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Purpose: To create and evaluate prediction models of local tumor recurrence after successful conventional transcatheter arterial chemoembolization (c-TACE) via radiomics analysis of lipiodol deposition using cone-beam computed tomography (CBCT) images obtained at the completion of TACE., Materials and Methods: A total of 103 hepatocellular carcinoma nodules in 71 patients, who achieved a complete response (CR) based on the modified Response Evaluation Criteria in Solid Tumors 1 month after TACE, were categorized into two groups: prolonged CR and recurrence groups. Three types of areas were segmented on CBCT: whole segment (WS), tumor segment (TS), and peritumor segment (PS). From each segment, 105 radiomic features were extracted. The nodules were randomly divided into training and test datasets at a ratio of 7:3. Following feature reduction for each segment, three models (clinical, radiomics, and clinical-radiomics models) were developed to predict recurrence based on logistic regression., Results: The clinical-radiomics model of WS showed the best performance, with the area under the curve values of 0.853 (95% confidence interval: 0.765-0.941) in training and 0.752 (0.580-0.924) in test dataset. In the analysis of radiomic feature importance of all models, among all radiomic features, glcm_MaximumProbability, shape_MeshVolume and shape_MajorAxisLength had negative coefficients. In contrast, shape_SurfaceVolumeRatio, shape_Elongation, glszm_SizeZoneNonUniformityNormalized, and gldm_GrayLevelNonUniformity had positive coefficients., Conclusion: In this study, a machine-learning model based on cone-beam CT images obtained at the completion of c-TACE was able to predict local tumor recurrence after successful c-TACE. Nonuniform lipiodol deposition and irregular shapes may increase the likelihood of recurrence., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Artificial control of intracellular protein dynamics with high precision provides deep insight into complicated biomolecular networks. Optogenetics and caged compound-based chemically induced dimerization (CID) systems are emerging as tools for spatiotemporally regulating intracellular protein dynamics. However, both technologies face several challenges for accurate control such as the duration of activation, deactivation rate and repetition cycles. Herein, we report a photochromic CID system that uses the photoisomerization of a ligand so that both association and dissociation are controlled by light, enabling quick, repetitive and quantitative regulation of the target protein localization upon illumination with violet and green light. We also demonstrate the usability of the photochromic CID system as a potential tool to finely manipulate intracellular protein dynamics during multicolor fluorescence imaging to study diverse cellular processes. We use this system to manipulate PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy, showing that PINK1 recruitment to the mitochondria can promote Parkin recruitment to proceed with mitophagy., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis., Methods: This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria., Results: Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis., Conclusion: In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis., (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.)

We have developed an ion diagnostic method for laser-driven ion acceleration experiments that uses fluorescent nuclear track detectors (FNTDs). An FNTD records the particle tracks as color centers and does not require chemical etching, unlike CR-39 track detectors. The color centers are observed using a confocal laser microscope, and 3D particle tracks can be obtained by changing its focal position. The intensity of the color centers corresponds to the energy deposited by the ions. The nuclides of the ions can be determined from the intensity distribution of the color centers as a function of depth and the distance between the stopping point and the surface of the detector. To extract the intensity distribution, we must track the same ion tracks in the depth-layered microscopic images from the surface to the stopping point, even if they overlap with those of other ions. In addition, since an FNTD is sensitive not only to ions but also to electrons and photons, we must identify ion tracks among those from the latter particles. To analyze a statistical number of ion tracks, it is necessary to automate these processes. We have thus developed a method for automated ion detection and 3D tracking that relies on a support vector classifier and a kernelized correlation filter. This method was tested on a laser ion acceleration experiment performed using the J-KAREN-P laser. The method automatically detects ion tracks on FNTDs and tracks them in the depth direction. The training data are sampled from the Heavy-Ion Medical Accelerator in Chiba., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: A number of antibody test kits for detecting prior SARS-CoV-2 infection and post-immunization status have been commercialized. Indirect immunoperoxidase assay (IIP) is a conventional method to test antibodies. We evaluated the diagnostic accuracy and antibody titer profile of the IIP in COVID-19 and pre- and post-vaccination., Methods: We conducted a hospital-based observational study in Fukushima prefecture, Japan. We enrolled COVID-19 inpatients who tested positive by PCR. We used serum samples collected > 10 years before the pandemic as the negative control. We also included volunteers vaccinated at the hospital. All participants were tested using an IIP with whole-cell antigen of the six SARS-CoV-2 variants isolated in Japan during the epidemic and an IgG ELISA kit. Negative controls and vaccinated volunteers were also tested using a lateral flow assay (LFA) kit. We conducted receiver operating characteristic (ROC) analysis to evaluate diagnostic accuracy and performed logistic regression analysis to explore factors associated with antibody titer., Results: We included 146 COVID-19 inpatients, 38 negative controls, and 36 vaccinated volunteers. Most participants had the highest titer for IgG and IgM in the wild type-A antigen among the six variants. The sensitivity, specificity, and accuracy of the IgG ELISA kit were 60.3%, 100%, and 68.5%; of the IIP for IgG with the cutoff titer at 1:80, 82.2%, 94.7%, and 84.8%, respectively. The ROC curves of the ELISA and IIP for IgG were almost identical. In the IgG tests of the 36 volunteers, 35 were positive for ELISA and IIP and 34 for LFA after two vaccinations. IgM titers in the IIP were <  = 1:40 in 114 patients and 32 volunteers after two vaccinations; therefore, the IgM titer is unsuitable for diagnosis. In COVID-19 patients, age, days from disease onset, >  = 7 days after the second vaccination, and immunosuppressants for comorbidity were associated with IgG titer of >  = 1:640 in the IIP., Conclusions: The diagnostic accuracy of the IIP for detecting IgG antibodies in COVID-19 or after two vaccinations is equivalent to that of an ELISA. Further investigations are required to address the association between antibody titers in the IIP and their protective or harmful effects against COVID-19., (© 2024. The Author(s).)

