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OBJECTIVE. To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee. METHODS: We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real-time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data. RESULTS: About 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed >/=2-fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n = 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound-healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real-time quantitative PCR data with the previously reported data support the validity of our microarray data. CONCLUSION: Differences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the role of platelet-activating factor (PAF) and PAF acetylhydrolase (AH) in conjunctiva. The influence of PAF on conjunctival vascular permeability and the presence of PAF or its metabolites in tears from guinea pigs with allergic conjunctivitis were investigated. We instilled PAF to the eyes of guinea pigs and evaluated vascular permeability. Tear samples were collected from passively sensitized guinea pigs, and the concentration of PAF and its metabolites determined by liquid chromatography-tandem mass spectrometry. Exogenous PAF degradation in tear samples was evaluated with or without diisopropyl fluorophosphate (DFP). Topically applied PAF increased vascular permeability in conjunctiva. In the tear samples from guinea pigs with allergic conjunctivitis, PAF could not be detected. However, 40 +/- 6 ng/ml of lyso-platelet activating factor (lyso-PAF) and 230 +/- 50 ng/ml of 1-alkyl-2-acyl-sn-glycero-3-phosphocholine were detected at 10 min after challenge. Exogenous PAF was rapidly degraded in the tear samples from guinea pigs with allergic conjunctivitis, but not from normal guinea pigs. This PAF degradation was inhibited by DFP. These results suggest that PAF in the tear fluid is quickly hydrolyzed to lyso-PAF by PAF AH, which may be released or activated in allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

Topical infection of entomopathogenic fungi in insects occurs when the fungal conidia attach to the insect's surface (cuticle), germinate, and then form appressoria that penetrate the cuticle and enter their bodies. In this study, we inoculated silkworm larvae with three entomopathogenic fungi, Cordyceps militaris, Beauveria bassiana, and Metarhizium anisopliae, and investigated their mechanisms of infection. Attachment of the conidia of the three entomopathogenic fungi to the surface of silkworm larvae was observed under a microscope. We counted the number of conidia attached to the surface of the silkworm larvae and the number of conidia detached from the surface was counted. The number of C. militaris conidia that attached to the surface was less than that of B. bassiana and M. anisopliae; however, it germinated and formed appressoria on hydrophobic surfaces, similar to the other two strains. Mycelial growth of C. militaris was inhibited compared to that of B. bassiana in PDA medium containing 0.1% linoleic and linolenic acids. The germination of C. militaris conidia was also inhibited in PD medium containing 0.1% linoleic or linolenic acids. These results suggest that the attachment of low numbers of C. militaris conidia on the surface of silkworm larvae and presence of inhibitory linoleic or linolenic acids in the silkworm cuticles may cause low topical infectivity by C. militaris. This study improves the efficacy of topically infecting silkworms with C. militaris to produce fungal fruiting bodies for use in traditional Chinese medicine and dietary supplement production., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Neck and upper-back stiffness involves discomfort/ache in the trapezius muscle (TM). The pathogenesis of 'essential neck and upper-back stiffness' without obvious causes remains uncertain. In symptomatic subjects, TM hardness correlates with decreased transverse cervical artery (TCA) blood flow to the TM. Neck and upper-back stiffness could be associated with both hemodynamic and neurological factors affecting the TM. We therefore sonographically evaluated structural factors around the accessory nerve innervating the TM impacting neck and upper-back stiffness., Methods: Participants comprised 69 healthy young adults (33 men, 36 women; 21 ± 1 y) who completed questionnaires and underwent elastography to determine TM hardness as a strain ratio and pulsed Doppler sonography to determine TCA hemodynamics. Intermuscular length was measured as the distance between sternocleidomastoid and levator scapulae muscles around the accessory nerve. Relationships of intermuscular length with symptoms, TM hardness, and TCA hemodynamics were analyzed., Results: Intermuscular length was greater in symptomatic subjects (median 2.3 mm, interquartile range 1.5-3.1 mm) than in asymptomatic subjects (median 1.8 mm, interquartile range 1.5-2.3 mm; p = 0.032). Intermuscular length correlated positively with symptom severity (r = 0.43, p = 0.014) and negatively with strain ratio for the TM (r = -0.39, p = 0.025) and peak systolic velocity in the TCA (r = -0.40, p = 0.022). Intermuscular length contributed independently to the presence of symptoms (p = 0.025, odds ratio 2.26, 95% confidence interval 1.11-4.62)., Conclusion: In symptomatic subjects, symptom severity, TM hardness and TCA hemodynamics all correlated with greater intermuscular length. Structures around the accessory nerve could be associated with the pathogenesis of essential neck and upper-back stiffness., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Purpose: The exact incidence of and risk factors for interstitial lung disease (ILD), a serious side effect of abemaciclib, remain unknown in real-world settings. We examined the incidence of and risk factors for abemaciclib-induced ILD in patients with advanced breast cancer (ABC) in Japan., Patients and Methods: Retrospective clinical information was collected from charts of patients with ABC who had started abemaciclib treatment at 77 participating institutions between November 30, 2018 and December 31, 2019. The clinical information of patients who developed ILD (including suspected cases) were reviewed by an independent committee of extramural experts to adjudicate abemaciclib-induced ILD. We performed a nested case-control study for efficient identification of ILD risk factors and conducted multivariate Cox regression analysis to identify independent predictors of ILD., Results: Among patients taking abemaciclib, the incidence of abemaciclib-induced ILD was 5.0% (n = 59/1189), and the mortality rate was 0.7% (n = 8). The timing of ILD onset varied but occurred most frequently within 180 days of beginning abemaciclib treatment (64.4%). The incidence of abemaciclib-induced ILD was significantly associated with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2 [hazard ratio (HR) 5.03; 95% confidence interval (CI) 2.26-11.11] or a past medical history of interstitial pneumonia (IP) (HR 6.49; 95% CI 3.09-13.70)., Conclusions: In this study, we have for the first time determined the real-world incidence of and risk factors for abemaciclib-induced ILD in Japan. Although abemaciclib-induced ILD is serious in real-world settings, careful patient selection and close monitoring of those with poor ECOG PS and/or a history of IP may minimize ILD risk. This study was registered on the UMIN registry (Date: May 11, 2020/ ID: UMIN000040357)., Competing Interests: Declarations Conflict