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We present a new measurement of the Λ4H hypernuclear lifetime using in-flight K− + 4He → Λ4H + π0 reaction at the J-PARC hadron facility. We demonstrate, for the first time, the effective selection of the hypernuclear bound state using only the γ-ray energy decayed from π0. This opens the possibility for a systematic study of isospin partner hypernuclei through comparison with data from (K−, π−) reaction. As the first application of this method, our result for the Λ4H lifetime, τ(HΛ4)=206±8(stat.)±12(syst.)ps, is one of the most precise measurements to date. We are also preparing to measure the lifetime of the hypertriton (Λ3H) using the same setup in the near future.

We measured a set of π±Σ∓, π0Σ0, and π−Σ0 invariant mass spectra below and above the K¯N mass threshold in K−-induced reactions on deuteron. The measured πΣ mass spectral shape is well reproduced via the two-step mechanism, i.e., a neutron knocked out at a forward angle from a deuteron by an incident K−, with the K¯ recoiled backward reacting with the residual nucleon to produce π and Σ. We deduced the S-wave K¯N→πΣ and K¯N→K¯N scattering amplitudes in the isospin 0 channel in the framework of a K¯N and πΣ coupled channel. We find that a resonance pole corresponding to Λ(1405) is located at 1417.7−7.4+6.0 (fitting errors)−1.0+1.1 (systematic errors) + [−26.1−7.9+6.0 (fitting errors)−2.0+1.7 (systematic errors)] i MeV/c2, closer to the K¯N mass threshold than the value determined by the Particle Data Group.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe illness and mortality in patients with immunodeficiency. Although vaccination has been recommended, the induction of protective antibodies by immunization, and thus the disease-preventive effect, has proven insufficient in immunodeficient patients, especially in those with predominantly antibody deficiency. A monoclonal antibody combination of tixagevimab and cilgavimab (TIX/CIL) was developed as a pre-exposure prophylaxis (PrEP). In this study, we investigated the post-PrEP increase in antiviral antibody titers and detailed the breakthrough infections that occurred despite PrEP in Japanese immunodeficient patients who had received TIX/CIL., Methods: Blood samples were collected before and after TIX/CIL administration between November 2022 and August 2023. Antibody titers against the S-protein of SARS-CoV-2 were measured to evaluate TIX/CIL-induced protection. Information regarding breakthrough infection, as evidenced by positive antigen and/or PCR tests, was collected., Results: A significant increase in the anti-S antibody titer was observed in all 89 immunodeficient patients who had received TIX/CIL. However, 14 (16%) patients experienced breakthrough SARS-CoV-2 infections, of which one died of respiratory failure., Conclusion: The shift in the SARS-CoV-2 circulating strain might have reduced the efficacy of TIX/CIL, leading to an increased number of breakthrough infections., (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.)

Tracheal reconstruction is necessary in patients with large tracheal defects. Previously, artificial tracheae made of polypropylene and collagen sponge have been used clinically by our group. As a basic research aimed at promoting epithelialization for infection defense, we transplanted cell sheets of human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (iAECs) with artificial tracheae into tracheal defects of rats and confirmed their engraftment. In this study, we examined the difference in the cell engraftment between hiPSC-derived airway epithelial progenitor cells (iAEPCs) and iAECs. Cell sheets were collected on days 38, 45, and 56 of induction into iAECs, then transplanted into nude rats with tracheal defects along with the artificial trachea. Two weeks after transplantation, surviving human nuclear antigen (HNA)-positive epithelial cells were observed none of six rats in the 38-day group, two out of six in 45-day group, and five out of six in the 56-day group. The proportion of surviving HNA+ cells among the epithelial cells of 56-day group was significantly higher those of 38-day group. Differentiated iAECs are more suitable for the transplantation of hiPSCs into tracheal defects. Our findings propose the use of differentiated cells for improvement of engraftment efficiency.