The surface pre-reacted glass ionomer (S-PRG) filler is a type of bioactive functional glass that releases six different ions. This study examined the effects of the S-PRG filler eluate on Streptococcus mutans in the presence of sucrose. In a solution containing S. mutans , the concentrations of BO 3 3- , Al 3+ , Sr 2+ were significantly higher in the presence of the S-PRG filler eluate than in its absence ( - < 0.001). The concentrations of these ions further increased in the presence of sucrose. Additionally, the S-PRG filler eluate significantly reduced glucan formation by p < 0.001). The concentrations of these ions further increased in the presence of sucrose. Additionally, the S-PRG filler eluate significantly reduced glucan formation by S. mutans ( p < 0.001). Bioinformatic analyses revealed that the S-PRG filler eluate downregulated genes involved in purine biosynthesis (purC, purF, purL, purM, and purN) and upregulated genes involved in osmotic pressure (opuAa and opuAb). At a low pH (5.0), the S-PRG filler eluate completely inhibited the growth of p < 0.001). Bioinformatic analyses revealed that the S-PRG filler eluate downregulated genes involved in purine biosynthesis (purC, purF, purL, purM, and purN) and upregulated genes involved in osmotic pressure (opuAa and opuAb). At a low pH (5.0), the S-PRG filler eluate completely inhibited the growth of S. mutans < 0.001). These findings suggest that ions released from the S-PRG filler induce gene expression changes and exert an inhibitory effect on p < 0.001). These findings suggest that ions released from the S-PRG filler induce gene expression changes and exert an inhibitory effect on S. mutans in the presence of sucrose.

Competing Interests: Declarations of competing interest None.

Competing Interests: Declaration of competing interest None.

Rationale: Primary hyperparathyroidism (PHPT), which is characterized by increased parathyroid hormone secretion, typically manifests as hypercalcemia and hypertension. Here, we report a case of severe hypotension following tracheal intubation during anesthesia induction in a patient with PHPT, in contrast to the expected hypertensive response., Patient Concerns: A 52-year-old man presented with nausea after eating, leg pain when walking, and headaches., Diagnosis: Based on the blood test and computed tomography results, he was diagnosed with PHPT., Interventions: The patient underwent parathyroidectomy under general anesthesia. After induction anesthesia and tracheal intubation, severe acute hypotension and tachycardia suddenly developed. To treat hypotensive shock, we immediately administered ephedrine and phenylephrine and infused Ringer solution., Outcomes: The symptoms of hypotensive shock were alleviated by this intervention., Lessons: We speculate that the cause of his severe hypotension was vasodilation due to the transient release of parathyroid hormone from mechanical stimulation by anesthetic procedures, such as tracheal intubation, combined with hypercalcemia-induced severe dehydration. Moreover, we speculate that fluid resuscitation stabilized his condition and helped achieve a successful surgical outcome. The possibility of severe hypotension after anesthesia induction should be anticipated, and management of cases with severe dehydration should be optimized during the anesthetic management of patients with PHPT., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The developmental changes in the excitation-contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca 2+ handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation-contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca 2+ extrusion by the Na + -Ca 2+ exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na + -Ca 2+ exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function.

Introduction: Elucidating the characteristic odors of microbes can facilitate microorganism identification. This study aimed to evaluate the accuracy of microbial identification based on odor and its association with years of experience among microbiological technologists., Methods: A cross-sectional study was conducted on February 19, 2023, in Osaka, Japan, in a laboratory capable of handling microorganisms that were rated at or below biosafety level 2. This study included 70 microbiological technologists (including 45 women) with a mean experience of 7.1 years (standard deviation, 5.7). Ten bacterial strains with distinct odors were selected. Participants were blindfolded and asked to identify the bacterial strains based on odor of cultured microbes alone. Linear and logistic regression analyses were used for data analysis. The primary outcome was the number of accurately identified bacterial strains per year of experience., Results: The number of years of experience was not significantly associated with the accuracy of odor identification (regression coefficient = 0.037 [95 % confidence interval: 0.038 to 0.113]). Additionally, generally low accuracy was noted in the identification of individual microbial species., Conclusions: Our findings indicate that microorganism identification based solely on odor is challenging. Incorporating additional information, such as visual cues, may enhance the identification accuracy., 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.)

The effects of enhanced late I Na , a persistent component of the Na + channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late I Na , caused increases in the basal Na + and Ca 2+ concentrations, increases in the number of Ca 2+ sparks and Ca 2+ waves, and the generation of repetitive Ca 2+ transients. These phenomena were inhibited by eleclazine, a blocker of the late I Na ; SEA0400, an inhibitor of the Na + /Ca 2+ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late I Na in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca 2+ -dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.

