Strongly correlated perovskite fuel cells.

Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.

Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma.

PURPOSE: Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma. METHODS: We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs. RESULTS: Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most. CONCLUSION: These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

Gangliocytic paraganglioma: a multi-institutional retrospective study in Japan.

BACKGROUND: Gangliocytic paraganglioma (GP) is an extremely rare benign tumor that commonly arises from the second part of the duodenum. Since GP exhibit neither prominent mitotic activity nor Ki-67 immunoreactivity, this tumor is often misdiagnosed as neuroendocrine tumor (NET) G1 (carcinoid tumor). However, patients with GP may have a better prognosis than patients with NET G1. This fact emphasizes the importance of differentiating GP from NET G1, but few studies have reported the epidemiology and histopathology of GP because of its rarity. To differentiate GP from NET G1 with ease, we conducted a multi-institutional retrospective study analyzing the morphometric and immunohistochemical features of this tumor. METHODS: Since only a limited number of patients with GP could be identified in our institute, we conducted a multi-institutional retrospective study of GP in Japan, which was approved by the Ethics Committee of our medical institute. The obtained tissue sections underwent detailed morphometric and immunohistochemical analyses. Additionally, to differentiate GP from NET G1 with ease, immunohistochemical findings were compared. RESULTS: In our examination of 12 cases of duodenal GP, we found that epithelioid cells of GP exhibited positive reactivity for progesterone receptor and pancreatic polypeptide, whereas tumor cells of NET G1 were completely negative reactivity for both. Additionally, although GP is considered to be an extremely rare NET, we found that four (40.0%) of the ten patients at our institute with duodenal NET G1 actually had GP. CONCLUSIONS: Although GP is regarded as a rare NET, our results suggest that it accounts for a substantial percentage of duodenal NETs. Additionally, confirmation of immunoreactivity for progesterone receptor and pancreatic polypeptide can assist in differentiating GP from NET G1.

Efficacy of laparoscopic liver resection in colorectal liver metastases and the influence of preoperative chemotherapy.

BACKGROUND: Since 1993, we have performed minimally invasive laparoscopic liver resection (LLR) to treat malignant liver cancer, including colorectal liver metastases (CLM). However, further studies are needed to accumulate sufficient evidence on the oncological outcome of LLR for CLM. METHODS: To elucidate the efficacy of LLR for CLM, this study comparatively analyzed the invasiveness and short-term prognosis of LLR (n=43 cases) and open liver resection (OR) (n=62 cases) performed for CLM after 2006 and also investigated the safety of LLR following chemotherapy. RESULTS: Compared with the OR group, the LLR group had significantly less blood loss (P<0.001) and a shorter hospital stay (P<0.001). The E-PASS scoring system was used to compare surgical invasiveness, and although the preoperative risk score did not differ between the groups, the surgical stress score and comprehensive risk score were significantly lower in the LLR group (P<0.001). Concerning the survival rate and disease-free survival rate, there were no significant differences between procedures. However, more clinical cases and longer follow-up periods are needed to reach a definitive conclusion.Preoperative hemanalysis, intraoperative bleeding, complications, and postoperative length of stay did not differ significantly between LLR patients with preoperative chemotherapy and those with surgery alone, indicating no adverse effects of chemotherapy. CONCLUSIONS: LLR can be an effective minimally invasive surgery in CLM patients receiving both perioperative chemotherapy and surgery. Because LLR is comparable with OR with regard to short-term oncological outcome, LLR may be a valuable option for CLM.

[A case of pancreatic cancer with distant metastasis successfully resected after neoadjuvant chemotherapy with a combination of S-1 and gemcitabine].

The patient was a 70-year-old man with a chief complaint of cough.After careful examination, he was diagnosed with pancreatic body cancer with metastasis to the liver and right pleura and with early gastric cancer.He was treated with S-1 and gemcitabine combination chemotherapy.After completing 3 courses, the distant metastasis could no longer be observed. After completing 4 courses, the tumor marker level in the serum was normalized.The pancreatic lesion was restricted by the end of 10 courses, and the pancreas body and tail were resected.After additional chemotherapy with S-1, he was switched to weekly paclitaxel therapy because of peritoneal dissemination.The patient survived for 15 months after surgery.In cases of unresectable pancreatic cancer with distant metastasis, it may be possible to consider the surgical option when chemotherapy is effective.

