Akedanones A-C, In Vitro and In Vivo Antiplasmodial 2,3-Dihydronaphthoquinones Produced by Streptomyces sp. K20-0187.

Three new antiplasmodial compounds, named akedanones A (1), B (2), and C (3), were discovered from the cultured material of Streptomyces sp. K20-0187 isolated from a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures of compounds 1-3 were elucidated as new 2,3-dihydronaphthoquinones having prenyl and reverse prenyl groups by mass spectrometry and nuclear magnetic resonance analyses. Compound 1 and the known furanonaphthoquinone I (4) showed potent in vitro antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with half-maximal inhibitory concentration values ranging from 0.06 to 0.3 µM. Compounds 1 and 4 also displayed potent in vivo antiplasmodial activity against drug-sensitive rodent malaria Plasmodium berghei N strain, with inhibition rates of 47.6 and 43.1%, respectively, on intraperitoneal administration at a dose of 5 mg kg-1 day-1 for 4 days.

Current status of the surgical training system in Japan: results of a nationwide questionnaire survey of graduating surgical trainees.

PURPOSE: To identify the problems trainees face during surgical training in Japan. METHODS: A nationwide online questionnaire survey was conducted targeting newly certified surgical trainees. RESULTS: The response rate was 53.8% (758/1410). Among those respondents, 25.6% were women, 71.4% were either married or had a partner, 41.3% had children, 72.7% had performed over 200 surgeries under general anesthesia, and 54.1% had chosen, before graduating from medical school, to become a surgeon. While 88.8% were interested in learning surgical techniques, 63.8% were hesitant to become a surgeon for fear of a compromised quality of private life (QOL). Conversely, only 1.4% chose their surgical training programs based on QOL. Overall, 84.6% of the trainees were satisfied with their training and this correlated with the number of surgeries performed. Only 29.9% received non-technical skill training. The average number of night shifts per month was 5.6, and 10.6% worked over 80 h per week. Harassment was reported by 41.5% of the respondents. Moreover, 33.0% had considered dropping out at some time, primarily because of their QOL (51.1%) or the harassment they had encountered (50.4%). CONCLUSION: This survey revealed that while trainees were satisfied with the overall training system, issues such as long working hours and harassment are prevalent. Working to improve these issues could make surgery more attractive for young trainees.

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001.

Actinomycetes are well-known as the main producers of bioactive compounds such as antibiotics, anticancers, and immunosuppressants. Screening of natural products from actinomycetes has been an essential part of several drug discovery programs. Finding such novel biologically active metabolites is immensely important because of their beneficial health effects. Recently, the discovery of new compounds has diverted attention to rare actinomycetes, since they are rich sources of natural products. In this study, a collection of rare actinomycetes at Kitasato University has been screened for potential novel compound producers. Among the rare actinomycetes, Saccharopolyspora sp. KR21-0001 isolated from soil on Oha Island, Okinawa, Japan was selected as a potential producer. The strain was cultured in 20 L of production medium in a jar fermenter and the culture broth was extracted. Further purification revealed the presence of a new compound designated KR21-0001A (1). The structure was elucidated by NMR, and the absolute stereochemistry was determined by advanced Marfey's method. The results indicated that 1 is a new analog of dihydroxybenzoic acid. 1 has no antimicrobial activity against bacteria and fungi but showed potent antioxidant activity.

Impella Implantation as a Bridge to Surgery for Repair of Aorto-Right Ventricular Fistula Following Prosthetic Valve Endocarditis: A Case Report.

For patients with cardiogenic shock, delaying surgery with mechanical circulatory support is reported to yield better outcomes than emergency surgery. We report on an 82-year-old man diagnosed with vertebral osteomyelitis with concomitant infective endocarditis. Chest radiographs revealed a growing abscess, which resulted in an aorto-right ventricular fistula. Providing Impella support allowed for hemodynamic stabilization prior to surgery. The patient had an uneventful postoperative course and reported to be well in a follow-up 1 year later. Impella support can be used as a bridge to surgery for repairing fistulous tract formation in patients in cardiogenic shock.

