Association between serum level of uric acid in Japanese young patients with coronary spastic angina receiving coronary angiography.

Endothelial dysfunction may trigger coronary spastic angina (CSA). However, the risk factors for CSA in young patients remain unclear. This study aimed to investigate the age-dependent role of serum uric acid levels in patients with CSA. We enrolled 423 patients who underwent an ergonovine tolerance test during coronary angiography for the CSA evaluation. We categorized the patients as (1) young (age ≤ 65 years) CSA-positive (n = 33), (2) young CSA-negative (n = 138), (3) elderly (age > 66 years) CSA-positive (n = 42), and (4) elderly CSA-negative (n = 210) groups. In the young groups, the smoker proportion (57.6 vs. 38.4%, p = 0.04) and serum uric acid levels (6.3 ± 1.4 vs. 5.4 ± 1.5 mg/dl, p = 0.006) were significantly higher in the CSA-positive compared with the CSA-negative group. Conversely, in the elderly group, the male proportion (66.6 vs. 47.1%, p = 0.02) and alcohol consumption level (40.5 vs. 21.0%, p = 0.01) were significantly higher in the CSA-positive compared with the CSA-negative group. The multivariate analysis in young groups revealed the independent association between the serum uric acid level (p = 0.02) and the presence of CSA. Our results indicate that elevated serum uric acid levels may affect CSA development in young patients.

Generation and application of CES1-knockout Tet-Off-regulated CYP3A4 and UGT1A1-expressing Caco-2 cells.

Caco-2 cells, a human colorectal adenocarcinoma cell line, are widely used to model small intestinal epithelial cells in the drug development process because they can predict drug absorption with high accuracy. However, Caco-2 cells have several issues. First, Caco-2 cells have little expression of cytochrome P450 3A4 (CYP3A4), which is a major drug-metabolizing enzyme in the human intestine. We previously developed Caco-2 cells whose expression of CYP3A4 can be controlled using doxycycline (Dox) (CYP3A4-Caco-2 cells) (Ichikawa et al., Sci. Rep, 2021). However, since the Tet-On system was used to regulate CYP3A4 expression in these cells, there was concern about drug-drug interactions. The second issue is that in the human small intestine, carboxylesterase 2 (CES2) is more highly expressed than carboxylesterase 1 (CES1), while in Caco-2 cells CES1 is more highly expressed. The third issue is the low level expression of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), a phase II drug-metabolizing enzyme. In this study, we used genome-editing technology to establish CES1-knockout Caco-2 cells whose CYP3A4 and UGT1A1 expression can be regulated by the Tet-Off system. These cell lines would be useful in pharmaceutical researches, including intestinal toxicological studies, as an in vitro model for orally administered drugs.

Complication frequency of mechanical chest compression devices: A single-center, blinded study using retrospective data.

Aim: Use of mechanical chest compression devices for patients with cardiac arrest is increasing. As cardiopulmonary resuscitation (CPR) guidelines and LUCAS are updated, the evidence requires updating. Methods: This single-center, retrospective study observed adult patients with out-of-hospital cardiac arrest receiving CPR from emergency services. Patients were assigned to LUCAS or manual CPR groups, matched by propensity score, and evaluated through computed tomography images by a radiologist blinded to their data. The primary outcome was complications from chest compressions, and logistic regression was used to analyze their risk factors. Results: Overall, 261 patients were selected and divided into manual and LUCAS groups (n = 69 each). The manual CPR group exhibited higher witnessed cardiac arrest percentages (p = 0.023) and shorter times from scene to emergency department (p = 0.001) and total CPR duration (p = 0.002), versus the LUCAS group. Complication rates showed no significant intergroup differences in overall CPR complications (p = 0.462); however, the LUCAS group reported more hemothorax incidents (p = 0.028), versus the manual group. Logistic regression indicated that female sex (odds ratio [OR] 3.743, 95 % confidence interval [CI] 1.333-10.506), older age (OR 1.089, 95 % CI 1.048-1.132), and longer CPR durations (OR 1.045, 95 % CI 1.006-1.085) significantly correlated with compression complications, whereas LUCAS use did not (OR 0.713, 95 % CI 0.304-1.673). Conclusion: No association was observed between LUCAS use and the overall incidence of chest compression complications in adults with OHCA. LUCAS is associated with more hemothorax cases and longer transport time, versus manual CPR. Evaluating LUCAS's benefits necessitates multiple perspectives and further research.

