Visceral Adipose Tissue Percentage Compared to Body Mass Index as Better Indicator of Surgical Outcomes in Women With Obesity and Endometrial Cancer.

STUDY OBJECTIVE: To assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DESIGN: Retrospective observational cohort study. SETTING: Mie University Hospital, Japan. PATIENTS: Of the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. INTERVENTIONS: We investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). MEASUREMENTS AND MAIN RESULTS: Abdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = -0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (ß = 0.338 vs 0.267, ß = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. CONCLUSION: VAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.

Evaluation of Changes in Activities of Daily Living and Quality of Life of Patients with Bone Metastasis Who Underwent Conservative Therapy through Bone Metastasis Cancer Boards.

Background and Objectives: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods: We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2-8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results: Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements (p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions: Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.

Laparoscopic repair of segmental obturator nerve injury defect using an artificial nerve conduit: A case report.

Obturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension-free direct end-to-end anastomosis. A 36-year-old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.

Laparoscopic retroperitoneal para-aortic lymph node biopsy in advanced cervical cancer with pelvic lymph node metastases: A single-center prospective study.

AIM: Extended-field concurrent chemoradiation therapy (Ex-CCRT) has been widely used for para-aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. METHODS: From May 2017 to March 2020, stage IIB-IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography-computed tomography (PET-CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. RESULTS: Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB (n = 7) and IIIB (n = 7). The median operating time was 138 min (range, 104-184 min). The median number of harvested PANs was 19 (range, 6-36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. CONCLUSION: Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Synthesis of a Nitrogenase PN -Cluster Model with [Fe8 S7 (µ-Sthiolate )2 ] Core from the All-Ferric [Fe4 S4 (Sthiolate )4 ] Cubane Synthon.

Constructing synthetic models of the nitrogenase PN -cluster has been a long-standing synthetic challenge. Here, we report an optimal nitrogenase PN -cluster model [{(TbtS)(OEt2 )Fe4 S3 }2 (µ-STbt)2 (µ6 -S)] (2) [Tbt=2,4,6-tris{bis(trimethylsilyl)methyl}phenyl] that is the closest synthetic mimic constructed to date. Of note is that two thiolate ligands and one hexacoordinated sulfide are connecting the two Fe4 S3 incomplete cubanes similar to the native PN -cluster, which has never been achieved. Cluster 2 has been characterized by X-ray crystallography and relevant physico-chemical methods. The variable temperature magnetic moments of 2 indicate a singlet ground state (S=0). The Mössbauer spectrum of 2 exhibits two doublets with an intensity ratio of 3:1, which suggests the presence of two types of iron sites. The synthetic pathway of the cluster 2 could indicate the native PN -cluster maturation process as it has been achieved from the Fe4 S4 cubane Fe4 S4 (STbt)4 (1).

A Dithiolato and Hydrido Bridged (CO/CN)Fe-Ni Complex with Unprotected CN: A Model for the [Ni-R] State of the [Ni-Fe] Hydrogenase Active Site.

A dithiolate/hydride bridged Fe-Ni complex, [(CN)(CO)2FeII(µ-pdt)(µ-H)NiII(CN)(PCy3)]- (2, pdt = propane-1,3-dithiolate) has been synthesized by the reaction of [(CN)2(CO)2FeII(pdt)]2- with [NiII(Cl)(H)(PCy3)2] as a synthetic analogue of the Ni-R state of the active site of the [Ni-Fe] hydrogenase. X-ray crystallography of this model complex suggests that the hydride unsymmetrically binds to Ni and Fe similar to natural [Ni-Fe] hydrogenases.

Clinical Prediction Rules to Classify Types of Stroke at Prehospital Stage.