Mesenteric Ischemia After Cardiac Surgery in Dialysis Patients: An Overlooked Risk Factor.

BACKGROUND: No study has examined the association of the calcification of abdominal artery orifices with nonocclusive mesenteric ischemia (NOMI) in dialysis patients undergoing cardiac surgery. Thus, this study aimed to determine whether calcification of abdominal blood vessel orifices in hemodialysis patients may be a risk factor for NOMI and examine the long-term survival of dialysis patients after undergoing cardiac surgery. METHODS: From April 2014 to September 2020, 100 dialysis patients underwent cardiac surgery at our hospital. The calcification of the celiac artery (CA) and superior mesenteric artery (SMA) was evaluated by computed tomography, and the degree of orifice stenosis was graded as follows: patent, 0; partial occlusion, 1; and complete occlusion, 2. RESULTS: Eight patients experienced NOMI, and all of them died. SMA calcification scores were not significantly different between the NOMI and non-NOMI groups (1.38±0.52 vs. 1.13±0.69; P = 0.247). However, the average CA orifice calcification score was significantly greater in the NOMI group than in the non-NOMI group (1.63±0.52 vs. 1.15±0.65; P = 0.039), and the SMA+CA orifice calcification scores were significantly different between the groups (3.00±0.76 vs. [non-NOMI] 2.25±1.18; P = 0.028). In all patients, the 30-day and in-hospital mortality rates were 13% and 18%, respectively. All patients were completely followed up with a mean follow-up period of 604±585 days. Kaplan-Meier survival curves showed that patients with SMA and CA calcification tended to have a shorter overall survival than patients without calcification; however, no significant difference was noted. CONCLUSIONS: The calcification of CA and/or SMA orifices was associated with postoperative NOMI and poor long-term survival among dialysis patients undergoing cardiac surgery.

Chloroplast Autophagy and Ubiquitination Combine to Manage Oxidative Damage and Starvation Responses.

Autophagy and the ubiquitin-proteasome system are the major degradation processes for intracellular components in eukaryotes. Although ubiquitination acts as a signal inducing organelle-targeting autophagy, the interaction between ubiquitination and autophagy in chloroplast turnover has not been addressed. In this study, we found that two chloroplast-associated E3 enzymes, SUPPRESSOR OF PPI1 LOCUS1 and PLANT U-BOX4 (PUB4), are not necessary for the induction of either piecemeal autophagy of chloroplast stroma or chlorophagy of whole damaged chloroplasts in Arabidopsis (Arabidopsis thaliana). Double mutations of an autophagy gene and PUB4 caused synergistic phenotypes relative to single mutations. The double mutants developed accelerated leaf chlorosis linked to the overaccumulation of reactive oxygen species during senescence and had reduced seed production. Biochemical detection of ubiquitinated proteins indicated that both autophagy and PUB4-associated ubiquitination contributed to protein degradation in the senescing leaves. Furthermore, the double mutants had enhanced susceptibility to carbon or nitrogen starvation relative to single mutants. Together, these results indicate that autophagy and chloroplast-associated E3s cooperate for protein turnover, management of reactive oxygen species accumulation, and adaptation to starvation.

Repeated partial tissue bite with inadequate cooling time for an energy device may cause thermal injury.

