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Photochemical reactions are powerful tools for synthesizing organic molecules. The input of energy provided by light offers a means to produce strained and unique molecules that cannot be assembled using thermal protocols, allowing for the production of immense molecular complexity in a single chemical step. Furthermore, unlike thermal reactions, photochemical reactions do not require active reagents such as acids, bases, metals, or enzymes. Photochemical reactions play a central role in green chemistry. This article reports the isolation and structure determination of four new compounds (1-4) from the photoreaction products of the Polyozellus multiplex MeOH ext. The structures of the new compounds were elucidated using MS, IR, comprehensive NMR measurements and microED. The four compounds were formed by deacetylation of polyozellin, the main secondary metabolite of P. multiplex, and addition of singlet oxygen generated by sunlight. To develop drugs for treating Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the compounds (1-4) obtained by photoreaction were evaluated for BACE1 inhibitory activity. The hydrolysates (5 and 6) of polyozellin, the main secondary metabolites of P. multiplex, were also evaluated. The photoreaction products (3 and 4) and hydrolysates (5 and 6) of polyozellin showed BACE1 inhibitory activity (IC 50 : 2.2, 16.4, 23.3, and 5.3 μM, respectively)., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Scope: Obesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)-supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure., Methods and Results: ICR mice are fed AIN-93G formula-based cellulose -, FOS-, acetate-, or propionate-supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS-fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice., Conclusion: The findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

The initial means of detecting right ventricular (RV) dilatation is often transthoracic echocardiography (TTE), and once the presence of RV dilatation is suspected, there is the possibility of RV volume overload, RV pressure overload, RV myocardial disease, and even nonpathological RV dilatation. With respect to congenital heart disease with RV volume overload, defects or valvular abnormalities can be easily detected with TTE, with the exception of some diseases. Volumetric assessment using three-dimensional echocardiography may be useful in determining the intervention timing in these diseases. When the disease progresses in patients with pulmonary hypertension as a result of RV pressure overload, RV dilatation becomes more prominent than hypertrophy, and RV functional parameters predict the prognosis at this stage of maladaptive remodeling. The differential diagnosis of cardiomyopathy or comparison with nonpathological RV dilatation may be difficult in the setting of RV myocardial disease. The characteristics of RV functional parameters such as two-dimensional speckle tracking may help differentiate RV cardiomyopathy from other conditions. We review the diseases presenting with RV dilatation, their characteristics, and echocardiographic findings and parameters that are significant in assessing their status or intervention timing., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Staphylococcus lugdunensis, a minor species of coagulase-negative staphylococci, has attracted attention because of its formidable pathogenicity. We present a case of infective endocarditis (IE) caused by S. lugdunensis in a 72-year-old woman with a history of breast cancer and metastases who presented with fever. Two of two blood culture bottles were positive for gram-positive cocci. Transesophageal echocardiography revealed vegetation attached to the right cusp of the aortic valve and an abscess in the annulus, which was less evident on transthoracic echocardiography. This case underscores the importance of considering S. lugdunensis as a potential cause of IE.