of interest Junji Tsurutani has received lecture fee received donation and/or research compensation from Daiichi Sankyo, Eli Lilly and Astra Zeneca. He is an advisory board of Daiichi Sankyo, Astra Zeneca. Yasunari Miyazaki and Yuichiro Kikawa has received lecture fees from Eli Lilly. Terufumi Kato has received honoraria from Amgen Inc., AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai Pharmaceuticals Co., Ltd., Daiichi-Sankyo, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical Co., Ltd., Pfizer, Taiho Pharmaceutical and Takeda. His institution has received research support from AbbVie Inc., Amgen Inc., AstraZeneca, BeiGene, Blueprint Medicines, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Eli Lilly and Company, HaiHe Biopharma, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Takeda and Turning Point Therapeutics Inc. He is consulting or advisory roles of AstraZeneca, BeiGene, Daiichi Sankyo, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis and Pfizer. His spouse's employment is Eli Lilly and company. Hirofumi Mukai has received personal fees as honoraria from Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical out of this research. All remaining authors have declared no conflicts of interest. Ethical approval This study protocol and all amendments received approval from the Research Ethics Committee of Showa University, Japan (Date: March 27, 2020/ No.3076)., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background and Aim: Periodic endoscopic screening for gastric cancer (GC) is widely performed in East Asia; however, the optimal screening strategy remains unclear. This study aimed to determine the most cost-effective endoscopic screening strategy for the detection and treatment of GC in a cohort with a low Helicobacter pylori prevalence., Methods: The following data were retrospectively extracted from participants who received screening endoscopy between April 2019 and March 2023: age, H. pylori infection status, presence of intestinal metaplasia, pathological diagnosis of GC, and the interval between the most recent endoscopies. A Markov state transition model was constructed based on the cohort data. The cost-effectiveness of 15 strategies with different starting ages (40/50/60 years) and screening intervals (1/2/3/4/5 years) was compared. The net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) of quality-adjusted life-years gained by treatment were used as outcomes., Results: A simulation model was constructed based on the cohort data of 94 137 participants (mean age 54.5 years, males 57.9%; 74.4% H. pylori-naïve, 94.2% intestinal metaplasia-negative). The results of the base-case analysis showed that the screening strategy of 4-year intervals starting at the age of 40 years had the highest NMB (97 401 578 yen). In both the Monte Carlo simulation and one-way sensitivity analysis with a varying probability of H. pylori infection status transition, the ICER was superior in the screening strategy every 4 years, starting at age 40 years., Conclusions: Our simulation showed that endoscopic screening at 4-year intervals starting at the age of 40 years was the most cost-effective method., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Living anionic polymerization-the most common living polymerization and the one with the longest history-generally requires stringent, water-free conditions and one metal initiator per polymer chain. Here we present the proton transfer anionic polymerization of methacrylates using acidic C-H bonds as the dormant species that are activated by base catalysts. The polymerization mechanism involves reversible chain transfer or termination of the growing enolate species. A weakly acidic compound, such as an alkyl isobutyrate, serves as the initiator or chain-transfer agent in the presence of a bulky potassium base catalyst to produce a polymer chain and, thereby, diminishes the metal compound per chain ratio. An added alcohol serves as a reversible terminator to tame the propagation. End-functionalized, star, block and graft polymers are easily accessible from compounds with C-H bonds., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

As a commercially available esterified compound derived from sucrose and palmitoyl acids, sucrose ester palmitic acid (SEPA) has been used as an emulsifier in food processing. It possesses antibacterial activity against vegetative and spore-forming bacteria, including Clostridium, Moorella, Bacillus, and Geobacillus species, prompting the food industry to use it as a food additive to achieve a desirable shelf life; however, the precise mechanism by which the compound affects the physiological processes of bacteria and how it inhibits bacterial growth remains unclear. In this study, we focused on the inhibitory effect of SEPA on the germination-to-outgrowth process of Clostridium perfringens SM101 spores, a strain widely used as a model of C. perfringens. When the isolated spores were exposed to ≧ 20 μg/ml of SEPA on brain heart infusion agar, bacterial colony formation was completely inhibited. Time-resolved phase-contrast microscopy was employed to visualize the effect of SEPA on the entire regrowth process of SM101 spores. SEPA did not affect the "germination stage," where each spore changes its optical density from phase-bright to phase-dark. In contrast, the presence of SEPA completely blocked the "outgrowth stage," in which the newly synthesized vegetative cell body emerges from the cracked spore shell. The results demonstrate that SEPA inhibits the revival process of the spores of a pathogenic strain of C. perfringens and that the site of its action is the "outgrowth stage" and not the "germination stage," as evidenced by single- cell analysis., Competing Interests: Declaration of competing interest Satoshi Sekimoto is an employee of Mitsubishi Chemical Corporation. The other authors declare no potential conflicts of interest. The funder played no role in the study design, data collection and interpretation, or the decision to submit the work for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and irreversible neurodegenerative disease with limited treatment options. Advances in regenerative medicine have opened up new treatment options. The primary and exploratory objectives of this retrospective cohort study were to evaluate the safety and efficacy of stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM)., Methods: Safety assessments included adverse events, vital signs, and laboratory test changes before and after administration, and efficacy was measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), grip strength, and forced vital capacity in 24 patients with ALS treated at a single facility between 1 January 2022, and 30 November 2023., Results: While ALSFRS-R scores typically decline over time, the progression rate in this cohort was slower, suggesting a potential delay in disease progression. Alternatively, improvements in muscle strength and mobility were observed in some patients. Although adverse events were reported in only 3% of cases (no serious allergic reactions), the treatment-induced changes in vital signs and laboratory results were not clinically significant., Conclusions: The SHED-CM treatment is a safe and potentially effective therapeutic option for patients with ALS. Further research is needed to optimize the SHED-CM treatment; however, this study lays the groundwork for future exploration of regenerative therapies for ALS.