BACKGROUND: Over the past three decades, the use of ultrasonically activated device (USAD) and advanced bipolar device (ABD) has grown in minimally invasive surgeries. However, the thermal profile differences during repeated dissection with different grasping ranges of energy devices, which provide valuable information for preventing thermal injury by energy devices, remain unclear. METHODS: We developed an ex vivo benchtop model to examine the temperature profile of the blade and jaws of two USADs (HARMONIC® ACE + and Sonicision™) and a ABD (Ligasure™ Maryland) with different grasping ranges (partial tissue and full tissue bite) in repeated dissection with minimum cooling time. The maximum temperature, time required for completion to dissection of 10 cm of porcine muscle, thermal spread, and cooling time to reach 60 °C were continuously measured using video thermography. In addition, to evaluate one more grasping range "no tissue", we performed a stress test that activated the USAD without tissue intervention to assess the effects of excessive load on the blade and jaw. RESULTS: Repeated dissection of energy devices with minimal cooling time results in high blade and jaw temperatures proportional to the incision distance. In particular, the USADs with partial tissue bite showed a significantly higher temperatures at the blade and jaw, longer cooling times, and higher lateral thermal spread than those with a full tissue bite and the ABD. The stress test with a USAD showed an extremely high blade temperature exceeding 400 °C, with the tissue pad melting only 13.2 s after activation. CONCLUSION: Although USAD with partial tissue bite help ensure precise dissection, repeated long activation with inadequate cooling time may increase the risk of thermal injury during surgery. These results suggest that surgeons should use energy devices properly while understanding the risks of adjacent organ damage that could result from abuse of the device.

[Degenerated Monocusp Valve Complicated with Infective Endocarditis after Total Correction of Tetralogy of Fallot;Report of a Case].

There have been few reports about degenerated monocusp-valve patches, which were used for right ventricular outflow tract( RVOT) reconstruction with complications of infective endocarditis after total correction of tetralogy of Fallot( TOF).A 44-year-old male patient, who had a total correction of TOF using Monocusp Valved Outflow Patch (MVOP) 34 years previous, was admitted for heart failure with aortic regurgitation. An echocardiographic study showed an infective endocarditis with vegetations, attached to the aortic valve and the monocusp-valve outflow patch. The aortic valve was replaced with a mechanical prosthesis and the pulmonary valve was replaced with a biological prosthesis. RVOT was reconstructed using a bovine pericardial patch. The explanted monocusp-valve was deteriorated and heavily calcified. The postoperative course was uneventful. The patient was discharged and returned to his preoperative lifestyle 36 days after the redo surgery.

[Mitral Valve Repair Using a New Artificial Ring which Enables to Decide the Length of Artificial Chordae].

Recently, mitral valve repair has been the mainstream of the operation for the treatment of mitral valve regurgitation. In particular, chorda reconstruction with artificial chordae is useful for the anterior leaflet. However, there has been no established method determining the length of chordae. In this report, we performed mitral valve repair using Memo 3D ReChord ring which enables to decide the length of chordae more easily. It is based on the concept of folding leaflet technique by Garcia et al. We used this ring in 7 patients (of which 2 were reoperation) in our institution. There was no postoperative death nor complication. Postoperative transthoracic echocardiography showed class 0~ Ⅰ mitral valve regurgitation in each case at discharge. This ring helps to make the repair more reproducible and we consider that it enables to decide the length of chordae more easily even in reoperative cases.

[Aortic Valve Repair for Bicuspid Aortic Valve (BAV) Regurgitation Combined with Stanford Type A Acute Aortic Dissection].

A 44-year-old male developed Stanford type A acute aortic dissection combined with bicuspid aortic valve( BAV) regurgitation. Aortic valve repair was performed by central plication and subcommissural annuloplasty. Additionally, replacement of the ascending aorta and the aortic root were performed with hemi-remodeling technique by replacing the non-coronary sinus. In this procedure, the angle of the 2 commissures were set at 180°. Postoperative transesophageal echocardiography revealed no aortic valve regurgitation. Changing the commissural orientation is considered to be important for the treatment of BAV regurgitation.

[A Case of Survival Following Fourth-Line Outpatient Chemotherapy 19 Months after Surgery for Small Intestinal Cancer with Multiple Liver Metastases in a Patient with Good General Condition].

A 59-year-old woman who complained of melena and lightheadedness visited the outpatient clinic at our hospital.According to her blood test result, she had anemia, and her tumor marker levels were high.Enhanced computed tomography(CT) findings showed small intestinal cancer with multiple liver metastases.Partial resection of the small bowel for the small intestinal cancer was performed.Following the administration of fourth-line outpatient chemotherapy containing S-1 plus irinotecan( IRIS)and IRIS plus bevacizumab(IRIS plus Bev), S-1 plus oxaliplatin plus Bev(SOX plus Bev), and weekly paclitaxel (wPAC), she survived with good condition for 19 months after the surgery.

