Search

Abstract Purpose Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. Methods We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. Results The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. Conclusions With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject’s VH in forensic examination.

A 24-year-old woman with chronic active Epstein-Barr virus (CAEBV) infection successfully underwent coronary artery bypass grafting for triple coronary arteries with chronic total occlusion and aneurysms. This case underscores the importance of accurate assessment and treatment of coronary artery lesions in patients with CAEBV infection.

Analyzing the spatial patterns and associations among tree species may help to elucidate the importance of the ecological processes behind population formation and the mechanisms of species coexistence. To explore this mechanism, we mapped and studied eight dominant tree species in Korean pine broad-leaved mixed forests in a temperate forest region in Jilin Province, Northeast China. The spatial distribution patterns and spatial associations of the eight dominant tree species at different life history stages and spatial scales were analyzed using the second-order spatial point pattern method based on pair correlation functions. The results indicated the following: (1) The diameter class structure of all individuals in the plots showed an obvious “L” shape, indicating that the community was well regenerated and belonged to a growing stand. (2) The distribution of trees was affected by scale, size, and habitat heterogeneity. The degree of aggregation decreased as the diameter class increased. (3) Out of the 56 pairs of individuals, a small number showed a significant correlation, while most were negatively correlated. It is concluded that seed dispersal limitations, competitive ability, and topography and light requirements may influence the spatial distribution and association of species to maintain species coexistence and diversity in Korean pine broad-leaved mixed forests. The results can provide insights into the ecological processes of population assembly, the mechanisms of species coexistence, and the relationship between forest management and restoration.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

Summary: Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.

Summary: Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder caused by overnutrition and can lead to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The transcription factor Forkhead box K1 (FOXK1) is implicated in regulation of lipid metabolism downstream of mechanistic target of rapamycin complex 1 (mTORC1), but its role in NAFLD-NASH pathogenesis is understudied. Here, we show that FOXK1 mediates nutrient-dependent suppression of lipid catabolism in the liver. Hepatocyte-specific deletion of Foxk1 in mice fed a NASH-inducing diet ameliorates not only hepatic steatosis but also associated inflammation, fibrosis, and tumorigenesis, resulting in improved survival. Genome-wide transcriptomic and chromatin immunoprecipitation analyses identify several lipid metabolism-related genes, including Ppara, as direct targets of FOXK1 in the liver. Our results suggest that FOXK1 plays a key role in the regulation of hepatic lipid metabolism and that its inhibition is a promising therapeutic strategy for NAFLD-NASH, as well as for HCC.

ObjectivesWe aimed to elucidate the perioperative and short-term clinical outcomes of the Najuta thoracic stent graft system with fenestrations for supra-aortic vessels.MethodsWe retrospectively investigated the perioperative and short-term clinical outcomes of 20 patients treated for arch or distal arch aneurysms using the Najuta thoracic stent graft system during the period from May 2019 to February 2023.ResultsThe technical success rate of the Najuta thoracic stent graft system was 95%. Of the 20 patients, 17 patients (85.0%) underwent concomitant extra-anatomical supra-aortic bypass. Postoperative CT revealed type Ia (n = 2) and type II (n = 3) endoleaks which disappeared on follow-up. The postoperative complications were stroke (n = 2, 10.0%), paraplegia (n = 1, 5.0%), and paraparesis (n = 1, 5.0%). In a very old patient, a blood transfusion was performed from the common iliac artery using the retroperitoneal approach. There were no aorta-related complications such as retrograde type A dissection or distal stent graft–induced new entry.ConclusionsWe treated arch or distal arch thoracic aneurysms by inserting a tube-type stent graft as a scaffold on the peripheral site and placing the Najuta thoracic stent graft on the proximal site. By extending the landing zone to Zone 0 and using a low radial force, which is a feature of the Najuta thoracic stent graft system, postoperative bird-beak and aorta-related complications were avoided. The treatment of arch and distal arch aortic aneurysms using the Najuta thoracic stent graft system showed acceptable perioperative and short-term clinical outcomes. Thoracic endovascular aortic repair using the Najuta thoracic stent graft system may be a potential treatment option for arch and distal arch aortic aneurysms, warranting further studies.

