An Increase in the Ratio of Brain Natriuretic Peptide to Peak Transvalvular Pressure Gradient Suggests Coexistence of Cardiovascular Complications in Elderly Aortic Stenosis Patients.

The aim of this study was to differentiate between elderly aortic stenosis (AS) patients with and without cardiovascular complications (CCs).In total, 156 consecutive patients with AS aged ≥ 70 years were enrolled. Patients were divided into 2 groups as follows: AS without CCs (group I; n = 110) and AS with CCs (group II; n = 46). Routine electrocardiographic and echocardiographic parameters, peak and mean transvalvular pressure gradients (TPGs), aortic valve area (AVA), brain natriuretic peptide (BNP) levels, and BNP/peak TPG ratio were measured.The mean ages in groups I and II were 80.4 ± 5.5 and 82.5 ± 7.2 years. Left ventricular hypertrophy was greater in group II than in group I. Left ventricular end-diastolic and end-systolic dimensions and left ventricular fractional shortening were normal in both groups. Peak and mean TPGs were greater in group II (67.2 ± 39.3 and 40.2 ± 26.4 mmHg) than in group I (52.0 ± 23.0 and 30.2 ± 13.9, both P < 0.005); however, the AVA showed no significant difference between the 2 groups. The median BNP levels were 65.9 and 433.7 pg/mL in groups I and II (P < 0.0001). A correlation between peak TPG and BNP levels was observed in both groups. The BNP/peak TPG ratio was < 3.0 in all patients of group I and ≥ 3.0 in almost all patients of group II (P< 0.0001). The area under the curve using BNP/peak TPG ratio was 0.9883.BNP and BNP/peak TPG ratio could differentiate between AS with and without CCs in elderly patients.

Enhancing 3-hydroxypropionic acid production in Saccharomyces cerevisiae through enzyme localization within mitochondria.

Microbial 3-hydroxypropionic acid (3-HP) production can potentially replace petroleum-based production methods for acrylic acid. Here, we constructed a yeast strain that expressed enzymes related to 3-HP biosynthesis within the mitochondria. This approach aimed to enhance the 3-HP production by utilizing the mitochondrial acetyl-CoA, an important intermediate for synthesizing 3-HP. The strain that expressed 3-HP-producing enzymes in the mitochondria (YPH-mtA3HP) showed improved production of 3-HP compared to that shown by the strain expressing 3-HP-producing enzymes in the cytosol (YPH-cyA3HP). Additionally, cMCR was overexpressed, which regulates a rate-limiting reaction in synthesizing 3-HP. In this study, we aimed to further enhance 3-HP production by expressing multiple copies of cMCR in the mitochondria using the δ-integration strategy to optimize the expression level of cMCR (YPH-mtA3HPx*). The results of flask-scale cultivation showed that 3-HP production by cMCR δ-integration was significantly higher, exhibiting a yield of 160 mg/L in YPH-mtA3HP6* strain and 257 mg/L in YPH-mtA3HP22* strain. Notably, YPH-mtA3HP22*, exhibited the highest 3-HP titer, which was 3.2-fold higher than that of YPH-cyA3HP. Our results demonstrated the potential of utilizing the mitochondrial compartment within S. cerevisiae for enhancing 3-HP production.

[Strategy to Avoid Reoperation after Ascending Aortic Replacement for DeBakey Typeâ Acute Aortic Dissection].

When ascending aortic replacement (AAR) is performed in patients with DeBakey typeⅠ acute aortic dissection( AAD), residual false lumen of the aortic arch after AAR is a risk factor of remote aortic reoperation. We have principally considered entry resection as a surgical policy for AAD, but since 2013, for cases of re-entry in the brachiocephalic artery, reconstruction of the brachiocephalic artery has been added. We verified whether brachiocephalic artery reconstruction contributes to the thrombus closure of the false lumen of the aortic arch after the operation. Of 68 patients who underwent AAR for DeBakey typeⅠ AAD within a 12 year period, 17 had re-entry in the brachiocephalic artery on preoperative computed tomography (CT). Six patients who underwent brachiocephalic artery reconstruction were assigned to group A, and 11 patients who did not were assigned to group B. We compared the 2 groups. Aortic clamp and selective cerebral perfusion times were significantly longer in group A. By postoperative CT, false lumen of the aortic arch was not found in any case (0%) in group A, but was found in 10( 90.9%) of the 11 cases in group B( p=0.0006). The risk of residual false lumen of the aortic arch significantly decreased in group A. In conclusion, in cases where re-entry is found in the brachiocephalic artery, a false lumen often remains in the aortic arch after AAR. However, by reconstructing the dissected brachiocephalic artery, the false lumen of the aortic arch can be obliterated, which contributes to avoidance of reoperation in a chronic phase.