Biodegradation of high concentrations of formaldehyde using Escherichia coli expressing the formaldehyde dismutase gene of Methylobacterium sp. FD1.

In the present study, formaldehyde dismutase from Methylobacterium sp. FD1 was partially purified and analyzed by nanoLC-MS/MS; it was then cloned from the genomic DNA of FD1 by PCR. The open reading frame of the formaldehyde dismutase gene of FD1 was estimated to be 1203 bp in length. The molecular weight and pI of formaldehyde dismutase (401 aa), as deduced from the FD1 gene, were calculated at 42,877.32 and 6.56, respectively. NAD(H)-binding residues and zinc-binding residues were found in the amino acid sequence of the deduced formaldehyde dismutase of FD1 by BLAST search. The resting Escherichia coli cells that were transformed with the FD1 formaldehyde dismutase gene degraded high concentrations of formaldehyde and produced formic acid and methanol that were molar equivalents of one-half of the degraded formaldehyde. The lyophilized cells of the recombinant E. coli also degraded high concentrations of formaldehyde.

[Trial of the Profit Optimization of the Department of Cardiac Surgery in the Local National University Hospital].

In recent years economic sense is required in hospital management, the national university hospital is also no exception. We performed duty improvement efforts as well as the current state analysis in the department of cardiac surgery for the purpose of revenue optimization in our hospital. At result, we succeeded in the improvement of the medical index as well as medical profit and found the key of solution to the serious problem that national university hospital has.

Total synthesis of pectenotoxin-2.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

Correlation between the spread of IMP-producing bacteria and the promoter strength of blaIMP genes.

The first report of transmissible carbapenem resistance encoded by blaIMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and blaIMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of blaIMPs exist, and point mutations in the blaIMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of blaIMP-1, first reported in P. aeruginosa GN17203, was a weak promoter (PcW) with low-level expression intensity. This study investigates whether point mutations in the promoter region have helped to create strong promoters under antimicrobial selection pressure. Using bioinformatic approaches, we retrieved 115 blaIMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved blaIMPs showed that most of them used the Pc located in class 1 integrons (n = 112, 97.4%). The promoter analysis by year revealed that the blaIMP population with the strong promoter, PcS, was transient. In contrast, the PcW-TG population, which had acquired a TGn-extended -10 motif in PcW and had an intermediate promoter strength, gradually spread throughout the world. An inverse correlation between Pc promoter strength and Intl1 integrase excision efficiency has been reported previously [1]. Because of this trade-off, it is unlikely that blaIMPs with strong promoters will increase rapidly, but the possibility that promoter strength will increase with the use of other integrons cannot be ruled out. Monitoring of the blaIMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.

Mitral regurgitation increases systolic strains in remote zone and worsens left ventricular dyssynchrony in a swine model of ischemic cardiomyopathy.

Background: Ischemic mitral regurgitation (IMR) imposes volume overload on the left ventricle (LV), accelerating adverse LV remodeling. In this study, we sought to investigate the impact of volume overload due to IMR on regional myocardial contractile mechanics. Methods: Ten Yorkshire swine were induced with myocardial infarction (MI) by occluding the left circumflex coronary artery (LCx). Cardiac MRI was performed at baseline (BL) and 2.5 months (2.5M) post-MI. IMR was quantified with epicardial echocardiography 3 months post-MI. The animals were then assigned to 2 groups: no/mild MR (nmMR, n = 4) and moderate/severe MR (msMR, n = 6). MRI images were analyzed to assess infarction size, end-diastolic and end-systolic volume (EDV and ESV, respectively), ejection fraction (EF), longitudinal strain (LS), circumferential strain (CS), and systolic dyssynchrony index (SDI). The myocardial region was divided into infarction, border, and remote zones based on the LCx-supplied region. Results: There was no difference in the infarction size. Group-wise comparison of LS and CS between BL and 2.5M demonstrated that LS and CS in the infarction zone and the border zone decreased at 2.5M in both groups. However, LS and CS in the remote zone were elevated only in the msMR group (LS: -9.81 ± 3.96 vs. -12.58 ± 5.07, p < 0.01; CS; -12.78 ± 3.81 vs. -16.09 ± 3.33, p < 0.01) at 2.5M compared to BL. The SDI of CS was significantly elevated in the msMR group (0.1255 vs. 0.0974, p = 0.015) at 2.5M compared to BL. Conclusions: Elevated LS and CS in the remote zone were observed in moderate/severe MR and ventricular dyssynchrony. These elevated cardiac strains, coupled with ventricular dyssynchrony, may contribute to the progression of MR, thereby accelerating heart failure.