Platypnea-orthodeoxia syndrome (POS) attributed to patent foramen ovale (PFO) can be caused by a variety of clinical conditions. A 70-year-old woman was admitted to our hospital for further evaluation of POS. Her symptoms developed along with the spread of infiltrative shadows in both lower lung fields during the preceding 2 years. Contrast transthoracic echocardiography with agitated saline revealed grade III intracardiac right-to-left shunting, presumably across a PFO. Transesophageal echocardiography demonstrated severe tricuspid regurgitation (TR) caused by the prolapse of the anterior leaflet. Bidirectional shunt flow, mainly from right-to-left across a PFO, that increased in the sitting position was also observed. She was diagnosed as having PFO associated with severe primary TR. Therefore, tricuspid valve repair and direct PFO closure were performed. Her symptoms resolved completely soon after the operation and her oxygen saturation was maintained. This patient's disease seemed to have worsened with the spread of pulmonary parenchymal involvement, which caused ventilation-perfusion mismatch and elevation of alveolar pressures. Echocardiography is an essential imaging modality in addition to other diagnostic examinations and imaging studies when assessing the pathogenesis in patients with POS., Learning Objective: Platypnea-orthodeoxia syndrome (POS) associated with patent foramen ovale may be caused by a variety of clinical conditions, and POS in our patient may be caused by the worsening of pulmonary parenchymal involvement. Examinations to evaluate all causes of POS are essential for making the diagnosis. Contrast transthoracic echocardiography was useful in assessing the cause of POS., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: Collaboration among medical facilities is crucial to deliver comprehensive epilepsy care to a diverse and large population of people with epilepsy. We conducted a survey among medical facilities of various sizes throughout Japan to investigate the status of epilepsy care delivery, functioning, and referral., Methods: With the cooperation of the Japan Neurological Society (1428 facilities), Japanese Neurosurgical Society (3489 specialists), and Epilepsy Care Network (948 facilities), a questionnaire was mailed to 5865 locations that provide epilepsy care in Japan. The facilities were classified into clinics (19 beds or less), small hospitals (SH, 20-199 beds), large hospitals (LH, 200 beds or more), and epilepsy centers (EC). The status of epilepsy care delivery, functioning, and referral was compared among the four groups., Results: Responses were received from 1014 facilities (17.3% response rate). After excluding duplicate responses, 957 facilities were analyzed (394 clinics, 149 SH, 388 LH, 26 EC). EC responded "manageable" in more items of epilepsy care functions in general, especially those related to epilepsy surgery, compared to LH with similar facility size. However, EC responded being less manageable in psychiatric service (61.5%), dietary therapy (46.2%), rehabilitation (53.8%), and patient employment support (61.5%). The percentage of facilities that responded "always able to refer" was highest in clinics (67.6%) and the lowest in EC (40%). Referral difficulties were more commonly encountered in EC, and less common in clinics. In EC, the most common reason for inability to refer was patient or family refusal (64%)., Significance: We have clarified the epilepsy care delivery, functioning, and referral in facilities of various sizes in Japan. This study highlights the issues of downward referral and patient stagnation in EC, which have not received much attention., Plain Language Summary: A nationwide survey of healthcare facilities ranging in size from small clinics to large hospitals in Japan examined medical care delivery and patient referrals related to epilepsy. Compared to other facilities, epilepsy centers provided a variety of medical services to people with epilepsy but were inadequate in addressing psychiatric symptoms, providing dietary therapy, rehabilitation, and patient employment support. Referrals from epilepsy centers to other medical facilities were often refused by patients and their families. This results in patient crowding at epilepsy centers., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Worsening mitral regurgitation (MR) is a complication of intervention for atrial septal defect (ASD). Little is known about mitral valve (MV) characteristics associated with worsening MR. We aimed to elucidate MR outcomes and predictors of worsening MR after transcatheter ASD closure., Methods: We analyzed changes in MR from prior to transcatheter ASD closure to 6 months after the procedure and predictors of worsening MR via baseline transthoracic echocardiography in 238 patients (64.7% females; mean age, 53 ± 22 years)., Results: Worsening MR was defined as worsening to moderate in patients with less than or equal to mild MR at baseline or vena contracta width increasing of ≥2 mm by 6-month follow-up in patients with moderate MR. Worsening MR was observed in 29 patients (12.2%). The associated echocardiographic findings were pseudoprolapse, hamstringing, stiffness, and anteroposterior and intercommissural mitral annulus diameter in the univariable logistic regression analysis (all P < 0.05). Multivariable analysis after adjusting for age; long-standing persistent atrial fibrillation; and ASD size showed that models combining MV leaflet findings such as pseudoprolapse or hamstringing, or anterior leaflet stiffness with the ratio of the sum of anterior and posterior leaflet lengths to intercommissural mitral annulus diameter were statistically significant for predicting worsening MR (R 2  = 0.393, P < 0.001 and R 2  = 0.385, P < 0.001, respectively)., Conclusions: Worsening MR after transcatheter ASD closure might depend on MV leaflet findings and annulus size in patients with long-standing persistent atrial fibrillation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Open axillary arterial injury is life-threatening, and upper-extremity reperfusion must be performed within approximately 6 h. We present the case of a patient who underwent reperfusion of the upper limb and nerve reconstruction of the post-ganglionic brachial plexus injury in one stage while maintaining stable vital signs. The injury was an avulsion with no fracture. Nerve grafting was necessary to reconstruct the nerves without tension. Although the sural nerve is commonly used, we decided to sacrifice the ipsilateral ruptured ulnar nerve because it was less likely to recover over a long reinnervation distance. Nine months postoperatively, the patient was able to flex the elbow and rotate the forearm, although finger function was poor. Nevertheless, the patient could use the hand to assist her in performing daily activities and return to the previous workplace as a clerk. J. Med. Invest. 71 : 332-334, August, 2024.

Background: Residual regurgitation after transcatheter edge-to-edge mitral valve repair (TMVR) is a predictor of poor prognosis in patients with functional mitral regurgitation (FMR). This study sought to identify the mitral valve (MV) parameters measured by three-dimensional transesophageal echocardiography (3D-TEE) and MV leaflet features that predict residual mitral regurgitation (MR) after TMVR in patients with FMR., Methods: Consecutive patients with FMR who underwent TMVR were classified into two groups based on the degree of residual MR just after TMVR: < 2+ in the optimal MR reduction group and ≥ 2+ in the suboptimal MR reduction group. The two groups were compared with respect to 3D-TEE parameters and the MV leaflet features, including the following parameters: stiffness, defined as a leaflet that remains at a fixed angle even during diastole, and thickness, measured in both clear and rough zones., Results: Thirty-four of 46 patients (74%) were classified as the optimal MR reduction group. Multivariable analysis showed that anterior mitral leaflet + posterior mitral leaflet length/anteroposterior annulus diameter (p = .044) and MV leaflet stiffness (p = .007) were independent predictors of residual MR., Conclusion: MV leaflet stiffness and the ratio of MV leaflet lengths to the annulus diameter may be good predictors of residual MR after TMVR in patients with FMR., (© 2023 Wiley Periodicals LLC.)