Abstract Background Ubiquitylation of the ligands and the receptor plays an important part in the regulation of the activity of the evolutionary conserved Notch signalling pathway. However, its function for activation of Notch is not completely understood, despite the identification of several E3 ligases devoted to the receptor. Results Here we analysed a variant of the Notch receptor where all lysines in its intracellular domain are replaced by arginines. Our analysis of this variant revealed that ubiquitylation of Notch is not essential for its endocytosis. We identified two functions for ubiquitylation of lysines in the Notch receptor. First, it is required for the degradation of free Notch intracellular domain (NICD) in the nucleus, which prevents a prolonged activation of the pathway. More importantly, it is also required for the incorporation of Notch into intraluminal vesicles of maturing endosomes to prevent ligand-independent activation of the pathway from late endosomal compartments. Conclusions The findings clarify the role of lysine-dependent ubiquitylation of the Notch receptor and indicate that Notch is endocytosed by several independent operating mechanisms.

A number of testes-specific lncRNAs have been annotated but their roles remain largely unexplored. Here the authors identify two small peptides encoded by the lncRNA Gm9999, Kastor and Polluks, both of which are required for male fertility in mice.

Background Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) on multidetector computed tomography, is common after transcatheter aortic valve replacement (TAVR). Because little is known about the long‐term natural history of subclinical HALT, we aimed to investigate this in patients who underwent TAVR without using additional anticoagulation. Methods and Results We retrospectively evaluated patients who underwent TAVR with the Edwards SAPIEN‐XT at our institute between October 2013 and December 2015. Patients were grouped according to the presence or absence of HALT within 1 year after TAVR (HALT and No‐HALT groups). The primary outcome, defined as the composite of all‐cause mortality, heart failure readmission, and ischemic stroke, was compared. Valve performance was assessed over time by transthoracic echocardiography. Among 124 patients (men: 29.1%; median age, 85 years), 27 (21.8%) showed HALT on multidetector computed tomography within 1 year after TAVR. No patient required additional anticoagulation for treating HALT because of the absence of valve‐related symptomatic deterioration. During the median follow‐up period of 4.7 years (interquartile range, 4.0–5.6), the rate of primary outcome and valve performance was not statistically different between the 2 groups (37.0% versus 38.1%; log‐rank test P=0.92; mean pressure gradient, 9 mm Hg [8–14 mm Hg] versus 10 mm Hg [7–15 mm Hg]; P=0.51, respectively). Conclusions Approximately 20% of patients after TAVR had HALT within 1 year; however, that did not change the risk of subsequent adverse cardiovascular events or the valve performance with statistical significance for up to 5 years despite no additional anticoagulation therapy.

Summary: One of the bottlenecks in the application of basic research findings to patients is the enormous cost, time, and effort required for high-throughput screening of potential drugs for given therapeutic targets. Here we have developed LIGHTHOUSE, a graph-based deep learning approach for discovery of the hidden principles underlying the association of small-molecule compounds with target proteins. Without any 3D structural information for proteins or chemicals, LIGHTHOUSE estimates protein-compound scores that incorporate known evolutionary relations and available experimental data. It identified therapeutics for cancer, lifestyle related disease, and bacterial infection. Moreover, LIGHTHOUSE predicted ethoxzolamide as a therapeutic for coronavirus disease 2019 (COVID-19), and this agent was indeed effective against alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are rampant worldwide. We envision that LIGHTHOUSE will help accelerate drug discovery and fill the gap between bench side and bedside.