Simultaneous prognostic score validation in patients with out-of-hospital cardiac arrest by a post-hoc analysis based on national multicenter registry.

Using a nationwide multicenter prospective registry in Japan's data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores' accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score's discrimination ability was evaluated by the receiver operating characteristic curve's area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems.

Medication Optimization Protocol Efficacy for Geriatric Inpatients: A Randomized Clinical Trial.

Importance: There is currently no consensus on clinically effective interventions for polypharmacy among older inpatients. Objective: To evaluate the effect of multidisciplinary team-based medication optimization on survival, unscheduled hospital visits, and rehospitalization in older inpatients with polypharmacy. Design, Setting, and Participants: This open-label randomized clinical trial was conducted at 8 internal medicine inpatient wards within a community hospital in Japan. Participants included medical inpatients 65 years or older who were receiving 5 or more regular medications. Enrollment took place between May 21, 2019, and March 14, 2022. Statistical analysis was performed from September 2023 to May 2024. Intervention: The participants were randomly assigned to receive either an intervention for medication optimization or usual care including medication reconciliation. The intervention consisted of a medication review using the STOPP (Screening Tool of Older Persons' Prescriptions)/START (Screening Tool to Alert to Right Treatment) criteria, followed by a medication optimization proposal for participants and their attending physicians developed by a multidisciplinary team. On discharge, the medication optimization summary was sent to patients' primary care physicians and community pharmacists. Main Outcomes and Measures: The primary outcome was a composite of death, unscheduled hospital visits, and rehospitalization within 12 months. Secondary outcomes included the number of prescribed medications, falls, and adverse events. Results: Between May 21, 2019, and March 14, 2022, 442 participants (mean [SD] age, 81.8 [7.1] years; 223 [50.5%] women) were randomly assigned to the intervention (n = 215) and usual care (n = 227). The intervention group had a significantly lower percentage of patients with 1 or more potentially inappropriate medications than the usual care group at discharge (26.2% vs 33.0%; adjusted odds ratio [OR], 0.56 [95% CI, 0.33-0.94]; P = .03), at 6 months (27.7% vs 37.5%; adjusted OR, 0.50 [95% CI, 0.29-0.86]; P = .01), and at 12 months (26.7% vs 37.4%; adjusted OR, 0.45 [95% CI, 0.25-0.80]; P = .007). The primary composite outcome occurred in 106 participants (49.3%) in the intervention group and 117 (51.5%) in the usual care group (stratified hazard ratio, 0.98 [95% CI, 0.75-1.27]). Adverse events were similar between each group (123 [57.2%] in the intervention group and 135 [59.5%] in the usual care group). Conclusions and Relevance: In this randomized clinical trial of older inpatients with polypharmacy, the multidisciplinary deprescribing intervention did not reduce death, unscheduled hospital visits, or rehospitalization within 12 months. The intervention was effective in reducing the number of medications with no significant adverse effects on clinical outcomes, even among older inpatients with polypharmacy. Trial Registration: UMIN Clinical Trials Registry: UMIN000035265.

Dietary Rhythmicity and Mental Health Among Airline Personnel.