In recent years, the incidence of syphilis in Tokyo has increased. This descriptive epidemiological study aimed to elucidate the status of syphilis within the city. Data regarding age, sex, disease stage, and presumed sexual partners of patients with syphilis reported in Tokyo were compiled and analyzed. A total of 9,419 patients with syphilis were diagnosed between 2019 and 2022. A sharp rise was observed in the number of reported cases from 2021 to 2022. Between 2020 and 2022, the number of women in their 20s who developed syphilis rapidly increased by more than 3-fold. Furthermore, the number of pregnant women with syphilis increased the end of 2022. Despite a rapid increase in the number of young women with syphilis, the incidence of congenital syphilis has remained stable. This stability may be attributed to the early detection of syphilis during pregnancy, facilitated by the high rate of antenatal checkups in Tokyo. However, the growing incidence of syphilis among young women could potentially lead to a rise congenital syphilis cases in the future. Therefore, public health strategies should include educational initiatives targeting high-risk populations and adolescents, along with early and appropriate testing and treatment to prevent the progression of syphilis.

Background: The therapeutic effectiveness of dupilumab for severe asthma in real-world settings is yet to be prospectively investigated across multiple institutions, and uncertainties persist regarding predictive factors for its effectiveness. We aimed to assess the effectiveness of dupilumab and identify predictors of its effectiveness in real-world settings using two type-2 biomarkers: FeNO concentration and blood eosinophil count., Methods: This prospective multicenter study included 103 patients with severe asthma. Exacerbations and respiratory functions were monitored for 24 weeks. Asthma control was evaluated using the Asthma Control Questionnaire-5. Clinical symptoms and their impact on cough and sputum were assessed using the Cough and Sputum Assessment Questionnaire (CASA-Q). Subgroup analyses of type-2 biomarkers were conducted based on FeNO levels and blood eosinophil counts at baseline., Results: Treatment with dupilumab led to a reduction in exacerbations and enhancement in asthma control, FEV 1 , and CASA-Q scores. FEV 1 improvement was correlated with enhancement in the sputum domain of the CASA-Q. Patients exhibiting elevated FeNO levels and blood eosinophil counts demonstrated more significant enhancements in FEV 1 . CASA-Q sputum domain scores were significantly higher in the group with elevated eosinophil counts. Regression analysis revealed that FeNO levels and blood eosinophil counts are significant predictors of FEV 1 improvement, with blood eosinophil counts also predicting sputum improvement in patients treated with dupilumab., Conclusions: Type-2 biomarkers may act as indicators of improvement in FEV 1 and sputum outcomes among patients with severe asthma undergoing dupilumab treatment in real-world settings., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Few studies have investigated the prevalence of pathogens in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), specifically, the interactions between respiratory pathogens and AE-IPF during the coronavirus disease 2019 (COVID-19) pandemic., Objectives: We aimed to analyze pathogens in patients with AE-IPF between September 2020 and December 2022., Methods: This retrospective observational study was conducted at our hospital between September 2020 and December 2022. In patients with AE-IPF, pre-hospitalization polymerase chain reaction (PCR) tests for respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were performed using multiplex PCR or Smart Gene assay with nasopharyngeal swab specimens. Microbiological assays, including Gram staining, sputum cultures, blood cultures, and urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila, were also performed., Results: Forty-nine patients with AE-IPF were included. The median age was 75 years old and 42 (86 %) were male. Only one of the 49 patients (2 %) was positive for SARS-CoV-2. Two of 28 patients (7 %) were positive for human rhinovirus/enterovirus. No bacteria were detected in sputum culture, blood culture, or urinary antigen tests., Conclusions: The detection frequency of SARS-CoV-2 infection in patients with AE-IPF was lower than that of human rhinovirus/enterovirus. Continuous analysis for the presence of pathogens is necessary for appropriate infection control because respiratory viruses may increase as the coronavirus pandemic subsides., 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 Inc. All rights reserved.)