Abstract Saphenous veins (SVs) are frequently employed as bypass grafts. The SV graft failure is predominantly seen at the valve site. Avoiding valves during vein harvest would help reduce graft failure. We endeavored to detect SV valves, tributaries, and vessel size employing upright computed tomography (CT) for the raw cadaver venous samples and in healthy volunteers. Five cadaver legs were scanned. Anatomical analysis showed 3.0 (IQR: 2.0–3.0) valves and 13.50 (IQR: 10.00–16.25) tributaries. The upright CT completely detected, compared to 2.0 (IQR: 1.5–2.5, p = 0.06) valves and 9.5 (IQR: 7.5–13.0, p = 0.13) tributaries by supine CT. From a total of 190 volunteers, 138 (men:75, women:63) were included. The number of valves from the SF junction to 35 cm were significantly higher in upright CT than in supine CT bilaterally [upright vs. supine, Right: 4 (IQR: 3–5) vs. 2 (IQR:1–2), p

Abstract Colorectal and gastric cancers are a leading cause of cancer deaths in developed countries. Precise estimation of prognosis is important with regard to clinical decision making for individuals with such cancers. We here comprehensively compiled a complete atlas of prognostic genes based on an integrated meta-analysis of one of the largest assembled colorectal cancer cohorts. A simple yet robust machine learning approach was then applied to establish a universal molecular prognostic score (mPS_colon) that relies on the expression status of only 16 genes and which was validated with independent data sets. This score was found to be an independent prognostic indicator in multivariate models including cancer stage, to be valid independent of tumor characteristics or patient ethnicity, and to be also applicable to gastric cancer. We conclude that mPS_colon is a universal prognostic classifier for patients with gastrointestinal cancers and that it should prove informative for optimization of personalized therapy for such patients.

Background The practice pattern and outcome of medical devices following their regulatory approval may differ by country. The aim of this study is to compare postapproval national clinical registry data on transcatheter aortic valve replacement between the United States and Japan on patient characteristics, periprocedural outcomes, and the variability of outcomes as a part of a partnership program (Harmonization‐by‐Doing) between the 2 countries. Methods and Results The patient‐level data were extracted from the US Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) and the J‐TVT (Japanese Transcatheter Valvular Therapy) registry, respectively, to analyze transcatheter aortic valve replacement outcomes between 2013 and 2019. Data entry for these registries was mandated by the federal regulators, and the majority of variable definitions were harmonized to allow direct data comparison. A total of 244 722 transcatheter aortic valve replacements from 646 institutions in the United States and 26 673 transcatheter aortic valve replacements from 171 institutions in Japan were analyzed. Median volume per site was 65 (interquartile range, 45–97) in the United States and 28 (interquartile range, 19–41) in Japan. Overall, patients in J‐TVT were older (United States: mean‐age, 80.1±8.7 versus Japan: 84.4±5.2; P

Infected aortic aneurysm (IAA) is a rare, life-threatening disease with rapid progression and a high mortality rate. An 84-year-old man developed IAA caused by urosepsis owing to extended-spectrum β-lactamase–producing Escherichia coli infection. Considering surgical risk and perioperative mortality, the patient underwent computed tomography–guided percutaneous abscess drainage and continuous irrigation with optimal antibiotic therapy. We controlled his systemic inflammation without surgery; thus, he was discharged. Six months later, we confirmed that the abscess had almost disappeared in the follow-up computed tomography scan. Percutaneous abscess drainage and irrigation may be an effective therapeutic option for surgical high-risk patients with IAA. Résumé: L’anévrisme aortique infecté (AAI) est une affection rare menaçant le pronostic vital, qui évolue rapidement et est associée à un taux de mortalité élevé. Nous exposons le cas d’un homme de 84 ans présentant un AAI secondaire à un urosepsis, lui-même causé par une infection à Escherichia coli productrice de bêta-lactamases à spectre étendu. Compte tenu du risque associé à une intervention chirurgicale et du risque de mortalité périopératoire, nous avons procédé à un drainage percutané de l’abcès guidé par tomographie assistée par ordinateur et sous irrigation continue, puis prescrit une antibiothérapie optimale. Nous avons ainsi réussi à maîtriser l’inflammation générale sans intervention chirurgicale, et le patient a pu recevoir son congé de l’hôpital. Six mois plus tard, une tomodensitométrie de suivi a permis de confirmer la disparition presque complète de l’abcès. Le drainage et l’irrigation d’un abcès par voie percutanée peuvent donc être une option thérapeutique efficace dans le cas des patients présentant un AAI les exposant à un risque chirurgical élevé.

