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Thermal plasticity of melanin pigmentation patterns in Drosophila species has been studied as a model to investigate developmental mechanisms of phenotypic plasticity. The developmental process of melanin pigmentation patterns on wings of Drosophila is divided into two parts, prepattern specification during the pupal period and wing vein-dependent transportation of melanin precursors after eclosion. Which part can be affected by thermal changes? To address this question, we used polka-dotted melanin spots on wings of Drosophila guttifera, whose spot areas are specified by wingless morphogen. In this research, we reared D. guttifera at different temperatures to test whether wing spots show thermal plasticity. We found that wing size becomes larger at lower temperature and that different spots have different reaction norms. Furthermore, we changed the rearing temperature in the middle of the pupal period and found that the most sensitive developmental periods for wing size and spot size are different. The results suggest that the size control mechanisms for the thermal plasticity of wing size and spot size are independent. We also found that the most sensitive stage for spot size was part of the pupal period including stages at which wingless is expressed in the polka-dotted pattern. Therefore, it is suggested that temperature change might affect the prepattern specification process and might not affect transportation through wing veins.

Abstract Background It is unclear whether hepatectomy, which ranges in invasiveness from partial to major hepatectomy, is safe and feasible for older adult patients. Therefore, we compared its postoperative complications and long-term outcomes between younger and older adult patients. Methods Patients who underwent hepatectomies for hepatocellular carcinoma (N = 883) were evaluated. Patients were divided into two groups: aged

Abstract Background Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples. Methods We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC). Results We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p

Abstract Background Anastomotic leakage after esophagectomy is a common complication. Laser Doppler flowmetry (LDF) can quantitatively evaluate the blood flow in the gastric conduit. Methods A total of 326 patients who underwent thoracoscopic/robot‐assisted esophagectomy followed by gastric conduit reconstruction and end‐to‐side anastomosis were enrolled. We divided the gastric conduit into zones I (dominated by the right gastroepiploic vessels), II (dominated by the left gastroepiploic vessels), and III (perfused with short gastric vessels). Before pulling up the gastric conduit to the neck, LDF values were measured at the pylorus, the border between zones I and II (zone I/II), the border between zones II and III (zone II/III), and the gastric conduit tip (tip). The blood flow ratio was calculated as the LDF value divided by the LDF value at the pylorus. Results Anastomotic leakage developed in 32 of 326 patients. Leakage was significantly associated with the blood flow ratio at the tip (p

Abstract Objective Managing the risk of epileptic seizures in older adults is increasingly important as the population ages. Leukotriene receptor antagonists (LTRAs) are commonly used to treat asthma or allergic rhinitis. Preclinical studies suggest that LTRAs have antiepileptic effects; however, few population‐based etiological studies on this topic have been available. Our study explored whether LTRAs reduce hospitalization risk associated with epileptic seizures in older individuals with asthma or allergic rhinitis. Methods We conducted a new‐user design analysis using the Shizuoka Kokuho database. We included all individuals aged 60‐89 years who had at least one episode of allergic rhinitis or asthma during the study period. We compared individuals who newly started LTRAs with those who did not take LTRAs. Propensity score matching was used to balance the baseline characteristics of the participants. We compared the hazard ratios for seizure‐related hospitalization between new LTRA users and non‐users and performed subgroup analyses. Results Our matched cohorts consisted of 64 724 new users and non‐users of LTRAs who were aged 60‐89 years and had asthma or allergic rhinitis. During the observation period, 377 (0.58%) and 595 (0.92%) incidents were observed in the LTRA new‐user and non‐user groups, respectively. The hazard ratio for seizure‐related hospitalization was 0.75 (95% confidence interval [CI]: 0.62‐0.92) in the LTRA new‐user group compared with the non‐user group. Subgroup analysis revealed that the hazard ratio was weak in diabetic patients (1.31; 95% CI: 0.72‐2.38). Significance This study indicated that LTRAs reduced seizure‐related hospitalization in older adult patients with allergic rhinitis or asthma. We could not evaluate the severity and related diseases of epileptic seizures during LTRAs. Further studies, including observational studies, detailed multicenter prospective studies, and clinical trials, are needed to validate these findings. Plain Language Summary This study examined if leukotriene receptor antagonists (LTRAs), commonly used for asthma or allergies, could lower seizure risk in older adults. Analyzing health records of 60‐89 year‐olds with asthma or allergies, we found a reduced rate of seizure‐related hospitalizations in those starting LTRAs, though this was not as evident in diabetic patients. Our results suggest potential benefits of LTRAs in preventing seizures in older adults with respiratory issues, but further research is needed to confirm these findings.