Hypertension increases the risk of cerebrovascular disease and death. In addition to aerobic exercise, which is currently recommended for its antihypertensive effects, recent studies have suggested that dynamic and isometric resistance exercises also have antihypertensive effects. However, the magnitude of the antihypertensive effect of such resistance exercises is not well known. To clarify the differences in these effects, we conducted an umbrella review of a meta-analysis of randomized controlled trials (RCTs). A systematic search was performed on the Ovid MEDLINE and Cochrane Library, covering the period from inception to August 1, 2023. Eligible studies were RCTs comparing the effects of exercise and non-exercise on office, home, or ambulatory blood pressure (BP) in hypertensive patients aged 18 years or older. A random effects model meta-analysis was performed to estimate the effect size across multiple studies. A sub-analysis determined outcomes by the type of exercise (aerobic exercise, dynamic resistance exercise, isometric resistance exercise, and combined exercise). Eighty-four RCTs with 5065 hypertensive patients were included in the study. All exercise significantly reduced systolic BP (SBP) and diastolic BP (DBP) compared to non-exercise (SBP:-7.52 mmHg, 95% confidence interval [CI] -8.77 to -6.27, p < 0.001; DBP: -4.36 mmHg, 95% CI - 5.15 to -3.57, p < 0.001). There were no significant differences in the magnitude of the reduction in BP between the types of exercise (p for interaction = 0.815 for SBP, p = 0.417 for DBP). These data from 84 RCTs showed that exercise intervention significantly reduced BP and that resistance exercise has a similar antihypertensive effect to aerobic exercise in hypertensive patients. This meta-analysis showed that exercise significantly reduced blood pressure in hypertensive patients. There were no significant differences in the magnitude of this reduction in BP between the types of exercise., Competing Interests: Compliance with ethical standards. Conflict of interest: KO has received grants from Otsuka Holdings. KN has received honoraria from AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma and, Novo Nordisk Pharma, Otsuka, research grants from Astellas, Bayer Yakuhin, Boehringer Ingelheim Japan, Fuji Yakuhin, Mochida Pharmaceutical, and Novartis Pharma, and scholarships from Abbott Medical, Boehringer Ingelheim Japan, Daiichi Sankyo Healthcare, Mitsubishi Tanabe Pharma, and Teijin Pharma. SM has received honoraria from Daiichi Sankyo, Otsuka Pharma. and Novartis Pharma, scholarships from Abbott Medical and Sumitomo Pharma, and research grants from AMGEN, Bayer Yakuhin, Novo Nordisk Pharma, and MSD., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Alzheimer's disease (AD) is associated with impairments in not only memory but also visuospatial cognitive function. Despite its adverse effects on the quality of life, patients with early-stage AD are often neglected. Emerging evidence suggests that patients with AD exhibit increased vulnerability of myelin, a crucial component for neuronal conduction and survival. To test our hypothesis that myelin damage was associated with cognitive deficits in AD, we examined correlations of myelin integrity, quantified by T1-weighted/T2-weighted (T1w/T2w) ratios, with visuospatial cognitive abilities and compared them between patients with AD and cognitively normal (CN) individuals., Methods: Fifty-seven patients with AD and 22 CN subjects were enrolled in this study. To assess subjects' visuo-constructive abilities, we employed the Rey-Osterrieth Complex Figure Copy Test (ROCFT-c) paired with analysis of T1- and T2-weighted magnetic resonance imaging brain images. Voxel-based associations between T1w/T2w ratios and ROCFT-c scores in the AD group were assessed, controlling for age and handedness (voxel threshold uncorrected P < 0.001, cluster threshold uncorrected P < 0.05). Additionally, we compared the T1w/T2w ratios of these identified brain regions between the AD and CN groups., Results: The voxel-based analysis demonstrated positive correlations between T1w/T2w ratios and ROCFT-c scores in the right middle temporal gyrus and right praecuneus in patients with AD who exhibited significantly lower T1w/T2w ratios in the right middle temporal gyrus (P = 0.038) and a trend toward lower T1w/T2w ratios in the right praecuneus (P = 0.055)., Conclusions: Our results demonstrated a strong association between reduced myelin integrity in the right middle temporal gyrus and right praecuneus and visuospatial cognitive dysfunction in patients with AD. These findings are believed to shed light on the neural basis of visuospatial processing in patients with AD, underlining the necessity for developing objective biomarkers for assessing patients' visuospatial cognitive function., (© 2024 Japanese Psychogeriatric Society.)

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.)

Hypertension that develops during early pregnancy has several causes. However, there have been no reported cases of full-term delivery, particularly when it is caused by renin-secreting renal tumors. We present the case of a 28-year-old pregnant patient who delivered with a renin-secreting renal tumor and provide a literature search of similar cases. A patient with no history of hypertension was referred to our hospital for severe hypertension during early pregnancy and was admitted for antihypertensive and aspirin therapy. The renin level of the patient was abnormally high, and a renal tumor was detected in the right kidney. Robot-assisted partial nephrectomy was performed at 16 weeks of gestation, after which antihypertensive medication was discontinued because hypertension was not observed. The pregnancy progressed favorably, leading to an uncomplicated delivery of a healthy baby at 40 weeks of gestation. The successful treatment of our patient can be attributed to three key factors: early hospitalization for strict blood pressure control, aspirin administration, and prompt diagnosis and treatment. Medication and thorough investigation of secondary hypertension are crucial in pregnant women with hypertension., Competing Interests: Human subjects: Consent for treatment and open access publication 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, Tamura et al.)

The pathophysiology of laryngopharyngeal reflux (LPR) and its impact on the vocal fold is not well understood, but may involve acid damage to vocal fold barrier functions. Two different components encompass vocal fold barrier function: the mucus barrier and tight junctions. Mucus retained on epithelial microprojections protects the inside of the vocal fold by neutralizing acidic damage. Tight junctions control permeability between cells. Here we developed an in vitro experimental system to evaluate acidic injury and repair of vocal fold barrier functions. We first established an in vitro model of rat vocal fold epithelium that could survive at least one week after barrier function maturation. The model enabled repeated evaluation of the course of vocal fold repair processes. Then, an injury experiment was conducted in which vocal fold cells were exposed to a 5-min treatment with acidic pepsin that injured tight junctions and cell surface microprojections. Both of them healed within one day of injury. Comparing vocal fold cells treated with acid alone with cells treated with acidic pepsin showed that acidic pepsin had a stronger effect on intercellular permeability than acid alone, whereas pepsin had little effect on microprojections. This result suggests that the proteolytic action of pepsin has a larger effect on protein-based tight junctions than on phospholipids in microprojections. This experimental system could contribute to a better understanding of vocal fold repair processes after chemical or physical injuries, as well as voice problems due to LPR pathogenesis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masanobu Mizuta, Ichiro Tateya reports financial support was provided by Japan Society for the Promotion of Science. If there are other authors, they 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.)