Background: The transmission of carbapenemase-producing Enterobacterales (CPE) in the external environment, especially through food, presents a significant public health risk., Objectives: To investigate the prevalence and genetic characteristics of CPE in food markets of Dhaka, Bangladesh, using WGS., Methods: CPE isolates were obtained from different food and water samples collected from food markets in the southern part of Dhaka, Bangladesh. The isolates subsequently underwent molecular typing, WGS employing both short- and long-read sequencers, and plasmid analysis., Results: This study unveiled an extensive spread of CPE, with no significant difference in contamination rates observed in samples ( N  = 136), including meat ( n  = 8), fish ( n  = 5), vegetables ( n  = 36) or various food-washed water ( n  = 65) from markets near hospitals or residential areas. Thirty-eight Enterobacterales from 33 samples carried carbapenemase genes ( bla NDM-1, -4, -7 , bla KPC-2 , bla OXA-181 or bla IMI-1 ). Among these, the high-risk Escherichia coli ST410 clone was the most prevalent and distributed across various locations. Furthermore, the identification of IncHI2 plasmids co-harbouring resistance genes like bla NDM-5 and mcr-1.1 , without discernible epidemiological connections, is a unique finding, suggesting their widespread dissemination., Conclusions: The analysis unveils a dynamic landscape of CPE dissemination in food markets, underscored by the proliferation of novel IncHI2 hybrid plasmids carrying both colistin- and carbapenem-resistance genes. This illuminates the ever-evolving landscape of antimicrobial resistance in Dhaka, urging us to confront its emergent challenges., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: The internal jugular vein (IJV) is one of the most used sites for central venous access. Some authors revealed the association of a higher deformation rate of the IJV wall with posterior wall penetration, which may cause a hemorrhagic complication. A newly developed thin-tip needle (three-dimensional (3D) needle) reduced the deformation rate in an ex vivo study. Therefore, we conducted a clinical study to investigate its efficacy in reducing vessel deformity during IJV puncture., Methods: This study retrospectively enrolled 80 adult patients who received central venous port (CVP) implantation via the IJV from April 1, 2022, to November 10, 2023, in our institution. Traditional needle-and-catheter was used for ultrasound (US)-guided IJV puncture (usual group) for the former 40 patients before July 18, 2023. Afterward, the 3D needle was used for the latter 40 patients (3D needle group). US images were stored and analyzed to calculate the deformation rate., Results: The deformation rate was 58.6% (13.2-100) for the usual needle and 41.8% (10.6-100) for the 3D needle ( p  = 0.0034). Patients who required several punctures included 2 for the usual needle and 12 for the 3D needle, respectively ( p  = 0.0032). All patients and the usual needle group demonstrated a weak negative correlation between the deformation rate and pre-puncture vessel diameter ( r  = 0.24 and 0.41, respectively), with no correlation in the 3D needle group., Conclusion: The deformation rate of the IJV wall was smaller in the 3D needle group than in the usual needle group. The use of a 3D needle would be safer when puncturing the IJV., 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.

Purpose: To evaluate the angiographic recanalization rate of patients who underwent embolization juxta-proximal to the sac with AMPLATZER Vascular Plug type IV (AVP IV) for a simple pulmonary arteriovenous malformation (PAVM)., Material and Methods: Ten patients (7 females and 3 males; median age, 47 years [range 28-83 years]) with 19 simple-type PAVMs who underwent embolization using an AVP IV between May 2015 and November 2021 were included in this retrospective study. The median feeding artery diameter on computed tomography was 4.0 mm (range 3-5.9 mm), and the median ratio of AVP IV size to feeding artery diameter on computed tomography was 1.5 (range 1.3-2.1). Technical success was defined by AVP IV placement at the junction between the pulmonary artery and the sac, or the pulmonary artery within 1 cm from the junction and beyond the last normal branch. The primary endpoint was the PAVM recanalization rate in selective or segmental pulmonary angiography performed 1 year post-embolization., Results: The technical success rate of embolization juxta-proximal to the sac for simple-type PAVMs was 100%. None of the 19 lesions showed recanalization in pulmonary angiography performed 1 year after embolization. One patient experienced hemoptysis and pneumonia., Conclusion: Embolization of simple-type PAVMs' feeding vessel using AVP IV is safe and effective, with a high technical success rate and no recanalization on pulmonary angiography performed at 1 year post-embolization., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Ruthenibacterium lactatiformans, a Gram-stain-negative, rod-shaped, obligate anaerobic bacterium of the Oscillospiraceae family, has not been previously reported in human infections. This study reports the first case of bacteraemia and potential vertebral osteomyelitis caused by Ruthenibacterium lactatiformans., Case Presentation: An 82-year-old man with a history of diabetes, chronic renal failure, and prior spinal surgery for spondylolisthesis and spinal stenosis presented with fever and lower back pain. Magnetic resonance imaging revealed multiple vertebral osteomyelitis lesions. Initial blood cultures identified methicillin-resistant Staphylococcus aureus (MRSA), which prompted vancomycin treatment. However, repeated blood cultures not only confirmed persistent MRSA, but also detected Gram-negative bacilli (GNB). Despite surgical removal of the spinal hardware and antimicrobial therapy, the patient's osteomyelitis worsened, necessitating transfer for further management. Subsequent analysis using 16S rRNA gene sequencing identified the GNB as Ruthenibacterium lactatiformans., Conclusions: This is the first documented instance of human infection with Ruthenibacterium lactatiformans, signifying its pathogenic potential in vertebral osteomyelitis. The involvement of anaerobic bacteria and the possibility of polymicrobial infections complicate the diagnosis and treatment of vertebral osteomyelitis. This report underscores the need for caution when identifying the causative organism and selecting an appropriate treatment., (© 2024. The Author(s).)