(-)-Epigallocatechin gallate (EGCG), a key component of green tea, exerts therapeutic anticancer and antiallergic properties through its binding to the 67 kDa laminin receptor. The functionalization of EGCG is a promising strategy for creating new drug candidates and chemical probes. In our study, we developed a method for effectively modifying the A ring of EGCG through an electrophilic aromatic substitution with amidomethyl 2-alkynylbenzoates initiated with a gold complex. The 2-alkynylbenzoates treated with (Ph 3 P)AuOTf under neutral conditions yielded N -acylimines. A further electrophilic aromatic substitution resulted in a mixture of EGCG substituted with acylaminomethyl groups at the 6 and 8 positions with a significant amount noted at the 6 position. We then explored the synthesis of 18 F-labeled EGCG with a neopentyl labeling group, an effective labeling group for radiohalogens of not only fluorine-18 but also of astatine-211. To achieve this, we prepared precursors that possessed acid-sensitive protecting groups and base-unstable leaving groups using our established method. Substitution of EGCG with a neopentyl labeling group at either the C6 or C8 position did not affect its anticancer efficacy in U266 cells. Finally, we investigated the preparation of 18 F-labeled EGCG. The 18 F-fluorination of a mixture of 6- and 8-substituted precursors yielded the corresponding 18 F-labeled compounds in 4.5% and 3.0% radiochemical yields (RCYs), respectively. Under acidic conditions, the 18 F-labeled 8-substituted compound produced 18 F-labeled EGCG in 37% RCY, which heralds the potential of our functionalization approach.

Objectives: Ultrasonography is an essential examination performed in various clinical fields. The number of clinical sonographers has been increasing. However, the working environments and conditions at each facility are different, leading to diverse problems. Among them, the emerging issue is the sexual disagreement between the sonographer and patient at the time of echocardiography. Since the patient must expose their breast during echocardiography, female patients may refuse to undergo the examination when conducted by a male sonographer. This study aimed to conduct a questionnaire survey to understand the measures for sonographer-patient gender mismatch at different facilities., Methods: A questionnaire on the implementation of echocardiography by male sonographers for female patients was answered by representatives and specialist technicians of the Japanese Society of Echocardiography., Results: Questionnaire responses were obtained from 50 facilities (59 participants). A total of 70% of the facilities restricted male sonographers from conducting echocardiography examinations for female patients. Among them, 81% of the facilities serviced female patients aged 60 years or younger., Conclusions: It has become clear that the gender selection of echocardiographic examiners varies from facility to facility, and providing a sufficient explanation before echocardiographic examination is necessary to avoid causing uncomfortable situations for female patients., (© 2022. Japanese Society of Echocardiography.)

We sought to clarify characteristics of patients with severe aortic stenosis (AS) in whom transvalvular mean pressure gradient (MPG) was underestimated with Doppler compared with catheterization. Study subjects included 127 patients with severe AS who underwent transcatheter aortic valve implantation. Between subjects with Doppler MPG underestimation ≥10 mm Hg (group U) and those without (group C), we retrospectively compared echocardiographic parameters and aortic valve calcification score using the Agatston method. Despite a strong correlation (r S = 0.88) and small absolute difference (2.1 ± 10.1 mm Hg) between Doppler and catheter MPG, 27 patients (21%) were in group U. Among 48 patients with catheter MPG ≥60 mm Hg, 10 patients (21%) revealed Doppler MPG of 40 to 59 mm Hg, suggesting they had been misclassified as having severe AS instead of very severe AS. According to the guidelines, indication of valve replacement for patients without symptoms should be considered for very severe AS but not for severe AS. Therefore, sole reliance on Doppler MPG could cause clinical misjudgments. Group U had larger relative wall thickness (median [interquartile range: 0.60 [0.50 to 0.69] vs 0.53 [0.46 to 0.60], p = 0.003) and higher calcification score (3,024 [2,066 to 3,555] vs 1,790 [1,293 to 2,501] arbitrary units, p <0.001). Both calcification score (per 100 arbitrary unit increment, odds ratio 1.10, 1.04 to 1.17, p = 0.002) and relative wall thickness (per 0.05 increment, odds ratio 1.29, 95% confidence interval 1.05 to 1.60, p = 0.02) were independently associated with Doppler underestimation. In conclusion, Doppler might underestimate transvalvular gradient compared with catheterization in patients with severe AS who have heavy valve calcification and prominent concentric remodeling left ventricular geometry., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: This study aimed to clarify the relationship between cardiovascular prognosis and left ventricular hypertrophy (LVH) in patients with severe aortic stenosis who underwent transcatheter aortic valve replacement (TAVR) and to investigate the relationship between cardiac sympathetic nerve (CSN) function and these factors using 123 I-metaiodobenzylguanidine scintigraphy., Methods and Results: In this single-centre, retrospective observational study, 349 patients who underwent TAVR at our institution between July 2017 and May 2020 were divided into two groups: those with severe LVH pre-operatively [severe LVH (+) group] and those without LVH pre-operatively [severe LVH (-) group]. The rates of freedom from cardiovascular events (cardiovascular death and heart failure hospitalization) were compared. The relationship between changes in left ventricular mass index (LVMi) and changes in delay heart-mediastinum ratio (H/M) from before TAVR to 6 months after TAVR was also investigated. The event-free rate was significantly lower in the severe LVH (+) group (87.1% vs. 96.0%, log-rank P = 0.021). The severe LVH (+) group exhibited a significantly lower delay H/M value, scored by 123 I-metaiodobenzylguanidine scintigraphy, than the severe LVH (-) group (2.33 [1.92-2.67] vs. 2.67 [2.17-3.68], respectively, P < 0.001). Moreover, the event-free rate of post-operative cardiovascular events was lower among patients with a delay H/M value < 2.50 than that among other patients (87.7% vs. 97.2%, log-rank P = 0.012). LVMi was significantly higher (115 [99-130] vs. 90 [78-111] g/m 2 , P < 0.001) and delay H/M value was significantly lower (2.53 [1.98-2.83] vs. 2.71 [2.25-3.19], P = 0.025) in the severe LVH (+) group than in the severe LVH (-) group at 6 months after TAVR. Patients with improved LVH at 6 months after TAVR also had increased delay H/M (from 2.51 [2.01-2.81] to 2.67 [2.26-3.02], P < 0.001), whereas those without improved LVH had no significant change in delay H/M (from 2.64 [2.23-3.06] to 2.53 [1.97-3.00], P = 0.829)., Conclusions: Severe LVH before TAVR is a prognostic factor for poor post-operative cardiovascular outcomes. LVH associated with aortic stenosis and CSN function are correlated, suggesting their involvement in LVH prognosis., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Lower limbs' arterial calcification is significantly associated with the clinical severity of lower extremity artery disease (LEAD) in patients undergoing hemodialysis (HD). However, the association between arterial calcification of the lower limbs and long-term clinical outcomes in patients on HD has not been elucidated. Calcification scores of the superficial femoral artery (SFACS) and below-knee arteries (BKACS) were quantitatively evaluated in 97 HD patients who were followed for 10 years. Clinical outcomes, including all-cause and cardiovascular mortality, cardiovascular events, and limb amputation were evaluated. Risk factors for clinical outcomes were evaluated using univariate and multivariate Cox proportional hazard analyses. Furthermore, SFACS and BKACS were divided into three groups (low, middle, and high), and their associations with clinical outcomes were evaluated using Kaplan-Meier analysis. SFACS, BKACS, C-reactive protein, serum albumin, age, diabetes, presence of ischemic heart disease, and critical limb-threatening ischemia were significantly associated with 3-year and 10-year clinical outcomes in the univariate analysis. Multivariate analysis showed that SFACS was an independent factor associated with 10-year cardiovascular events and limb amputations. Kaplan-Meier life table analysis showed that higher SFACS and BKACS levels were significantly associated with cardiovascular events and mortality. In conclusion, long-term clinical outcomes and the risk factors in patients undergoing HD were evaluated. Arterial calcification of the lower limbs was strongly associated with 10-year cardiovascular events and mortality in patients undergoing HD.

