is slightly stronger than that of the cyclic SS PTE gapmer AON. These results suggest that the conversion rates may be related to the expression of the antisense activity., (© 2023 Wiley-VCH GmbH.)

Background: We aim to investigate the costs associated with growth in the administrators, health care staff, and physicians to provide direction to establish a sustainable and cost-effective U.S. health care system., Methods: Data from the U.S. Bureau of Labor Statistics, particularly the Labor Force Statistics from the Current Population Survey, were utilized from 2009 to 2020. Wages and employment of medical and health service managers (administrators), health care practitioners and technical operations (health care staff), and physicians were used to calculate the total cost., Results: Administrator wages have grown similarly to health care staff wages (-4.40 vs -3.01%, P = .454) and physician wages (-4.40 vs -3.29%, P = .672). Additionally, there has been a similar increase in health care staff employment (9.91 vs 14.23%, P = .269) and physician employment (9.91 vs 15.35%, P = .252) compared to administrator employment. Overall, the total growth in administrator cost is similar to the growth in total health care staff cost (6.23 vs 11.80, P = .104) and total physician cost (6.23 vs 13.02%, P = .079). In 2020, physicians had the highest employment growth but the smallest wage increase., Conclusion: Although health care staff experienced a greater percent growth in employment and cost per employee than administrators since 2009, the cost per administrator remains greater than that of health care staff. Understanding differences in wages and costs is essential to reduce health care spending without compromising access, delivery, and quality of health care services., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial infection-causing pathogen. The clonal shift from staphylococcal cassette chromosome mec (SCCmec) type II MRSA to SCCmec type IV MRSA has occurred rapidly in acute-care hospitals. However, the epidemiology and clinical impacts of MRSA in geriatric hospitals are poorly documented. We performed a molecular epidemiological analysis of the clinical isolates and retrospectively investigated the clinical characteristics of SCCmec type IV MRSA in elderly individuals., Methods: MRSA isolates were grouped according to the SCCmec type and virulence genes (tst, sea, seb, sec, and lukS/F-PV), and multi-locus sequence typing (MLST) was performed., Results: Of the 145 MRSA isolates obtained from patients with a median age of 85 years, 100 (69.0%) were obtained from sputum samples, 22 (15.2%) from skin and soft tissues, and seven (4.8%) from blood samples. The most prevalent clone was SCCmec type IV/clonal complex (CC)1/sea+ (59.3%), followed by SCCmec type I/sequence type (ST) 8 (17.3%). Of the 17 (11.7%) strains to which an anti-MRSA drug was administered by a physician, only three were SCCmec type IV/CC1/sea+ (17.6%) and five were SCCmec type I/ST8 (29.4%). SCCmec type IV/CC1/sea+ MRSA was more frequently isolated in long-term care wards than were SCCmec type I/ST8 strains (odds ratio: 2.85, 95% confidence interval: 1.08-7.54) and was less frequently treated as the cause of MRSA infections (odds ratio: 0.15, 95% confidence interval: 0.03-0.73)., Conclusions: SCCmec type IV/CC1/sea+ MRSA was the predominant clone and could be easily transmissible and be capable of colonization. Geriatr Gerontol Int 2023; 23: 744-749., (© 2023 Japan Geriatrics Society.)

Crystal structures of Pseudomonas veroniil-arginine dehydrogenase (l-ArgDH), belonging to the μ-crystallin/ornithine cyclodeaminase family, were determined for the enzyme in complex with l-lysine and NADP + and with l-arginine and NADPH. The main chain coordinates of the P. veroniil-ArgDH monomer showed notable similarity to those of Archaeoglobus fulgidusl-AlaDH, belonging to the same family, and pro-R specificity similar to l-AlaDH for hydride transfer to NADP + was postulated. However, the residues recognizing the α-amino group of the substrates differed between the two enzymes. Based on a substrate modeling study, it was proposed that in A. fulgidusl-AlaDH, the amino group of l-alanine interacts via a water molecule (W510) with the side chains of Lys41 and Arg52. By contrast, the α-amino group of l-arginine formed hydrogen bonds with the side chains of Thr224 and Asn225 in P. veroniil-ArgDH. Moreover, the guanidino group of l-arginine was fixed into the active site via hydrogen bonds with the side chain of Asp54. Site-directed mutagenesis suggested that Asp54 plays an important role in maintaining high reactivity against the substrate and that Tyr58 and Lys71 play critical roles in enzyme catalysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fulminant myocarditis is a fatal development from profound biventricular heart failure and often requires both right- and left-ventricular assistance to maintain hemodynamics, even at the risk of increased mortality and morbidity. Here, we present a 42-year-old female with profound biventricular failure due to fulminant myocarditis, resolved by an isolated durable left-ventricular assist device support under a fenestrated, Fontan-like circulation and managed low-pulmonary vascular resistance., (© 2022. The Japanese Society for Artificial Organs.)