Background: The association between pet exposure in infancy, early childhood eczema, and FLG mutations remains unclear., Methods: This was a birth cohort study performed in Tokyo, Japan. The primary outcome was current eczema based on questionnaire responses collected repeatedly from birth to 5 years of age. Generalized estimating equations and generalized linear modeling were used to evaluate the association., Results: Data from 1448 participants were used for analyses. Household dog ownership during gestation, early infancy, and 18 months of age significantly reduced the risk of current eczema. Household cat ownership also reduced the risk of current eczema, albeit without statistical significance. The combined evaluation of children from households with pets, be it cats, dogs or both, the risk of current eczema at 1-5 years of age was lower in those with household pet exposure ownership during gestation (RR = 0.59, 95 % CI 0.45-0.77) and at 6 months (RR = 0.49, 95 % CI 0.36-0.68). , Reduced risks of eczema were also observed at 2-5 (RR = 0.52, 95 % CI 0.37-0.73) and 3-5 years of age (RR = 0.50 95 % CI 0.35-0.74) when the respective household pet ownership were evaluated at 18 months and 3 years of age. These protective associations of reduced risk of eczema were only observed in children without FLG mutations., Conclusions: Household dog and pet (dog, cat, or both) ownership was protective against early childhood eczema in a birth cohort dataset. This protective association was observed only in children without FLG mutations, which should be confirmed in studies with larger cohorts., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by skin rash, organ involvement, lymph node swelling, eosinophilia, and atypical lymphocytosis, with myocarditis being a rare but potentially fatal complication. It has been reported that in patients with cardiac involvement due to DRESS, older age and shorter periods between offending drug exposure and symptom onset are associated with mortality. We report a case of fatal DRESS-associated myocarditis in a young woman, occurring one month after drug exposure, despite intensive immunosuppressive therapy. This case report highlights the risk of mortality from DRESS-associated myocarditis even in patients lacking known risk factors., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Watanabe et al.)

Background: Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients., Methods: We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively., Results: We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain., Conclusions: Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment., (© 2024. The Author(s).)

Background: There is a lack of data regarding the early introduction of the consumption of allergenic food among Asian infants., Methods: We examined infants who had early-onset eczema before 6 months of age and received instructions from certified allergists for the early introduction of hen's eggs, milk, wheat, peanuts, and tree nuts., Results: The consumption rates of hen's eggs were 100% at 24 months. For peanuts and walnuts, the consumption rate was moderate at 12 months (48.5% and 30.3%, respectively), but by 24 months, it had progressed to 78.8% and 81.3%, respectively. In contrast, cashews remained at lower levels than other allergens at 20.7% at 12 months and 41.4% at 24 months. No adverse events related to early introductions occurred., Conclusions: In infants with eczema, allergenic foods could be introduced early and well tolerated in Asian infants. However, having eczema may indicate a predisposition to food allergies, so caution is necessary when introducing allergenic foods. The early introduction of peanuts and tree nuts was still more challenging in real-world practice in Asia as well as in Western countries.

Background: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19., Methods: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load., Results: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447)., Conclusions: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings., (© 2024. The Author(s).)

Clostridium butyricum, a probiotic commonly prescribed in Asia, most notably as MIYA-BM (Miyarisan Pharmaceutical Co., Ltd.; https://www.miyarisan.com), occasionally leads to bacteremia. The prevalence and characteristics of C. butyricum bacteremia and its bacteriologic and genetic underpinnings remain unknown. We retrospectively investigated patients admitted to Osaka University Hospital during September 2011-February 2023. Whole-genome sequencing revealed 5 (0.08%) cases of C. butyricum bacteremia among 6,576 case-patients who had blood cultures positive for any bacteria. Four patients consumed MIYA-BM, and 1 patient consumed a different C. butyricum-containing probiotic. Most patients had compromised immune systems, and common symptoms included fever and abdominal distress. One patient died of nonocclusive mesenteric ischemia. Sequencing results confirmed that all identified C. butyricum bacteremia strains were probiotic derivatives. Our findings underscore the risk for bacteremia resulting from probiotic use, especially in hospitalized patients, necessitating judicious prescription practices.

Pneumolysin (Ply) is an indispensable cholesterol-dependent cytolysin for pneumococcal infection. Although Ply-induced disruption of pneumococci-containing endosomal vesicles is a prerequisite for the evasion of endolysosomal bacterial clearance, its potent activity can be a double-edged sword, having a detrimental effect on bacterial survivability by inducing severe endosomal disruption, bactericidal autophagy, and scaffold epithelial cell death. Thus, Ply activity must be maintained at optimal levels. We develop a highly sensitive assay to monitor endosomal disruption using NanoBiT-Nanobody, which shows that the pneumococcal sialidase NanA can fine-tune Ply activity by trimming sialic acid from cell-membrane-bound glycans. In addition, oseltamivir, an influenza A virus sialidase inhibitor, promotes Ply-induced endosomal disruption and cytotoxicity by inhibiting NanA activity in vitro and greater tissue damage and bacterial clearance in vivo. Our findings provide a foundation for innovative therapeutic strategies for severe pneumococcal infections by exploiting the duality of Ply activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Methods for identifying bacterial pathogens are broadly categorised into conventional culture-based microbiology, nucleic acid-based tests, and mass spectrometry. The conventional method requires several days to isolate and identify bacteria. Nucleic acid-based tests and mass spectrometry are relatively rapid and reliable, but they require trained technicians. Moreover, mass spectrometry requires expensive equipment. The development of a novel, inexpensive, and simple technique for identifying bacterial pathogens is needed. Through combining micropore technology and assembly machine learning, we developed a novel classifier whose receiver operating characteristic (ROC) curve showed an area under the ROC curve of 0.94, which rapidly differentiated between Staphylococcus aureus and Staphylococcus epidermidis in this proof-of-concept study. Morphologically similar bacteria belonging to an identical genus can be distinguished using our method, which requires no specific training, and may facilitate the diagnosis and treatment of patients with bacterial infections in remote areas and in developing countries., (© 2024. The Author(s).)