Objectives: Zinc deficiency (Zn < 60 μg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis (HD) patients., Methods: Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn <60 μg/dL during pre-HD blood sampling. The association between zinc deficiency and aorta stiffness was analyzed. Aorta stiffness was evaluated as brachial-ankle pulse wave velocity (baPWV). Other surrogate markers for cardiovascular complications were also measured., Results: The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (p<0.05). After adjusting for hypoalbuminemia, and CRP, multivariate analysis showed that age and zinc level were independent predictors of baPWV., Conclusion: The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ishioka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accumulating evidence indicates that social stress in the juvenile period affects hypothalamic-pituitary-adrenal (HPA) axis activity in adulthood. The biological mechanisms underlying this phenomenon remain unclear. We aimed to elucidate them by comparing adult mice that had experienced social isolation from postnatal day 21-35 (juvenile social isolation (JSI) group) with those reared normally (control group). JSI group mice showed an attenuated HPA response to acute swim stress, while the control group had a normal response to this stress. Activity levels of the paraventricular nucleus in both groups were comparable, as shown by c-Fos immunoreactivities and mRNA expression of c-Fos, Corticotropin-releasing factor (CRF), Glucocorticoid receptor, and Mineralocorticoid receptor. We found greater vascular coverage by tanycytic endfeet in the median eminence of the JSI group mice than in that of the control group mice under basal condition and after acute swim stress. Moreover, CRF content after acute swim stress was greater in the median eminence of the JSI group mice than in that of the control group mice. The attenuated HPA response to acute swim stress was specific to JSI group mice, but not to control group mice. Although a direct link awaits further experiments, tanycyte morphological changes in the median eminence could be related to the HPA response., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Fermented foods demonstrate remarkable health benefits owing to probiotic bacteria or microproducts produced via bacterial fermentation. Fermented foods are produced by the fermentative action of several lactic acid bacteria, including Leuconostoc mesenteroides ; however, the exact mechanism of action of these foods remains unclear. Here, we observed that prebiotics associated with L. mesenteroides -produced exopolysaccharides (EPS) demonstrate substantial host metabolic benefits. L. mesenteroides -produced EPS is an indigestible α-glucan, and intake of the purified form of EPS improved glucose metabolism and energy homeostasis through EPS-derived gut microbial short-chain fatty acids, and changed gut microbial composition. Our findings reveal an important mechanism that accounts for the effects of diet, prebiotics, and probiotics on energy homeostasis and suggests an approach for preventing lifestyle-related diseases by targeting bacterial EPS.