Abstract Background Plasmodium lacks an mRNA export receptor ortholog, such as yeast Mex67. Yeast Mex67 contains a nuclear transport factor 2 (NTF2)-like domain, suggesting that NTF2-like domain-containing proteins might be associated with mRNA export in Plasmodium. In this study, the relationship between mRNA export and an NTF2-like domain-containing protein, PBANKA_1019700, was investigated using the ANKA strain of rodent malaria parasite Plasmodium berghei. Methods The deletion mutant Δ1019700 was generated by introducing gene-targeting vectors into the P. berghei ANKA genome, and parasite growth and virulence were examined. To investigate whether PBANKA_1019700 is involved in mRNA export, live-cell fluorescence imaging and immunoprecipitation coupled to mass spectrometry (IP-MS) were performed using transgenic parasites expressing fusion proteins (1019700::mCherry). Results Deletion of PBANKA_1019700 affected the sexual phase but not the asexual phase of malaria parasites. Live-cell fluorescence imaging showed that PBANKA_1019700 localizes to the cytoplasm. Moreover, IP-MS analysis of 1019700::mCherry indicated that PBANKA_1019700 interacts with ubiquitin-related proteins but not nuclear proteins. Conclusions PBANKA_1019700 is a noncanonical NTF2-like superfamily protein.

A 53-year-old patient experienced 2 Anisakis-induced allergic episodes: the first with anaphylaxis, the second presenting with gastric symptoms and progressing to systemic anaphylaxis. The case could suggest a common pathophysiology involving allergic reactions in gastric anisakiasis and Anisakis allergy.

Summary: Syntaxin-1A (stx1a) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5-HT release in vitro. Furthermore, glucose-derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/−) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild-type mice. Finally, in wild-type and stx1a (−/−) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator-induced LI improvement is a direct consequence of KAT3B-stx1a pathway, not a side effect. In conclusion, KAT3B can positively regulate stx1a transcription in neurons, and increasing neuronal stx1a expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the stx1a ablation mouse model.

Many people are exposed every day to vehicle exhaust particulates (VEPs), which are thought to be taken up by epithelial cells that are the first barrier in our biological defense. The study aim was to investigate how VEPs are processed in the lysosomal degradation system. BEAS-2B airway epithelial cells easily ingest VEPs and have been shown to accumulate in cells for several days, but no elevated cytotoxicity was observed over that time period. An analysis of 3D images confirmed the presence of VEPs in or near lysosomes, and an accumulation of VEPs resulted in an increase in the normal acidic pH in lysosomes and the extracellular release of the lysosomal enzyme β-hexosaminidase. Epithelial cells were thought to activate the lysosome-mediated secretion of extracellular vesicles to avoid damage caused by non-degradable foreign substances, such as VEPs, and as a side reaction, the acidic pH environment of the lysosomes could not be maintained.