Importance: Misaligned dietary rhythmicity has been associated with metabolic diseases; however, its association with mental health remains largely unexplored. Objective: To examine the association between dietary rhythms and the mental health condition of shift workers, specifically airline crew members. Design, Setting, and Participants: This cross-sectional study analyzed data collected from the Civil Aviation Health Cohort of China, an ongoing large-scale health survey of pilots, flight attendants, and air security officers employed by major airline companies in China. Participants aged 18 to 60 years were invited through text messages to complete a web-based survey. The data collection period was December 2022 to March 2023. Statistical analysis was performed from July 24, 2023, to April 12, 2024. Exposure: Data on timing of breakfast and dinner on workdays and rest days, daily time windows for food intake, and meal and eating jet lags were collected and calculated. Main Outcomes and Measures: Anxiety and depressive symptoms were measured using the 7-item Generalized Anxiety Disorder Assessment and the 9-item Patient Health Questionnaire. Multivariate logistic regressions were performed to evaluate the associations of anxiety and depression with meal timing, eating window time, meal jet lag (ie, delayed meals), and eating jet lag (ie, delayed eating). All models were adjusted for individual socioeconomic, demographic, and lifestyle characteristics. Results: Of the 22 617 participants (median [IQR] age, 29.1 [26.3-33.7] years; 13 712 males [60.6%]), 1755 (7.8%) had anxiety and 2768 (12.2%) had depression. After controlling for confounding factors, having dinner after 8 pm on morning-shift days was associated with increased odds of anxiety (adjusted odds ratio [AOR], 1.78; 95% CI, 1.53-2.05) and depression (AOR, 2.01; 95% CI, 1.78-2.27), compared with consuming dinner before 8 pm. Similar results were observed on night-shift days and rest days. An eating window of less than 12 hours was associated with reduced odds of anxiety (AOR, 0.84; 95% CI, 0.75-0.93) and depression (AOR, 0.81; 95% CI, 0.75-0.89) on morning-shift days; the results remained significant on rest days. Delayed dinner on morning-shift days was associated with increased odds of anxiety (AOR, 1.32; 95% CI, 1.13-1.54) and depression (AOR, 1.39; 95% CI, 1.22-1.58). On night-shift days, delayed dinner was associated with higher odds of anxiety (AOR, 1.22; 95% CI, 1.06-1.39) and depression (AOR, 1.21; 95% CI, 1.08-1.36). On morning-shift days, delayed eating rhythms were associated with higher odds of depression (AOR, 1.35; 95% CI, 1.13-1.61), whereas advanced eating rhythms were associated with lower odds of anxiety (AOR, 0.78; 95% CI, 0.70-0.87). Conclusions and Relevance: This cross-sectional study found that meal timing, long eating window, and meal jet lags were associated with increased odds of depression and anxiety. These findings underscore the need for interventions and supportive policies that help mitigate the adverse implications of shift work and irregular working hours for the mental health of shift workers.

Electron Transfer Enhanced by a Minimal Energetic Driving Force at the Organic-Semiconductor Interface.

The energetic driving force for electron transfer must be minimized to realize efficient optoelectronic devices including organic light-emitting diodes (OLEDs) and organic photovoltaics (OPVs). Exploring the dynamics of a charge-transfer (CT) state at an interface leads to a comprehension of the relationship between energetics, electron-transfer efficiency, and device performance. Here, we investigate the electron transfer from the CT state to the triplet excited state (T1) in upconversion OLEDs with 45 material combinations. By analyzing the CT emission and the singlet excited-state emission from triplet-triplet annihilation via the dark T1, their energetics and electron-transfer efficiencies are extracted. We demonstrate that the CT→T1 electron transfer is enhanced by the stronger CT interaction and a minimal energetic driving force (<0.1 eV), which is explained using the Marcus theory with a small reorganization energy of <0.1 eV. Through our analysis, a novel donor-acceptor combination for the OLED is developed and shows an efficient blue emission with an extremely low turn-on voltage of 1.57 V. This work provides a solution to control interfacial CT states for efficient optoelectronic devices without energy loss.

Morning physical activity may be more beneficial for blood lipids than afternoon physical activity in older adults: a cross-sectional study.