Background: When the initial rhythm of cardiac arrest is non-shockable, resuscitation outcomes tend to be unfavorable. However, signs of life (gasping, pupillary light reaction, or any form of body movement) have been suggested as favorable prognostic factors for patients with refractory cardiac arrest who are undergoing extracorporeal cardiopulmonary resuscitation (ECPR). This study determined whether signs of life are favorable neurological prognostic factors for patients undergoing ECPR post non-shockable cardiac arrest., Methods and Results: This single-center retrospective study included 227 refractory out-of-hospital cardiac-arrest patients who had undergone ECPR, divided into four groups according to shockability of initial cardiac rhythms and presence of signs of life. Initial cardiac rhythms were shockable in 154 patients (67.8 %) and non-shockable in 73 (32.2). Favorable neurological outcomes were observed in 4.1 %, 48.2 %, 0.0 %, and 38.7 % of patients with shockable rhythm without signs of life, shockable rhythm with signs of life, non-shockable rhythm without signs of life, and non-shockable rhythm with signs of life, respectively, with significant differences. Multivariate logistic regression analysis showed an independent association of signs of life during resuscitation with favorable neurological outcomes. The adjusted odds ratios for patients with shockable and non-shockable rhythm with signs of life were 34.33 and 96.51, respectively, compared with those without signs of life., Conclusions: Signs of life during resuscitation were favorable prognostic factors in patients with refractory cardiac arrest and non-shockable rhythm. When these patients are considered for ECPR, the status of signs of life during resuscitation may facilitate the decision to perform ECPR., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study aimed to investigate the utility of neutrophil-related cell population data obtained by automated hematology analyzers in assessing myelodysplastic syndrome cases with decreased granules in neutrophils., Methods: A total of 108 subjects were classified into normal granule (n = 35), hypogranulation (n = 37), or hypergranulation (n = 36) groups. Neutrophil cell area and granule area were measured by ImageJ. All samples were analyzed on the XR-1000 and UniCel DxH 800, and neutrophil-related parameters were compared among the 3 groups., Results: Neutrophil cell area and the ratio of the granular area showed significant differences among the 3 groups; they were the highest in the hypergranulation group and lowest in the hypogranulation group. XR-1000 data showed significant differences in NE-SFL and NE-FSC among the 3 groups (P < .0001). NE-SFL and NE-FSC discriminated most accurately hypogranulation group against other groups. UniCel DxH 800 data showed significant differences in MN-V-NE, MN-MALS-N, MN-UMALS-NE, SD-UMALS-NE (P <.01), MN-LMALS-NE, and SD-LMALS-NE (P <.05) among the 3 groups. The combination of SD-V-NE and SD-LMALS-NE discriminated most accurately the hypogranulation group against the other groups., Conclusion: NE-SFL and NE-FSC and the combination of SD-V-NE and SD-LMALS-NE are useful in detecting cases with decreased granules in neutrophils., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Although hypertension is a major cause of cardiovascular disease, the control of blood pressure (BP) is insufficient worldwide. Exercise is an effective treatment for reducing BP, but the differences in the blood pressure lowering effects of exercise according to the underlying pathophysiological condition, the type of exercise, and the geographic region are not fully understood. An umbrella review with a meta-analysis of 435 randomized controlled trials that investigated the BP-lowering effects of exercise was performed using Ovid MEDLINE and the Cochrane Library, covering the period from inception to August 1, 2023. A random effects model meta-analysis was performed to estimate the effect size across multiple studies. Exercise significantly reduced systolic BP in healthy subjects (-3.51 mmHg, 95% confidence interval: -3.90, -3.11; p < 0.001) and in those with lifestyle-related diseases including hypertension (-5.48 mmHg, -6.51, -4.45; p < 0.001), but not in those with cardiovascular diseases (-1.16 mmHg, -4.08, 1.76; p = 0.44). According to the type of exercise, all types significantly reduced systolic BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases. According to the region, in Oceania, there were no reductions in systolic BP. In Asia, systolic BP was reduced in patients with cardiovascular diseases. In conclusion, any type of exercise reduced BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases, and the region affected the effect of exercise. When using exercise to reduce hypertension, it is important to consider the patient's pathophysiological condition and the region., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The efficacy and safety of mucolytics in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis or exacerbations of COPD have been reported. We conducted a systematic review and meta-analysis of mucolytics in patients with stable COPD., Methods: Reports from randomized controlled trials to evaluate the efficacy and safety of mucolytics, including ambroxol, bromhexine, carbocisteine, erdosteine, fudosteine, l-methylcysteine, and N-acetylcysteine used in patients with stable COPD were searched for in PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and the Igaku Cyuo Zasshi database., Results: Twenty-three reports with ambroxol, carbocisteine, erdosteine, l-methylcysteine, or N-acetylcysteine were included in the review. Mucolytics significantly reduced the rates of exacerbation and hospitalization, shortened the duration of antibiotic use and exacerbations, prolonged the time to first exacerbation, and had a tendency to reduce the occurrence of two or more exacerbations in patients with stable COPD compared to placebo. Mucolytics did not improve mortality, number of lost workdays, scores on St. George's respiratory questionnaire, forced expiratory volume in 1 s, or forced vital capacity. The safety profile of mucolytics was comparable to that of placebo., Conclusions: Mucolytics reduce exacerbations and hospitalizations in patients with stable COPD and have a safety profile comparable to that of placebo., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs)., Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction. Subsequently, DBS samples from 43 IEI patients were analyzed to determine whether patients can be identified by reduced expression of disease-associated proteins., Results: DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1110 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with IEIs by detecting reduced levels of disease causative proteins and their interacting proteins, as well as cell-phenotypical alterations., Conclusion: Our results indicate that non-targeted quantitative protein profiling of DBS samples can be used to identify patients with IEIs and develop a novel newborn screening platform for genetic disorders., (© 2024. The Author(s).)