Background: Abnormal blood pressure response (ABPR) has been reported to be a risk factor for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). We aimed to elucidate the relationship between ABPR during exercise stress echocardiography (ESE) and impaired left ventricular (LV) contractile reserve based on two-dimensional strain in patients with HCM., Methods: Patients with HCM underwent ESE with treadmill exercise. Patients whose blood pressure elevation at maximum workload was lower than 20 mmHg from baseline were classified as having ABPR. Echocardiographic parameters were compared between patients with and without ABPR.  Results: Of 26 patients with HCM, nine patients were diagnosed with ABPR. Significant LV outflow tract obstruction (>50 mmHg) was provoked only in one patient with ABPR (baseline to the conclusion of the exercise, 15.2 mmHg to 63.0 mmHg). Change in cardiac output (CO) and the ratio of early diastolic velocity to early annular velocity (E/e') from baseline to just after the conclusion of exercise did not differ between patients with and without ABPR (CO, 102±40% vs. 122±45%, P = 0.19; E/e', 4±22% vs. 2±20%, P = 0.86). Change in systemic vascular resistance change was not significant (patients with vs. without ABPR, -52±10% vs. -46±13%, P = 0.24). Percent change in LV global longitudinal strain was lower in patients with ABPR than patients without ABPR (12±17% vs. 27±15%, P = 0.02)., Conclusion: In conclusion, impaired LV contractile reserve during exercise might contribute to ABPR in patients with HCM., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Takeoka et al.)

This case involved an 82-year-old man with a history of diabetes mellitus and myocardial infarction. He was undergoing treatment with 2 oral antiplatelet agents. The patient presented to our hospital for carcinomatous pyloric stenosis caused by type 4 advanced gastric cancer. Although distal gastrectomy was planned, preoperative coronary angiography revealed triple- vessel coronary artery disease. Therefore, surgery was performed under management of intra-aortic balloon pumping (IABP)therapy. The patient's hemodynamics at the time of the operation were stable, and no perioperative cardiovascular complications occurred. However, the patient was not able to start an oral diet because of impaired swallowing function. Although he underwent daily swallowing rehabilitation, he died of aspiration pneumonia 40 days postoperatively. There are many reports of cancer resection under IABP management for patients with severe heart disease. Because the perioperative hemodynamics were stable in all 21 reported cases of digestive malignant tumor resections in Japan, an IABP is suggested to be very effective for patients with severe heart disease. However, early death has also occurred, as in the present case. Close attention to the indications for IABP therapy is needed, especially in elderly patients, in consideration of not only cancer and heart disease but also preoperative activities of daily living.

Dysbiosis is associated with various diseases. The composition and diversity of gut microbiota affect host physiology through the production of bioactive metabolites. Short-chain fatty acids are the main metabolites produced by microbial fermentation of dietary fiber. They play a crucial role in maintaining metabolic, nervous, and immune system. Short-chain fatty acids not only serve as an energy source for the host but also act as for G-protein-coupled receptor signaling molecules and histone deacetylase inhibitors. In particular, the discovery and deorphanization of free fatty acid receptors 2 and 3 (GPR43/41) have shed light on the molecular mechanisms underlying the regulation of physiological processes by short-chain fatty acids. The short-chain fatty acid receptors sense the nutrient status and transduce signals to maintain cellular homeostasis. Dysbiosis affects short-chain fatty acid production and impairs the signaling, leading to cellular dysfunction. We review the current understanding of short-chain fatty acid-mediated regulation of physiological processes and discuss the molecular pharmacology of short-chain fatty acid and the receptor. We also discuss recent advances in the use of prebiotics and probiotics in the treatment of disease., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear., Methods: Patients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. 123 I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart-mediastinum ratio (H/M) and washout rate., Results: Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029)., Conclusion: CSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity., (© 2021. American Society of Nuclear Cardiology.)