Objectives: In older patients, the diagnosis of acute pyelonephritis (APN) is challenging. The aim was to evaluate the added value of CT to history, physical examination and urinalysis for the diagnosis of APN in older patients with suspected infection with an unknown focus., Design: Retrospective diagnostic study., Setting: Department of General Medicine in an acute care hospital in Japan., Participants: Patients aged ≥65 years who underwent blood cultures, a urine culture, and chest and abdominal CT to detect the focus of infection were included., Primary Outcome Measures: Two radiologists independently reviewed four non-contrast CT signs: perirenal fat stranding, pelvicalyceal wall thickening, enlargement of the kidney and thickening of Gerota's fascia. Findings on contrast-enhanced CT could not be evaluated due to an insufficient number of patients in whom contrast-enhanced CT was performed. An expert panel was used as the reference standard for APN. The added value of CT findings was quantified by comparing the diagnostic performance between a model based on 10 predictors available before CT and an extended model including the CT findings., Results: Of 473 patients, 61 (14.8%) were diagnosed with APN. When the laterality of the CT findings was taken into account, the model fit was not improved by adding them. In the laterality-insensitive analysis, the model performance was significantly improved by adding the CT signs (likelihood-ratio test p=0.03; c-index 0.89 vs 0.91, p=0.03). However, their clinical utility was only to improve the classification of 11.5% of patients with APN., Conclusions: The added value of non-contrast CT findings to history, physical examination and urinalysis was limited for the diagnosis of APN in older patients with a suspected infection with an unknown focus., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mouthwashes containing cetylpyridinium chloride (CPC) or on-demand aqueous chlorine dioxide (ACD) have potential to reduce the salivary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load in individuals with SARS-CoV-2 infection. This study will evaluate the effect of CPC and on-demand ACD mouthwashes on salivary SARS-CoV-2 levels in individuals with acute asymptomatic or mild SARS-CoV-2 infection (COVID-19) staying in a residential recuperation facility in Osaka, Japan. This randomized, open-label clinical trial will include three equal-sized groups (CPC mouthwash, on-demand ACD mouthwash, and placebo), with 30 participants per group. A stratified replacement block method will be used to ensure balanced allocation based on symptom presence and days since symptom onset. Participants will use mouthwash at set times for 7 days or until the end of recuperation. Saliva samples will be collected at multiple time points and tested for SARS-CoV-2 using quantitative reverse transcription polymerase chain reaction. The primary outcome will be changes in salivary SARS-CoV-2 viral load 2 h after the first mouthwash use compared with the pre-mouthwash level. Secondary outcomes will include changes in salivary viral load and clinical parameters at different time points. This study was registered with the Japan Registry of Clinical Trials on 18 October 2022 (jRCTs051220107).

We examined the effects of a dihydropyridine analog, PAK-200, on guinea pig myocardium during experimental ischemia and reperfusion. In isolated ventricular cardiomyocytes, PAK-200 (1 μM) had no effect on the basal peak inward and steady-state currents but inhibited the isoprenaline-induced time-independent Cl - current. In the right atria, PAK-200 had no effect on the beating rate and the chronotropic response to isoprenaline. In an ischemia-reperfusion model with coronary-perfused right ventricular tissue, a decrease in contractile force and a rise in tension were observed during a period of 30-min no-flow ischemia. Upon reperfusion, contractile force returned to less than 50% of preischemic values. PAK-200 had no effect on the decline in contractile force during the no-flow ischemia but reduced the rise in resting tension. PAK-200 significantly improved the recovery of contractile force after reperfusion to about 70% of the preischemic value. PAK-200 was also shown to attenuate the decrease in tissue ATP during ischemia. Treatment of ventricular myocytes with an ischemia-mimetic solution resulted in depolarization of the mitochondrial membrane potential and an increase in cytoplasmic and mitochondrial Ca 2+ concentrations. PAK-200 significantly delayed these changes. Thus, PAK-200 inhibits the cAMP-activated chloride current in cardiac muscle and may have protective effects against ischemia-reperfusion injury through novel mechanisms.

Background: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques., Methods: C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia., Results: Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection., Conclusions: Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques., (© 2023. The Author(s).)

Introduction Establishing a scale that can easily be used to appropriately measure the impact of constipation on the quality of life in Japan is a first step toward addressing this important health issue. We developed a Japanese language version of the Constipation-Related Quality of Life scale, which has 18 items and four subscales, and then subjected it to validation testing. Methods After translation according to a standardized and commonly used procedure, the Japanese version of the Constipation-Related Quality of Life scale was administered to people in an internet-based panel, in March 2023. The participants included 1,276 adults who had constipation (median age: 60 years, 690 {54.1%} males). The outcome measures included the Constipation-Related Quality of Life scale, the Constipation Scoring System (an index of constipation severity), and the Medical Outcomes Study (MOS) eight-item short form (a measure of generic health-related quality of life). Results Confirmatory factor analysis (four-factor model) indicated that all 18 Constipation-Related Quality of Life items had sufficiently high factor loadings (0.686-0.926). Internal consistency reliability was high (Cronbach's alpha: 0.86-0.94). Scores on the social impairment subscale and on the distress subscale of the Constipation-Related Quality of Life scale were significantly worse in the participants who had worse scores on the social functioning and mental health domains, respectively, of the MOS eight-item short form, which indicates good concurrent validity. Regarding criterion-based validity, the four subscale scores differed significantly among the four constipation-severity groups. The four subscale scores were also 1.16-4.53 times more sensitive than the MOS eight-item short form's mental component score to differences among the four constipation-severity groups (relative validity: 1.16-4.53), which indicates good discriminant validity. Conclusion The Japanese version of the Constipation-Related Quality of Life scale can be used with confidence in its factor structure, its concurrent, criterion-based, and discriminant validity, and its internal consistency reliability., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hamaguchi et al.)