Brachytherapy (BT), especially in high dose rate (HDR), has become increasingly complex owing to the use of image-guided techniques and the introduction of advanced applicators. Consequently, radiotherapy technologists and medical physicists (RTMPs) require substantial training to enhance their knowledge and technical skills in image-guided brachytherapy. However, the current status of the RTMP workload, individual abilities and quality control (QC) of BT units in Japan remains unclear. To address this issue, we conducted a questionnaire survey from June to August 2022 in all 837 radiation treatment facilities in Japan involving RTMPs. This survey focused on gynecological cancers treated with HDR-BT (GY-HDR) and permanent prostate implantation using low-dose-rate BT (PR-LDR). The responses revealed that the average working time in the overall process for HDR varied: 120 min for intracavitary BT and 180 min for intracavitary BT combined with interstitial BT. The QC implementation rate, in accordance with domestic guidelines, was 65% for GY-HDR and 44% for PR-LDR, which was lower than the 69% observed for external beam radiation therapy (EBRT). Additionally, the implementation rate during regular working hours was low. Even among RTMP working in facilities performing BT, the proportion of those able to perform QC for BT units was ~30% for GY-HDR and <20% for PR-LDR, significantly lower than the 80% achieved for EBRT. This study highlights the vulnerabilities of Japan's BT unit QC implementation structure. Addressing these issues requires appropriate training of the RTMP staff to safely perform BT tasks and improvements in practical education and training systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Oral food challenge tests are considered the reference standard for diagnosing food allergies; however, studies on their real-world implementation rates are limited., Objective: The study aimed to investigate the proportion of school-age children who underwent the oral food challenge test and to understand the motivations behind food elimination and utilization of various health care services., Methods: The questionnaire-based survey for the parents of the students who submitted the "Certificate for School Life Management (For Allergic Diseases)" was conducted across public elementary and junior high schools in Gifu prefecture, Japan., Results: The study encompassed parents of 3457 children with food allergies who submitted the certificate. Approximately one third of those eliminating the 3 major allergens-eggs (32.5%), milk (27.6%), and wheat (33.5%)-were diagnosed via oral food challenge tests, and approximately two thirds were diagnosed using a combination of symptoms and blood tests, suggesting most children were diagnosed appropriately. However, many children were diagnosed and eliminated foods based solely on blood tests without any symptoms of other allergens, such as buckwheat (55.8%), peanuts (29.2%), and tree nuts (21.2%), suggesting that it was likely that these children unnecessarily eliminated foods. Elimination of buckwheat because of anxiety was associated with eliminating other foods for the same reason and with eliminating 2 or more foods., Conclusion: Examination of the real-world application of the proposed recommendations for the accurate diagnosis of food allergies suggests that closely monitoring their practical application should be conducted in each case to avoid unnecessary food elimination from children's diets., Competing Interests: Commissioned by Gifu prefecture. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Students with developmental disabilities are anxious about a change in environment when graduating from high school to college. Existing research, which is scarce, focuses on the mental health status of students with developmental disabilities entering university. This study investigated the frequency of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) among first-year Japanese university students and their mental health risks post-admission. We conducted a cross-sectional survey for university students within a month of admission, using the Autism Spectrum Quotient (AQ) and Adult ADHD Test (A-ADHD) to demonstrate the frequency of ASD and ADHD. The Counseling Center Assessment of Psychological Symptoms (CCAPS)-Japanese (depression, eating concerns, hostility, social anxiety, family distress, alcohol use, generalized anxiety, and academic distress) evaluated their mental health condition.Of 711 students (20.3 ± 2.1 years; 330 male, 381 female), the number of those showing either ASD or ADHD tendencies was 61 (8.58%). Twenty-three (3.23%) showed symptoms of only ASD, 34 (4.78%) of ADHD, and four (0.56%) of ASD and ADHD. No significant differences existed in the frequency of ASD and ADHD between each sex and major. The scores and frequency of high risk (over the cut-off points) students on all CCAPS-Japanese subscales (except alcohol use) were significantly higher among the ASD and ADHD groups than the control group, which showed no ASD or ADHD tendencies. The frequency of ASD and ADHD characteristics among first-year Japanese university students was 8.58%. They have a high risk of mental health problems when they enter university., (© 2024. The Author(s).)

