Kinetic resolution of 1,1'-binaphthyl-2,2'-diamine derivatives by chiral calcium phosphate-catalyzed acylation.

1,1'-Binaphthyl-2,2'-diamine (BINAM) is a useful axially chiral compound. The kinetic resolution of BINAM is one of the most crucial methods for synthesizing chiral BINAM. We have developed a chiral calcium phosphate-catalyzed kinetic resolution of BINAM by utilizing an acylation reaction to produce a mono-amide. The kinetic resolution of BINAM derivatives was achieved by using isobutyric anhydride in the presence of chiral calcium phosphate and 4-morpholinopyridine with up to s = 127. 6,6'-Substituted BINAM derivatives were also applicable for this reaction. The resulting mono-acylated BINAM could be transformed into BINAM by hydrolysis under acidic conditions.

A Novel Dressing Method to Achieve Early Natural Tracheostoma Closure.

Tracheotomy is a routine surgical procedure in oral and maxillofacial surgery. After decannulation, spontaneous tracheostoma closure is usually expected. However, wound healing is often delayed, requiring 1 to 2 weeks for healing and resulting in the need for surgical closure. Although many reports have described the surgical closure of a tracheostoma, few reports have focused on the dressing methods for closure of tracheal openings after decannulation. Herein, the authors report a new tracheostoma closure method that does not rely on surgical closure or the adhesive strength of the tape. The authors' conventional dressing method was to place gauze over the tracheostoma after decannulation and apply pressure through elastic tape or with a film dressing to seal the tracheostoma and achieve natural closure by reducing the leakage of air and tracheal secretions. However, the conventional method cannot completely prevent the leakage of air and tracheal secretions. We developed a novel method to achieve early closure by markedly reducing the leakage by partially inserting the gauze into the tracheostoma.

Characteristics and Risk Factors for the Fracture of One-Piece Implants.

Objective: The one-piece dental implant was originally designed to overcome the structural weaknesses of the two-piece implant. However, a fractured one-piece implant requires removal because the abutment cannot be repaired or replaced to support new prosthetic restorations. The aim of this study was to clarify the features and risk factors for fracture of the one-piece implant. Methods: This study was designed as a retrospective case series research. The subjects were patients who were treated for fractures of the one-piece implant at a clinic in Japan between 2012 and 2021. Fractures of the one-piece implant were diagnosed by cone-beam computed tomography, and the association between age and duration from implant placement to fracture was analyzed by one-way ANOVA followed by the Tukey test. Results: Eighteen patients and 20 one-piece implants (under 39 years: 5 patients and 6 implants; 40-59 years: 7 patients and 7 implants; over 60 years: 6 patients and 7 implants) had fractures in their one-piece implants. Of the fractured implants, 11 had a diameter of 3 mm, and 9 had a diameter of 4 mm. The mean durations up to implant fracture were 662 days in the younger group, 1467 days in the middle group, and 1239 days in older group, and the duration was significantly shorter in the younger group. In addition, 83.3% of fracture implants in the younger group were in the molar region. All fractures of the one-piece implants occurred under the bone margin. Two patients had torus mandibularis, and 1 patient was had bruxism. Conclusions: One-piece implants in younger patients that are located in the lower molar position are the most susceptible to implant fracture, and the fracture occurred under the bone margin in all cases.

Computed tomography evaluation of risk factors for an undesirable buccal split during sagittal split ramus osteotomy.

Sagittal split ramus osteotomy (SSRO) sometimes induces an irregular split pattern referred to as a bad split. We investigated the risk factors for bad splits in the buccal plate of the ramus during SSRO. Ramus morphology and bad splits in the buccal plate of the ramus were assessed using preoperative and postoperative computed tomography images. Of the 53 rami analyzed, 45 had a successful split, and 8 had a bad split in the buccal plate. Horizontal images at the height of the mandibular foramen showed that there were significant differences in the ratio of the forward thickness to the backward thickness of the ramus between patients with a successful split and those with a bad split. In addition, the distal region of the cortical bone tended to be thicker and the curve of the lateral region of the cortical bone tended to be smaller in the bad split group than in the good split group. These results indicated that a ramus shape in which the width becomes thinner towards the back frequently induces bad splits in the buccal plate of the ramus during SSRO, and more attention should be paid to patients who have rami of these shapes in future surgeries.