The miniaturization of satellite systems has compounded the need to protect microelectronic components from damaging radiation. Current approaches to mitigate this damage, such as indiscriminate mass shielding, built-in redundancies, and radiation-hardened electronics, introduce high size, weight, power, and cost penalties that impact the overall performance of the satellite or launch opportunities. Additive manufacturing provides an appealing strategy to deposit radiation shielding only on susceptible components within an electronic assembly. Here, a versatile material platform and process to conformally print customized composite inks at room temperature directly and selectively onto commercial-off-the-shelf electronics is described. The suite of inks uses a flexible styrene-isoprene-styrene block copolymer binder that can be filled with particles of different atomic densities for diverging radiation shielding capabilities. Additionally, the system enables the combination of multiple distinct particle species within the same printed structure. The method can produce graded shielding that offers improved radiation attenuation by tailoring both shield geometry and composition to provide comprehensive protection from a broad range of radiation species. The authors anticipate this alternative to traditional shielding methods will enable the rapid proliferation of the next generation of compact satellite designs., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Both imagery and acupuncture are the oldest medical practices. Recently, we have developed a new treatment modality, video-guided acupuncture imagery treatment (VGAIT), which combines acupuncture and imagery. In this crossover study, we investigated the modulation effects of video-guided acupuncture imagery treatment compared with placebo acupuncture using no-touch double-blind placebo acupuncture needles and a no-treatment resting control. Pressure pain threshold and electroencephalogram (EEG) data were collected before and after each intervention. 12 healthy participants completed the study. Results showed that pressure pain thresholds were significantly increased after VGAIT compared to the resting control condition. In addition, we found that VGAIT, but not the no-touch placebo acupuncture or the resting control, significantly increased alpha and beta band power. Our findings demonstrate the potential of VGAIT as a remote therapeutic method (e-health treatment option) for pain and the value of no-touch double-blind placebo acupuncture in acupuncture research., Competing Interests: Declaration of Competing Interest J.K has a disclosure to report (holding equity in startup companies (MNT, BTT) and a pending patent on VGAIT treatment of chronic pain), but declares no conflict of interest. There are conflict of interest among all authors.

Background and Aim: Regular endoscopy or fecal immunochemical test (FIT) is ideal for screening colorectal cancer. However, only a limited number of individuals undergo regular screening. This study aimed to compare the cost-effectiveness of a single colonoscopy with a single FIT performed for colorectal cancer screening., Methods: A microsimulation model was constructed based on real-world observational data collected from three institutions between 2019 and 2022 that compared colonoscopy-based screening with FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated. The incremental cost-effectiveness ratio (ICER) per life year gained (LYG) of the colonoscopy-based strategy was calculated., Results: Data from 11 407 patients undergoing colonoscopies and 59 176 patients undergoing FITs were used to establish a model. In the base case analysis of screening strategies, colonoscopy was more cost-effective than FIT (ICER 415 193 yen/LYG). The ICER of the colonoscopy-based strategy among 60- to 69-year-old patients was lowest at 394 200 yen/LYG, whereas that in 20- to 29-year-old patients was highest. Monte Carlo simulations showed that the colonoscopy-based strategy was more cost-effective than the FIT-based strategy (net monetary benefit [NMB]: 5 695 957 yen vs 5 348 253 yen). When the adenoma detection rate in the colonoscopy was over 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy, the NMB of the colonoscopy-based strategy exceeded that of the FIT-based strategy., Conclusion: In the microsimulation model, colonoscopy is recommended as a one-time screening procedure in patients aged >60 years with >30% ADR or <8.6% positive FIT rate., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: Neck and upper-back stiffness is encountered in daily life, with symptoms appearing as dullness or aches predominantly in the trapezius muscle (TM). Our previous study demonstrated that TM hardness as measured with a muscle hardness meter correlates well with transverse cervical artery (TCA) flow supplying the TM. Muscle hardness meters, however, cannot measure hardness in the TM alone. Meanwhile, recent advances in ultrasound elastography have enabled the evaluation of localized hardness in targeted tissues. The present study, therefore, aimed to clarify the relationship between TM hardness as measured by elastography and TCA hemodynamics as measured on Doppler sonography, with reference to daily symptoms of upper-back stiffness., Methods: The study population comprised 66 healthy young adults (32 males, 34 females; mean age, 21 ± 1 years). Relationships were evaluated between TM hardness as a negative correlate of strain ratio from elastography and TCA hemodynamics on Doppler sonography. Hemodynamics in the TCA were evaluated according to the frequency of neck and upper-back stiffness., Results: TM strain ratio correlated with peak systolic velocity (PSV) in the TCA (r = 0.273, p = 0.036), particularly in symptomatic subjects (r = 0.417, p = 0.022). PSV in the TCA decreased with increasing frequency of daily symptoms (p = 0.045)., Conclusion: TCA hemodynamics correlated with muscle hardness when evaluating localized TM hardness. This relationship and low PSV in the TCA were evident in symptomatic subjects. These results suggest that PSV in the TCA is associated with neck and upper-back stiffness., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plasmodium falciparum accounts for the majority of malaria deaths, due to pathology provoked by the ability of infected erythrocytes to adhere to vascular endothelium within deep tissues. The parasite recognizes endothelium by trafficking and displaying protein ligands on the surface of asexual stage infected erythrocytes, such as members of the large family of pathogenic proteins, P. falciparum erythrocyte membrane protein 1 (PfEMP1). Parasite-encoded skeleton binding protein 1 (SBP1) plays an important role in the transport of these binding-related surface proteins, via cleft-like membranous structures termed Maurer's clefts, which are present within the cytoplasm of infected erythrocytes. Erythrocytes infected with gametocyte stages accumulate in the extravascular compartment of bone marrow; and it was suggested that their surface-expressed adhesion molecule profile and protein trafficking mechanisms might differ from those in asexual stage parasites. Protein trafficking mechanisms via Maurer's clefts have been well investigated in asexual stage parasite-infected erythrocytes; but little is known regarding the gametocyte stages. In this study, we characterized