[Distal Stentgraft-induced New Entry Developed after Surgery for Aortic Dissection].

We experienced 2 cases with distal stentgraft-induced new entry (distal SINE) after thoracic endovascular aortic repair( TEVAR) for type B aortic dissection and 1 case after total arch replacement and frozen elephant trunk method for type A dissection. We successfully performed additional TEVAR in all cases. If the stent graft is bent at deployment, distal SINE may occur on the great curvature side of the aorta by the spring back force. Therefore, we must pay attention to appropriate device selection, and even when remodeling of the aorta is good, meticulous follow-up is necessary.

Dibenzopyrrolo[1,2-a][1,8]naphthyridines: Synthesis and Structural Modification of Fluorescent L-Shaped Heteroarenes.

The L-shaped, π-extended pentacycle dibenzopyrrolo[1,2-a][1,8]naphthyridine and its derivatives were synthesized using two methods: fully intramolecular [2 + 2 + 2] cycloaddition and oxidative aromatization using substituted carbodiimide and modification of an electron-rich indole ring of an L-shaped skeleton via electrophilic reaction and cross-coupling. These L-shaped compounds emitted fluorescence in high quantum yield. The position of substituents affected the fluorescence color through two different mechanisms, π-conjugation and skeletal distortion, which caused the substituted L-shaped compounds to emit fluorescence in a variety of colors and to exhibit solvato-fluorochromism.

Listen to the outpatient: qualitative explanatory study on medical students' recognition of outpatients' narratives in combined ambulatory clerkship and peer role-play.

BACKGROUND: Understanding patients' narratives has been associated with methods of improving care that go beyond what may be regarded as a "narrow" view of scientific medicine. Medical interview training in which medical students develop understanding of the importance of patients' narratives is receiving increased attention. However, students generally receive education on patients' narratives that does not distinguish inpatients and outpatients. No studies exploring the characteristics of outpatients' narratives have been reported. We developed an educational program combining ambulatory clerkship and peer role-play using actual narratives from outpatients that students had encountered during their clerkship. These narratives were used as peer role-play scenarios in which the students acted as outpatients. This study explored what and how medical students learned about the characteristics of outpatients' narratives through this original educational program. METHODS: Participants were 70 fifth-year medical students from Nagoya University, Japan. We conducted 13 focus groups, based on a convenience sample of 11 groups in 2012, one group in 2013, and one group in 2017 (from 17 clinical groups in each year). Focus group transcripts were analyzed using the "Steps for Coding and Theorization" qualitative data analysis method. We assessed medical anthropological findings regarding narratives in a conceptual framework. RESULTS: Patients' narratives as perceived by medical students were divided into four quadrants by two axes: medical versus lived content, and objective versus subjective structure. Students recognized that outpatients' narratives mainly used a subjective structure, but were mixed and crossed each quadrant. This was described as "irreproducibility." Students also recognized that narratives of simulated patients and inpatients were mainly limited to a medical-lived content with an objective structure. These differences in narrative characteristics were recognized through students' previous interactions with simulated patients and inpatients. CONCLUSIONS: Despite some limitations, medical students learn about patients' narratives in our original educational program in a way that would be difficult to achieve through training using simulated patients or inpatients.

Integrating patients' perceptions into clinical practice guidelines for the management of rheumatoid arthritis in Japan.

OBJECTIVE: Patients' values and preferences are among the key factors that determine the strength of recommendations presented in clinical practice guidelines (CPG). The aim of this study was to summarize the integration process for patients' perceptions into the development of CPG for rheumatoid arthritis (RA) management in Japan. METHODS: We used a mixed-methods approach. Questionnaires that could be self-administered were mailed to 2222 RA patients randomly selected from the Japan Rheumatism Friendship Association (JRFA) membership list that was age- and prefecture-stratified. A focus group with five JRFA executive members was formed to verify the results of the questionnaire. RESULTS: A total of 1470 patients aged 20-79 years old returned the questionnaire. Analysis of the questionnaire data revealed that the topics selected by the CPG task force met the patients' needs. The focus group participants showed reluctance to use the term 'preference' because patients would not want to take any medications but would have to take them out of necessity. CONCLUSIONS: We confirmed that the new CPG successfully addressed clinical issues that were important to both rheumatologists and patients. Clinicians should understand patients' reluctance to take medications and explain the role of each medication well to increase adherence.