Glucose metabolism is known to be dysregulated in cancer. Here, the authors show that glutamine nitrogen is also affected in cancer and demonstrate that glutaminase 1 and phosphoribosyl pyrophosphate amidotransferase are the key enzymes that control this metabolic switch.

Abstract Background Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD. Methods Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. Results In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P

Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular EHTs (T-EHTs) using hiPSC-COs and bio-3D printing with needle arrays. The bio-3D printed T-EHTs were cut open and transplanted around the abdominal aorta as well as the inferior vena cava (IVC) of NOG mice. The transplanted T-EHTs were covered with the omentum, and the abdomen was closed after completion of the procedure. Additionally, to compare the functionality of hiPSC-COs with that of T-EHTs, we transplanted the former around the aorta and IVC as well as injecting them into the subcutaneous tissue on the back of the mice. After 1 m of the transplantation procedures, we observed the beating of the T-EHTs in the mice. In histological analysis, the T-EHTs showed clear striation of the myocardium and vascularization compared to hiPSC-COs transplanted around the aorta or in subcutaneous tissue. Based on these results, bio-3D-printed T-EHTs exhibited a better maturation in vivo as compared to the hiPSC-COs. Therefore, these beating T-EHTs may form conduits for congenital heart disease patients, and T-EHT transplantation can form a treatment option in such cases.

Aortic sarcoma is a rare primary tumor with dismal prognosis. Here, we report a case involving a 74-year-old female patient with aortic sarcoma masquerading as a mycotic aneurysm in the thoracoabdominal aorta. She underwent aortic resection with Dacron prosthetic graft replacement because of rapid growth. The postoperative pathological findings of the resected specimen confirmed the diagnosis of aortic mural sarcoma, which was an unexpected result based on repeat computed tomography angiography performed within 2 months preoperatively. The preoperative diagnosis of aortic sarcoma is often difficult because of its rarity, and this case demonstrates some of the diagnostic pitfalls. Key words: Aortic mural sarcoma, Aortic intimal sarcoma, Gastric sarcoma, Gastrointestinal metastasis, Pseudoaneurysm

The purpose of this study is to investigate the protective effect of dimethyl fumarate (DMF), the methyl-ester of fumaric acid, against blue-light (BL) exposure in retinal pigment epithelial (RPE) cells. ARPE-19 cells, a human RPE cell line, were cultured with DMF followed by exposure to BL. Reactive oxygen species (ROS) generation, cell viability, and cell death rate were determined. Real-time polymerase chain reaction and Western blotting were performed to determine the change in nuclear factor (erythroid-derived)-like 2 (NRF2) expression. Twenty-seven inflammatory cytokines in the supernatant of culture medium were measured. BL exposure induced ROS generation in ARPE-19 cells, which DMF alleviated in a concentration-dependent manner. BL exposure increased the ARPE-19 cell death rate, which DMF alleviated. BL exposure induced ARPE-19 cell apoptosis, again alleviated by DMF. Under BL exposure, DMF increased the NRF2 mRNA level and promoted NRF2 expression in the nucleus. BL also strongly increased interleukin (IL)-1β and fibroblast growth factor (FGF) expression. BL strongly induced RPE cell damage with apoptotic change while DMF mainly reduced inflammation in BL-induced RPE damage, resulting in blockade of cell death. DMF has a protective effect in RPE cells against BL exposure via activation of the NRF2 pathway.