SBP1 during gametocyte maturation and demonstrated that SBP1 is expressed and localizes to dot-like Maurer's cleft structures in the cytoplasm of gametocyte-infected erythrocytes. Co-immunoprecipitation and mass spectrometry assays indicated that SBP1 interacts with the molecular chaperones PfHSP70-1 and PfHSP70-x. Localization analysis suggested that some PfHSP70-1 and/or PfHSP70-x localize in a dot-like pattern within the cytoplasm of immature gametocyte-infected erythrocytes. These findings suggest that SBP1 may interact with HSP70 chaperones in the infected erythrocyte cytoplasm during the immature gametocyte stages., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quality indicators during the insertion phase of colonoscopy require exploration. Unsatisfactory insertion experiences cause endoscopist psychophysiological fatigue and affect the quality of their inspection. This comparative study used propensity score matching (PSM) to determine whether endoscopist satisfaction during scope insertion was related to polyp detection rate (PDR). Patients who underwent colonoscopy screening between April 2019 and December 2022 were enrolled in this study. The endoscopist satisfaction score (high and low) during the insertion phase in each examination was recorded based on the level of fatigue and presence of paradoxical scope movement. All examinations were classified into 2 groups: a high and a low satisfaction score group. After PSM with potential confounding factors related to polyp detection (endoscopist, insertion and withdrawal time, and sedative agent use), the PDR and adenoma detection rate (ADR) were compared. Overall, 4142 patients (average age, 54.1 years old; 54.4% male) underwent colonoscopies performed by twelve experienced endoscopists. Analysis using a logistic regression model revealed that a high satisfaction score during the insertion phase was an independent predictor of polyp detection (P < .001, odds ratio 1.79, 95% CI 1.41-2.33), whereas insertion time was not. After PSM, 513 patients from both groups were eligible for comparison. Polyp detection rate and ADR were significantly higher in the high-satisfaction group than in the low-satisfaction group (49.5% vs. 36.6%, P < .001; 35.1% vs. 27.1%, P = .007). The endoscopists' level of satisfaction with the insertion phase was shown to be a potential predictor of PDR in screening colonoscopy.

Megafauna are important seed dispersers because they can disperse large quantities of seeds over long distances. In Hokkaido, Japan, the largest terrestrial animal is the brown bear (Ursus arctos) and other megafauna seed dispersers are lacking. Thus, brown bears are expected to have an important function as seed dispersers in Hokkaido. In this study, we, for the first time, evaluated the seed dispersal function of brown bears in Hokkaido using three fleshy-fruited trees and studied: (1) gut passage time (GPT) in feeding experiments, (2) seed dispersal distance using tracking data of wild bears, and (3) the effect of gut passage and pulp removal on germination rate. Most seeds were defecated intact, and less than 6% were broken. The average GPT without pulp was 3 h and 56 min to 6 h and 13 min, depending on the plant and trial. Each plant's average simulated seed dispersal distance was 202-512 m. The dispersal distance of Actinidia arguta seeds with pulp was significantly longer than those without pulp because of their longer GPT. The germination rate of defecated seeds without pulp was 19-51%, depending on the plant, and was significantly higher or not different comparing with that of seeds with pulp. We concluded that brown bears in Hokkaido are effective seed dispersers. In managing brown bears in Hokkaido, such ecological functions should be considered along with conserving the bear population and reducing human-bear conflicts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Taking a short rest after lunch suppresses increases in blood flow to the digestive organs and maintains blood flow to the brain in the afternoon, possibly providing beneficial effects in preventing post-prandial drowsiness. The present study investigated sex-dependent influences on changes in hemodynamics produced by taking a short rest after lunch., Methods: Subjects comprised 20 healthy young adults (10 men, 10 women; mean age 21 ± 1 years). Doppler sonography was performed to measure blood flow in the superior mesenteric artery (SMA) and common carotid artery (CCA) before and after lunch every hour on each day, with and without a 15-min rest with eyes closed after lunch. Blood pressure and heart rate (HR) were also measured., Results: For both men and women, peak systolic velocity (PSV) in the SMA was suppressed by taking a rest. PSV in the CCA in men was increased at 0.5 h after lunch in the resting condition but was decreased in the non-resting condition (median 109%, interquartile range [IQR] 102-120% vs. median 98%, IQR 90-107%; P = 0.037). No such differences were observed in women. Although post-prandial increases in HR were observed in women, a similar increase was only found for men in the resting condition., Conclusion: An increase in CCA blood flow was observed only in men. The present study suggests that a short rest after lunch could better promote the maintenance of blood flow to the brain in men than in women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: No studies have reported corrugator muscle activity associated with pain in people with pain. This study aimed to develop an objective pain assessment method using corrugator muscle activity with pressure pain stimulation to the skeletal muscle. Methods: Participants were 20 adults (a mean ± SD age of 22.0 ± 3.1 years) with chronic neck/shoulder pain. Surface electromyography (sEMG) of corrugator muscle activity at rest (baseline) and without and with pressure pain stimulation applied to the most painful tender point in the shoulder was recorded. Participants evaluated the intensity of the neck/shoulder pain and the sensory and affective components of pain with pressure stimulation using a visual analogue scale (VAS). The percentages of integrated sEMG (% corrugator activity) without and with pressure pain stimulation to the baseline integrated sEMG were compared, and the relationships between the % corrugator activity and the sensory and affective components of pain VAS scores were evaluated. Results: Without pressure stimulation, an increase in corrugator muscle activity due to chronic neck/shoulder pain was not observed. The % corrugator activity with pressure pain stimulation was significantly higher than that without stimulation ( p < 0.01). A significant positive correlation between corrugator muscle activity and the affective components of pain VAS scores with pressure stimulation was found (ρ = 0.465, p = 0.039) and a tendency of positive correlation was found for the sensory component of pain VAS scores (ρ = 0.423, p = 0.063). Conclusions: The increase in corrugator muscle activity with pressure pain stimulation to the tender point in adults with chronic neck/shoulder pain was observed, although increased corrugator muscle activity resulting from the chronic neck/shoulder pain was not. These findings suggest that corrugator muscle activity with pressure pain stimulation can be a useful objective indication for tender point sensitivity assessment in the skeletal muscle with pain.