Background and Purpose- Endovascular therapy is effective against acute cerebral large vessel occlusion (LVO). However, many patients do not receive such interventions because of the lack of timely identification of the type of stroke. If the types of stroke (any stroke, LVO, intracranial hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) were to be predicted at the prehospital stage, better access to appropriate interventions would be possible. Japan Urgent Stroke Triage (JUST) score was clinical prediction rule to classify suspected patients of acute stroke into different types at the prehospital stage. Methods- We obtained information for signs and symptoms and medical history of consecutive suspected patients of acute stroke at prehospital stage from paramedics and final diagnosis from the receiving hospital. We constructed derivation cohort in the historical multicenter cohort study from June 2015 to March 2016 and validation cohort in the prospective multicenter cohort study from August 2016 to July 2017. The derivation and the validation cohorts included 1229 and 1007 patients, respectively. We constructed multivariate logistic regression models with 21 variables to develop clinical prediction rules, which distinguish between different types of stroke: any stroke, LVO, ICH, and SAH. Results- Among the 1229 patients (median age, 72 years; 55% men) in the derivation cohort, 533 stroke, 104 LVO, 169 ICH, and 57 SAH cases were observed. The developed rules showed that the areas under the receiver operating curves were 0.88 for any stroke, 0.92 for LVO, 0.84 for ICH, and 0.89 for SAH. The validation cohort of 1007 patients (median age, 75 years; 56% men) showed that the areas under the curves of any stroke, LVO, ICH, and SAH were 0.80, 0.85, 0.77, and 0.94, respectively. Conclusions- These clinical prediction rules can help paramedics classify the suspected patients of stroke into any stroke, LVO, ICH, and SAH groups with excellent accuracy.

Relationship Between the Brain Natriuretic Peptide (BNP) Level and Prognosis of Diabetic Nephropathy with Microalbuminuria: A 7-Year Follow-Up Study.

The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and prognosis of diabetic nephropathy. The subjects were 100 Japanese outpatients with type 2 diabetes mellitus with microalbuminuria. Associations between metabolic parameters at baseline, including BNP, and prognosis of diabetic nephropathy (progression of diabetic nephropathy, cardiovascular events, and death) were examined for 7 years. In Cox proportional hazard analysis, HbA1c, albumin-creatinine ratio (ACR) and BNP were identified as significant factors for progression of diabetic nephropathy (p=0.033, p=0.037, and p=0.044, respectively), BNP was identified as significant factor for cardiovascular events (p=0.046), and estimated glomerular filtration rate (eGFR) and BNP were identified as significant factors for death (p=0.046 and p=0.048, respectively). In Kaplan-Meier analysis, risks of progression of diabetic nephropathy, cardiovascular events, and death were significantly different between patients with a low and a high BNP level (p=0.046, p=0.002, and p=0.025, respectively). ROC curve analysis gave cutoff values for BNP of 14.9 pg/ml for progression of diabetic nephropathy, 16.3 pg/ml for cardiovascular events, and 17.6 pg/ml for death (p=0.047, p=0.035, p=0.018, respectively). In conclusion, the BNP level is associated with prognosis in diabetic nephropathy.

Synthesis of an All-Ferric Cuboidal Iron-Sulfur Cluster [FeIII4 S4 (SAr)4 ].

An unprecedented, super oxidized all-ferric iron-sulfur cubanoid cluster with all terminal thiolates, Fe4 S4 (STbt)4 (3) [Tbt=2,4,6-tris{bis(trimethylsilyl)methyl}phenyl], has been isolated from the reaction of the bis-thiolate complex Fe(STbt)2 (2) with elemental sulfur. This cluster 3 has been characterized by X-ray crystallography, zero-field 57 Fe Mössbauer spectroscopy, cyclic voltammetry, and other relevant physico-chemical methods. Based on all the data, the electronic ground state of the cluster has been assigned to be Stot =0.

Heterolytic activation of dihydrogen molecule by hydroxo-/sulfido-bridged ruthenium-germanium dinuclear complex. Theoretical insights.