Facile Two-Step Synthesis of 1,10-Phenanthroline-Derived Polyaza[7]helicenes with High Fluorescence and CPL Efficiency.

A facile two-step synthesis of aza[7]helicenes possessing a 6-5-6-6-6-5-6 skeleton from commercially available 2,9-dichloro-1,10-phenanthroline via double amination with aniline derivatives followed by hypervalent iodine reagent-mediated intramolecular double-NH/CH couplings was developed. Single-crystal X-ray analyses of the helicenes revealed unique structures, including both a significantly twisted center and planar terminals of the skeleton. The azahelicenes show high fluorescent quantum yields (Φs) under both neutral (Φ: 0.25-0.55) and acidic conditions (Φ: up to 0.80). An enantiomerically pure aza[7]helicene showed high circularly polarized luminescence (CPL) activity under both neutral and acidic conditions (glum : up to 0.009).

Biodegradation of γ-hexachlorocyclohexane by transgenic hairy root cultures of Cucurbita moschata that accumulate recombinant bacterial LinA.

KEY MESSAGE: γ-HCH was successfully degraded using LinA-expressed transgenic hairy root cultures of Cucurbita moschata . Fusing an endoplasmic reticulum-targeting signal peptide to LinA was essential for stable accumulation in the hairy roots. The pesticide γ-hexachlorocyclohexane (γ-HCH) is a persistent organic pollutant (POP) that raises public health and environmental pollution concerns worldwide. Although several isolates of γ-HCH-degrading bacteria are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the bacterial survival rate. Cucurbita species incorporate significant amounts of POPs from soils compared with other plant species. Here, we describe a novel bioremediation strategy that combines the bacterial degradation of γ-HCH and the efficient uptake of γ-HCH by Cucurbita species. We produced transgenic hairy root cultures of Cucurbita moschata that expressed recombinant bacterial linA, isolated from the bacterium Sphingobium japonicum UT26. The LinA protein was accumulated stably in the hairy root cultures by fusing an endoplasmic reticulum (ER)-targeting signal peptide to LinA. Then, we demonstrated that the cultures degraded more than 90 % of γ-HCH (1 ppm) overnight and produced the γ-HCH metabolite 1,2,4-trichlorobenzene, indicating that LinA degraded γ-HCH. These results indicate that the gene linA has high potential for phytoremediation of environmental γ-HCH.

Potential application of immunoassays for simple, rapid and quantitative detections of phytoavailable neonicotinoid insecticides in cropland soils.

This study evaluated the applicability of commercially available kit-based enzyme-linked immunosorbent assay (ELISA) to simple, quick, and quantitative detection for three water-extractable (phytoavailable) neonicotinoid insecticides: dinotefuran, clothianidin, and imidacloprid in soils. ELISA showed excellent analytical sensitivity for determination, but with cross-reaction to structurally related neonicotinoid analogues, which might produce false positives. To analyze insecticides in soil samples of diverse physicochemical properties, they were extracted with water. The aqueous soil extracts were assayed directly with ELISA. No matrix interference was observed without additional dilution with water. Recovery experiments for the insecticides from aqueous soil extracts spiked at 2-10 ng/mL showed good accuracy (72-126%) and precision (<16%). Kit-based ELISAs were used to estimate soil-water distribution coefficients (Kd). Values estimated using this method showed positive correlation between organic carbon contents in soil and those for evaluated insecticides. Results indicate that the evaluated kit-based ELISA has applicability for simple, quick, and reliable detection of phytoavailable insecticides in soils and for estimating Kd values in soil.

Stereo-controlled synthesis of polyheterocycles via the diene-transmissive hetero-Diels-Alder reaction of ß,γ-unsaturated α-keto esters.

We describe the stereoselective synthesis of polyring-fused heterocyclic compounds based on diene-transmissive hetero-Diels-Alder reactions utilizing ß,γ-unsaturated α-keto esters. This protocol involves the initial endo- or exo-selective Diels-Alder (DA) reactions with electron-rich dienophiles, methylenation of the ester carbonyl groups with the Tebbe reagent, and a stereoselective second DA reaction with electron-deficient dienophiles. The use of enantioselective DA reactions in the initial reaction enables access to chiral polyring-fused heterocyclic compounds with multiple chiral centres.