During transfemoral (TF) or transcatheter aortic valve replacement (TAVR), transesophageal echocardiography (TEE) sometimes reveals an unexpected mobile membranous mass on the catheter tip within the proximal part of the descending thoracic aorta. Such mobile masses may cause critical embolic events if the TAVR device advances into the ascending aorta in the absence of preventive measures. This study aimed to investigate the incidence and predictors of emboligenic matter (EM) during TAVR, impact of EM on the procedure, and incidence of symptomatic ischemic stroke post procedure. Among 436 consecutive patients who underwent TF-TAVR, 407 were evaluated in this study. The primary end point was incidence of symptomatic ischemic stroke within 24 h post procedure while taking appropriate preventive measures. Incidence of EM, factors associated with EM, and the impact of EM on the procedure were also investigated. Among the 407 cases, 15 cases (3.7%) of EM were identified but no ischemic stroke occurred in the EM (+) group (0% vs. 2.04%, p = 1.00). In the EM (+) group, a self-expandable valve was used in all 15 cases (100% vs. 42.6%, p < 0.0001) while 14 cases used a CoreValve's InLine sheath system initially (93.3% vs. 27.3%, p < 0.0001). CoreValve's InLine sheath system usage was the only independent predictor of EM. The CoreValve's InLine delivery system was identified as a predictor of EM during TF-TAVR, but symptomatic ischemic stroke was avoided while taking appropriate embolization preventive measures., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: No study has evaluated the prognostic value of the chronic kidney disease (CKD) classification by cystatin C-based estimated glomerular filtration rate (eGFR) (CKD Cys classification) in patients undergoing transcatheter aortic valve replacement (TAVR). This study aimed to compare the prognostic value of CKD Cys classification and CKD classification by creatinine-based eGFR (CKD Cr classification) in risk prediction after TAVR., Methods and Results: We retrospectively analysed consecutive 219 patients with symptomatic severe aortic stenosis who underwent TAVR at our institute between December 2016 and June 2019. Pre-operative CKD Cr and CKD Cys classifications were evaluated for their prognostic value of 2-year major adverse cardiovascular and cerebrovascular events (MACCE) after TAVR. MACCE was defined as the composite of all-cause mortality, non-fatal myocardial infarction, stroke, and rehospitalization for worsening congestive heart failure. Participants had a median age of 86.0 years and were predominantly female (76.9%). In 96.6% of the cases, TAVR was performed using transfemoral access. The median creatinine-based eGFR (52.85 mL/min/1.73 m 2 ) was higher than the cystatin C-based eGFR (41.50 mL/min/1.73 m 2 ). Downward reclassification in CKD stages based on eGFR Cys was observed in 49.0% of patients. During a median follow-up period of 575.5 (interquartile range: 367.0-730.0) days, 58 patients presented with MACCE. CKD Cys classification, but not CKD Cr classification, significantly stratified the risk of 2-year MACCE in patients after TAVR by log-rank test (P = 0.003). In multivariate Cox regression analysis, only CKD Cys stage 3b [hazard ratio (HR) = 4.37; 95% confidence interval (CI): 1.28-14.91; P = 0.019] and CKD Cys stage 4 + 5 (HR = 3.72; 95% CI: 1.06-12.99; P = 0.040) were significant predictors of MACCE after adjustment for potential confounders., Conclusions: The CKD Cys classification could better assess the risk than the CKD Cr classification in patients undergoing TAVR. CKD Cys stage 3b and stage 4 + 5 correlated with adverse outcomes., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Silk fibroin exhibits high biocompatibility and biodegradability, making it a versatile biomaterial for medical applications. However, contaminated silkworm-derived substances in remnant sericin from the filature and degumming process can result in undesired immune reactions and silk allergy, limiting the widespread use of fibroin. Here, we established transgenic silkworms with modified middle silk glands, in which sericin expression was repressed by the ectopic expression of cabbage butterfly-derived cytotoxin pierisin-1A, to produce cocoons composed solely of fibroin. Intact, nondegraded fibroin can be prepared from the transgenic cocoons without the need for sericin removal by the filature and degumming steps that cause fibroin degradation. A wide-angle X-ray diffraction analysis revealed low crystallinity in the transgenic cocoons. However, nondegraded fibroin obtained from transgenic cocoons enabled the formation of fibroin sponges with varying densities by using 1-5% ( v / v ) alcohol. The effective chondrogenic differentiation of ATDC5 cells was induced following their cultivation on substrates coated with intact fibroin. Our results showed that intact, allergen-free fibroin can be obtained from transgenic cocoons without the need for sericin removal, providing a method to produce fibroin-based materials with high biocompatibility for biomedical uses.

Background: The reduction in exercise capacity after mitral valve repair (MVr) for severe degenerative mitral regurgitation is an unsolved issue. This study aimed to evaluate hemodynamics after MVr using a partial semirigid band during exercise stress echocardiography and to identify predictive factors for achieving better exercise capacity after MVr., Methods: We retrospectively analyzed 48 patients using exercise stress echocardiography within 5 years of having undergone MVr using a partial semirigid band between 2013 and 2019. Values of maximal workload were converted into numbers of metabolic equivalents (METs) achieved for each patient. Age and sex expected METs (eMETs) were obtained, and percent eMETs (%eMETs [achieved METs / eMETs × 100]) were calculated. Multivariable linear regression analysis was used to identify the determinants of %eMETs., Results: Only one third of patients achieved eMETs. Significant determinants of %eMETs were age at exercise stress echocardiography (β coefficient 0.64; 95% confidence interval, 0.31 to 0.96; P < .001), female sex (β coefficient 16.9; 95% confidence interval, 8.58 to 25.17; P < .001), and larger indexed device size (device size/body surface area; β coefficient 4.10; 95% confidence interval, 1.74 to 6.46; P = .001). Receiver-operating characteristic curve analysis revealed that a cutoff value of 19.5 mm/m 2 or greater indexed device size was optimal for achieving %eMETs greater than 100%, with a sensitivity and specificity of 87% and 79%, respectively., Conclusions: Patients with larger indexed device size achieved greater exercise capacity after MVr using a partial semirigid band. Preoperative evaluation to decide whether we can use an annuloplasty device larger than 19.5 mm/m 2 may be important for patients who intend to exercise with high intensity., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We reconstructed a segmental bone defect in a finger associated with a dorsal skin defect using a bone graft covered with a free medial femoral condyle periosteal flap and a skin graft in two patients. The vascularised periosteal flap (VPF) improved the survival of the bone graft and allowed the take of the skin graft. The use of a VPF can be considered in patients with crush injury of the digits with segmental loss of bone and dorsal skin Level of Evidence: Level V (Therapeutic).