Heterolytic activation of dihydrogen molecule (H2) by hydroxo-/sulfido-bridged ruthenium-germanium dinuclear complex [Dmp(Dep)Ge(µ-S)(µ-OH)Ru(PPh3)](+) (1) (Dmp = 2,6-dimesitylphenyl, Dep = 2,6-diethylphenyl) is theoretically investigated with the ONIOM(DFT:MM) method. H2 approaches 1 to afford an intermediate [Dmp(Dep)(HO)Ge(µ-S)Ru(PPh3)](+)-(H2) (2). In 2, the Ru-OH coordinate bond is broken but H2 does not yet coordinate with the Ru center. Then, the H2 further approaches the Ru center through a transition state TS2-3 to afford a dihydrogen σ-complex [Dmp(Dep)(HO)Ge(µ-S)Ru(η(2)-H2)(PPh3)](+) (3). Starting from 3, the H-H σ-bond is cleaved by the Ru and Ge-OH moieties to form [Dmp(Dep)(H2O)Ge(µ-S)Ru(H)(PPh3)](+) (4). In 4, hydride and H2O coordinate with the Ru and Ge centers, respectively. Electron population changes clearly indicate that this H-H σ-bond cleavage occurs in a heterolytic manner like H2 activation by hydrogenase. Finally, the H2O dissociates from the Ge center to afford [Dmp(Dep)Ge(µ-S)Ru(H)(PPh3)](+) (PRD). This step is rate-determining. The activation energy of the backward reaction is moderately smaller than that of the forward reaction, which is consistent with the experimental result that PRD reacts with H2O to form 1 and H2. In the Si analogue [Dmp(Dep)Si(µ-S)(µ-OH)Ru(PPh3)](+) (1Si), the isomerization of 1Si to 2Si easily occurs with a small activation energy, while the dissociation of H2O from the Si center needs a considerably large activation energy. Based on these computational findings, it is emphasized that the reaction of 1 resembles well that of hydrogenase and the use of Ge in 1 is crucial for this heterolytic H-H σ-bond activation.

Host plant genome overcomes the lack of a bacterial gene for symbiotic nitrogen fixation.

Homocitrate is a component of the iron-molybdenum cofactor in nitrogenase, where nitrogen fixation occurs. NifV, which encodes homocitrate synthase (HCS), has been identified from various diazotrophs but is not present in most rhizobial species that perform efficient nitrogen fixation only in symbiotic association with legumes. Here we show that the FEN1 gene of a model legume, Lotus japonicus, overcomes the lack of NifV in rhizobia for symbiotic nitrogen fixation. A Fix(-) (non-fixing) plant mutant, fen1, forms morphologically normal but ineffective nodules. The causal gene, FEN1, was shown to encode HCS by its ability to complement a HCS-defective mutant of Saccharomyces cerevisiae. Homocitrate was present abundantly in wild-type nodules but was absent from ineffective fen1 nodules. Inoculation with Mesorhizobium loti carrying FEN1 or Azotobacter vinelandii NifV rescued the defect in nitrogen-fixing activity of the fen1 nodules. Exogenous supply of homocitrate also recovered the nitrogen-fixing activity of the fen1 nodules through de novo nitrogenase synthesis in the rhizobial bacteroids. These results indicate that homocitrate derived from the host plant cells is essential for the efficient and continuing synthesis of the nitrogenase system in endosymbionts, and thus provide a molecular basis for the complementary and indispensable partnership between legumes and rhizobia in symbiotic nitrogen fixation.

Activity of Daily Living and Walking Ability of Patients with Severe COVID-19 at Discharge from an Acute Care Hospital.

