Efficient Synthesis and Structural Analysis of Chiral 4,4'-Biazulene.

4,4'-Biazulene is a potentially attractive key component of an axially chiral biaryl compound, however, its structure and properties have not been clarified owing to the lack of its efficient synthesis. We report a breakthrough in the reliable synthesis of 4,4'-biazulene, which is achieved by the access to azulen-4-ylboronic acid pinacol ester and 4-iodoazulene as novel key synthetic intermediates for the Suzuki-Miyaura cross-coupling reaction. The X-ray crystallographic analysis of 4,4'-biazulene confirmed its axial chirality. The enantiomers of 4,4'-biazulene were successfully resolved by HPLC on the chiral stationary phase column. The kinetic experiments and DFT calculations indicate that the racemization energy barrier of 4,4'-biazulene is comparable to that of 1,1'-binaphthyl.

Effect of upper extremity load on pelvic movements during wheeled upright walker use.

[Purpose] This study aimed to elucidate the effects of upper extremity loading on pelvic movements during wheeled upright walker use. [Participants and Methods] Thirteen healthy male adults participated in this intervention study. Participants walked under five conditions with targeted loads on their upper extremities of 0%, 10%, 20%, 30%, and 40% of their body weights using a wheeled upright walker with armrests. Measured items included gait velocity and stride length; the angle of the maximum trunk anterior tilt; the range of motion of the trunk and pelvis in the movements of obliquity, tilt, and rotation; and the amplitude of the center of mass in the vertical and lateral directions captured and calculated using a three-dimensional motion analysis system. [Results] Increasing the load on the upper extremities did not shorten the stride or restrict pelvic movement during gait using upright walker use. The range of pelvic rotation with walker use increased versus that of the standard gait. [Conclusion] The pelvis showed quantitative movements during gait using the wheeled upright walker with armrests. These results could be helpful in the development of robotic assistive devices.

Acute effect of passive one-legged intermittent static stretching on regional blood flow in young men.

PURPOSE: Passive stretching reduces stiffness in the lower limb arteries of the stretched limb. To address this physiological mechanism, we measured the change in shear rate in the posterior tibial artery during a single bout of one-legged passive calf stretching compared with that in the non-stretched leg. METHODS: The diameter, mean blood velocity, blood flow, and shear rate in the posterior tibial artery were measured using Doppler ultrasound before (baseline), during, and after a one-legged passive intermittent calf stretching procedure (six repetitions of 30-s static stretch with 10-s relaxation) in nine healthy young men. RESULTS: In the posterior tibial artery of the stretched leg, the arterial diameter significantly decreased from baseline during the stretching period (baseline vs. stretching period of the 6th set, 0.19 ± 0.01 vs. 0.18 ± 0.01 cm, P < 0.05) without any change in shear rate and mean blood velocity. In contrast, during the relaxation period, the mean blood velocity (baseline vs. relaxation period of the 5th set, 2.98 ± 0.54 vs. 6.25 ± 1.48 cm/s) increased, and consequently, the shear rate (baseline vs. relaxation period of the 5th set, 66.75 ± 15.39 vs. 122.85 ± 29.40 s-1) increased (each P < 0.01); however, there was no change in arterial diameter. In contrast, these values in the non-stretched leg were unchanged at all-time points. CONCLUSIONS: The stretching procedure increased the shear rate in the peripheral artery of the stretched leg during the relaxation period. This finding indicates that the local hemodynamic response (possibly through endothelial function), resulting from an increase in shear stress, may contribute to stretching-induced attenuation of local arterial stiffness.

[A Case Report on a Successful Resection after FOLFIRI plus Cetuximab Therapy for Unresectable Colorectal Cancer with Multiple Liver Metastases].

The patient was a 66-year-old woman with a history of right breast cancer 20 years prior. Her chief complaint was hematochezia, and she was diagnosed as having rectal cancer. She underwent laparoscopic high anterior resection. We made a diagnosis of moderately differentiated adenocarcinoma, type 2, 25×20 mm, pMP, pN0, Stage I, KRAS being wild-type. Multiple liver metastases were detected 6 months after the surgery. Tumor contacted with grison. The tumor was not completely resected as evidenced by the small liver remnant volume. Conversion therapy was administered, and the patient received 6 courses of FOLFIRI plus cetuximab therapy. Alopecia and grade 1 eruption were observed as adverse effects of the chemotherapy. The tumor size was reduced, and we resected the tumor by performing right lobectomy and partial hepatectomy. At 1 year 3 months after surgery, no recurrence was observed.