The global dietary supplement market is valued at over USD 100 billion. One popular dietary supplement, S-adenosylmethionine, is marketed to improve joints, liver health and emotional well-being in the US since 1999, and has been a prescription drug in Europe to treat depression and arthritis since 1975, but recent studies questioned its efficacy. In our body, S-adenosylmethionine is critical for the methylation of nucleic acids, proteins and many other targets. The marketing of SAM implies that more S-adenosylmethionine is better since it would stimulate methylations and improve health. Previously, we have shown that methylation reactions regulate biological rhythms in many organisms. Here, using biological rhythms to assess the effects of exogenous S-adenosylmethionine, we reveal that excess S-adenosylmethionine disrupts rhythms and, rather than promoting methylation, is catabolized to adenine and methylthioadenosine, toxic methylation inhibitors. These findings further our understanding of methyl metabolism and question the safety of S-adenosylmethionine as a supplement., (© 2022. The Author(s).)

Background: It remains unclear whether contrast-induced nephropathy (CIN) has a prognostic impact on subsequent renal dysfunction and whether deteriorating renal function is a risk factor for CIN. This study aimed to evaluate the occurrence of CIN in patients with pre-existing renal dysfunction and investigate the long-term effects of worsening renal function after coronary angiography or contrast-enhanced computed tomography (CT). The prognostic factors of worsening renal dysfunction were also analyzed., Methods: This was a prospective cohort study of patients at risk for CIN, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 on coronary angiography or eGFR <45 mL/min/1.73 m 2 on contrast-enhanced CT. Serum creatinine levels and the 2-year prognosis were evaluated. CIN was defined as an increase in serum creatinine level by more than 0.5 mg/dL or a 25% increase from the previous value within 72 hours after contrast administration. The primary endpoint was the proportion of patients who had serum Cr doubling or induction of dialysis within 2 years according to CIN occurrence., Results: Of the 410 patients, 19 patients developed CIN (8/142 patients on coronary angiography and 11/268 patients on contrast-enhanced CT), and 38 patients had worsened renal function (21/142 patients on coronary angiography and 17/268 patients on contrast-enhanced CT). CIN was not associated with worsening renal function at 2 years. Analysis by renal function at the time of coronary angiography or contrast-enhanced CT (i.e., eGFR ≥30 ml/min/1.73 m 2 and eGFR ≤1.73 m 2 ) found no between-group difference in the occurrence of CIN., Conclusions: CIN is not a prognostic risk factor for the long-term of chronic kidney disease after coronary angiography or contrast-enhanced CT. Pre-existing renal dysfunction is also not a risk factor for CIN, even if the eGFR is <30 ml/min/1.73 m 2 ., Competing Interests: Competing Interests The authors report no conflicts of interest.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has demonstrated high efficacy at preventing coronavirus disease 2019 (COVID-19) and a favorable safety profile, however it has also been reported that COVID-19 vaccines may put increase of immune-mediated disease. We herein report a case of MPO-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis following the mRNA vaccine BNT162b2 (Pfizer/BioNTech) for COVID-19. Although the causal relationship between vaccine and ANCA-associated vasculitis is uncertain, environmental and genetic factors may have set the stage for the development of vasculitis, and the vaccine may have triggered a domino effect., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

A scalable synthesis of the cis -1,3-disubstituted cyclobutane carboxylic acid scaffold of TAK-828F ( 1 ) has been developed, featuring the diastereoselective reduction of a cyclobutylidene Meldrum's acid derivative with NaBH 4 . Controlling acidic impurities was crucial for improving the diastereomeric ratio by recrystallization. Furthermore, reaction optimization and the streamlining of several steps established a scalable synthetic method free from column chromatography purification with an overall yield improved from 23 to 39%.

Alzheimer disease (AD) is an irreversible, progressive brain disease. Amyloid β plays a critical role in AD development. Some Chinese traditional medicines, such as the fossilized plant resin, amber, have been applied as mental stabilizers. However, the effects of amber on AD pathogenesis remain unknown. Therefore, we aimed to determine the potential of amber extract for treating AD by evaluating its effects on amyloid-β (1-42) (Aβ (1-42))-induced neuronal cell death. We measured levels of ROS, Bcl-2, and Bax mRNA, and found that amber extract decreased Aβ (1-42)-induced cell apoptosis via the reactive oxygen species (ROS)-mediated mitochondrial pathway. Amber extract also decreased β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and increased microtubule-associated proteins 1A/1B light chain 3B (LC3II) and Beclin 1. These findings suggested that amber extract protects neuronal cells against Aβ (1-42)-induced cell apoptosis by upregulating autophagy and downregulating BACE1., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Indigestible polysaccharides, such as dietary fibers, benefit the host by improving the intestinal environment. Short-chain fatty acids (SCFAs) produced by gut microbial fermentation from dietary fibers exert various physiological effects. The bacterial polysaccharide curdlan benefits the host intestinal environment, although its effect on energy metabolism and SCFA production remains unclear. Hence, this study aimed to elucidate the effect of curdlan intake on gut microbial profiles, SCFA production, and energy metabolism in a high-fat diet (HFD)-induced obese mouse model. Gut microbial composition of fecal samples from curdlan-supplemented HFD-fed mice indicated an elevated abundance of Bacteroidetes, whereas a reduced abundance of Firmicutes was noted at the phylum level compared with that in cellulose-supplemented HFD-fed mice. Moreover, curdlan supplementation resulted in an abundance of the family Bacteroidales S24-7 and Erysipelotrichaceae, and a reduction in Deferribacteres in the feces. Furthermore, curdlan supplementation elevated fecal SCFA levels, particularly butyrate. Although body weight and fat mass were not affected by curdlan supplementation in HFD-induced obese mice, HFD-induced hyperglycemia was significantly suppressed with an increase in plasma insulin and incretin GLP-1 levels. Curdlan supplementation elevated fecal bile acid and SCFA production, improved host metabolic functions by altering the gut microbial composition in mice., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Amber-the fossilized resin of trees-is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases.