Background: Arterio-venous fistula is a rare clinical entity that occurs as a result of a ruptured abdominal aortic aneurysm into the inferior vena cava or iliac vein. Open surgery has been considered the treatment of choice for this condition; however, endovascular repair has become an evolving therapeutic option over the past 20 years. The endovascular treatment has contributed to a decrease in the perioperative mortality; nevertheless, some endovascular repair specific concern for residual fistula still remains., Case Presentation: A 70-year-old man was referred to our department for an enlarged inferior vena cava without any complaint. Contrast-enhanced computed tomography demonstrated a 40-mm AAA and a 42-mm right saccular CIAA, with a fistula between the CIAA and left CIV. Endovascular aneurysm repair which focused on the exclusion of the right CIAA and prevention of endoleak formation was performed. To prevent type 2 endoleaks, which cause residual arterio-venous shunt flow, right internal iliac artery was embolized with a vascular plug prior to stent graft procedure. Successful aneurysm exclusion without residual arterio-venous shunt flow was confirmed with a final angiographic examination. The patient had an uneventful recovery, and computed tomography 1 month later showed no sign of persistent fistula., Conclusions: Although endovascular treatment for AVF has a negative possibility of residual shunt, stent graft with a focus on type 2 endoleak prevention can be an attractive treatment option, reducing the incidence of residual AVF., (© 2023. The Author(s).)

Background: The association between lipoprotein subclasses and carotid intima-media thickness (cIMT) progression has yet to be fully evaluated. We assessed which lipoprotein subclasses were associated with maximum cIMT levels in the general population., Methods: In this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using gel permeation high-performance liquid chromatography (GP-HPLC) in 864 Japanese women and men (mean age 57 y, free of chronic liver or kidney diseases and off lipid-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses and univariate and partial correlation analyses were performed to examine the relationships between lipoprotein subclasses and maximum cIMT levels., Results: After adjusting for age, sex, systolic blood pressure, smoking, diabetes, and anti-hypertensive agents, elevated low-density lipoprotein (LDL)-2 and -3 cholesterol (particle diameter 25.5 nm and 23.0 nm, respectively; medium and small LDL) were associated with higher maximum cIMT levels in both women and men (all p for trend < 0.05). These associations were significant even after participants taking anti-diabetic or anti-hypertensive agents were excluded. No significant associations were found between any triglyceride subclasses and maximum cIMT levels., Conclusions: Smaller LDL particle cholesterol values are the most atherogenic lipoprotein parameter., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate factors affecting discharge to an inpatient rehabilitation facility or home following total hip arthroplasty, using a clinical pathway in Japan., Methods: Five hundred hips with osteoarthritis who underwent unilateral total hip arthroplasty at our institution, with no deviation from the pathway, were included in this retrospective study. The variables were examined by univariate analysis. Multivariate logistic regression analysis was used to identify the independent factors that influenced the discharge outcome., Results: Four hundred and thirty-four hips were discharged home directly, and 66 were discharged to an inpatient rehabilitation facility. Patients discharged to an inpatient rehabilitation facility were significantly older, shorter, lighter, and more likely to live alone. Additionally, the preoperative clinical score was significantly lower in the inpatient rehabilitation facility Group for all items. Logistic regression analysis showed a significant association between being discharged to an inpatient rehabilitation facility and higher age [odds ratio 3.87, 95% confidence interval 2.03-7.38, P < 0.001], lower total score in the preoperative Japanese Orthopaedic Association hip score [odds ratio 2.42, 95% confidence interval 1.38-4.23, P = 0.002] and living alone [odds ratio 1.84, 95% confidence interval 1.01-3.35, P = 0.046]., Conclusions: In this study, age, the preoperative Japanese Orthopaedic Association hip score, and living arrangement impacted the discharge destination after THA., Competing Interests: Declaration of competing interest None. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Appendiceal goblet cell adenocarcinoma(AGCA)is a newly designated pathological term adopted in the 5th edition of the WHO classification. It is synonymous with goblet cell carcinoid, which was previously categorized as a part of appendiceal carcinoid. However, since 2018, it has been classified as a subtype of adenocarcinoma. We have experienced 3 cases of this relatively rare tumor, of which 2 were initially diagnosed with acute appendicitis and were diagnosed with AGCA by pathological examination after an emergency appendectomy. Each of them underwent additional ileocolic resection with lymph node dissection as the second surgery. In the 3rd case, an appendiceal tumor was detected during preoperative examinations for an ovarian tumor. Staging laparoscopy revealed comorbid peritoneal dissemination, and only the appendix and right ovary were removed in the consecutive surgery. The ovarian tumor was pathologically diagnosed as a metastasis of AGCA. In this case, the introduction of oxaliplatin-based systemic chemotherapy after surgery achieved a complete response after more than 2 years. Although no recurrence has been observed in all 3 cases to date, AGCA is considered highly malignant compared to conventional appendiceal carcinoids. Therefore, it is crucial to practice multidisciplinary treatments, including sufficient radical surgery based on a precise diagnosis of AGCA, as is performed for advanced colorectal cancer.