Triflic acid-promoted cycloisomerization of 2-alkynylphenyl isothiocyanates and isocyanates: a novel synthetic method for a variety of indole derivatives.

A new approach towards the synthesis of indole derivatives via triflic acid-promoted cycloisomerization with rearrangement of 2-(alkyn-1-yl)phenyl isothiocyanates and 2-(alkyn-1-yl)phenyl isocyanates has been achieved. By this methodology, structurally diverse types of indole derivatives such as thieno- and furo-indoles, spiro-indolethiones, spiro-oxindoles, and 3-alkylidene-oxindoles were synthesized.

The diene-transmissive hetero-Diels-Alder reaction of 2-vinyl α,ß-unsaturated aldimines: stereoselective synthesis of hexahydroquinazolin-2-ones.

Stereoselective synthesis of hexahydroquinazolin-2(1H)-ones has been achieved through the application of the diene-transmissive hetero-Diels-Alder methodology to 2-vinyl-1-aza-1,3-butadienes. The cross-conjugated 1-azatriene underwent an initial hetero-Diels-Alder reaction on the 1-aza-1,3-butadiene system with tosyl isocyanate to afford the [4 + 2] mono-cycloadduct pyrimidinone. The second Diels-Alder reaction on the electron-rich 1-amino-1,3-diene unit of the mono-cycloadduct with dienophiles provided hexahydroquinazolin-2(1H)-ones with high stereoselectivity.

Medical students' and residents' conceptual structure of empathy: a qualitative study.

BACKGROUND: Empathy is a crucial component of medicine. However, many studies that have used quantitative methods have revealed decline of learners' empathy during undergraduate and postgraduate medical education. We identified medical students' and residents' conceptual structures of empathy in medicine to examine possible differences between the groups in how they conceive empathy. METHODS: We conducted a qualitative study with two focus group discussions in which six medical students and seven residents participated separately. The transcripts of the focus group discussions were analysed combining qualitative data analysis and theoretical coding. RESULTS: Medical students and residents had different conceptual structures of empathy. While medical students thought that sharing emotions with patients was essential to showing empathy, residents expressed empathy according to their evaluation of patients' physical and mental health status. If the residents thought that showing empathy was necessary for the care of patients, they could show it, regardless of whether they shared the patients' emotions or not. CONCLUSIONS: The comparison of medical students' and residents' conceptual structures of empathy reveals a qualitative difference. Residents show more empathy to their patients by a cognitive decision as clinicians than medical students do. Communication skills training should consider the qualitative change of students' and residents' empathy with clinical experience. We should consider the change when we evaluate learners' empathy and introduce methods that cover the qualitative range of empathy.

Rh(III)-catalyzed directed C-H bond amidation of ferrocenes with isocyanates.

[RhCp*(OAc)(2)(H(2)O)] [Cp* = pentamethylcyclopentadienyl] catalyzed the C-H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF(4)·OEt(2). A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities.

Changes of left ventricular remodeling due to increased afterload in patients with essential hypertension.

BACKGROUND: It is unclear whether afterload mismatch occurs during the initial stage of essential hypertension (EHT). Additionally, critical left ventricular hypertrophy (LVH) between preserved and reduced systolic functions in hypertension is also unclear. Thus, we aimed to clarify these points. METHODS: Forty-five normal control subjects (NCS) and 140 EHT patients participated. EHT patients were subdivided into three groups: group I, without LVH (n = 37); group II, with LVH (n = 80); and group III, with LVH and LV heart failure (LVHF) (n = 23). Routine electrocardiographic and echocardiographic parameters, V5R/V6R ratio, relative wall thickness (RWT), LV mass (LVM) index, and peak systolic wall stress (PSWS) were measured. RESULTS: In group I, LV systolic functions were preserved despite the increase of PSWS. In group II, LVH advanced, but LV systolic functions remained normal. A negative T-wave was observed in 69% of group II and 100% of group III. A significant correlation between RWT and LVM index was seen in NCS and groups I and II (r2 = 0.545, P < 0.0001) but not in group III. Afterload mismatch occurred in group III due to the decrease in V5R/V6R ratio, the increase of LV end-diastolic dimension, and the LV systolic dysfunctions, which are caused by exhaustion of preload reserve. The boundary of the LVM index between groups II and III was approximately 180 g/m2. CONCLUSION: Afterload mismatch did not occur in group I, but it was observed in group III due to the exhaustion of preload reserve.