There has been increasing interest in examining physician well-being and its predictive factors. However, few studies have revealed the characteristics associated with physician well-being and work-life integration using a machine learning approach. To investigate predictive factors of well-being and obtain insights into work-life integration, the survey was conducted by letter mail in a sample of Japanese physicians. A total of 422 responses were collected from 846 physicians. The mean age was 47.9 years, males constituted 83.3% of the physicians, and 88.6% were considered to be well. The most accurate machine learning model showed a mean area under the curve of 0.72. The mean permutation importance of career satisfaction, work hours per week, existence of family support, gender, and existence of power harassment were 0.057, 0.022, 0.009, 0.01, and 0.006, respectively. Using a machine learning model, physician well-being could be predicted. It seems to be influenced by multiple factors, such as career satisfaction, work hours per week, family support, gender, and power harassment. Career satisfaction has the highest impact, while long work hours have a negative effect on well-being. These findings support the need for organizational interventions to promote physician well-being and improve the quality of medical care., Competing Interests: The authors have declared that no competing interests exist.

Plate bending-related normal faults (i.e. bend-faults) develop at the outer trench-slope of the oceanic plate incoming into the subduction zone. Numerous geophysical studies and numerical simulations suggest that bend-faults play a key role by providing pathways for seawater to flow into the oceanic crust and the upper mantle, thereby promoting hydration of the oceanic plate. However, deep penetration of seawater along bend-faults remains controversial because fluids that have percolated down into the mantle are difficult to detect. This report presents anomalously high helium isotope ( 3 He/ 4 He) ratios in sediment pore water and seismic reflection data which suggest fluid infiltration into the upper mantle and subsequent outflow through bend-faults across the outer slope of the Japan trench. The 3 He/ 4 He and 4 He/ 20 Ne ratios at sites near-trench bend-faults, which are close to the isotopic ratios of bottom seawater, are almost constant with depth, supporting local seawater inflow. Our findings provide the first reported evidence for a potentially large-scale active hydrothermal circulation system through bend-faults across the Moho (crust-mantle boundary) in and out of the oceanic lithospheric mantle.

A highly direct asymmetric reductive amination of a variety of ketone substrates, including 2-acetyl-6-substituted pyridines, β-keto esters, β-keto amides, and 1-(6-methylpyridin-2-yl)propan-2-one, has been disclosed for the first time (94.6% to >99.9% ee). With ammonium trifluoroacetate as the nitrogen source, various chiral corresponding primary amines were prepared in excellent enantioselectivity and conversion in the presence of a commercially available and inexpensive chiral catalyst, Ru(OAc) 2 {( S )-binap}, under 0.8 MPa of hydrogen gas pressure.

Introduction: There are limited reports regarding renal paratransplant hernia (RPH), which is a rare type of internal hernia. Herein, we report a case of successful laparoscopic treatment of RPH., Presentation of Case: A kidney transplant recipient presented to our emergency department with a 6-h history of abdominal pain and vomiting. The patient had received a living-related donor kidney transplantation and native nephrectomy in our hospital last year. Computed tomography (CT) confirmed a diagnosis of RPH. We performed laparoscopic exploration, and the findings showed an incarcerated small bowel in the retroperitoneal space through a peritoneal defect. Short laparotomy was performed to resect the non-viable bowel. The peritoneal defect was opened adequately. The patient's postoperative course was uneventful, with no complications., Discussion: RPH is an uncommon variant of internal hernia, which is a rare surgical complication after kidney transplantation. Early diagnosis and treatment are important once RPH develops. Due to immunosuppression in kidney transplant recipients, typical signs of peritonitis were not observed. This event can be critical to the patient. Laparoscopic surgery has recently become a treatment option for small bowel obstructions. We believe that this surgical procedure is useful for patients with RPH., Conclusion: We report a case of RPH treated laparoscopically. This approach can be a treatment of choice for RPH., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported. The prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR., Methods and Results: This single-centre prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and soon after TAVR to evaluate the late heart-mediastinum ratio (L-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR L-H/M (≥2.0 or <2.0) and on the presence of TAVR-related improvement in L-H/M. The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with L-H/M improvement and/or high post-TAVR L-H/M (≥2.0). Baseline L-H/M and frailty were associated with poor response of L-H/M to TAVR treatment. TAVR-related improvement in L-H/M had significant effects on MACE, with an adjusted hazard ratio of 0.233 (95% confidence interval, 0.064-0.856; P = 0.028)., Conclusions: TAVR-related improvement in L-H/M was an independent predictor of cardiac events, 1 year after TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)