[An analysis of cases with malignant pyloroduodenal obstruction from unresectable pancreatic cancer who underwent palliative gastrojejunostomy].

The aims of this study were to examine the effectiveness of palliative gastrojejunostomy in terms of the postoperative food intake and hospital stay in patients with advanced pancreatic cancer. Retrospective data from 17 consecutive patients who underwent gastrojejunostomy from 2008 to 2013 in Toho University Omori Medical Center were analyzed. In our analysis, patients without peritoneal dissemination and distant metastasis were associated with poor oral intake and patients with lower neutrophil to lymphocyte ratio (NLR) were associated with rate of discharge.

Low serum creatine kinase level is associated with poor prognosis in patients with hepatocellular carcinoma: A retrospective single­center study.

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma.

Bidirectional binding property of high glycine-tyrosine keratin-associated protein contributes to the mechanical strength and shape of hair.

Since their first finding in wool 50years ago, keratin-associated proteins (KAPs), which are classified into three groups; high sulfur (HS) KAPs, ultra high sulfur (UHS) KAPs, and high glycine-tyrosine (HGT) KAPs, have been the target of curiosity for scientists due to their characteristic amino acid sequences. While HS and UHS KAPs are known to function in disulfide bond crosslinking, the function of HGT KAPs remains unknown. To clarify the function as well as the binding partners of HGT KAPs, we prepared KAP8.1 and other KAP family proteins, the trichocyte intermediate filament proteins (IFP) K85 and K35, the head domain of K85, and the C subdomain of desmoplakin C-terminus (DPCT-C) and investigated the interactions between them in vitro. Western blot analysis and isothermal titration calorimetry (ITC) indicate that KAP8.1 binds to the head domain of K85, which is helically aligned around the axis of the intermediate filament (IF). From these results and transmission electron microscopy (TEM) observations of bundled filament complex in vitro, we propose that the helical arrangement of IFs found in the orthocortex, which is uniquely distributed on the convex fiber side of the hair, is regulated by KAP8.1. Structure-dependent binding of DPCT-C to trichocyte IFP was confirmed by Western blotting, ITC, and circular dichroism. Moreover, DPCT-C also binds to some HGT KAPs. It is probable that such bidirectional binding property of HGT KAPs contribute to the mechanical robustness of hair.

Piriform Fossa Injury during Calibration Tube Insertion in Laparoscopic Sleeve Gastrectomy.

Piriform fossa and/or esophageal injuries caused by calibration tubes are relatively rare and remain unelucidated. Herein, we report the case of a 36-year-old woman with morbid obesity, sleep apnea, and menstrual abnormalities who was scheduled to undergo laparoscopic sleeve gastrectomy (LSG). We inserted a 36-Fr Nelaton catheter made of natural rubber as a calibration tube during the surgery. However, excessive resistance was observed. We confirmed a submucosal layer detachment approximately 5 cm from the left piriform fossa to the esophagus using intraoperative endoscopy. Additionally, LSG was performed using an endoscope as the guiding calibration tube. We inserted a nasogastric tube under endoscopy with a guidewire before completing the surgery, hoping for a guiding effect on the saliva flow. After 17 months, the patient had successfully lost weight postoperatively without complaints of neck pain or discomfort during swallowing. Therefore, in cases where the damage is limited to the submucosal layer, as in this case, conservative therapy should be considered; this is similar to the concept of endoscopic submucosal dissection not requiring suture closure. This case highlights the risk of iatrogenic injuries to the piriform fossa and/or esophagus during LSG and the importance of careful calibration tube insertion to prevent them.

Safety of laparoscopic liver resection for high-risk patients.