Objectives: The effectiveness of acute rehabilitation treatment for severe coronavirus disease 2019 (COVID-19) has not yet been established. This study examined the efficacy of treatment provided to patients with severe COVID-19 in an acute care facility. Methods: A total of 98 patients with severe COVID-19 requiring inpatient management in our intensive care unit (ICU) were included between December 2020 and October 2021. They were divided into two groups: those who received physiotherapy (PT group; n=44) and those who did not receive physiotherapy (non-PT group; n=54). Their backgrounds, clinical characteristics, and activities of daily life (ADL) at discharge were compared to examine factors that influenced the need for physiotherapy (PT). We also evaluated the effect of PT on ADL by comparing the Barthel Index (BI) before PT and at discharge. Results: The PT group patients were significantly older, had longer hospital and ICU stays, and used invasive mechanical ventilators (IMV) more frequently than those in the non-PT group. More patients in the non-PT group were able to walk at discharge than in the PT group. The PT group patients showed significant improvement in BI and ADL at discharge when compared with BI at the start of PT, regardless of whether an IMV was used. Conclusions: Older patients with severe COVID-19 with prolonged hospitalization or ICU stay or on an IMV are prone to a decline in ADL and may need to be considered for early PT.

[3:1] site-differentiated [4Fe-4S] clusters having one carboxylate and three thiolates.

[4Fe-4S] clusters modeled after those in organisms having three cysteine thiolates and one carboxylate were synthesized by using the tridentate thiolato chelate. X-ray structural analysis reveals that the carboxylates coordinate to the unique irons in an η(1) manner rather than η(2). Redox potentials show a positive shift from that of the cluster having ethanethiolate and the tridentate thiolato chelate. These properties conform to the arrangement of the [4Fe-4S] clusters in the electron transfer systems included in Rc dark operative protochlorophyllide oxidoreductase (DPOR) and formaldehyde oxidoreductase (FOR) with Pf ferredoxin.

Reliability and Validity of Quadriceps Muscle Thickness Measurements in Ultrasonography: A Comparison with Muscle Mass and Strength.

Objectives: Measurement of skeletal muscle using ultrasonography (US) has received considerable attention as an alternative method of muscle assessment. However, intra- and inter-rater reliability remains controversial. Furthermore, there is no consensus regarding the relationship between muscle assessment using US and muscle mass or physical assessment. We aimed to verify the validity and reliability of muscle measurements using US and its relationships with muscle strength and physical assessment. Methods: The 22 participants were all healthy men. Quadriceps muscle thickness was measured by US by three different raters. Intraclass correlation coefficient (ICC) was used to assess inter- and intra-rater reliability. The maximum isokinetic strength of the quadriceps and handgrip strength were used as measures of lower and upper muscle strength, respectively. Leg muscle mass was assessed using the leg skeletal muscle index (SMI), measured by body impedance analysis, and calf circumference. Results: The intra-rater reliability was excellent which the ICC(1,1) ranges 0.957-0.993, and ICC(1,3) ranges 0.985-0.998. For inter-rater reliability, the values of 0.904 for ICC(2,1) and 0.966 for ICC(2,3) indicated excellent reliability. Leg SMI was significantly correlated with quadriceps thickness (r=0.36). Maximum isokinetic strength and handgrip strength showed weak but statistically significant correlations with quadriceps thickness (r=0.20, r=0.30, respectively). The correlation between quadriceps thickness and calf circumference was not statistically significant. Conclusions: Quadriceps muscle assessment using US is a valid and reliable technique for healthy individuals. Quadriceps muscle thickness was significantly positively correlated with upper and lower muscle strength and leg SMI. Muscle thickness assessment could replace full body muscle assessment in clinical settings.

Investigation of Changes in Skeletal Muscle Mass and Muscle Quality and Factors Affecting Changes in Deceased Donor Liver Transplantation.