BACKGROUND: The effect of differences in daily physical activity patterns on blood lipids has not been determined. This study examines the effects of the differences in free-living daily physical activity patterns (amount and intensity) on blood lipid levels in older adults. METHODS: This cross-sectional study included 51 older participants (71.8 ± 0.6 years, men = 8, women = 43). A triaxial accelerometer was used to assess physical activity patterns. The time from awakening to bedtime for each participant was used for group classification based on the amount (number of steps) and intensity (moderate-to-vigorous physical activity, MVPA) of physical activity. The morning step group (M Step) was defined as those who took more steps in the morning, and the afternoon step group (A Step) was defined as those who took more steps in the afternoon. The same method was used for MVPA (morning MVPA: M MVPA; afternoon MVPA: A MVPA). Blood samples were collected at the start of the study to determine blood lipid levels. RESULTS: Number of steps taken showed a trend toward lower low-density lipoprotein cholesterol (LDL-C) levels in the M Step group compared with the A Step group. The LDL/high-density lipoprotein (HDL) ratio was significantly lower in the M Step group than the A Step group (p < 0.05). The M MVPA group also had higher HDL-C levels and significantly lower LDL/HDL ratios than the A MVPA group (p < 0.05). CONCLUSIONS: These results suggest that compared with afternoon physical activity, daily morning physical activity (amount and intensity) is more effective in improving blood lipid levels.

Summer Nutritional Status and Appetite Are Associated with the Frequency of Hot Meal/Drink Intake among Japanese Older People.

This study examined the relationship between the frequency of consuming cold or hot meal/drink during summer and the nutritional status, appetite, and energy intake among Japanese older people. The cross-sectional study was conducted in August 2021, targeting 60 adults aged 65 y and older. The Mini Nutritional Assessment (MNA) was used for nutritional status evaluation, the Simplified Nutritional Appetite Questionnaire (SNAQ) for appetite scoring, and food frequency questionnaire to assess energy intake. Participants reported on the frequency of consuming cold or hot meal/drink during the summer. Those who reported consuming hot meals "moderate" (p=0.033) or "frequent" (p=0.005) during summer had a higher BMI than those who reported minimal consumption. Participants who reported "frequent" consumption of hot meals in summer had higher MNA scores than those who reported "minimal" consumption (p=0.014). Participants who reported a "frequent" consumption of hot meals had higher SNAQ scores compared to those who reported "minimal" (p<0.001) or "moderate" (p=0.001). Similarly, participants who reported a "frequent" consumption of hot drinks had higher SNAQ scores than those reporting "minimal" (p=0.021) or "moderate" (p=0.008). The nutritional status and appetite during summer in Japanese older people were associated with the frequency of consuming hot meals and drinks.

Domain structure and function of α-1,3-glucanase Agl-EK14 from the gram-negative bacterium Flavobacterium sp. EK-14.

The α-1,3-glucanase Agl-EK14 from Flavobacterium sp. EK-14 comprises a signal peptide (SP), a catalytic domain (CAT), a first immunoglobulin-like domain (Ig1), a second immunoglobulin-like domain (Ig2), a ricin B-like lectin domain (RicinB), and a carboxy-terminal domain (CTD). SP and CTD are predicted to be involved in extracellular secretion, while the roles of Ig1, Ig2, and RicinB are unclear. To clarify their roles, domain deletion enzymes Agl-EK14ΔRicinB, Agl-EK14ΔIg2RicinB, and Agl-EK14ΔIg1Ig2RicinB were constructed. The insoluble α-1,3-glucan hydrolytic, α-1,3-glucan binding, and fungal cell wall hydrolytic activities of the deletion enzymes were almost the same and lower than those of Agl-EK14. Kinetic analysis revealed that the Km values of the deletion enzymes were similar and uniformly higher than those of Agl-EK14. These results suggest that the deletion of RicinB causes a decline in binding and hydrolytic activity and increases the Km value. To confirm the role of RicinB, Ig1, Ig2, and RicinB were fused with green fluorescent protein (GFP). As a result, RicinB-fused GFP (GFP-RicinB) showed binding to insoluble α-1,3-glucan and Aspergillus oryzae cell walls, whereas Ig1- and Ig2-fused GFP did not. These results indicated that RicinB is involved in α-1,3-glucan binding. The fusion protein GFP-Ig1Ig2RicinB was also constructed and GFP-Ig1Ig2RicinB showed strong binding to the cell wall of A. oryzae compared to GFP-RicinB. Gel filtration column chromatography suggested that the strong binding was due to GFP-Ig1Ig2RicinB loosely associated with itself.