Background: Systemic hypertension (HT) is associated with the development of increased intraocular pressure (IOP), a risk factor for glaucoma. However, it remains unclear whether high IOP is a risk factor for HT.Methods and Results: We investigated 7,487 Japanese individuals (4,714 men, 2,773 women; mean [±SD] age 49±9 years) who underwent annual health checkups in 2006. Over the 10-year follow-up period, 1,232 (24.3%) men and 370 (11.5%) women developed new-onset HT, defined as initiation of antihypertensive drug treatment or blood pressure ≥140/90 mmHg. After dividing IOP into tertiles (T1-T3), Cox proportional hazards analysis (adjusted for age, sex, systolic blood pressure, obesity, current smoking, alcohol consumption, family history of HT, estimated glomerular filtration rate, and diabetes and dyslipidemia diagnoses at baseline) revealed a significantly higher risk of newly developed HT in T3 (IOP ≥14 mmHg; hazard ratio 1.14; 95% confidence interval 1.01-1.29; P=0.038) using T1 (IOP ≤11 mmHg) as the reference group. There was no significant interaction between sex and IOP tertile (P=0.153). A restricted cubic spline model showed a gradual but robust increase in the hazard ratio for new-onset HT with increasing IOP., Conclusions: High IOP is an independent risk factor for the development of HT over a 10-year period.

Background: The 3Rs (Reduction, Refinement, Replacement) principle is driving the need for alternative methods in animal testing. Despite advancements in in vitro testing, complex systemic toxicity tests still necessitate in vivo approaches. The aim of this study was to develop a developmental toxicity test protocol using the Iberian ribbed newt ( Pleurodeles waltl ) as a model organism, integrating AI image analysis for embryo selection to improve test accuracy and reproducibility., Methods: We established a developmental toxicity test protocol based on the zebrafish test. Gonadotropin was administered to induce ovulation, and in vitro fertilization was performed. Embryos were imaged at 5-6 and 6-7 h post-fertilization. AI image analysis was utilized to assess embryo viability. The test chemical was administered 24-48 h post-fertilization, and morphological changes were observed daily until day 8. Additionally, a time-lapse photography system was constructed to monitor embryonic development., Results: Out of 24 cultured embryos, 75% developed normally to the late tail bud stage or initial hatching stage, whereas 25% experienced developmental arrest or death. AI image analysis achieved high accuracy in classifying embryos, with overall accuracies of 92.0% and 92.9% for two learning models. The AI system demonstrated higher precision in the selection of viable embryos compared to visual inspection., Conclusion: The Iberian ribbed newt presents a viable alternative model for developmental toxicity testing, adhering to the 3Rs principles. The integration of AI image analysis substantially enhances the accuracy and reproducibility of embryo selection, providing a reliable method for evaluating developmental toxicity in pharmaceuticals., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

Generalized lymphatic anomaly (GLA) and kaposiform lymphangiomatosis (KLA) are rare congenital disorders that arise through anomalous embryogenesis of the lymphatic system. A somatic activating NRAS p.Q61R variant has been recently detected in GLA and KLA tissues, suggesting that the NRAS p.Q61R variant plays an important role in the development of these diseases. To address this role, we studied the effect of the NRAS p.Q61R variant in lymphatic endothelial cells (LECs) on the structure of the lymphatics during embryonic and postnatal lymphangiogenesis applying inducible, LEC-specific NRAS p.Q61R variant in mice. Lox-stop-Lox NrasQ61R mice were crossed with Prox1-CreERT2 mice expressing tamoxifen-inducible Cre recombinase specifically in LECs. Whole-mount immunostaining of embryonic back skin using an antibody against the LEC surface marker VEGFR3 showed considerably greater lymphatic vessel width in LEC-specific NRAS p.Q61R mutant embryos than in littermate controls. These mutant embryos also showed a significant reduction in the number of lymphatic vessel branches. Furthermore, immunofluorescence staining of whole-mount embryonic back skin using an antibody against the LEC-specific nuclear marker Prox1 showed a large increase in the number of LECs in LEC-specific NRAS p.Q61R mutants. In contrast, postnatal induction of the NRAS p.Q61R variant in LECs did not cause abnormal lymphatic vessel morphogenesis. These results suggest that the NRAS p.Q61R variant in LECs plays a role in development of lymphatic anomalies. While this model does not directly reflect the human pathology of GLA and KLA, there are overlapping features, suggesting that further study of this model may help in studying GLA and KLA mechanisms., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