Introduction: Intravenous antibiotics are the primary treatment of choice for pyogenic vertebral osteomyelitis (PVO). Surgical intervention is required when the initial antibiotic treatment fails but is often difficult to perform, especially in older adults with multiple comorbidities, because of the reduced physical activity. The size of the infection signal in the spinal bone on magnetic resonance imaging (MRI) at the time of diagnosis was reported to have a high predictive accuracy for antibiotic treatment failure. However, the sample size was too small for this result to be adopted in clinical practice. Thus, we conducted a validation study of the previous research using a larger sample size., Methods: We conducted a retrospective review of electronic medical records of patients admitted to the orthopedic department of a university hospital with a diagnosis of PVO between 2006 and 2021, and consecutively included patients without planned PVO surgery on admission and with a sagittal view of T1-weighted spinal MRI at the time of diagnosis. The index test was the percentage involvement of the affected areas in one motion segment on sagittal MRI. We also evaluated other MRI findings, such as bone destruction, segmental instability, epidural abscesses, and multiple sites for their predictive accuracy for antibiotic treatment failure., Results: A total of 82 participants were eligible for the analysis. The presence of ≥90% affected area of one motion segment had a sensitivity of 16.7% and a specificity of 70.3% for future antibiotic treatment failure, resulting in poor predictive performance, with positive (LR+) and negative likelihood ratios of 0.56 and 1.19, respectively. The area under the receiver operating characteristic curve for a 10% increase in the affected area was 0.48. Among the other MRI findings, the presence of bone destruction had a significantly higher predictive accuracy (LR+ 3.11, 95% confidence interval 1.30-7.42)., Conclusion: An infection signal ≥90% on a T1-weighted MRI of one spinal motion segment did not show sufficient predictive performance for antibiotic treatment failure. Spinal bone destruction had a mild-to-moderate predictive accuracy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hamaguchi et al.)

Background Most risk factors for developing community-acquired pneumonia (CAP) are age-related and chronic medical conditions; modifying these factors can be challenging, especially in the elderly. Poor social functioning, however, has a negative impact on medical conditions but can be improved through interventions. Therefore, the social functioning domain of health-related quality of life (HRQOL) may be a modifiable risk factor for the development of CAP. This study investigated the association between poor social functioning and the incidence of CAP in elderly individuals. Methodology We conducted a retrospective cohort study using a dataset from 2018 to 2021, derived from an annual questionnaire-based survey of a cohort of community-dwelling people aged 75 years or older (the Sukagawa Study). The dataset included social functioning subscale scores of HRQOL obtained from the Eight-Item Short Form (SF-8) questionnaire. Health insurance claims data were matched with these HRQOL data. For each participant, the exposure (HRQOL) was measured, and outcomes (incidence of CAP) were observed yearly from 2018 through 2021. Results The four observation years had a total of 17,016 observation periods among 6,513 participants. The annual incidence rate of CAP was 0.90-1.77%. Lower social functioning was associated with a higher risk of CAP. Specifically, for each standard deviation difference in social functioning score, the adjusted rate ratio for CAP incidence was 1.26 (95% confidence interval (CI) = 1.08-1.48). In a subgroup analysis, the association between social functioning and CAP differed by sex (p = 0.037). Specifically, the adjusted rate ratio for CAP incidence was 1.41 (95% CI = 1.17-1.70) in men and 1.00 (95% CI = 0.76-1.35) in women. Conclusions Poor social functioning is an important risk factor for CAP in the elderly, especially in men. Interventions that improve social functioning may help to prevent CAP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hamaguchi et al.)

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n  = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase., (© 2022. The Author(s).)

Background Older adults commonly experience both sleep disturbances and constipation. Pathophysiological mechanisms such as inhibition of colonic peristalsis due to sympathetic activation associated with sleep disturbances have been postulated. Here, we aimed to assess the temporal association between the degree of sleep quality and the incidence of constipation. Methods We conducted a prospective cohort study of independent community-dwelling older adults aged ≥75 years (the Sukagawa Study). Using a self-administered questionnaire inquiring about awareness of own constipation or the use of laxatives in 2019 and 2020, we determined the onset of constipation. The Japanese version of the Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality in 2019. The global PSQI score was divided into quartiles. We analyzed the association between the degree of sleep quality and the incidence of constipation using logistic regression models. Results Overall, 1,696 participants without constipation at baseline were analyzed after 1 year, of whom 823 (48.5%) were male. The mean age of participants was 79.9 years. In total, 191 participants (11.3%) developed constipation. The median (interquartile range; IQR) global PSQI score was 4 (2, 6). According to the quartiles of the global PSQI scores (0-2, 3-4, 5-6, and ≥7), 35 (7.8%), 55 (11.3%), 48 (12.8%), and 53 (13.8%), respectively, developed constipation. Compared to those with global PSQI scores of 0-2, the odds ratios, adjusted by age, sex, smoking status, alcohol status, educational level, working status, exercise, and medical history were 1.57, 1.78, and 2.02 for participants with global PSQI scores of 3-4, 5-6, and ≥7, respectively ( p = 0.003 for trend). Conclusions We identified poor sleep quality as a new risk factor for developing constipation in independent, community-dwelling, older adults aged ≥75 years., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nakagawa et al.)