Damage-Associated Molecular Patterns as Mediators of Thrombus Formation on Dialyzer Membrane in Critically Ill Patients.

This prospective study investigated the relationship between inflammation, damage-associated molecular patterns (DAMPs), and thrombus formation on dialyzer membranes in critically ill patients undergoing renal replacement therapy (RRT) from July 2020 to August 2022, identifying mechanisms and interventions to prevent clotting. The patients were divided into two groups: inflammatory (n = 56, serum C-reactive protein >10 mg/dl) and noninflammatory control (n = 45, serum C-reactive protein <5 mg/dl). Cell-free deoxyribonucleic acid (DNA) levels, high mobility group box 1 protein (HMGB1), histone H3, and myeloperoxidase (MPO) in the lumen of the hollow fiber membrane of the dialyzer were quantified. Immunostaining assessed leukocytes, fibrin fibers, and platelet thrombi on the luminal surface of the hollow fiber membrane. The inflammatory group, compared to controls, exhibited elevated cell-free DNA, HMGB1, and MPO levels, although histone H3 remained unchanged. Damage-associated molecular patterns increased with disseminated intravascular coagulation (DIC) severity. Immunostaining in the inflammatory group revealed leukocytes, amorphous nuclei, neutrophil extracellular trap-like structures, fibrin fibers, and platelet thrombi on the hollow fiber membrane's luminal surface. Elevated DAMP levels in severely inflamed patients' dialyzer membranes, correlating with DIC severity, indicate a link between inflammation, coagulation activation, and dialyzer clotting. Research into thrombus prevention in RRT for DIC-affected critically ill patients is warranted.

Consumption of hot protein-containing drink accelerates gastric emptying rate and is associated with higher hunger levels in older adults.

Meal temperature is known to affect gastric emptying and appetite. While protein intake is recommended for older age, gastric emptying is delayed with age, resulting in loss of appetite. This study aimed to investigate whether adjusting the temperature of protein-containing drinks could improve gastric emptying and appetite in older individuals. Twenty male and female participants aged 65 years and older underwent three one-day trials in random order. Participants visited the laboratory after a 10-hour fast and consumed 200 mL of protein-containing drink dissolved in 13C-sodium acetate at 4°C, 37°C, or 60°C in a 3-minute period. Then, participants sat in a chair for 90 minutes to measure gastric emptying rate by the 13C-sodium acetate breath test and subjective appetite by a visual analog scale. The results showed that 37°C and 60°C drinks had faster gastric emptying at 5 and 10 min after ingestion than did the 4°C drink (trial-time interaction, p = 0.014). Tmax-calc, an indicator of gastric emptying rate, tended to be faster for the 37°C and 60°C drinks than for the 4°C drink (49.7 ± 17.5 min vs. 44.1 ± 18.5 min vs. 45.3 ± 25.8 min for the 4°C, 37°C, and 60°C, respectively; p = 0.085). There were no significant differences in the change in hunger from baseline among the three different temperature drinks (p > 0.05). Only in the 60°C trial, a shorter gastric emptying time was associated with greater hunger (r=-0.554, p = 0.021). These findings suggest that hot protein-containing drinks may accelerate gastric emptying and contribute to rapid nutrient intake and increased appetite in older adults.

Maternal dietary and environmental factors associated with infant circadian rhythm, growth, and temperament: Research protocol for a prospective cohort study.

Introduction: Emerging evidence has been explored to determine the factors affecting the development of infant circadian rhythm. While fetal programming happens during the pregnancy period, external environmental cues and infant nutritional programming can have substantial effects on the infant circadian rhythm. Understanding prenatal and postnatal factors determining infant circadian rhythm can improve future interventions in optimizing maternal and infant health. Methods: This is a prospective observational cohort study, targeting 216 pregnant women from government maternity clinics in Kuala Lumpur, Malaysia. Pregnant women will be recruited at third trimester (baseline), and follow up at 3 months, and 6 months. A subsample will be collected for salivary cortisol analysis to determine circadian rhythm of the mother and infant at third trimester and 3 months. Data of eating misalignment, light exposure, chronotype, infant temperament, sleep quality, and mood will be collected via validated questionnaires. Anthropometric data and birth outcomes will be collected from antenatal and postnatal health records. Summary: Studies on infant circadian rhythm development have yet to be explored and established, hence this study presents a novel approach to identify the factors from prenatal to postnatal periods on infant circadian rhythm and its influence on growth and temperament. Findings from this study will provide insights in the critical timing which has larger effects on infant circadian rhythm development for future interventions to be conducted.