What We Can Learn from Cases of Synchronous Acute Mesenteric Obstruction and Nonocclusive Mesenteric Ischemia: How to Reduce the Acute Mesenteric Ischemia-Related Mortality Rate.

Although the survival rate of patients with ischemic heart disease has recently increased, it remains unknown why the mortality rate of acute mesenteric ischemia (AMI) remains high. Here, we report a possible method of improving the survival rate of patients with AMI obtained through 2 cases of simultaneous acute mesenteric obstruction (AMO) and nonocclusive mesenteric ischemia (NOMI). Case 1 was a 74-year-old woman with atrial fibrillation, hypertension, and dyslipidemia as underlying diseases who developed NOMI immediately after undergoing SMA thrombolysis. Case 2 was a 69-year-old man with atrial fibrillation, hypertension, chronic heart failure, chronic renal failure, and old myocardial infarction who was diagnosed with SMA occlusion complicated by NOMI on the basis of abdominal angiography findings during the first visit. Cure was achieved by thrombolytic therapy, resection of the necrotic intestine, and continuous intra-arterial and/or intravenous injection of prostaglandin E1 (PGE1) in case 1 and by resection of the necrotic intestine and continuous intra-arterial and/or intravenous injection of PGE1 in case 2. AMO and NOMI have many background similarities (e.g., atherosclerosis, hypertension, and ischemic heart disease), making their coexistence very likely. However, no case of AMO plus NOMI has been reported until now. It is highly probable that concomitant NOMI is overlooked in cases of AMO. When managing AMO, NOMI should be considered as a complication, which may lower the patient's potential risk of developing NOMI and contribute to improved prognosis of both AMO and AMI.

Giant symptomatic splenic cyst treated with laparoscopic fenestration using single-incision plus one-port laparoscopic surgery: A case report.

Laparoscopic fenestration is the preferred treatment for symptomatic splenic cysts because it is curative and spleen-sparing. We report a case of a 25-year-old female who underwent laparoscopic fenestration for a giant splenic cyst using a single-incision plus one-port approach. She presented to our hospital with repeated vomiting. Imaging showed a 23 × 18 cm splenic cyst with no solid components, strongly compressing the stomach to the right side. Laparoscopic fenestration was initiated through a 2.5-cm umbilical incision, and a 5-mm port was added in the left abdomen intraoperatively. The drain placement was deemed necessary to prevent abscess formation and post-operative bleeding because of a thick cyst component and unexpectedly thick wall. Splenic cysts are typically benign and commonly develop in young people, hence, organ preservation and cosmetic results are crucial. Laparoscopic fenestration using single-incision plus one-port is considered to be an appropriate procedure for giant splenic cysts with non-serous contents.

Low prognostic nutrition index as a prognostic biomarker in elderly patients with early gastric cancer after gastrectomy.

Purpose Non-invasive biomarkers including systemic inflammatory or nutrition-based index including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) can be useful in determining treatment strategies for elderly patients with early gastric cancer (EGC). The aim of this study was to investigate the significance of these index for predicting the long-term survival of EGC patients aged 80 years over. Methods This study included 80 elderly EGC patients with pStageIA after gastrectomy. Optimal cutoff value for PNI, NLR, PLR and LMR were set by using receiver operating curve analysis. The long-term outcomes after gastrectomy were analyzed by univariate and multivariate Cox regression analyses. Results Cut-off value for PNI, NLR, PLR and LMR was set at 46.5, 2.8, 210 and 4.6, respectively. By univariate analyses, low PNI, high NLR, high PLR and low LMR were significantly associated with worse prognosis. By multivariate analysis, low PNI was confirmed as an independent prognostic factor after gastrectomy (HR 0.17 ; 95% CI 0.03-0.91 ; P = 0.04). 5-year overall survival rate of patients with low PNI (≤ 46.5) were 52.4%. Conclusion Low PNI might be useful biomarker to predict worse prognosis of elderly EGC patients after gastrectomy. J. Med. Invest. 71 : 113-120, February, 2024.

Laparoscopic versus open pancreaticoduodenectomy for ampullary cancer: A retrospective study.