Background: Methods that minimize the time for on-site bowel preparation before colonoscopy are needed. We prospectively validated that a novel algorithm-based active cleansing (ABAC) protocol could reduce the time for preparation compared with the conventional method., Methods: This was an open-label, multicenter, prospective comparative study from April to October 2021. The study compared the bowel preparation time for colonoscopy between patients instructed with the ABAC protocol and control groups. Patients in the ABAC protocol group as well as the control group were administered 2000 mL of polyethylene glycol (PEG) within 2 hours. After the first two hours, patients in the protocol group voluntarily took 300 ml of the solution without the instruction of nursing staff depending on the number of defecations in the first 2 hours. The intervention and control groups were adjusted for background characteristics by propensity score matching (PSM)., Results: After adjustment by PSM, 174 patients in each of the two groups were included in the final analysis. In the intention-to-treat analysis, the preparation time was significantly shorter in the intervention group than that in the control group (126.3 ± 32.7 min vs. 144.9 ± 39.9 min, P = 0.018). The proportion of additional PEG intake was significantly higher in the intervention group (16 [9.2%] vs. 6 [3.4%], P = 0.047). The number of defecations was also higher in the intervention group than in the control group (7.8 ± 2.5 vs. 6.3 ± 2.2, P = 0.001)., Conclusions: Simple active instruction protocol is effective to reduce on-site bowel preparation time and nursing staff labor for colonoscopy., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Gastroenterology.)

While brain-derived neurotrophic factor (BDNF), which is a growth factor associated with cognitive improvement and the alleviation of depression symptoms, is known to regulate food intake and body weight, the role of BDNF in peripheral disease is not fully understood. Here, we show that reduced BDNF expression is associated with weight gain and the chronic liver disease non-alcoholic steatohepatitis (NASH). At 10 months of age, BDNF-heterozygous (BDNF +/- ) mice developed symptoms of NASH: centrilobular/perivenular steatosis, lobular inflammation with infiltration of neutrophils, ballooning hepatocytes, and fibrosis of the liver. Obesity and higher serum levels of glucose and insulin - major pathologic features in human NASH - were dramatic. Dying adipocytes were surrounded by macrophages in visceral fat, suggesting that chronic inflammation occurs in peripheral organs. RNA sequencing (RNA-seq) studies of the liver revealed that the most significantly enriched Gene Ontology term involved fatty acid metabolic processes and the modulation of neutrophil aggregation, pathologies that well characterise NASH. Gene expression analysis by RNA-seq also support the notion that BDNF +/- mice are under oxidative stress, as indicated by alterations in the expression of the cytochrome P450 family and a reduction in glutathione S-transferase p, an antioxidant enzyme. Histopathologic phenotypes of NASH were also observed in a knock-in mouse (BDNF +/pro ), in which the precursor BDNF is inefficiently converted into the mature form of BDNF. Lastly, as BDNF reduction causes overeating and subsequent obesity, a food restriction study was conducted in BDNF +/pro mice. Pair-fed BDNF +/pro mice developed hepatocellular damage and showed infiltration of inflammatory cells, including neutrophils in the liver, despite having body weights and blood parameters that were comparable to those of controls. This is the first report demonstrating that reduced BDNF expression plays a role in the pathogenic mechanism of NASH, which is a hepatic manifestation of metabolic syndrome. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Detection of allergen-specific immunoglobulin E (IgE) antibodies (Abs) in serum would allow for screening of the causative allergen in patients with type-I allergy. In this study, we developed a new assay method to detect allergen-specific IgE Abs, which involved crosslinking the plural FcεRIα molecules with an allergen and detection using an amplified luminescence proximity homogeneous assay (AlphaCL). First, the allergen concentration, bead concentrations, and incubation time were optimized for the detection of anti-2,4-dinitrophenyl (DNP) IgE Abs in buffer. Under optimal conditions, AlphaCL was able to detect DNP-specific IgE Abs in simulated human serum at levels comparable to those in serum from type-I allergic patients. When AlphaCL was used to detect anti-DNP IgE Abs, no signal counts were obtained with the monovalent allergen 2,4-dinitrophenylated poly-γ-glutamic acid, whereas high signal counts were obtained with the multivalent allergen DNP-BSA. This confirmed that AlphaCL could specifically detect allergen-specific IgE Abs with the ability to crosslink a multivalent allergen. In summary, we have established a new assay model using AlphaCL to detect allergen-specific IgE Abs with FcεRIα crosslinking ability in human serum. This simple and practical assay model may be applied as a new diagnostic tool for patients with type-I allergy., (© 2023. The Author(s).)