Can Japanese students embrace learner-centered methods for teaching medical interviewing skills? Focus groups.

BACKGROUND: Students' perceptions of learner-centered methods for teaching medical interviewing skills have not been fully explored. AIM: To explore Japanese students' perceptions of learner-centered methods for teaching medical interviewing skills such as role play with student-created scenarios, peer-assisted video reviews, and student-led small group debriefing. METHODS: We conducted three focus groups with a total of 15 students who participated in the learner-centered seminars on medical interviewing skills at the Nagoya University School of Medicine. The transcripts were analyzed by two authors independently. Keywords and concepts were identified and a thematic framework was developed. RESULTS: Overall, students valued the experience of writing their own scenarios for role play, but some questioned their realism. Many students commented that peer-assisted video reviews provided them with more objective perspectives on their performance. However, some students expressed concerns about competitiveness during the video reviews. While students appreciated teachers' minimum involvement in the group debriefing, some criticized that teachers did not explain the objectives of the seminar clearly. Many students had difficulties in exchanging constructive feedback. CONCLUSION: We were able to gain new insights into positive and negative perceptions of students about learner-centered methods for teaching medical interviewing skills at one medical school in Japan.

Baby's Online Live Database: An Open Platform for Developmental Science.

Efficient data collection in developmental studies is facing challenges due to the decreased birth rates in many regions, reproducibility problems in psychology research, and the COVID-19 pandemic. Here, we propose a novel platform for online developmental science research, the Baby's Online Live Database (BOLD), which extends the scope of the accessible participant pool, simplifies its management, and enables participant recruitment for longitudinal studies. Through BOLD, researchers can conduct online recruitment of participants preregistered to BOLD simply by specifying their attributes, such as gender and age, and direct the participants to dedicated webpages for each study. Moreover, BOLD handles participant recruitment and reward payment, thereby freeing researchers from the labor of participant management. BOLD also allows researchers the opportunity to access data that were collected from participants in previous research studies. This enables researchers to carry out longitudinal analyses at a relatively low cost. To make BOLD widely accessible, a consortium was formed within the Japan Society of Baby Science, where members from diverse research groups discussed the blueprint of this system. Once in full-scaled operation, BOLD is expected to serve as a platform for various types of online studies and facilitate international collaboration among developmental scientists in the near future.

A facile synthesis of pyrrolo[2,3-b]quinolines via a Rh(I)-catalyzed carbodiimide-Pauson-Khand-type reaction.

A new straightforward synthetic method for 2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-2-ones via a [RhCl(CO)(2)](2)-dppp catalyzed Pauson-Khand-type reaction of N-[2-(2-alkyn-1-yl)phenyl]carbodiimides is reported.

Dieldrin uptake and translocation in plants growing in hydroponic medium.

It has been known that the Cucurbitaceae family takes up a large amount of persistent organic pollutants from soils and that the translocation of those compounds in cucurbits is higher than those in non-cucurbits. To understand the persistent organic pollutant uptake mechanisms of plant species, we compared the dieldrin absorption and transportation potentials of several plants in hydroponic medium. Sorghum (Sorghum vulgare Moench), sunflower (Helianthus annuus L.), soybean (Glycine max), komatsuna (Brassica rapa var. peruviridis), white-flowered gourd (Lagenaria siceraria var. hispida), cucumber (Cucumis sativus L.), and zucchini (Cucurbita pepo L.) were grown in a dieldrin-added hydroponic medium for 10 d, and then the amount of dieldrin in their shoots and roots was measured. All of the roots contained dieldrin, whereas only the cucurbits (white-flowered gourd, cucumber, and zucchini) contained considerable amounts of dieldrin in their shoots. The dieldrin uptake to the roots depended on the concentration of the n-hexane soluble components in the roots, regardless of whether the dieldrin in the roots was translocated to shoots or not. The dieldrin uptake from the solution to the roots was thought to be due to a passive response, such as adsorption on the roots. The translocation of dieldrin from the roots to the shoots was probably through the xylems. The amounts of dieldrin in the shoots per transpiration rates were higher for cucurbits than for non-cucurbits. It seems likely that cucurbits have uptake mechanisms for hydrophobic organic chemicals.