Approximately 19% of the population is suffering from "Long COVID", also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), which often results in exercise intolerance. As COVID infections continue to be common, studying the long-term consequences of coronavirus disease (COVID) on physical function has become increasingly important. This narrative review will aim to summarize the current literature surrounding exercise intolerance following COVID infection in terms of mechanism, current management approaches, and comparison with similar conditions and will aim to define limitations in the current literature. Multiple organ systems have been implicated in the onset of long-lasting exercise intolerance post-COVID, including cardiac impairment, endothelial dysfunction, decreased VO 2 max and oxygen extraction, deconditioning due to bed rest, and fatigue. Treatment modalities for severe COVID have also been shown to cause myopathy and/or worsen deconditioning. Besides COVID-specific pathophysiology, general febrile illness as commonly experienced during infection will cause hypermetabolic muscle catabolism, impaired cooling, and dehydration, which acutely cause exercise intolerance. The mechanisms of exercise intolerance seen with PASC also appear similar to post-infectious fatigue syndrome and infectious mononucleosis. However, the severity and duration of the exercise intolerance seen with PASC is greater than that of any of the isolated mechanisms described above and thus is likely a combination of the proposed mechanisms. Physicians should consider post-infectious fatigue syndrome (PIFS), especially if fatigue persists after six months following COVID recovery. It is important for physicians, patients, and social systems to anticipate exercise intolerance lasting for weeks to months in patients with long COVID. These findings underscore the importance of long-term management of patients with COVID and the need for ongoing research to identify effective treatments for exercise intolerance in this population. By recognizing and addressing exercise intolerance in patients with long COVID, clinicians can provide proper supportive interventions, such as exercise programs, physical therapy, and mental health counseling, to improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Weldon et al.)

One of the major functions of peroxisomes in mammals is oxidation of very long-chain fatty acids (VLCFAs). Genetic defects in peroxisomal β-oxidation result in the accumulation of VLCFAs and lead to a variety of health problems, such as demyelination of nervous tissues. However, the mechanisms by which VLCFAs cause tissue degeneration have not been fully elucidated. Recently, we found that the addition of small amounts of isopropanol can enhance the solubility of saturated VLCFAs in an aqueous medium. In this study, we characterized the biological effect of extracellular VLCFAs in peroxisome-deficient Chinese hamster ovary (CHO) cells, neural crest-derived pheochromocytoma cells (PC12), and immortalized adult Fischer rat Schwann cells (IFRS1) using this solubilizing technique. C20:0 FA was the most toxic of the C16-C26 FAs tested in all cells. The basis of the toxicity of C20:0 FA was apoptosis and was observed at 5 μM and 30 μM in peroxisome-deficient and wild-type CHO cells, respectively. The sensitivity of wild-type CHO cells to cytotoxic C20:0 FA was enhanced in the presence of a peroxisomal β-oxidation inhibitor. Further, a positive correlation was evident between cell toxicity and the extent of intracellular accumulation of toxic FA. These results suggest that peroxisomes are pivotal in the detoxification of apoptotic VLCFAs by preventing their accumulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)