Background: Long-term hospital stay is associated with functional decline in patients with pneumonia, especially in the elderly. Among elderly patients with pneumonia, aspiration pneumonia is a major category. Clinical definition is usually used because it can occur without apparent aspiration episodes. It is still not clear whether a long-term hospital stay is due to aspiration pneumonia itself caused by underlying oropharyngeal dysfunction or simply due to functional decline in elderly patients with multiple comorbidities during acute infection. The aim of this study is to identify whether clinically defined aspiration pneumonia itself was associated with a long-term hospital stay., Methods: A prospective observational study on community-acquired (CAP) or healthcare-associated pneumonia (HCAP) was conducted from January 2012 through January 2014. Aspiration pneumonia was clinically defined as pneumonia not only occurring in patients after documented aspiration episodes, but also occurring in those with underlying oropharyngeal dysfunction: chronic disturbances of consciousness and/or chronic neuromuscular diseases. We defined thirty-day hospital stay as a long-term hospital stay and compared it with logistic regression analysis. Potential confounders included age, sex, HCAP, body mass index (BMI), long-term bed-ridden state, heart failure, cerebrovascular disorders, dementia, antipsychotics use, hypnotics use, and CURB score which is a clinical prediction tool used to assess the severity, standing for; C (presence of Confusion), U (high blood Urea nitrogen level), R (high Respiratory rate), and B (low Blood pressure). In a sub-analysis, we also explored factors associated with long-term hospital stay in patients with aspiration pneumonia., Results: Of 2,795 patients, 878 (31.4%) had aspiration pneumonia. After adjusting potential confounders, the aspiration pneumonia itself was significantly associated with long-term hospital stay (adjusted odds ratio 1.44; 95% confidence interval 1.09-1.89, p < 0.01), as were higher age, male sex, high CURB score, HCAP, low BMI, heart failure, cerebrovascular disease, and antipsychotics use. Sub-analysis revealed factors associated with long-term hospital stay in the aspiration pneumonia, which included male sex, and multi-lobar chest X-ray involvement., Conclusions: Clinically defined aspiration pneumonia itself was independently associated with long-term hospital stay. This result could potentially lead to specific rehabilitation strategies for pneumonia patients with underlying oropharyngeal dysfunction., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Streptococcus pneumoniae (pneumococcus) is a pathogenic gram-positive bacterium that causes pneumonia, meningitis, and sepsis. Pneumococcal surface protein A (PspA) induces antibodies that protect against lethal infections by pneumococci. PspA is a choline-binding protein present on the cell surface of almost all pneumococcal strains and is a non-capsular polysaccharide vaccine candidate. For research and development of PspA-based vaccines, an in-vitro test system to measure the activity of functional antibodies capable of killing pneumococci is essential. The opsonophagocytic killing (OPK) assay is used to evaluate the opsonic activity of functional antibodies induced by capsular polysaccharide (CPS)-based vaccines (standard OPK assay). Despite the potential of anti-PspA antibodies to protect against lethal infections in mice, the standard OPK assay fails to evaluate anti-PspA antibodies. Using a pneumococcal surface protein C-deficient strain and extending the incubation time of opsonized bacteria, complement, and HL-60 cells reportedly results in enhanced bactericidal activity (modified OPK assay). We aimed to measure the bactericidal activity of anti-PspA antibodies in intact pneumococcal strains. We optimized the pneumococcal culture method used in the OPK assay to increase the efficiency of anti-PspA antibody-mediated phagocytosis of HL-60 cells. As thick capsules hinder phagocytosis, we attempted to obtain pneumococci with thin capsules through an improved culture method. As pneumococci attached to cells exhibit thin capsules, pneumococci cultured in Todd Hewitt yeast extract (THY) broth were spread on blood agar plates and incubated for 4 h. cpsA mRNA transcript levels in pneumococci cultured on blood agar were lower than those in pneumococci cultured in THY broth. OPK activity against pneumococci expressing PspA of clades 1-5 was reasonably well detected using pneumococci cultured on blood agar in the modified OPK assay. The modified OPK assay for anti-PspA antibody using pneumococci cultured on blood agar represents a useful assay to determine the killing activity of functional anti-PspA antibodies against pneumococci., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Yuka Koizumi, Zhenyu Piao, and Hiroki Nakayama are employees of The Research Foundation for Microbial Diseases of Osaka University. The other authors have no financial interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Diagnosis of perioperative anaphylaxis is difficult because of its non-specific and variable signs and symptoms. Therapeutic agents used to treat anaphylaxis and anaesthesiologist responses also vary depending on the case, which might affect outcomes; however, only a few studies have focused on these factors., Methods: This prospective study of perioperative anaphylaxis, a part of the Japanese Epidemiologic Study for Perioperative Anaphylaxis, investigated the clinical signs, its severity, therapeutic drugs, epinephrine administration, and anaesthesiologist responses in cases of perioperative anaphylaxis to assess trends and variability. Shock index was used to assess severity of cardiovascular collapse., Results: In 43 patients analysed in this study, cardiovascular signs (88.4%) were the most frequent, followed by skin (81.4%) and respiratory signs (60.5%). The presence of signs increased during the clinical course. The median time from the first signs to diagnosis of anaphylaxis was 10 (5.0-17.8) min. The rates of epinephrine use were 30.2% (unused), 48.8% (i.v.), and 20.9% (i.m.). The median time from diagnosis of anaphylaxis to epinephrine administration was 7 (inter-quartile range: 1.5-8.0) min. Antihistamines and corticosteroids were each used in 69.8% of cases. The worst shock index was higher in patients who received i.v. epinephrine (2.77 [0.90] mean [standard deviation]) than in both no epinephrine use cases (1.35 [0.41]) and i.m. epinephrine cases (1.89 [0.77] (P<0.001])., Conclusions: The clinical signs and treatments of perioperative anaphylaxis are variable, and the choice regarding epinephrine administration is based on symptom severity., Clinical Trial Registration: UMIN000035350., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of rickettsiosis-endemic areas in Honshu Island during August-November 2020. Rickettsia typhi seroprevalence rate was higher than that of Orientia tsutsugamushi, indicating that murine typhus is a neglected disease.