Transition from epoprostenol to selexipag in a patient with systemic sclerosis and pulmonary hypertension during the postoperative period of colon cancer surgery: A case report.

Introduction: Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively. Case Description: A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud's phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40. Conclusion: In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.

Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and folate metabolism-related genes in the placenta of rats.

Valproate (VPA), an antiepileptic drug, is known to inhibit histone deacetylases (HDACs). Exposure to VPA during pregnancy increases several fetal risks. The maintenance of folate level during pregnancy is essential for adequate fetal development, and the placenta plays a critical role in supplying nutrients to the fetus. The aim of this study was to elucidate the effects of VPA on the gene expression of folate carriers and metabolizing enzymes in the rat placenta at both mid and late gestation periods. Pregnant rats were orally administered VPA on a single day or 4 days (repeated administration). Gene expression of folate carriers (Folr1, Slc19a1, Slc46a1) and metabolizing enzymes (Cth, Mtr, Mtrr, Mthfr, Dhfr) was assessed in the placenta on gestational day (GD) 13 or GD20. In the control rats, the expression of Folr1, Slc46a1, Cth, and Mthfr tended to be upregulated, whereas that of Mtrr and Dhfr was downregulated during gestation; the expression of Slc19a1 and Mtr did not change. Repeated VPA administration reduced the placental expression of Folr1and Mtr on GD20 and increased the expression of Dhfr on GD13 compared with the control. These findings indicate that administration of VPA alters the placental gene expression of folate carriers and metabolism-related enzymes.

Effects of Helioxanthin Derivative-Treated Human Dental Pulp Stem Cells on Fracture Healing.

Bone defects affect patients functionally and psychologically and can decrease quality of life. To resolve these problems, a simple and efficient method of bone regeneration is required. Human dental pulp stem cells (DPSCs) have high proliferative ability and multilineage differentiation potential. In our previous study, we reported a highly efficient method to induce osteogenic differentiation using DPSC sheets treated with a helioxanthin derivative (4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH)) in a mouse calvarial defect model. However, the localization of the DPSCs after transplantation remains unknown. Therefore, in this study, we investigated the localization of transplanted DPSCs in a mouse fracture model. DPSCs were collected from six healthy patients aged 18-29 years, cultured in normal medium (NM), osteogenic medium (OM), or OM with TH, and fabricated them into cell sheets. To evaluate the efficacy of fracture healing using DPSCs treated with OM+TH, and to clarify the localization of the transplanted DPSC sheets in vivo, we transplanted OM+TH-treated DPSC sheets labeled with PKH26 into mouse tibiae fractures. We demonstrated that transplanted OM+TH-treated DPSCs sheets were localized to the fracture site and facilitated bone formation. These results indicated that transplanted OM+TH-treated DPSCs were localized at fracture sites and directly promoted fracture healing.

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats: An analysis by gestational period.