Efficacy of Computed Tomography-Based Evaluation of Myocardial Extracellular Volume Combined With Red Flags for Early Screening of Concealed Cardiac Amyloidosis in Patients With Atrial Fibrillation.

BACKGROUND: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation. METHODS AND RESULTS: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate (99 mTc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 mTc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 mTc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing. CONCLUSIONS: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

Development, validation, and reliability of the Chrononutrition Profile Questionnaire-Pregnancy (CPQ-P).

BACKGROUND: During pregnancy, physiological changes can affect eating and sleeping habits, which may eventually have negative consequences for maternal and foetal health. To better understand these changes, it is essential to develop a reliable questionnaire that addresses lifestyle habits such as snacking and daytime napping. This study aimed to determine the validity and reliability of the Chrononutrition Profile Questionnaire-Pregnancy (CPQ-P). METHODS: A total of 399 women in their second and third trimester of pregnancy were recruited from government maternal and child health clinics in Kuala Lumpur and Putrajaya and completed a self-administered online questionnaire. Content validity was conducted with an expert panel consisting of 4 members. Confirmatory factor analysis (CFA) using maximum likelihood was conducted to determine the construct validity. Internal consistency was determined by Cronbach's alpha coefficient (CAC), while the test-retest reliability was conducted using intraclass correlation coefficient (ICC). RESULTS: The questionnaire had an appropriate content validity index of 0.91. The CPQ-P consists of 22 items, measuring 5 constructs, including morning chrono-habits, sleeping habits, evening eating, temporal eating, and pregnancy symptoms. The factor model showed good fit with χ2/df = 2.486, GFI = 0.893, CFI = 0.912, and RMSEA = 0.065. The 22 items in CPQ-P showed fair to excellent test-retest reliability (ICC: 0.42 to 0.98). The 5 constructs in CPQ-P were found to have a good to excellent internal consistency (α = 0.612-0.963). CONCLUSIONS: The CPQ-P is a valid and reliable tool for assessing lifestyle habits during pregnancy. The questionnaire can be used to identify areas where pregnant women may need additional support or intervention to adopt healthy behaviours and reduce the risk of adverse maternal and foetal outcomes. TRIAL REGISTRATION: NCT05700136 (clinicaltrials.gov). Trial registration date: 26/01/2023.

Addition of α-1,3-glucan-binding domains to α-1,3-glucanase Agn1p from　 Schizosaccharomyces pombe enhances hydrolytic activity of insoluble α-1,3-glucan.

The glycoside hydrolase (GH) 71 α-1,3-glucanase (Agn1p) from Schizosaccharomyces pombe consists of an N-terminal signal sequence and a catalytic domain. Meanwhile, the GH87 α-1,3-glucanase (Agl-KA) from Bacillus circulans KA-304 consists of an N-terminal signal sequence, a first discoidin domain (DS1), a carbohydrate-binding module family 6 (CBM6), a threonine and proline repeat linker (TP), a second discoidin domain (DS2), an uncharacterized domain, and a catalytic domain. DS1, CBM6, and DS2 exhibit α-1,3-glucan binding activity. This study involved genetically fusing TP, DS1, CBM6, TP, and DS2 to the C-terminus of Agn1p, generating the fusion enzyme Agn1p-DCD. The fusion enzyme was then expressed in Escherichia coli and purified from the cell-free extract. Agn1p-DCD and Agn1p exhibited similar characteristics, such as optimal pH, optimal temperature, pH stability, and thermostability. Insoluble α-1,3-glucan (1%) hydrolyzing assay showed that Agn1p-DCD and Agn1p released approximately 7.6 and 5.0 mM of reducing sugars, respectively, after 48 h of reaction. Kinetic analysis and an α-1,3-glucan binding assay indicated that the addition of DS1, CBM6, and DS2 enhanced the affinity of Agn1p for α-1,3-glucan. Moreover, Agn1p-DCD contributed to enhancing the fungal growth inhibition activity when combined with a mixture of GH19 chitinase and GH16 ß-1,3-glucanase.