When Epstein-Barr virus (EBV) infection is suspected, identification of infected cells is important to understand the pathogenesis, determinine the treatment strategy, and predict the prognosis. We used the PrimeFlow™ RNA Assay Kit with a probe to detect EBV-encoded small RNAs (EBERs) and multiple surface markers, to identify EBV-infected cells by flow cytometry. We analyzed a total of 24 patients [11 with chronic active EBV disease (CAEBV), 3 with hydroa vacciniforme lymphoproliferative disorder, 2 with X-linked lymphoproliferative disease type 1 (XLP1), 2 with EBV-associated hemophagocytic lymphohistiocytosis, and 6 with posttransplant lymphoproliferative disorder (PTLD)]. We compared infected cells using conventional quantitative PCR methods and confirmed that infected cell types were identical in most patients. Patients with CAEBV had widespread infection in T and NK cells, but a small amount of B cells were also infected, and infection in patients with XLP1 and PTLD was not limited to B cells. EBV-associated diseases are believed to be complex pathologies caused by EBV infecting a variety of cells other than B cells. We also demonstrated that infected cells were positive for HLA-DR in patients with CAEBV. EBER flow FISH can identify EBV-infected cells with high sensitivity and is useful for elucidating the pathogenesis., (© 2024. Japanese Society of Hematology.)

Objectives: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome., Methods: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median age of onset 69.3 years (interquartile range 62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR or targeted amplicon deep sequencing was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and -negative patients and assessed the diagnostic value of our system using receiver operating characteristics (ROC) curve analysis., Results: Forty patients (44.9%) with reported pathogenic UBA1 variants were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering age >50 years, cutaneous lesions, lung involvement, chondritis and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908)., Conclusion: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tracheal cartilage provides structural support to the airways to enable breathing. However, it can become damaged or impaired, sometimes requiring surgical resection and reconstruction. Previously, we clinically applied an artificial trachea composed of a polypropylene mesh and collagen sponge, with a favorable postoperative course. However, the artificial trachea presents a limitation, as the mesh is not biodegradable and cannot be used in pediatric patients. Compared to a polypropylene mesh, regenerated cartilage represents an ideal material for reconstruction of the damaged trachea. The use of mesenchymal stem cells (MSCs) as a source for cartilage regeneration has gained widespread acceptance, but challenges such as the invasiveness of harvesting and limited cell supply persist. Therefore, we focused on the potential of human-induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) for tracheal cartilage regeneration. In this study, we aimed to regenerate tracheal cartilage on an artificial trachea as a preliminary step to replace the polypropylene mesh. iMSCs were induced from hiPSCs through neural crest cells and transplanted with a polypropylene mesh covered with a collagen sponge into the damaged tracheal cartilage in immunodeficient rats. Human nuclear antigen (HNA)-positive cells were observed in all six rats at 4 weeks and in six out of seven rats at 12 weeks after transplantation, indicating that transplanted iMSCs survived within the tracheal cartilage defects of rats. The HNA-positive cells coexpressed SOX9, and type II collagen was detected around HNA-positive cells in four of six rats at 4 weeks and in three of seven rats at 12 weeks after transplantation, reflecting cartilage-like tissue regeneration. These results indicate that the transplanted iMSCs could differentiate into chondrogenic cells and promote tracheal cartilage regeneration. iMSC transplantation thus represents a promising approach for human tracheal reconstruction.

Purpose: Transcription factor 3 (TCF3) encodes 2 transcription factors generated by alternative splicing, E12 and E47, which contribute to early lymphocyte differentiation. In humans, autosomal dominant (AD) E47 transcription factor deficiency is an inborn error of immunity characterized by B-cell deficiency and agammaglobulinemia. Only the recurrent de novo p.E555K pathogenic variant has been associated with this disease and acts via a dominant-negative (DN) mechanism. In this study, we describe the first Asian patient with agammaglobulinemia caused by the TCF3 p.E555K variant and provide insights into the structure and function of this variant., Methods: TCF3 variant was identified by inborn errors of immunity-related gene panel sequencing. The variant E555K was characterized by alanine scanning of the E47 basic region and comprehensive mutational analysis focused on position 555., Results: The patient was a 25-year-old male with B-cell deficiency, agammaglobulinemia, and mild facial dysmorphic features. We confirmed the diagnosis of AD E47 transcription factor deficiency by identifying a heterozygous missense variant, c.1663 G>A; p.E555K, in TCF3. Alanine scanning of the E47 basic region revealed the structural importance of position 555. Comprehensive mutational analysis focused on position 555 showed that only the glutamate-to-lysine substitution had a strong DN effect. 3D modeling demonstrated that this variant not only abolished hydrogen bonds involved in protein‒DNA interactions, but also inverted the charge on the surface of the E47 protein., Conclusions: Our study reveals the causative mutation hotspot in the TCF3 DN variant and highlights the weak negative selection associated with the TCF3 gene., (© 2024. The Author(s).)