Relationship between prehabilitation responsiveness and postoperative physical functional recovery in cardiovascular surgery.

BACKGROUND: The purpose of this study was to examine the relationship between responsiveness to prehabilitation and postoperative recovery of physical function in cardiac surgery patients. METHODS: Ninety-three cardiac surgery patients (mean age: 76.4 years) were included in this retrospective cohort study. Preoperative physical function was measured using the Short Physical Performance Battery (SPPB), and a prehabilitation exercise program was implemented for the SPPB domains with low scores. Among the patients, those whose SPPB score was over 11 from the start of prehabilitation and remained over 11 on the day before surgery were defined as the high-functioning group, and those whose SPPB score improved by 2 points or more from the start of prehabilitation and exceeded 11 points were defined as the responder group. Those whose SPPB score did not exceed 11 immediately before surgery were classified as non-responders. The characteristics of each group and postoperative recovery of physical function were investigated. RESULTS: There were no serious adverse events during prehabilitation. Mean days of prehabilitation was 5.4 days. The responder group showed faster improvement in postoperative physical function and shorter time to ambulatory independence than the non-responder group. The non-responder group had lower preoperative skeletal muscle index, more severe preoperative New York Heart Association classification, and a history of musculoskeletal disease or stroke. CONCLUSION: There were responders and non-responders to prehabilitation among cardiac surgery patients. Cardiac surgery patients who respond to prehabilitation had faster recovery of physical function. Further research is needed to determine what type of prehabilitation is more effective in postoperative recovery of physical function in cardiac surgery patients.

Bail-Out TEVAR through a Branch of Four-Arm Dacron Graft for Misdeployment of a Frozen Elephant Trunk Prosthesis.

The frozen elephant trunk (FET) is an effective method for making the distal anastomosis more proximal and facilitating aortic remodeling in acute aortic dissection. However, misdeployment of FET to the false lumen has been reported in several cases. Such cases are usually treated with bail-out thoracic endovascular aortic repair (TEVAR) through the femoral artery or additional FET under direct vision to redirect the blood flow to the true lumen. We encountered a case of misdeployment of FET into the false lumen during open aortic surgery for the treatment of Stanford type A acute aortic dissection. After reconstruction of the aorta and all arch vessels, we performed antegrade bail-out TEVAR through a side branch of the four-arm Dacron graft as main access using a pull-through technique through the right femoral artery, which was perfused from the true lumen. This technique, which uses a Dacron graft branch for stent graft access, enabled us to confirm the true lumen because the distal anastomotic site was definitely the true lumen, and we were also able to avoid access difficulties at the iliac artery.

Emblestatin: a new peptide antibiotic from Embleya scabrispora K20-0267.

A new peptide, emblestatin (1), was discovered from a culture broth of Embleya scabrispora K20-0267. This strain was isolated from soil using an agar medium containing lysozyme. Based on NMR and mass spectrometric analyses, 1 consists of 2-(2-hydroxyphenyl)-2-oxazoline, ß-alanine, glutamine, Nα-methyl-Nω-hydroxyornithine and 3-amino-1-hydroxy-2-piperidone moieties. Further analysis using the advanced Marfey's method revealed that all amino acids with the stereogenic α-carbon in 1 had the L configuration. Compound 1 exhibited iron chelating activity and weak antibacterial activity against Proteus vulgaris and Staphylococcus aureus.