Background and Objectives: The relationship between social isolation/loneliness and oral health is unclear. This study investigated the association between social isolation/loneliness and tooth loss in older Japanese adults., Research Design and Methods: This was a cross-sectional study of a population-based cohort (the Sukagawa Study); 5,490 cohort study participants aged ≥75 years and who were independent answered a self-administered questionnaire in 2018. Social isolation was defined based on the 6-item Japanese version of the Lubben Social Network Scale. Loneliness was measured by the 3-item Japanese version of the University of California, Los Angeles (UCLA) Loneliness Scale version 3. The primary outcome was tooth loss, defined as having fewer than 20 teeth. The secondary outcomes were decreased toothbrushing frequency and diminished ability to chew food. Prevalence ratios (PRs) were estimated using a modified Poisson regression analysis in 2 models-Model 1, which adjusted for age, gender, smoking status, alcohol consumption, low annual income, and short education period, and Model 2, which added history of depression, history of diabetes mellitus, history of stroke, and cognitive impairment to Model 1., Results: The primary analysis included 4,645 participants. Adjusted PRs of social isolation and loneliness for tooth loss (Model 1) were 0.97 (95% confidence interval [CI] 0.92-1.01) and 1.06 (95% CI 1.01-1.12), respectively; those for decreased toothbrushing frequency were 1.13 (95% CI 0.95-1.36) and 1.56 (95% CI 1.26-1.92), respectively; and those for chewing difficulty were 1.61 (95% CI 1.06-2.43) and 2.94 (95% CI 1.91-4.53), respectively. The adjusted PRs in Model 2 demonstrated results similar to that of Model 1., Discussion and Implications: Loneliness is associated with tooth loss among older adults, whereas social isolation is not. Our findings can inform plans for policymakers, professionals, and organizations to identify lonely older adults and provide social prescriptions to improve their access to oral health care services., Competing Interests: None., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Purpose: In Japan, both a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available. Although randomized controlled trials have examined the effects of pneumococcal vaccines, few epidemiological studies have investigated the onset of pneumococcal pneumonia in general practice. In Izumo, Shimane Prefecture, Japan, a public subsidy for PPSV23 inoculation began in November 2012., Patients and Methods: The subjects were pneumonia patients aged 65 and over who were admitted to a hospital in Izumo. This retrospective study analyzed the following data extracted from medical records: pneumococcal pneumonia prevalence, pneumonia severity, mortality rate, PPSV23 vaccination rate, and length of hospital stay. The 2 years before the start of the public subsidy were defined as the early phase, and the 2 years after the subsidy initiation were defined as the late phase. We compared the two phases in terms of PPSV23 vaccination rate, prevalence and severity of pneumococcal pneumonia, and mortality rate., Results: We investigated data from a total of 1188 and 1086 patients in the early and late phases, respectively. The prevalence of pneumococcal pneumonia was 21.0% and 21.3% in the early and late phases, respectively. The mortality rate from pneumococcal pneumonia was 10.4% and 5.4% in the early and late phases, respectively (p = 0.080), indicating a 50% reduction. The PPSV23 vaccination rate (p < 0.001) and the comorbidity rates of chronic respiratory disease (p = 0.022) and chronic renal disease (p < 0.001) were significantly different between the early and late phases., Conclusion: This study showed that the rate of in-hospital deaths due to pneumococcal pneumonia was halved after the PPSV23 vaccine was subsidized. The causal relationship between the pneumococcal vaccination rate and the mortality rate of pneumococcal disease was unclear. Further investigation is deemed necessary., Competing Interests: Dr Kazuhisa Nakashima reports personal fees from TAIHO Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K., outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Hamaguchi et al.)

In this study, we aimed to determine whether paid work has an impact on health-related quality of life (HRQOL) among older adults. Over three years, we longitudinally collected data from 5,260 community-dwelling older adults aged 75 years or older from a city in Japan. We assessed HRQOL using the Short-Form-8. We estimated the mean difference between the physical component summary (PCS) and the mental component summary (MCS) scores, which were stratified based on gender using multivariate, generalized estimating equation models. We further conducted a subgroup analysis based on the participants' occupational backgrounds. Engagement in paid work was associated with increased MCS scores across both genders and with increased PCS scores among women. In the subgroup analysis, only women who had previously worked as managerial workers showed an inverse association with MCS scores. In this population, engagement in paid work may be a crucial factor associated with well-being.