BACKGROUND/PURPOSE: To investigate the safety of laparoscopic liver resections (LLRs) for high-risk patients (HRs) with preoperative comorbidities affecting the heart, lungs, kidneys, glucose tolerance, and central nervous system. METHODS: This retrospective study included 585 patients who had undergone total hepatectomies from 2006 to 2020. Among them, 239 patients underwent LLRs, and 349 underwent open liver resections (OLRs). The safety and validity of LLRs were analyzed by comparing outcomes and preoperative records between HRs and nonhigh-risk patients (nHRs). HRs were defined as patients with any type of chronic heart disease rated New York Heart Association II or higher, chronic obstructive pulmonary disease rated stage III or higher, chronic kidney disease rated stage III or higher, insulin-dependent diabetes mellitus, or cerebrovascular disease with neurological sequelae. RESULTS: A total of 117 LLRs (49.0%) were performed in HRs, and there were more patients with ASA class III or higher than nHRs. Complications of Clavien-Dindo classification grade 3b or higher were not observed in HRs and in only one nHR. Furthermore, no postoperative exacerbations of the five HRs factors were observed in either group. CONCLUSIONS: Rigorous assessment of surgical indications and perioperative management can promote safe LLRs, even in HRs with comorbidities.

Three-dimensional gait analysis of the effect of directional steering on gait in patients with Parkinson's disease.

INTRODUCTION: Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system. METHODS: Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control. RESULTS: Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°. CONCLUSION: Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.

Treatments for Staple Line Leakage after Laparoscopic Sleeve Gastrectomy.

The number of laparoscopic sleeve gastrectomies (LSGs) performed in patients with obesity who are eligible for bariatric and metabolic surgery is currently much lower in Japan than in other countries. Considering the large number of potential patients with obesity and type 2 diabetes and the unique Japanese national health insurance system that guarantees fair healthcare delivery, there is room to increase the number of LSGs in Japan in the near future. However, strict health insurance regulations may limit access to mandatory devices needed to treat postoperative complications, such as staple line leakage, which can cause severe morbidity and even mortality. Therefore, understanding the pathogenesis and treatment options for this complication is crucial. This article examined the current situation in Japan and its impact on staple line leakage management, including the role of endoscopic treatment in reducing reoperation. The authors suggest increasing education and collaboration between healthcare professionals to optimize management and improve patient outcomes.

Deletion of the Sox21 gene drastically affects hair lipids.

The effects of Sox21 gene deletion on hair lipids have been studied. For the cuticle-specific bound lipid 18-methyl eicosanoic acid (18-MEA), which was found to predominantly exist as the free form in Sox21(-/-) hair, total levels and distribution were unexpectedly unchanged. This indicates that while the biosynthesis of 18-MEA is unaffected, its covalent attachment to the cuticle surface is disrupted by loss of keratin-associated protein binding partners. Although the class compositions differed, the total ceramide (CER) levels were found to be comparable between Sox21(+/+) and Sox21(-/-) hairs. Deletion of the gene was also found to increase cholesterol sulphate (CS) levels. The biosynthesis process might be associated with cuticle keratinocyte maturation, because both CS and CERs are known bioactives in keratinocyte differentiation.

Efficacy of laparoscopic surgery for recurrent hepatocellular carcinoma.

BACKGROUND/AIMS: Although laparoscopic hepatectomy is increasingly performed for hepatocellular carcinoma, few studies have investigated the efficacy of laparoscopic surgery, including hepatectomy for the treatment of recurrent hepatocellular carcinoma. We report the results of our study on the efficacy of laparoscopic surgery. METHODOLOGY: Forty-three of 123 hepatocellular carcinoma patients underwent laparoscopic surgery in 2002-2009; 16 were treated for recurrent hepatocellular carcinoma. The characteristics and postoperative outcomes of these 16 patients were retrospectively investigated. RESULTS: Seven patients underwent laparoscopic hepatectomy, 1 underwent laparoscopic radiofrequency ablation, 7 underwent resection of an extrahepatic metastatic tumor and 1 patient received diagnostic assessment. Twelve of the 15 surgical patients had a repeat recurrence after surgery. Survival at 2 years was significantly higher in patients with intrahepatic vs. extrahepatic recurrence (100% vs. 42.9%). In addition, overall survival (51.2 vs. 23.0 months) was significantly longer in patients with intrahepatic recurrence, although disease-free survival (19.2 vs. 10.6 months) was not so. CONCLUSIONS: Laparoscopic surgery for recurrent hepatocellular carcinoma enabled precise tumor localization, more accurate diagnosis, and more careful selection of therapy based on hepatic functional reserve and recurrence type. Laparoscopic surgery appears to be an effective, minimally invasive option for the diagnosis and treatment of recurrent hepatocellular carcinoma.