INTRODUCTION: Studies comparing laparoscopic pancreaticoduodenectomy (LPD) with open pancreaticoduodenectomy (OPD) for ampullary carcinoma (AC) are limited. This study aimed to compare short- and long-term outcomes between LPD and OPD for AC. METHODS: This study included patients with AC who underwent pancreaticoduodenectomy (PD) with curative intention at Ogaki Municipal Hospital from April 2008 to March 2023. RESULTS: Fifty-five patients underwent LPD (n = 26) or OPD (n = 29). There were no significant differences in the demographics between the two groups. The LPD group had a significantly longer operative time (268 vs. 225 min), less blood loss (125 vs. 450 mL), and shorter postoperative hospital stay (18 vs. 23 days) than the OPD group. There was no significant difference in the morbidity ratio. Fewer lymph nodes were harvested in the LPD group than OPD group (9.5 vs. 16.0), but there were no significant differences in lymph node metastasis or pathological stages. There were no significant differences in overall survival (OS) or recurrence-free survival (RFS). The 3- and 5-year OS rates in the LPD group and the OPD group were 63.0% and 54%, 64.8%, and 61.2%, respectively. The 3- and 5-year RFS rates were 57.4% and 57.4%, 58.1%, and 54.4%, respectively. CONCLUSIONS: LPD for AC had short- and long-term outcomes comparable with those of OPD. LPD could be considered the standard treatments for AC because of less blood loss and a shorter hospital stay.

Drug-free remission of immune thrombocytopenic purpura following resection of perihilar cholangiocarcinoma: a case report.

Immune thrombocytopenic purpura (ITP) is a rare autoimmune disorder. Although secondary ITP, caused by various underlying diseases, including some malignant tumors, has been reported, instances of ITP resolving after successful treatment of the underlying cause are uncommon and noteworthy. Herein, we present a case of a patient with perihilar cholangiocarcinoma (pCCA) and ITP who achieved drug-free remission of ITP following tumor resection. A 76-year-old man presented with pCCA complicated by ITP. Prednisolone treatment successfully managed his thrombocytopenia, allowing for a left hepatopancreatoduodenectomy. ITP relapse did not occur after discontinuation of prednisolone postoperatively. This case suggests that surgical resection of the underlying malignancy may induce remission of secondary ITP associated with pCCA.

Efficacy of highly bioavailable oral curcumin in asymptomatic or mild COVID-19 patients: a double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties, can suppress vital proliferation and cytokine secretion in animal models. We developed a highly absorbable curcumin, curcuRouge® (cR), which is approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic COVID-19 patients. METHODS: This study evaluated the effect of 7-day oral intake of cR (360 mg twice daily). Patients within 5 days of COVID-19 diagnosis were randomly assigned to a placebo or cR group in a double-blind manner. RESULTS: Primary endpoint events [body temperature (BT) ≥ 37.5 °C and saturation of percutaneous oxygen (SpO2) < 96%] were fewer than expected, and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group (4/67); hazard ratio (HR) = 0.532, 95% confidence interval (CI) 0.097-2.902. Patients receiving cR tended to take fewer antipyretic medications than those receiving placebo (HR = 0.716, 95% CI 0.374-1.372). Among patients with a normal range of BT at baseline, the BT change rate was significantly (p = 0.014) lower in the cR group (- 0.34%) versus placebo (- 0.01%). CONCLUSION: The relative suppression of event rates and antipyretic medications taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR in asymptomatic or mildly symptomatic patients with COVID-19. TRIAL REGISTRATION: Japan Registry of Clinical Trials (CRB5200002).

Dorsal approach for advanced gastric cancer invading the transverse mesocolon.

Minimally invasive gastrectomy is increasingly performed for advanced gastric cancer, but the indication for this procedure for a tumor invading adjacent structures is still limited. In cases with tumors invading the transverse mesocolon, a large tumor together with the involved mesocolon blocks the surgical view, which prevents evaluation of the extent of invasion and makes it difficult to ensure oncologically adequate resection. To solve these technical issues, we established a novel method that uses a dorsal approach. By approaching the transverse mesocolon from the dorsal side, tumor penetration and involvement of the colic vessels or pancreas can be evaluated, and margin-free resection of the tumor becomes easier. In a series of 13 patients with mesocolon invasion, a dorsal approach enabled minimally invasive margin-free resection in 11 cases by resection of the anterior layer of the mesocolon (n = 6); enucleation of the mesocolon (n = 4); or enucleation plus distal pancreato-splenectomy (n = 1). Two patients with broad invasion that obstructed the view underwent combined colectomy by open conversion. A major postoperative complication of pancreatic fistula following distal pancreatectomy occurred in one case. These results suggest that a dorsal approach may be useful for minimally invasive combined resection of gastric cancer invading the transverse mesocolon.

Laparoscopic pancreaticoduodenectomy in patients with a history of right hemicolectomy : A report of three cases.