Background: Although paranasal sinuses are one of the most representative organs affected by eosinophilic granulomatosis with polyangiitis (EGPA), they have not been studied sufficiently. The aim of this study was to compare computed tomography (CT) findings in paranasal sinuses of EGPA with those of other eosinophilic sinus diseases and elucidate the clinical relevance of their severity. Methods: CT findings of paranasal sinuses in EGPA patients prior to therapeutic intervention (n = 30) were evaluated using the Lund–Mackay staging (LMS) system and compared with those of three control diseases [(NSAID-exacerbated respiratory disease (N-ERD), aspirin-tolerant asthma, and eosinophilic chronic rhinosinusitis without asthma (ECRS)]. We divided EGPA patients into three groups based on their LMS scores and examined their association with disease manifestation. Results: Total scores of the LMS system in EGPA were significantly lower than those of N-ERD and ECRS without asthma. There was a large variation in total LMS scores in EGPA, suggesting considerable heterogeneity of their sinus lesions. Although EGPA with low LMS system scores showed only minor findings in maxillary and anterior ethmoid regions, those with high LMS system scores were characterized by high scores in the ostiomeatal complex. However, the frequencies of patients with a Five-Factor Score ≥2 and with cardiac involvement were significantly higher for EGPA with low LMS system scores. Conclusions: Although paranasal sinus lesions in EGPA were less severe than those of other eosinophilic sinus diseases, their milder CT findings may be associated with a higher frequency of extra-respiratory organ involvement.

This study aimed to examine the chronic effect of a stair climbing–descending exercise (ST-EX) program on glycemic control in individuals with type 2 diabetes (T2D). Sixteen T2D participants were randomly divided into two groups and followed up over 12 weeks: they either performed regular ST-EX after meals at home (n = 8) or maintained their daily routine (CON; no training) (n = 8). The participants in the ST-EX group were instructed to perform a minimum of 12 sessions/week of ST-EX for more than three days/week. One session of ST-EX consisted of two repetitions of 3 min bouts of climbing to the second floor, followed by walking down to the first floor. Fourteen participants completed the study (seven for each group). The decrease in glycoalbumin levels was significantly greater in the ST-EX group (mean value: −1.0%) than in the CON group (+0.4%). Moreover, the knee extension force increased greatly in the ST-EX group (+0.2 Nm/kg) compared with that in the CON group (−0.1 Nm/kg), with no significant change in the skeletal muscle mass. Performing regular ST-EX after meals may be an effective strategy to improve glycemic control and lower-extremity muscle strength in individuals with T2D.

Abstract Background Among congenital anomalies of the portal venous system, prepancreatic postduodenal portal vein (PPPV) is very rare and has only been reported to date. Herein, we report a case of PPPV identified in preoperative examinations for hepatocellular carcinoma and a literature review. Case presentation A 63-year-old man was admitted to our hospital for treatment of a liver tumor. After examination, he was diagnosed with hepatocellular carcinoma with a diameter of 40 mm in segment 8. Contrast-enhanced computed tomography scan showed a portal vein passing between the duodenum and pancreas, hence called PPPV. At the hepatic hilus, the portal vein branched off in a complicated course with some porto-portal communications. We determined that anatomical resection with manipulation of the hepatic hilum in this case resulted in major vascular injury. Therefore, we performed partial liver resection, and the patient was discharged uneventfully on postoperative day 14. Conclusions Although PPPV is an extremely rare congenital vascular variant, it is important to carefully identify vascular patterns preoperatively and to recognize the possibility of such an anomaly to avoid misidentification and inadvertent injuries during surgery.

Background: Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma. Methods: We studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength. Results: Thirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend

Background: Information on changes in asthma prevalence and the treatment status for asthma is used as basic information for taking medical and administrative measures against asthma. However, this information among adults is relatively limited. Methods: To elucidate changes in the prevalence of asthma and treatment status over time among Japanese adults, health insurance claim data from some health insurance societies covering salaried employees and their dependents were studied longitudinally. Claim data from FY1999 to 2007 were obtained from two health insurance societies, and data from FY 2011 to 2019 were obtained from three different health insurance societies, and changes in standardized asthma prevalence among subjects aged 20–59 years, proportion of asthma patients prescribed ICS, leukotriene receptor antagonist (LTRA), and LABA, and the mean number of acute asthma exacerbations per year were analyzed. Results: The prevalence of asthma increased from 1.6% in 1999 to 3.0% in 2007 and 2.9% in 2011 to 4.6% in 2019. Increased trends in asthma prevalence from 2011 to 2019 were more noticeable in subjects in their 50s than those in their 20s for both sexes. The number of emergency visits related to asthma was 1.5 per year in 1999, which decreased to 0.8 per year in 2019. The proportion of people prescribed all anti-asthma medications (ICS, LTRA, and LABA) increased over time. Conclusions: The prevalence of adult asthma among Japanese salaried employees and their dependents has increased over the last 20 years, suggesting more attention should be paid to the prevention of this disease in adults.

Background: Asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterized by concurrent features of asthma and COPD. Since disease pathogenesis, severities, and treatments differ between asthma and ACO, it is important to differentiate them. Objective: To clarify and compare the characteristics of ACO and asthma and identify the serum biomarkers for differentiating them, especially in older patients. Methods: This study used the data of 639 participants from the nationwide cohort study, the NHOM-Asthma study, an asthma registry in Japan, with complete information on smoking history, respiratory function, and serum biomarkers. ACO was defined as the self-reported comorbidity of COPD or emphysema, or with obstructive pulmonary function and smoking history (pack-years≥10). The clinical characteristics of patients with ACO and asthma without COPD were compared. The serum biomarkers for differentiation were examined using receiver operating characteristic curves and multivariable analysis. The associations between the biomarkers and age were also analyzed. Results: Of the 639 asthma patients, 125 (19.6%) were diagnosed with ACO; these patients were older and male-dominant and had a higher prevalence of comorbidities such as hypertension, diabetes, and stroke. Among the serum biomarkers that were significantly different between ACO and asthma without COPD, the YKL-40/CHI3L1, MMP3, and IL-1RA levels showed a high area under the curve for discriminating ACO. Only the MMP3 and IL-1RA levels were significantly higher among ACO patients, regardless of age and sex; the YKL-40/CHI3L1 levels were not different due to the effect of age. Conclusion: MMP3 and IL-1RA may be useful serum biomarkers for distinguishing ACO from asthma.

Background: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. Methods: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1–3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal–Wallis, and chi-square tests were used to compare cluster differences. Results: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. Conclusions: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.)

Background: Asthma cases have been increasingly investigated using claims data. However, the validity of defining asthma cases using health insurance claims in Japan is unclear. This study aims to assess the positive and negative predictive values of our proposed discrimination criteria for asthma. Methods: We developed discrimination criteria for asthma based on both the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 disease codes for asthma and health insurance claims data for prescriptions and the treatment of asthma. Inclusion criteria were patients aged ≥16 years with at least one health insurance claim from April 2018 to March 2019 in all departments of our hospital. Physician-diagnosed asthma documented in the charts was used as the reference standard. Positive and negative predictive values of the discrimination criteria for physician-diagnosed asthma were estimated and compared with those estimated from discrimination criteria based solely on ICD-10 codes. Results: The new discrimination criteria had a high positive predictive value (PPV) of 86.0%, which was significantly higher than the PPV for the criteria defined solely by the ICD-10 codes (61.5%) (P

Previous studies suggest the importance of stable circadian environments for fetuses to achieve sound physiology and intrauterine development. This idea is also supported by epidemiological and animal studies, in which pregnant females exposed to repeated shifting of light–dark cycles had increased rates of reproductive abnormalities and adverse pregnancy outcomes. In response to such findings, artificial circadian environments with light–dark (LD) cycles have been introduced to NICUs to promote better physical development of preterm infants. Such LD cycles, however, may not be fully effective for preterm infants who are less than 30 weeks gestational age (WGA) since they are too premature to be adequately responsive to light. Instead, circadian rhythmicity of incubated preterm infants less than 30 WGA may be able to be developed through stimulation of the non-visual senses such as touch and sound.