[Laparoscopic surgery for pancreatic cancer].

Laparoscopic distal pancreatectomy is currently in widespread use because of its technical simplicity, although laparoscopic pancreaticoduodenectomy is practiced in only a limited number of surgical institutions due to the associated technical difficulties especially at reconstruction. The indication for the treatment of pancreatic cancer by a laparoscopic procedure remains controversial. Because pancreatic cancer is already advanced at the time of diagnosis in many cases, it requires a difficult radical operation in terms of lymphadenectomy with nerves plexus in laparoscopic surgery. The oncologic clearance of pancreatic resection may be achievable by laparoscopic surgery, although longer follow-up and larger series of treatment are still needed.

Literature survey on epidemiology and pathology of gangliocytic paraganglioma.

BACKGROUND: Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications. METHODS: We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case. RESULTS: 192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors. CONCLUSIONS: Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.

[Hepatic arterial infusion chemotherapy with oxaliplatin in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure].

UNLABELLED: We report 5 cases of colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) oxaliplatin after systemic infusion chemotherapy failure. Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (L-OHP 100 mg/body, 2 hours) combined with intravenous (iv) levofolinate calcium (175 mg/body, 2 hours) and iv bolus 5-FU (500 mg/body) every 2 weeks. RESULT: An average age was 58 years. All patients had previously received FOLFOX. Lung metastases had already existence before HAI oxaliplatin in 4 patients. A median of 10 treatments were administered (range 5-14). Serum level of CEA was decreased in 4 cases. In 2 patients, lung metastasis developed while a PR was obtained in the liver metastasis. Progress disease (PD) was confirmed in other 3 patients. No major toxicity was presented. The median time to progression free survival was 3.0 months and the median overall survival was 7.1 months. CONCLUSION: HAI oxaliplatin might be beneficial as a salvage therapy for CRLM without extrahepatic metastasis, which demonstrated an acceptable tolerability and maintenance of QOL.

Development of a cognitive function marker based on D-amino acid proportions using new chiral tandem LC-MS/MS systems.

The incidence of dementia, a clinical symptom characterized by severe cognitive decline, is increasing worldwide. Predictive biomarkers are therefore required for early identification and management. D-amino acids in the brain contribute to cognitive function and are suggested as useful biomarkers for diagnosing dementia risk. To clarify their relationship with human cognitive decline, we developed an identification method of chiral metabolomics for detecting slight differences in chiral amino acid amounts. Chiral tandem liquid chromatography-tandem mass spectrometry systems were applied for sensitive and selective amino acid species along with chiral species determination based on anion and zwitterion exchange mechanisms. In a comprehensive health cohort (cross-sectional study), we measured blood chiral amino acid levels from 305 women (65-80 years old) classified into Control, Mild-cognitive-Impairment (MCI), and Dementia groups using the Mini-Mental State Examination. MCI exhibited higher D-Pro (D-Pro/(D-Pro + L-Pro)) proportion vs the Control group, suggesting this proportion as a useful biomarker for MCI. Biomarker accuracy was improved in combination with D-Ser proportion. Receiver operating characteristics analysis of the Control vs. MCI proportion obtained area under the curve (0.80) with 70% sensitivity and 84% specificity at the optimal cutoff value (0.30). Thus, dementia monitoring can be improved by including trace D-amino acids measurements.

A multicenter prospective registration study on laparoscopic pancreatectomy in Japan: report on the assessment of 1,429 patients.

BACKGROUND: Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. METHODS: Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. RESULTS: Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. CONCLUSION: LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.