Objective Data on statin for patients with aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI) are limited. The present study aimed to evaluate the impact of statin on midterm mortality of TAVI patients.Design Observational study.Setting This study included patients with AS from a Japanese multicentre registry who underwent TAVI.Participants The overall cohort included 2588 patients (84.4±5.2 years); majority were women (69.3%). The Society of Thoracic Surgeons risk score was 6.55% (IQR 4.55%–9.50%), the Euro II score was 3.74% (IQR 2.34%–6.02%) and the Clinical Frailty Scale score was 3.9±1.2.Interventions We classified patients based on statin at admission and identified 936 matched pairs after propensity score matching.Primary and secondary outcome measures The outcomes were all-cause and cardiovascular mortality.Results The median follow-up was 660 days. Statin at admission was associated with a significant reduction in all-cause mortality (adjusted HR (aHR) 0.76, 95% CI 0.58 to 0.99, p=0.04) and cardiovascular mortality (aHR 0.64, 95% CI 0.42 to 0.97, p=0.04). In the octogenarians, statin was associated with significantly lower all-cause mortality (aHR 0.87, 95% CI 0.75 to 0.99, p=0.04); however, the impact in the nonagenarians appeared to be lower (aHR 0.84, 95% CI 0.62 to 1.13, p=0.25). Comparing four groups according to previous coronary artery disease (CAD) and statin, there was a significant difference in all-cause mortality, and patients who did not receive statin despite previous CAD showed the worst prognosis (aHR 1.33, 95% CI 1.12 to 1.57 (patients who received statin without previous CAD as a reference), p

Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism. This requirement for Deltex is bypassed by the downregulation of ESCRT-III. In contrast, while ESCRT-I depletion also activates Notch, it does so by an ADAM10-dependent/TRPML-independent mechanism and Notch is retained in the lipid raft-like microdomain. In the absence of such endosomal perturbation, different activating Notch mutations also localize to different microdomains and are activated by different mechanisms. Our findings demonstrate the interplay between Notch regulators, endosomal trafficking components, and Notch genetics, which defines membrane locations and activation mechanisms. [ABSTRACT FROM AUTHOR]

Background: Although many prognosis-predicting molecular scores for breast cancer have been developed, they are applicable to only limited disease subtypes. We aimed to develop a novel prognostic score that is applicable to a wider range of breast cancer patients. Methods: We initially examined The Cancer Genome Atlas breast cancer cohort to identify potential prognosis-related genes. We then performed a meta-analysis of 36 international breast cancer cohorts to validate such genes. We trained artificial intelligence models (random forest and neural network) to predict prognosis precisely, and we finally validated our prediction with the log-rank test. Findings: We identified a comprehensive list of 184 prognosis-related genes, most of which have been not extensively studied to date. We then established a universal molecular prognostic score (mPS) that relies on the expression status of only 23 of these genes. The mPS system is almost universally applicable to breast cancer patients (log-rank P

Background In patients undergoing transcatheter aortic valve replacement (TAVR), those with small left ventricle (LV) may have an increased risk of poor outcomes, because small LV is associated with low‐flow (LF), left ventricular hypertrophy. However, the impact of small LV on patients undergoing TAVR remains unknown. Methods and Results We examined 2584 patients who underwent TAVR between October 2013 and May 2017 using data from the Japanese multicenter registry. On the basis of the American Society of Echocardiography guidelines, small LV was defined as left ventricular end‐diastolic dimension

Objective There is paucity of data on optimal medical treatment, including use of beta blockers for patients undergoing transcatheter aortic valve replacement (TAVR). The study aimed to investigate the association of beta blockers and clinical outcomes following TAVR.Methods We examined data of 2563 patients who underwent TAVR between October 2013 and May 2017 obtained from a prospective multicentre cohort registry, the optimised catheter valvular intervention-TAVI registry. We compared the 2-year cardiovascular and non-cardiovascular mortality and in-hospital outcomes between patients with and without preprocedural beta-blocker administration by propensity score matching (PSM).Results Preprocedural beta blockers were prescribed in 867 patients (33.8%). After PSM, the incidence of in-hospital congestive heart failure was significantly lower in patients with preprocedural beta blocker (p=0.046). No differences were found in 2-year cardiovascular and non-cardiovascular mortality. In the subgroup analyses, beta-blocker administration was associated with a lower cardiovascular mortality within 2 years in patients with a history of coronary artery bypass grafting (CABG; log-rank p=0.017), presence of peripheral artery disease (PAD; log-rank p=0.003) and brain natriuretic peptide (BNP) ≥400 pg/mL (log-rank p=0.003). When stratified by postprocedural left ventricular ejection fraction (post-LVEF), beta-blocker administration was associated with a lower cardiovascular mortality among patients with post-LVEF