Wavily Curved Perylene Diimides: Synthesis, Characterization, and Photovoltaic Properties.

Solubility enhancement is a key issue for developing the perylene diimide-based functional materials. Introduction of curved structure proved an effective solubilizing method without employing steric repulsion. In this work, wavily curved perylene diimides were developed as a new family of highly soluble curved perylene diimides. Moreover, their conformational dynamics, aggregating properties, electronic properties, and photovoltaic performances were thoroughly examined in comparison to the previously reported isomer exhibiting an arched curvature. The waved isomer demonstrated heightened rigidity and a greater propensity for aggregation compared to the arched isomer, likely attributed to its more planar structure. Each benzoxepin unit played a role in cancelling out the curvature on the opposite side. While the difference in the molecular curvature did not cause significant alterations in the photophysical and electron-accepting properties, we identified that the modulation of the curved structure is effective in controlling the morphology of the photoelectric conversion layer.

Immune thrombocytopenic purpura and Guillain-Barré syndrome after 23-valent pneumococcal polysaccharide vaccination in Japan: The vaccine effectiveness, networking, and universal safety (VENUS) study.

BACKGROUND: To address the lack of an active vaccine safety surveillance system in Japan, the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study was initiated in 2021 as a pilot system using existing health insurance claims data and vaccination records. METHODS: This study evaluated the value of the VENUS study by assessing the incidence of immune thrombocytopenic purpura (ITP) and Guillain-Barré syndrome (GBS) following vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) using a self-controlled case series (SCCS) design. RESULTS: Incidence rate ratios for ITP during 28-day and 42-day risk periods were 0.89 (95% confidence interval [CI], 0.12-6.4), and 0.58 (95% CI, 0.081-4.2), respectively. Neither was statistically significant. Incidence rate ratios could not be estimated for GBS due to the limited sample size. CONCLUSION: The VENUS study can provide valuable insights to facilitate the establishment of an advanced vaccine monitoring system in Japan.

The Use of Carboxyfluorescein Reveals the Transport Function of MCT6/SLC16A5 Associated with CD147 as a Chloride-Sensitive Organic Anion Transporter in Mammalian Cells.

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a Km of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe.

α-1,3-Glucanase from the gram-negative bacterium Flavobacterium sp. EK-14 hydrolyzes fungal cell wall α-1,3-glucan.

The glycoside hydrolase (GH) 87 α-1,3-glucanase (Agl-EK14) gene was cloned from the genomic DNA of the gram-negative bacterium Flavobacterium sp. EK14. The gene consisted of 2940 nucleotides and encoded 980 amino acid residues. The deduced amino acid sequence of Agl-EK14 included a signal peptide, a catalytic domain, a first immunoglobulin-like domain, a second immunoglobulin-like domain, a ricin B-like lectin domain, and a carboxyl-terminal domain (CTD) involved in extracellular secretion. Phylogenetic analysis of the catalytic domain of GH87 enzymes suggested that Agl-EK14 is distinct from known clusters, such as clusters composed of α-1,3-glucanases from bacilli and mycodextranases from actinomycetes. Agl-EK14 without the signal peptide and CTD hydrolyzed α-1,3-glucan, and the reaction residues from 1 and 2% substrates were almost negligible after 1440 min reaction. Agl-EK14 hydrolyzed the cell wall preparation of Aspergillus oryzae and released glucose, nigerose, and nigero-triose from the cell wall preparation. After treatment of A. oryzae live mycelia with Agl-EK14 (at least 0.5 nmol/ml), mycelia were no longer stained by red fluorescent protein-fused α-1,3-glucan binding domains of α-1,3-glucanase Agl-KA from Bacillus circulans KA-304. Results suggested that Agl-EK14 can be applied to a fungal cell wall lytic enzyme.