The use of valproic acid (VPA), an antiepileptic drug, during pregnancy, is known to increase various fetal risks. Since VPA has been known to inhibit histone deacetylases (HDACs); its administration could alter gene transcription levels. However, in vivo effects of VPA administration on placental transporters have not been fully elucidated. The purpose of the present study was to comprehensively evaluate the effects of single and repetitive VPA administration on the expression of placental transporters and analyze them by gestational day. We investigated 18 transporters (8 ATP-binding cassette (ABC) and 10 solute carrier (SLC) transporters) in the placentas of pregnant rats that were orally administered 400 mg/kg/day VPA for one or four days, during mid- or late gestation. In the control rats, 4 ABC transporter genes (Abcb1a, 1b, Abcc2, Abcc4) were upregulated, 3 (Abcc3, Abcc5, Abcg2) downregulated through gestation, whereas 1 (Abcc1) was not changed. Regarding SLC transporters, 6 genes (Slc7a5, Slc16a3, Slc22a3, Slc22a4, Slco2b1, Slco4a1) were increased, 1 (Slc29a1) decreased through gestation, whereas 3 (Slc7a8, Slc22a5, Slco2a1) showed no significant change. Single VPA administration altered the expression of 9 transporters and repetitive administration, 13 transporters. In particular, VPA remarkably decreased Abcc4 and Slc22a4 in late gestation and increased Abcc5 during mid-gestation. Our findings indicated that VPA administration changed transporter expression levels in rat placenta, and suggested that sensitivity to VPA differs across gestational stages.

Prognostic impacts of changes in left ventricular ejection fraction in heart failure patients with preserved left ventricular ejection fraction.

Background: It has been reported that recovery of left ventricular ejection fraction (LVEF) is associated with better prognosis in heart failure (HF) patients with reduced EF (rEF). However, change of LVEF has not yet been investigated in cases of HF with preserved EF (HFpEF). Methods and results: Consecutive 1082 HFpEF patients, who had been admitted to hospital due to decompensated HF (EF >50% at the first LVEF assessment at discharge), were enrolled, and LVEF was reassessed within 6 months in the outpatient setting (second LVEF assessment). Among the HFpEF patients, LVEF of 758 patients remained above 50% (pEF group), 138 patients had LVEF of 40%-49% (midrange EF, mrEF group) and 186 patients had LVEF of less than 40% (rEF group). In the multivariable logistic regression analysis, younger age and presence of higher levels of troponin I were predictors of rEF (worsened HFpEF). In the Kaplan-Meier analysis, the cardiac event rate of the groups progressively increased from pEF, mrEF to rEF (log-rank, p<0.001), whereas all-cause mortality did not significantly differ among the groups. In the multivariable Cox proportional hazard analysis, rEF (vs pEF) was not a predictor of all-cause mortality, but an independent predictor of increased cardiac event rates (HR 1.424, 95% CI 1.020 to 1.861, p=0.039). Conclusion: An initial assessment of LVEF and LVEF changes are important for deciding treatment and predicting prognosis in HFpEF patients. In addition, several confounding factors are associated with LVEF changes in worsened HFpEF patients.

Associations of Benzodiazepine With Adverse Prognosis in Heart Failure Patients With Insomnia.

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z-drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P=0.010), had a higher prevalence of depression (17.4% versus 8.9%; P<0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%; P=0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/dL; P=0.001), sodium (139.0 versus 140.0 mEq/L; P=0.018), and albumin (3.7 versus 3.9 g/dL; P=0.003). Kaplan-Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for HF, log-rank P=0.001; cardiac death, log-rank P=0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for HF (hazard ratio, 1.530; 95% CI, 1.025-2.284; P=0.038). Furthermore, rehospitalization for HF was higher in the benzodiazepine group after propensity score matching (log-rank P=0.036). Conclusions Benzodiazepine is associated with higher risk of rehospitalization for HF compared with Z-drugs in patients with HF.

Recovered Left Ventricular Ejection Fraction and Its Prognostic Impacts in Hospitalized Heart Failure Patients with Reduced Ejection Fraction.