Background: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome., Methods: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups., Results: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011)., Conclusions: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. This study was approved by the Institutional Review Board of the Tokyo CCU Network Scientific Committee., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pathophysiologically, an elevated left ventricular (LV) filling pressure is the major reason for heart failure (HF) readmission. The 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines provide a simplified algorithm for the echocardiographic assessment of LV filling pressure; however, this algorithm is yet to be sufficiently validated., Materials and Methods: We retrospectively studied 139 consecutive patients with acute decompensated HF. High estimated left atrial pressure (eLAP) was defined according to the 2016 ASE/EACVI guidelines. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for HF readmission within one year of discharge., Results: Across the study cohort, 68 patients (49%) did not have a high eLAP, 32 (23%) had an indeterminate eLAP, and 39 (28%) had a high eLAP. The number of HF readmission events within one year in the without high eLAP, indeterminate, and high eLAP groups were 4 (7.5%), 5 (18.5%), and 10 (33.3%), respectively. The HF readmission rate was significantly higher in patients with high eLAP than in those without high eLAP. Multivariate analysis revealed high eLAP (odds ratio, 5.924; 95% confidence interval, 1.664-21.087; P = 0.006) as a significant risk factor for HF readmission within one year. Furthermore, the exploratory analysis of the two-year outcomes revealed a similar finding: patients with high eLAP had a significantly higher rate of readmission for HF., Conclusions: The present study demonstrated that echocardiographic assessment of elevated LAP based on the 2016 ASE/EACVI guidelines is clinically valid for predicting readmission in patients with HF., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Cold snare polypectomy (CSP) for small colorectal polyps is a safe technique; however, there is little evidence on whether dietary restriction after CSP is essential. This study aimed to determine whether dietary restriction after CSP is necessary to prevent delayed bleeding., Methods: This is a randomized, controlled, non-inferiority trial conducted between November 2021 and March 2022. Patients with non-pedunculated small colorectal polyps (<10 mm) and who did not take anticoagulants were randomly allocated to two groups: (i) the normal diet (ND) group, and (ii) the low-residue diet (LRD) group. The ND group was instructed to eat anything after CSP, whereas the LRD group was advised to take LRD for 3 days after CSP. The primary endpoint was the occurrence of delayed major bleeding that needed endoscopic hemostasis., Results: A total of 193 patients (average 57.5 years old, 51.9% male) were enrolled in the study. Subsequently, 97 and 96 patients were allocated to the ND and LRD group, respectively. The occurrence of delayed major bleeding was 1.0% in the ND group and 2.1% in the LRD group (95% confidence interval [CI]: -4.4% to 2.4%; difference: -1.1%), which showed the non-inferiority of the ND group. In addition, there was no difference between the two groups with respect to the occurrence of minor delayed bleeding (3.1% and 4.2%, respectively; difference: -1.1% [95% CI: -6.4% to 4.2%])., Conclusion: Dietary restriction after CSP for low-bleeding-risk colorectal polyps is not necessary for the prevention of delayed bleeding (Registration number: UMIN000045669)., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Co-selection is thought to occur when resistance genes are located on the same mobile genetic element. However, this mechanism is currently poorly understood. In this study, complete circular plasmids from swine-derived Escherichia coli were sequenced with short and long reads to confirm that resistance genes involved in co-resistance were co-transferred by the same plasmid. Conjugative transfer tests were performed, and multiple resistance genes were transmitted. The genes possessed by the donor, transconjugant, and plasmid of the donor were highly similar. In addition, the sequences of the plasmid of the donor and the plasmid of the transconjugant were almost identical. Resistance genes associated with statistically significant combinations of antimicrobial use and resistance were co-transmitted by the same plasmid. These results suggest that resistance genes may be involved in co-selection by their transfer between bacteria on the same plasmid.