Background In March 2011, the Fukushima Daiichi nuclear power plant disaster inflicted radiation damage across the Tohoku region of Northern Japan. The consequent harm to pregnant mothers and newborns was a matter of concern. We performed a registry‐based analysis of the incidence of congenital heart disease during 2010 to 2013 using the Japan Cardiovascular Surgery Database. Methods and Results We selected patients who had complex congenital heart disease and who were born between January 1, 2010 and December 31, 2013 undergoing surgery, and assessed the trend in the number of first‐time surgeries performed for patients aged 2 years and younger by birth year over time. The numbers of first‐time surgeries for birth years 2010 to 2013 were 2978, 2924, 3077, and 2940, and no increasing trend was detected. Additionally, no increasing yearly trend was detected when the number of cases was divided by the total number of births in Japan in each birth month. The mortality of first‐time surgeries performed for complex diseases, which often involves multiple subsequent surgeries, decreased from 4.7% in 2010 to 2.2% in 2013. Conclusions Our analyses showed no increase in the number of patients with congenital heart disease during 2010 to 2013. The yearly increase in the total number of surgeries following the Fukushima Daiichi nuclear disaster in a previous report can be explained by the decline in the mortality of first‐time surgeries for complex cases. Such use of only the increase in the total yearly number of surgeries to claim the effects of a nuclear disaster on the incidence of congenital heart disease is a far too simplistic and dangerous proposition.

The patient was a 76-year-old woman with an atypical descending thoracic aortic aneurysm due to a highly tortuous descending aorta. The surgical approach in this case required special consideration because of the aneurysm’s location. The main body of the aneurysm was in the right thoracic cavity. Descending thoracic aorta replacement with a prosthetic graft and aneurysmal total exclusion were performed through a left curvilinear thoracoabdominal incision. The patient’s postoperative course was uneventful. Surgical exclusion of a thoracic aortic aneurysm may be a useful technique in this special situation. Postoperative follow-up is needed to prevent early and late complications.

Abstract Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the “sub-silicone oil fluid (SOF)”, enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

It is generally assumed that plants can respond to varying degrees of physical damage by growth compensation via resprouting, and resprouting is a key functional trait in many species. Few studies have investigated how grass and shrub species distributed in moving dunes and semifixed dunes in semiarid areas respond to the combined effects of temperature and shoot removal. Medicago sativa, Artemisia ordosica, and Artemisia sphaerocephala plants were grown in a glasshouse for 8 weeks at air temperatures of 10/20°C, 12.5/22.5°C, 15/25°C, and 17.5/27.5°C (night/day) and were subjected to treatments of removing all leaves (LR), removing all leaves followed by cutting at half the plant height (HC), and removing all aboveground tissue (WC). The species, temperature, and damage extent had significant effects on the shoot number, leaf mass ratio, leaf area ratio and ratio of belowground to aboveground dry matter, and the species had a significant effect on the net assimilation rate, specific leaf area, and total biomass. The three species grew well under the HC and LR treatments, and high temperatures (15/25°C and 17.5/27.5°C) significantly promoted the regrowth of the three species. Medicago sativa grew faster than the two Artemisia species. Medicago sativa can be used for fertilizing or vegetation restoration in unimportant conservation areas, and the two Artemisia species can be effectively used for vegetation restoration in the Mu Us Sandland. Due to the low labor costs and the local climate conditions, plants should be clipped before the beginning of the main growing season (end of May or early June) to ensure rapid growth.