Laparoscopic pancreaticoduodenectomy (LPD) has been widely adopted in institutions with sufficiently skilled practitioners. This technique requires attentive dissection around the superior mesenteric vein (SMV) and artery. Dissection around the SMV and Henle's trunk is one of the key aspects of right hemicolectomy (RHC) ; adhesions and fibrosis around these vessels may impede LPD in patients with a history of RHC. We encountered three cases of periampullary tumors in patients with a history of RHC who were successfully treated with LPD. Cases 1, 2, and 3 were of 60-, 73-, and 74-year-old men with periampullary tumors. The operative durations in cases 1, 2, and 3 were 316, 267, and 265 min, respectively. The estimated blood loss volumes in cases 1, 2, and 3 were 20, 50, and 720 mL, respectively. The postoperative hospital stay durations in cases 1, 2, and 3 were of 13, 35, and 15 days, respectively. In conclusion, LPD following RHC may be safely completed with laparoscopy. J. Med. Invest. 70 : 285-289, February, 2023.

Intrathoracic anastomosis using handsewn purse-string suturing by the double-ligation method in laparo-thoracoscopic esophagectomy.

Purpose: In minimally invasive esophagectomy (MIE), it is important to reduce the rate of anastomotic leakage to ensure its safety. At our institute, the double-ligation method (DLM) has been introduced to insert and fix the anvil of the circular stapler for intracorporeal circular esophagojejunostomy in gastric surgery. We adopted this method for intrathoracic anastomosis (IA) in MIE. The aim of this study was to investigate the safety of IA with DLM in MIE. Methods: In this study, 48 patients diagnosed with primary middle or lower third segment thoracic esophageal carcinoma with clinical stage I, II, III or IV disease were retrospectively evaluated. Postoperative outcomes were assessed. Results: Among the 48 patients, 42 patients underwent laparo-thoracoscopic esophagectomy and IA using a circular stapler with the DLM. The average total operation time and thoracoscopic operation time were 433 and 229 minutes, respectively. The average purse-string suturing time was 4.7 minutes. The rates of anastomotic leakage and stenosis were 2.4% and 14.3%, respectively. The overall incidence of postoperative complications (Clavien-Dindo grade of ≥III) was 16.7%. The average postoperative stay was 16 days. Conclusion: The procedure of IA using a circular stapler with the DLM in MIE was safe and provided a low rate of anastomotic leakage.

Comparison of surgical outcomes of emergent laparoscopic cholecystectomy for acute cholecystitis between attending surgeons and senior residents: A propensity-matched analysis.

INTRODUCTION: Emergent laparoscopic cholecystectomy (LC) is routinely performed for acute cholecystitis (AC) at our institution. This study was conducted to investigate the feasibility and safety of emergent LC for AC performed by senior residents. MATERIALS AND METHODS: Data from 362 patients with AC who underwent emergent LC between January 2012 and June 2020 were retrospectively reviewed. Of these patients, 328 were operated on by senior residents (SR), and 34 were operated on by the attending surgeon (AS). Clinical characteristics and surgical and postoperative outcomes were compared between the SR and AS groups. Propensity score matching was used to minimize selection bias. When the operator was an SR, the LC was assisted by the AS. RESULTS: Before matching, in the SR group, more patients had a history of abdominal surgery, and C-reactive protein and white blood cell counts were significantly higher. In the image findings, the minor axis of the gallbladder (GB) was longer, and the wall of the GB was thicker in the SR group. After propensity score matching, 28 pairs were identified. There were no significant differences in operative time (83 vs 88 minutes, P = .92), the amount of blood loss (25 vs 10 mL, P = .13), conversion to open surgery (3.6% vs 3.6%, P = 1), postoperative complications (7.2% vs 0%, P = .74), and postoperative hospital stay (4 vs 4 days, P = .87). CONCLUSION: Emergent LC for AC performed by SR under supervision appears to be feasible and safe.

Artepillin C, a Key Component of Brazilian Propolis, Induces Thermogenesis in Inguinal White Adipose Tissue of Mice through a Creatine-Metabolism-Related Thermogenic Pathway.

Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. In this study, we investigated how artepillin C (ArtC) promotes thermogenesis in vivo. We demonstrated that 28 day administration of ArtC (10 mg/kg of body weight) to mice significantly induced thermogenesis in beige adipocytes in inguinal WAT (iWAT) and suppressed reductions in core body temperature induced by cold exposure at 4 °C. Moreover, ArtC-induced thermogenesis in iWAT was significantly inhibited by treatment with a creatine metabolism inhibitor, and ArtC significantly upregulated the expression of creatine-metabolism-related enzymes in the thermogenic pathway. These results indicate that ArtC induces thermogenesis in beige adipocytes in iWAT, and the observed ArtC-induced thermogenesis is associated with the creatine-metabolism-related thermogenic pathway, which is characteristically observed in beige adipocytes.

Co-Administration of Curcumin and Artepillin C Induces Development of Brown-Like Adipocytes in Association with Local Norepinephrine Production by Alternatively Activated Macrophages in Mice.

Classical brown adipocytes, characterized by interscapular depots, have multilocular fat depots and are known to release excess energy. Recent studies have shown that induction of brown-like adipocytes, also referred to as beige or brite cells, in white adipose tissue (WAT) results in the release of excess energy through mitochondrial heat production via uncoupling protein 1. This has potential a therapeutic strategy for obesity and related diseases as well as classical brown adipocytes. In our previous studies, we found that artepillin C (ArtC, 10 mg/kg body weight), a characteristic constituent of Brazilian propolis, significantly induced the development of brown-like adipocytes in inguinal WAT (iWAT) of mice. Furthermore, we recently demonstrated that curcumin (Cur, 4.5 mg/kg) also significantly induced the development of brown-like adipocytes in mice. The combined administration of several food-derived factors can enhance their bioactivity and reduce their required functional doses. In this study, we showed that co-administration of Cur and ArtC at lower doses (Cur, 1.5 mg/kg; ArtC, 5 mg/kg) additively induce brown-like adipocyte development in mouse iWAT. Moreover, this induction is associated with the localized production of norepinephrine following accumulation of alternatively activated macrophages in iWAT. These findings suggest that co-administration of Cur and ArtC is significantly effective to reduce the dose and enhance the formation of brown-like adipocyte via a unique molecular mechanism.

Comparison of respiratory muscle strength in individuals performing continuous and noncontinuous walking exercises in water after the 6-week program.

This study aimed to compare respiratory muscle strength in individuals performing continuous and noncontinuous walking exercises in water after the 6-week program. Twenty-nine healthy men were randomly divided into a continuous group (CG, n=14) and a noncontinuous group (NG, n=15). Firstly, both groups executed the 6-week program which set them to walk for 30 min, 4 times per week, over 6 weeks in a pool with the adjusted intensity that their walking speed increased the heart rate to 60% of the predicted maximum. After the 6-week program, participants in the CG continued the water-walking program for 4 weeks while those in the NG discontinued the water-walking program. In both groups, respiratory muscle strength evaluated by maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) increased significantly after the 6-week program compared with pre-exercise value. Compared to the value after the 6-week program, PEmax increased significantly in the CG after 10 weeks (P<0.05), but the PImax showed no significant change. Compared to the value after the 6-week program, after 10 weeks, in the NG, PEmax decreased significantly, with a considerable decrease after 9 and 10 weeks compared to the CG (P<0.05). The PImax in the NG significantly decreased after 10 weeks from the value observed after the 6-week program. We demonstrated that 6 weeks of walking in water at 60% of the predicted maximum heart rate enhances PImax and PEmax, and that PImax and PEmax decrease in 4 weeks without a water-walking program.

Highly Dispersible and Bioavailable Curcumin but not Native Curcumin Induces Brown-Like Adipocyte Formation in Mice.

SCOPE: The induction of brown-like adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity and metabolic disorders via the ability of these cells to release excess energy as heat in association with uncoupling protein 1. Some experimental trials suggest that curcumin (a yellow pigment from turmeric) has a suppressive effect on the accumulation of body fat. However, there is little evidence to show that curcumin induces the formation of brown-like adipocytes and the molecular mechanisms involved remain elusive. In addition, in most experimental trials, high doses of curcumin are administered. METHODS AND RESULTS: Highly dispersible and bioavailable curcumin (HC, i.e., 4.5 mg native curcumin kg-1 ) but not the same dose of native curcumin induces the formation of brown-like adipocytes in mouse inguinal WAT. Moreover, the formation of brown-like adipocytes induced by HC in inguinal WAT may be mediated by the production of local norepinephrine from accumulated alternatively activated macrophages. CONCLUSION: These novel findings suggest that curcumin increases energy expenditure by inducing the formation of brown-like adipocytes via a unique molecular mechanism. Importantly, they show that HC has significant bioactive effects in vivo at lower doses of curcumin.