Background and Objectives : Osteoporotic vertebral fractures in older patients cause lower back pain and abnormal posture, resulting in impaired activities of daily living (ADLs). Assessing pain using self-reported assessment tools is difficult, especially in patients with moderate-to-severe cognitive impairment. Recently, observational assessment tools have been used when self-reported ones were difficult to administer. No studies have reported the usefulness of observational assessment tools in patients with acute-phase orthopedic disorders without complication. This study aimed to examine the availability of observational tools for pain assessment in patients with lumbar vertebral fractures. Materials and Methods : Patients admitted to our hospital with acute-phase vertebral fractures were enrolled in this prospective observational study. Pain was assessed using Japanese versions of the Abbey pain scale and Doloplus-2 observational assessment tools, and the Numerical Rating Scale, a self-reported assessment tool. To compare the pain assessment tool, we examined whether each tool correlated with ADLs and ambulatory status. ADLs were assessed using the Barthel Index. Ambulatory status was assessed using the Functional Ambulation Categories and the 10-m walking test. Results : Similar to the Numerical Rating Scale scores, assessments with the Abbey pain scale and Doloplus-2 showed significant decreases in scores over time. A significant positive correlation was observed between the self-reported and observational assessment tools. Each pain assessment tool was significantly negatively correlated with ADLs and ambulatory status. Conclusions : When self-reported assessment with the Numerical Rating Scale is difficult for patients with cognitive impairment, pain can be estimated using the Abbey pain scale and Doloplus-2 observational assessment tools.

Background: Hand washing instructions for children have been implemented in school education to establish good lifestyle habits. However, repeated hand washing through education from early childhood was common for both teachers and children. If this continues, children might assume they already know how to wash their hands, stop taking handwashing instructions seriously, and become increasingly lax about washing their hands., Purpose: This study aimed to develop a new handwashing education method for children., Methods: We applied the adenosine triphosphate (ATP) test to health education on hand washing in elementary schools. This study was conducted as part of a class for elementary school students in October 2023, in Hokkaido, Japan. The subjects were 157 third-grade (9-10 years old) elementary school students. After excluding absent pupils, 147 were included in the analysis., Results: Both pre- and post-education, ATP values after handwashing were lower than those before handwashing. Following the education, children's handwashing behavior improved, with an increase in the number of point washed and appropriate timing of handwashing., Conclusion: The new handwashing education program utilizing the ATP-test succeeded in promoting handwashing behavior among many children. Visualizing handwashing using ATP values was effective in motivating children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oura, Naito, Yako-Suketomo, Nakata, Koyama and Ohnishi.)

Background: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma., Methods: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides., Results: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo., Conclusions: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

The differential diagnosis of a lung mass with multiple pulmonary nodules includes metastases of lung cancer, mycobacterial infections, and pulmonary mycosis. Pulmonary cryptococcosis should be recognized, especially in immunocompromised patients., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Background: Falls among older individuals contribute significantly to the rise in ambulance transport use. To recognize the importance of future countermeasures, we estimated the projected number and percentage of fall-related emergency medical service (EMS) calls., Methods: We examined the sex, age group, and location of falls among patients aged ≥ 65 years who contacted emergency services in Sapporo City from 2013 to 2021. Annual fall-related calls per population subgroup were calculated, and trends were analyzed. Four models were used to estimate the future number of fall-related calls from the 2025-2060 projected population: (1) based on the 2022 data, estimates from the 2013-2022 data using (2) Poisson progression, (3) neural network, (4) estimates from the 2013-2019 data using neural network. The number of all EMS calls was also determined using the same method to obtain the ratio of all EMS calls., Results: During 2013-2022, 70,262 fall-related calls were made for those aged ≥ 65 years. The rate was higher indoors among females and outdoor among males in most age groups and generally increased with age. After adjusting for age, the rate increased by year. Future estimates of the number of fall calls are approximately double the number in 2022 in 2040 and three times in 2060, with falls accounting for approximately 11% and 13% of all EMS calls in 2040 and 2060, respectively., Conclusion: The number of fall-related EMS calls among older people is expected to increase in the future, and the percentage of EMS calls will also increase; therefore, countermeasures are urgently needed., (© 2024. The Author(s).)

Background: Subacute myelo-optico-neuropathy (SMON) is a neurological disorder associated with the administration of clioquinol, particularly at very high doses. Although clioquinol has been used worldwide, there was an outbreak of SMON in the 1950s-1970s in which the majority of cases were in Japan, prompting speculation that the unique genetic background of the Japanese population may have contributed to the development of SMON. Recently, a possible association between loss-of-function polymorphisms in NQO1 and the development of SMON has been reported. In this study, we analyzed the relationship between NQO1 polymorphisms and SMON in Japan., Methods: We analyzed 125 Japanese patients with SMON. NQO1 loss-of-function polymorphisms (rs1800566, rs10517, rs689452, and rs689456) were evaluated. The allele frequency distribution of each polymorphism was compared between the patients and the healthy Japanese individuals (Human Genomic Variation Database and Integrative Japanese Genome Variation Database), as well as our in-house healthy controls., Results: The frequencies of the loss-of-function NQO1 alleles in patients with SMON and the normal control group did not differ significantly., Conclusion: We conclude that known NQO1 polymorphisms are not associated with the development of SMON., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

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.)

Objective: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab., Methods: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed., Results: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy., Conclusion: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment., (© 2024 American College of Rheumatology.)