It has been recently recognized that recovery of left ventricular ejection fraction (EF), termed "recovered EF", occurs in a proportion of heart failure patients with reduced EF (HFrEF), and is associated with better prognosis. However, the clinical characteristics of "recovered EF" have not been fully examined.Consecutive 567 patients hospitalized due to HFrEF (EF < 40% at 1st assessment at hospital discharge) were enrolled, and EF was re-assessed within half a year in an outpatient setting (2nd assessment). Among these HFrEF patients, 235 remained EF < 40% (reduced, rEF group), 82 changed to EF 40-49% (midrange, mrEF group), and 250 recovered to EF > 50% (preserved, pEF group "recovered EF" ) at the 2nd examination. Age was lower and body mass index and systolic blood pressure were higher in pEF than in rEF. The prevalence of atrial fibrillation (AF) and usage of an implantable cardiac defibrillator and cardiac resynchronization therapy were highest in pEF. Left ventricular end diastolic dimension (LVDd) was the smallest in the pEF group. Multivariable logistic regression analysis revealed that younger age, presence of AF, and lower levels of LVDd were predictors of "recovered EF". Kaplan-Meier analysis found that pEF presented the lowest cardiac event rate (P = 0.003) and all-cause mortality (P = 0.001). In multivariable Cox proportional hazard analyses, pEF (versus rEF) was an independent predictor of both cardiac event rate (HR = 0.668, 95%CI 0.450-0.994, P = 0.046) and all-cause mortality (HR = 0.655, 95%CI 0.459-0.934, P = 0.019).Hospitalized HFrEF patients with recovered EF are associated with younger age, higher presence of AF, and better prognosis.

Sporadic Cardiac Amyloidosis by Amyloidogenic Transthyretin V122I Variant.

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.

Prognostic Impact of Restless Legs Syndrome on Patients with Heart Failure.

The restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs or arms for relief of uncomfortable or unpleasant sensations. Prevalence and prognostic impact of RLS on patients with heart failure (HF) remain unclear. We aimed to investigate the clinical characteristics and prognostic impact of RLS on HF patients.Consecutive 338 HF patients were evaluated for RLS and divided into two groups on the basis of presence of RLS: HF patients with RLS (RLS group, n = 29) and HF patients without RLS (non-RLS group, n = 309). We compared clinical characteristics, parameters of laboratory data and echocardiography, and rate of follow-up cardiac events including worsening HF and cardiac death between the two groups. Compared with the non-RLS group, the RLS group had higher prevalence of anemia (65.5% versus 40.8%, P = 0.010), higher usage of inotropic agents (31.0% versus 15.2%, P = 0.028), higher levels of B-type natriuretic peptide (570.8 versus 215.8 pg/mL, P = 0.018), and lower levels of left ventricular ejection fraction (40.4% versus 48.4%, P = 0.019). By contrast, age, gender, prevalence of other co-morbidities and medications were comparable between the groups. In the Kaplan-Meier analysis, the cardiac event rate was significantly higher in the RLS group than in the non-RLS group (log-rank P = 0.034). In the Cox proportional hazard analysis, RLS was a predictor for cardiac events in HF patients (hazard ratio: 1.783, 95% confidence interval: 1.038-3.063).RLS is associated with adverse prognosis in HF patients.

Prior History and Incidence of Cancer Impacts on Cardiac Prognosis in Hospitalized Patients With Heart Failure.

BACKGROUND: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF.Methods and Results:Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030). CONCLUSIONS: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

Apolipoprotein B correlates with intra-plaque necrotic core volume in stable coronary artery disease.

OBJECTIVE: To determine the relationship between plaque composition and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo-B), and Apo-A1 using virtual-histology intravascular ultrasound (VH-IVUS). METHODS: We assessed plaque composition in patients with stable coronary artery disease (SCD) admitted to our hospital for percutaneous coronary intervention (PCI) between November 1, 2012, and March 10, 2015. Before PCI, fibrous (FI), fibrofatty (FF), necrotic core (NC), and dense calcium (DC) regions were evaluated using VH-IVUS, and the contributions of each to the culprit lesion volume were recorded. Plasma LDL-C, HDL-C, Apo-B, and Apo-A1 levels were assessed before PCI. The relationship between the regions on VH-IVUS and plasma lipid levels was assessed. Patients were categorized into low Apo-B (LAB) and high Apo-B (HAB) groups, based on the overall cohort median Apo-B level. RESULTS: We enrolled 115 patients (median Apo-B, 91 mg/dL, male n = 88) with 57 and 58 patients in the LAB (Apo-B ≤ 90 mg/dL) and HAB (Apo-B ≥ 91 mg/dL) groups, respectively. Vessel, plaque, and %NC volumes were significantly greater in the HAB group than in the LAB group. The %FI, %FF, and %DC volumes were similar in both groups. In all 115 patients, the %NC volume correlated with LDL-C (r = 0.2353, P = 0.0114) and Apo-B (r = 0.2487, P = 0.0074) but not with HDL-C and Apo A-1. The high-sensitivity C-reactive protein level tended to be higher in the HAB group than in the LAB group. Multiple regression analysis showed that being male, Apo-A1, and Apo-B were significant predictors of %NC volume extent. CONCLUSIONS: Elevated Apo-B level was related to the %NC in target coronary artery lesions in SCD patients, suggesting a role of Apo-B as a biomarker of unstable plaque in this population.