The analysis of otolith Sr isotope ratios ( 87 Sr/ 86 Sr) is a powerful method to study fish migration in freshwater areas. However, few studies have applied this method to study fish movement in brackish-water environments. Furthermore, despite the fact that habitat differentiation has been shown to drive genetic differentiation and reproductive isolation among stickleback fish, no studies have used the otolith 87 Sr/ 86 Sr ratios to analyze habitat differentiation between stickleback ecotypes and species. In this study, we analyzed the otolith 87 Sr/ 86 Sr ratios of three sympatric stickleback species of the genus Pungitius in the Shiomi River on Hokkaido Island, Japan: P. tymensis , the brackish-water type of the P. pungitius-P. sinensis complex, and the freshwater type of the P. pungitius-P. sinensis complex. First, we created a mixing equation to depict the relationship between habitat salinity and the 87 Sr/ 86 Sr ratios of river water. We found that the otolith 87 Sr/ 86 Sr ratios differed significantly among the three species, indicating that the three species utilize habitats with different salinities: P. tymensis and the brackish-water type inhabit freshwater and brackish-water environments, respectively, with the freshwater type using intermediate habitats. In addition, we found that some freshwater individuals moved to habitats with higher salinities as they grew. Our study demonstrates that the analysis of otolith 87 Sr/ 86 Sr ratios is a useful method for studying the habitat use of fish in brackish-water environments and habitat differentiation among closely related sympatric and parapatric species., Competing Interests: We have no conflicts of interest associated with this publication., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy., Methods: This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC., Results: The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level < 1136 pg/mL before chemotherapy, A/A + A/G of BHMT (742 G > A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m 2 , folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3-4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3-4 hematologic toxicities were vitamin B12 level < 486 pg/mL before premedication, leucocyte count < 6120 /µL before chemotherapy, folic acid level < 15.8 ng/mL before chemotherapy, status with a reduced dose of chemotherapy, and C/T + T/T of MTHFR (677 C > T). Risk factors for Grades 2-4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level < 21.5 mg/dL before chemotherapy, C/C + T/T of MTHFR (677 C > T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]., Conclusion: The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed., Trial Registration: This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Takotsubo syndrome (TTS) is an acute cardiovascular disease with clinical manifestations similar to those of acute myocardial infarction (AMI), and TTS sometimes occurs just after catastrophes. Large-scale studies of TTS in Japan are scarce, so we examined data over 9 years from Tokyo metropolitan acute cardiovascular care hospital network registry., Methods: A total of 1626 patients were diagnosed with TTS between 2010 and 2018 at Tokyo Cardiovascular Care Unit Network facilities, and data from all these patients were analyzed. We investigated annual and monthly captured incidence of TTS, temporal trend of the captured incidence proportion of TTS versus AMI, the occurrence of TTS on the day of the great earthquake, and we elucidated the prognostic factors for in-hospital death., Results: The annual incidence proportion of TTS versus AMI increased from 2.3 % to 4.5 % (p < 0.001) over 9 years. The mean TTS patient age was 74.4 years: the peak incidence of TTS was at 80 to 84 years of age for both male and female; females accounted for 78.5 % of patients. The monthly variation of the incidence of TTS was found (p = 0.009). In 2011, a total of 137 cases of TTS occurred, with as many as 6 occurring on March 11, the day of the Great East Japan Earthquake. There was a definable trigger for TTS in 64 % (physical: 36 %; emotional: 27 %; others: 2 %). All-cause in-hospital mortality was 5.3 % and was higher in males than in females (10.3 % vs 3.9 %; p < 0.001). Non-cardiac causes accounted for 62 % of in-hospital mortality. Factors at presentation that were associated with in-hospital all-cause mortality were male sex, low body mass index, and a high C-reactive protein level., Conclusions: This study elucidated the clinical features, in-hospital outcomes, and their attributed factors in patients with TTS in real-world clinical practice in Japan., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The considerable prevalence and worse outcomes of asthma-COPD overlap (ACO) in COPD have been reported, and optimal introduction of ICS is essential for ACO. However, diagnostic criteria for ACO consist of multiple laboratory tests, which is challenging during this COVID-19 era. The purpose of this study was to create a simple questionnaire to diagnose ACO in patients with COPD., Methods: Among 100 COPD patients, 53 were diagnosed with ACO based on the Japanese Respiratory Society Guidelines for ACO. Firstly, 10 candidate questionnaire items were generated and further selected by a logistic regression model. An integer-based scoring system was generated based on the scaled estimates of items., Results: Five items, namely a history of asthma, wheezing, dyspnea at rest, nocturnal awakening, and weather- or season-dependent symptoms, contributed significantly to the diagnosis of ACO in COPD. History of asthma was related to FeNO >35 ppb. Two points were assigned to history of asthma and 1 point to other items in the ACO screening questionnaire (ACO-Q), and the area under the receiver operating characteristic curve was 0.883 (95% CI: 0.806-0.933). The best cutoff point was 1 point, and the positive predictive value was 100% at a cutoff of 3 points or higher. The result was reproducible in the validation cohort of 53 patients with COPD., Conclusions: A simple questionnaire, ACO-Q, was developed. Patients with scores ≥3 could be reasonably recommended to be treated as ACO, and additional laboratory testing would be recommended for patients with 1 and 2 points., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Innate immune responses are important in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. We have previously found a lactic acid bacteria species, Lactococcus lactis strain Plasma (LC-Plasma), which possesses specific feature to activate plasmacytoid dendritic cells (pDCs) and thus may affect innate immune responses. Here, we investigated the impact of pDC activation by LC-Plasma on SARS-CoV-2 replication in vitro. Addition of the culture supernatant of pDCs stimulated with LC-Plasma resulted in suppression of SARS-CoV-2 replication in Vero and Calu-3 cells. We confirmed interferon-α (IFN-α) secretion in the supernatant of pDCs stimulated with LC-Plasma and induction of IFN-stimulated genes in cells treated with the pDC supernatant. Anti-IFN-α antibody impaired the suppression of SARS-CoV-2 replication by the supernatant of LC-Plasma-stimulated pDCs, suggesting that IFN-α plays an important role in the SARS-CoV-2 suppression. Our results indicate the potential of LC-Plasma to induce inhibitory responses against SARS-CoV-2 replication through pDC stimulation with IFN-α secretion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Hiroshi Ishii, Kenta Jounai, Konomi Ohshio, Daisuke Fujiwara, and Tetsuro Matano have patent #PCT/JP2022/40242 pending to Licensee., (Copyright © 2023 Elsevier Inc. All rights reserved.)