Aim: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. A method for estimating sdLDL-C by using Sampson's equation that includes levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides (TG) has recently been proposed. We investigated the validation and exploration of estimated sdLDL-C level., Methods: The associations between measured and estimated sdLDL-C levels were investigated in 605 Japanese subjects (men/women: 280/325; mean age: 65±15 years) who received annual health check-ups in the Tanno-Sobetsu Study, a population-based cohort., Results: Estimated sdLDL-C level was highly correlated with measured sdLDL-C level in all subjects (R 2 =0.701), nondiabetic subjects without any medication (n=254, R 2 =0.686) and subjects with diabetes mellitus (n=128, R 2 =0.721). Multivariable regression analysis showed that levels of non-HDL-C, TG and γ-glutamyl transpeptidase (γGTP) were independent predictors of measured sdLDL-C level. In a stratification of the LDL window, all of the subjects with a combination of high non-HDL-C (≥ 170 mg/dL) and high TG (≥ 150 mg/dL) had high levels of measured and estimated sdLDL-C (≥ 35 mg/dL). Furthermore, machine learning-based estimation of sdLDL-C level by artificial intelligence software, Prediction One, was substantially improved by using components of Sampson's equation (R 2 =0.803) and by using those components with the addition of γGTP and deletion of TC (R 2 =0.929)., Conclusions: sdLDL-C level estimated by Sampson's equation can be used instead of measured sdLDL-C level in general practice. By building multiple machine learning models of artificial intelligence, a more accurate and practical estimation of sdLDL-C level might be possible.

Objective: Spine surgeons are often at risk of radiation exposure due to intraoperative fluoroscopy, leading to health concerns such as carcinogenesis. This is due to the increasing use of percutaneous pedicle screw (PPS) in spinal surgeries, resulting from the widespread adoption of minimally invasive spine stabilization. This study aimed to elucidate the effectiveness of smart glasses (SG) in PPS insertion under fluoroscopy., Methods: SG were used as an alternative screen for fluoroscopic images. Operators A (2-year experience in spine surgery) and B (9-year experience) inserted the PPS into the bilateral L1-5 pedicles of the lumbar model bone under fluoroscopic guidance, repeating this procedure twice with and without SG (groups SG and N-SG, respectively). Each vertebral body's insertion time, radiation dose, and radiation exposure time were measured, and the deviation in screw trajectories was evaluated., Results: The groups SG and N-SG showed no significant difference in insertion time for the overall procedure and each operator. However, group SG had a significantly shorter radiation exposure time than group N-SG for the overall procedure (109.1 ± 43.5 seconds vs. 150.9 ± 38.7 seconds; p = 0.003) and operator A (100.0 ± 29.0 seconds vs. 157.9 ± 42.8 seconds; p = 0.003). The radiation dose was also significantly lower in group SG than in group N-SG for the overall procedure (1.3 ± 0.6 mGy vs. 1.7 ± 0.5 mGy; p = 0.023) and operator A (1.2 ± 0.4 mGy vs. 1.8 ± 0.5 mGy; p = 0.013). The 2 groups showed no significant difference in screw deviation., Conclusion: The application of SG in fluoroscopic imaging for PPS insertion holds potential as a useful method for reducing radiation exposure.

Purpose: The aim of this study was to apply the break-even point concept to express the dynamics of bone formation and resorption around implants., Methods: Published data on new bone and parent bone densities around implants from one human and three dog studies were selected and used for analysis. The break-even point (BEP) of the bone density (BD) was assessed. The BEP is the point at which, in a graph, the lines representing the formation of new bone and resorption of old bone intersect. BEP is expressed in time (x; days) of occurrence and percentage of bone (y; %) at which the break-even point occurs and illustrates the grade of bone modeling. The sooner the occurrence, the faster the bone formation in relation to the resorption of the old bone., Results: In the marrow and cortical compartments, BEP of bone density occurred after 7.9 days (BD% 24.5%) and >30 days, respectively. Different surfaces presented similar BEP, ranging between 9.7 and 11.2 days (BD% 19.1-22.5%). BEP at implants installed in the human maxilla occurred after 29-30.4 days (BD% 28.3-29.6%)., Conclusion: The present study showed that the parameters used to express the break-even point can provide information on the influence of the model used, surface characteristics, and bone quality on bone modeling/remodeling around implants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A population pharmacokinetic (PopPK) analysis was conducted using data from 215 Japanese administered oral sirolimus (tablet and granule) including healthy subjects and patients with intractable vascular anomalies and other diseases. The analysis included neonates, infants, and adults, and identified covariates that influence sirolimus pharmacokinetics (PK). The final model was used to predict sirolimus trough concentrations for various dosing regimens and covariates of interest. The results showed that sirolimus trough concentrations were predicted to increase with higher levels of hemoglobin, and that the granule formulation had a 1.23-fold higher exposure than the tablet formulation. Coadministration of CYP3A4 inducers was found to decrease trough concentrations by 54 %. The PK simulations showed that administration of the granule formulation at doses of 0.02, 0.04, 0.06, and 0.08 mg/kg/day in ages <3 months, 3 to <6 months, 6 to <12 months, and ≥1 year, respectively, resulted in >70 % target attainment within the therapeutic trough concentration range (5-15 ng/mL). In conclusion, incorporation of time-varying covariates (body weight and age) into the PopPK model appropriately predicted sirolimus concentrations in Japanese subjects from infants to adult sub-populations. This PopPK model would therefore be able to provide a reference for clinical individualization of sirolimus dosing., (Copyright © 2024. Published by Elsevier Ltd.)