Risk Factors for Surgical Site Infection in Patients Undergoing Free and Pedicled Myocutaneous Flap Reconstruction After Oral Cancer Resection.

PURPOSE: The aim of the study was to investigate risk factors for surgical site infection (SSI) at the recipient site in oral cancer resection surgery with neck dissection and reconstruction using a free or pedicled myocutaneous flap. PATIENTS AND METHODS: Eighty-eight patients who underwent this procedure composed a nonrandomized retrospective cohort. RESULTS: Recipient site SSIs occurred in 27 patients (30.7%). In multivariate analysis, flap necrosis (partial or total; P = .003; odds ratio [OR] = 12.8) and preoperative hypoalbuminemia (P = .025; OR = 3.9) were independent risk factors for recipient site SSI. In an analysis restricted to flap survival cases, free flap (vs pedicled flap; P = .026; OR = 25.0) and preoperative hypoalbuminemia (P = .014; OR = 11.0) were significant risk factors for recipient site SSI. CONCLUSIONS: These results suggest that different preoperative nutritional interventions, such as a diet enriched with energy and protein, oral nutritional supplements, and, in patients with compromised swallow, enteral tube feeding or parenteral nutrition, could be important to decrease the frequency of recipient site SSIs. Pedicled and free flaps might result in SSIs for different reasons. Partial necrosis occurred more often with pedicled flaps than with free flaps and it might be important to use different techniques to decrease skin flap necrosis to lower the rate of SSIs.

Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure.

BACKGROUND: We aimed to clarify the prognosis and pathophysiological parameters of low T3 syndrome in patients with heart failure (HF). METHODS AND RESULTS: Hospitalized patients with HF and euthyroidism (n = 911) were divided into 2 groups on the basis of free triiodothyronine (FT3) serum levels: the normal FT3 group (FT3 ≥2.3 pg/mL; n = 590; 64.8%) and the low FT3 group (FT3 <2.3 pg/mL; n = 321; 35.2%). We compared post-discharge cardiac and all-cause mortality by means of Kaplan-Meier analysis and Cox proportional hazard analysis, and the parameters of echocardiography and cardiopulmonary exercise testing by means of Student t test. In the follow-up period of median 991 (interquartile range 534-1659) days, there were 193 all-cause deaths, including 88 cardiac deaths. Cardiac and all-cause mortality were higher in the low FT3 group (log-rank P < .01). Low FT3 was a predictor of cardiac death (hazard ratio 1.926, 95% confidence interval [CI] 1.268-2.927; P = .002) and all-cause death (hazard ratio 2.304, 95% CI 1.736-3.058; P < .001). Although left ventricular ejection fraction was similar between the groups, the low FT3 group showed lower peak VO2 (13.6 ± 4.6 vs 16.6 ± 4.4 mL·kg-1·min,-oneP < .001) and higher VE/VCO2 slope (36.5 ± 8.2 vs 33.0 ± 7.5; P = .001). CONCLUSION: Low T3 syndrome in patients with HF is associated with higher cardiac and all cause-mortality.