Transcatheter aortic valve implantation (TAVI) in the presence of a preexisting mitral prosthesis is challenging and its influence on the morphology of mitral prosthesis and the positioning of transcatheter heart valve (THV) is unknown. We assessed the feasibility of TAVI for patients with preexisting mitral prostheses, its influence on mitral prosthesis morphology, and the positional interaction between a newly implanted THV and mitral prosthesis using serial multidetector computed tomography (MDCT). Thirty-one patients with preexisting mitral prosthesis undergoing TAVI were included. MDCT was performed before and after TAVI. Thirty patients successfully underwent TAVI without interference from preexisting mitral prosthesis. Although opening disturbance of the mechanical mitral prosthesis by the THV edge was observed in 1 patient, the patient was managed conservatively. No THV embolization occurred. THV shift during deployment occurred in 9 patients and was predicted by a larger aortic annulus area (odds ratio: 1.24 per 10 mm2, 1.03-1.49, p = 0.02), possibly because of large THVs. The mitral mean pressure gradient was slightly higher after TAVI (3.7 vs. 4.3 mmHg, p = 0.002), whereas the mitral regurgitation grade was similar. MDCT showed that the size of the mitral prosthesis housing was unchanged after TAVI. The median distance between the mitral prosthesis and THV was 2.6 mm. The postprocedural angle between the mitral prosthesis and THV was larger than the preprocedural angle between the mitral prosthesis and the left ventricular outflow tract (64° vs. 61°, p = 0.03). Thus, TAVI is feasible in the case of preexisting mitral prosthesis. Serial MDCT demonstrated favorable THV positioning and unchanged mitral prosthesis morphology after TAVI.

PurposeVessel maturation is considered to proceed by pruning branches resulting in less branching vessels. This study investigated the vessel junction densities of type 1 and type 2 choroidal neovascularizations (CNVs) using optical coherence tomography angiography (OCTA).MethodsWe collected consecutive data from treatment-naïve eyes diagnosed with typical age-related macular degeneration (AMD). The OCTA images with CNV were analyzed to calculate vessel areas, vessel lengths, and vessel junction densities.ResultsOf 60 eyes in 60 patients, type 1 CNV diagnoses had been made in 40 eyes, and type 2 CNV in 20 eyes. We found no significant difference in vessel areas between type 1 CNV and type 2 CNV (type 1 CNV, 0.44 ± 0.37 mm2; type 2 CNV, 0.37 ± 0.48 mm2), and no significant difference in vessel lengths (type 1 CNV, 18.24 ± 15.96 mm; type 2 CNV, 16.13 ± 21.45 mm). However, the vessel junction density of type 1 CNV was significantly lower than that of type 2 CNV by 16.0% (P = 0.008).ConclusionOCTA revealed that the vessel junction densities of type 1 CNVs were lower than those of type 2 CNVs, suggesting type 1 CNV vessels are more mature than type 2 CNV vessels.

BACKGROUND:Transcatheter aortic valve implantation (TAVI) is an alternative therapy for surgically high-risk patients with severe aortic stenosis (AS). Although TAVI improves survival of patients with severe AS, the mechanism of this effect remains to be clarified. We investigated the effects of TAVI on left ventricular (LV) function and identified the predictive parameters for cardiac events after TAVI. METHODS AND RESULTS:We studied 128 patients with severe symptomatic AS who underwent TAVI. Echocardiographic assessments were performed before and after TAVI. In addition to the conventional echocardiographic parameters such as LV ejection fraction (LVEF) and LV mass index (LVMI), the LV global longitudinal strain (GLS) and early diastolic peak strain rate (SR_E) using two-dimensional speckle tracking echocardiography were also evaluated. All patients were assessed for clinical events including major adverse cardiac events and stroke according to Valve Academic Research Consortium-2 criteria. GLS, early diastolic peak velocity (e'), aortic regurgitation (AR) severity, and SR_E were significantly improved after TAVI. Thirteen patients had an event during the observational period of 591 days (median). Patients with events had higher LVMI, more severe AR, and worse GLS compared to those without events. Furthermore, receiver-operating curve analysis revealed that GLS was the strongest predictor for clinical events (p = 0.009; area under the curve, 0.73). CONCLUSION:Preoperative LV geometric deformation and dysfunction, as a consequence of the cumulative burden of pressure overload, improved after TAVI and could predict cardiac events after TAVI.