BACKGROUND: In Japan, there are very few cases of deceased donor liver transplantation (DDLT) and even fewer studies on the effects of DDLT on sarcopenia. This study examined the changes in skeletal muscle mass and quality in DDLT, the factors related to these changes, and survival rates. METHODS: Using computed tomography (CT), we retrospectively measured L3 skeletal muscle index (L3SMI) and intramuscular adipose tissue content (IMAC) at admission, discharge, and 1-year post-DDLT in 23 patients with DDLT from our hospital between 2011 and 2020. We investigated the relationships between changes in L3SMI and IMAC associated with DDLT and between various admission factors and survival. RESULTS: Patients with DDLT showed significant decreases in L3SMI during hospitalization (P < .05). Although L3SMI tended to increase postdischarge, in 11 (73%) cases, it was lower at 1-year post-DDLT than that on admission. Moreover, decreases in L3SMI during hospitalization were correlated to L3SMI on admission (r = 0.475, P < 0.05). Intramuscular adipose tissue content increased from admission to discharge and decreased 1-year post-DDLT. Admission L3SMI and IMAC were not significantly correlated with survival. CONCLUSIONS: This study suggests that the skeletal muscle mass of DDLT patients decreased during hospitalization and showed a slight tendency to improve after discharge, but the decrease tended to be prolonged. In addition, patients with higher skeletal muscle mass at admission tended to lose more skeletal muscle mass during hospitalization. Deceased donor liver transplantation was identified as a potential contributor to improved muscle quality, whereas skeletal muscle mass and quality on admission did not affect post-DDLT survival.

Diffuse alveolar hemorrhage and acute eosinophilic pneumonia: A rare form of amiodarone pulmonary toxicity diagnosed by bronchoalveolar lavage.

A 56-year-old man presented with fever, cough, and bloody sputum. He had undergone mitral valve replacement with mechanical prosthesis 14 months prior for mitral valve disease. Subsequently, the patient was taking warfarin and amiodarone. Chest imaging revealed dense, infiltrative shadows, and blood tests showed prolonged prothrombin time and eosinophilia. Warfarin was withdrawn, and antibiotics were started, but bloody sputum and respiratory failure persisted. Considering that eosinophilia was observed after the administration of amiodarone, the drug was discontinued, and bronchoalveolar lavage was performed. Cytology showed foam cells, eosinophils, and hemosiderin-laden macrophages; amiodarone-induced diffuse alveolar hemorrhage (DAH) and acute eosinophilic pneumonia (AEP) were diagnosed, and the patient was treated with corticosteroids. This report describes the first documented case of amiodarone-induced DAH and AEP. When a patient taking amiodarone presents with antibiotic-refractory pneumonia with bloody sputum and eosinophilia, amiodarone-induced DAH and AEP should be considered. Learning objective: We report the first case of amiodarone-induced diffuse alveolar hemorrhage (DAH) and acute eosinophilic pneumonia (AEP) diagnosed by foam cells, eosinophils, and hemosiderin-laden macrophages on bronchoalveolar lavage cytology. When a patient taking amiodarone presents with antibiotic-refractory pneumonia with bloody sputum and eosinophilia, amiodarone-induced DAH and AEP should be considered.

Predictors of Activities of Daily Living in Intensive Care Unit Survivors: A Propensity Score Matching Analysis.

Objectives: Increased long-term impairment is common among intensive care unit (ICU) survivors. However, predictors of activities of daily living (ADL) in ICU survivors are poorly understood. We aimed to focus on the trajectory of physical function and explore the clinical variables that affect ADL at hospital discharge. Methods: We enrolled 411 patients admitted to the ICU from April 2018 to October 2020. Physical function was evaluated at ICU admission, ICU discharge, and hospital discharge. We assessed physical function (grip strength, arm and calf circumference, quadriceps thickness, and Barthel index). Patients were assigned to the high or low ADL group based on their Barthel index at discharge. Propensity score matching analysis was performed to minimize selection biases and differences in clinical characteristics. Results: After matching propensity scores, 114 of the 411 patients (aged 65±15 years) were evaluated. The high ADL group showed better physical function at ICU discharge and hospital discharge than the low ADL group. An overall decreasing trend in muscle mass was observed over time; the rates of decline were lower in the high ADL group than in the low ADL group. The cutoff values for relative changes in calf circumference and quadriceps thickness to predict high ADL were -7.89% (sensitivity: 77.8%, specificity: 55.6%) and -28.1% (sensitivity: 81.0%, specificity: 58.8%), respectively. Conclusions: The relative decreases in calf circumference and quadriceps thickness during hospitalization were lower in patients who maintained their ADL. Assessment of the trajectory of physical function can predict ADL status at hospital discharge among ICU survivors.

Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan.

To determine the impact of the coverage of risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) as well as genetic testing for BRCA pathogenic variants by the national insurance system in Japan. We compared the clinical background of women who underwent RRSO at our institution before and after its coverage by the national insurance system. Those who underwent RRSO between January 2017 and December 2019 and between April 2020 and March 2022 were classified as Period. A and B, respectively. Overall, 134 women underwent RRSO during the study period. In Period A and B, 45 and 89 women underwent RRSO for the study period was 36 and 24 months, respectively. Compared with Period A, the number of women who underwent RRSO per month increased by threefold in Period B (p < 0.01). In addition, the number of women who underwent surgery for breast cancer along with RRSO increased in Period B (p < 0.01). Although the number of women who underwent concurrent RRM with RRSO in Period B increased, the difference was not statistically significant. Compared with Period A, the number of women diagnosed with BRCA pathogenic variant increased by 3.9-fold, and the proportion of women who underwent concurrent hysterectomy at the time of RRSO decreased from 66 to 7.9% in Period B (p < 0.01). Owing to the introduction of the national insurance system, the number of women who underwent RRSO and concurrent surgery for breast cancer at the time of RRSO increased in Japan.

Model studies of methyl CoM reductase: methane formation via CH3-S bond cleavage of Ni(I) tetraazacyclic complexes having intramolecular methyl sulfide pendants.

The Ni(I) tetraazacycles [Ni(dmmtc)](+) and [Ni(mtc)](+), which have methylthioethyl pendants, were synthesized as models of the reduced state of the active site of methyl coenzyme M reductase (MCR), and their structures and redox properties were elucidated (dmmtc, 1,8-dimethyl-4,11-bis{(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane; mtc, 1,8-{bis(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane). The intramolecular CH(3)-S bond of the thioether pendant of [Ni(I)(dmmtc)](OTf) was cleaved in THF at 75 °C in the presence of the bulky thiol DmpSH, which acts as a proton source, and methane was formed in 31% yield and a Ni(II) thiolate complex was concomitantly obtained (Dmp = 2,6-dimesityphenyl). The CH(3)-S bond cleavage of [Ni(I)(mtc)](+) also proceeded similarly, but under milder conditions probably due to the lower potential of the [Ni(I)(mtc)](+) complex. These results indicate that the robust CH(3)-S bond can be homolytically cleaved by the Ni(I) center when they are properly arranged, which highlights the significance of the F430 Ni environment in the active site of the MCR protein.

Coordination of methyl coenzyme M and coenzyme M at divalent and trivalent nickel cyclams: model studies of methyl coenzyme M reductase active site.

Divalent and trivalent nickel complexes of 1,4,8,11-tetraazacyclotetradecane, denoted as cyclam hereafter, coordinated by methyl coenzyme M (MeSCoM(-)) and coenzyme M (HSCoM(-)) have been synthesized in the course our model studies of methyl coenzyme M reductase (MCR). The divalent nickel complexes Ni(cyclam)(RSCoM)(2) (R = Me, H) have two trans-disposed RSCoM(-) ligands at the nickel(II) center as sulfonates, and thus, the nickels have an octahedral coordination. The SCoM(2-) adduct Ni(cyclam)(SCoM) was also synthesized, in which the SCoM(2-) ligand chelates the nickel via the thiolate sulfur and a sulfonate oxygen. The trivalent MeSCoM adduct [Ni(cyclam)(MeSCoM)(2)](OTf) was synthesized by treatment of [Ni(cyclam)(NCCH(3))(2)](OTf)(3) with ((n)Bu(4)N)[MeSCoM]. A similar reaction with ((n)Bu(4)N)[HSCoM] did not afford the corresponding trivalent HSCoM(-) adduct, but rather the divalent nickel complex polymer [-Ni(II)(cyclam)(CoMSSCoM)-](n) was obtained, in which the terminal thiol of HSCoM(-) was oxidized to the disulfide (CoMSSCoM)(2-) by the Ni(III) center.