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Background: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma., Methods: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses., Results: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance., Conclusion: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

In vitro gametogenesis, the process of generating gametes from pluripotent cells in culture, is a powerful tool for improving our understanding of germ cell development and an alternative source of gametes. Here, we induced primordial germ cell-like cells (PGCLCs) from pluripotent stem cells of the northern white rhinoceros (NWR), a species for which only two females remain, and southern white rhinoceros (SWR), the closest species to the NWR. PGCLC differentiation from SWR embryonic stem cells is highly reliant on bone morphogenetic protein and WNT signals. Genetic analysis revealed that SRY-box transcription factor 17 (SOX17) is essential for SWR-PGCLC induction. Under the defined condition, NWR induced pluripotent stem cells differentiated into PGCLCs. We also identified cell surface markers, CD9 and Integrin subunit alpha 6 (ITGA6), that enabled us to isolate PGCLCs without genetic alteration in pluripotent stem cells. This study provides a first step toward the production of NWR gametes in culture and understanding of the basic mechanism of primordial germ cell specification in a large animal.

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that OVOL2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) that drives gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and, consequently, induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation. This article has an associated 'The people behind the papers' interview., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33 %, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The present study investigated whether a single pretreatment with clofibric acid suppresses liver injury in rats after CCl 4 intoxication. Rats received a single pretreatment with clofibric acid (100 mg/kg, i.p.) 1 h prior to a CCl 4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl 4 administration. A single pretreatment with clofibric acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl 4 challenge, whereas the pretreatment did not protect against CCl 4 -induced fatty liver. The clofibric acid pretreatment did not affect blood concentrations of CCl 4 in the early stage after CCl 4 dosing, or the level of the CCl 4 reaching the liver 1 h after the CCl 4 challenge. Moreover, the clofibric acid pretreatment did not affect the intensity of the covalent binding of the [ 14 C]CCl 4 metabolite to microsomal proteins and lipids. The clofibric acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl 4 -induced hepatocellular necrosis by a clofibric acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to clofibric acid prior to CCl 4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cancer cells surviving in ascites exhibit cancer stem cell (CSC)-like features. This study analyzed the expression of the CSC marker CD133 in the ascites-derived exosomes obtained from patients with unresectable pancreatic cancer. In addition, inverse correlation of CD133 expression with prognosis was examined. Of the 133 consecutive patients, 19 patients were enrolled in the study. Exosomes derived from the malignant ascites demonstrated higher density and wider variation in size than those from non-malignant ascites. Western blot revealed enhanced expression of CD133 in exosomes obtained from patients with pancreatic cancer compared to those obtained from patients with gastric cancer or liver cirrhosis. A xenograft mouse model with malignant ascites was established by intraperitoneal inoculation of human pancreatic cancer cells in nude mice. Results obtained from the human study were reproduced in the mouse model. Statistically significant equilateral correlation was identified between the band intensity of CD133 in western blot and overall survival of patients. Lectin microarray analyses revealed glycosylation of CD133 by sialic acids as the major glycosylation among diverse others responsible for the glycosylation of exosomal CD133. These findings suggest that highly glycosylated CD133 in ascites-derived exosomes as a potential biomarker for better prognosis of patients with advanced pancreatic cancer.

Background: Peri-implant crevicular fluid (PICF) contains calprotectin and NTx, which are markers for inflammation and bone resorption, respectively. The aims of this pilot study were to compare calprotectin and NTx levels in PICF from implant sites with or without peri-implant diseases and to evaluate the usefulness of calprotectin and NTx as diagnostic markers for peri-implant diseases., Methods: Thirty-five patients with dental implants participated in this pilot study. PICF samples were collected from peri-implant disease sites (n = 40) and non-diseased (healthy) sites (n = 34) after clinical indicators including probing depth (PD), bleeding on probing (BOP), gingival index (GI), and bone loss (BL) rate were investigated. Calprotectin and NTx amounts in PICF were measured using their respective ELISA kits and then compared between diseased and healthy samples. The relationship between PICF calprotectin or NTx levels and clinical indicator levels was investigated. A receiver operating characteristic (ROC) curve analysis of calprotectin and NTx was performed to predict peri-implant diseases., Results: Calprotectin and NTx levels in PICF were significantly higher from peri-implant disease sites than from healthy sites. PICF calprotectin amounts correlated with PD, and its levels were significantly higher in the GI-1 and GI-2 groups than in the GI-0 group. PICF NTx amounts correlated with PD and the BL rate. ROC curves indicated that PICF calprotectin and NTx are useful biomarkers for peri-implant diseases., Conclusions: Calprotectin and NTx in PICF have potential as biomarkers for the diagnosis of peri-implant diseases.

Background: There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants., Methods: A review was carried out of 61 neonates with ECMO between January 1995 and December 2015 at a single center. ECMO was used in neonates with oxygenation index >20 after conventional treatment. Background factors, such as etiology, vascular access mode (veno-venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO (within 24 h after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD)., Results: Survival to hospital discharge was achieved in 35 infants (57%), while the remaining 26 died during hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared with those with adverse outcome (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was significantly higher for those with VV than VA vascular access mode (78%, 18/23 vs 45%, 17/38, respectively; P = 0.016), and for those with than without early ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (86%, 12/14), persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47-37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5)., Conclusions: Neonates with early ECMO and those with ECMO duration <8 days may benefit from ECMO with respect to SHD., (© 2016 Japan Pediatric Society.)

Objective: To examine the effectiveness of dance on motor functions, cognitive functions, and mental symptoms of Parkinson's disease (PD)., Design: This study employed a quasi-randomised, between-group design., Setting: Dance, PD exercise, and all assessments were performed in community halls in different regions of Japan., Participants: Forty-six mild-moderate PD patients participated., Intervention: Six PD patient associations that agreed to participate in the study were randomly assigned to a dance group, PD exercise group, or non-intervention group. The dance and PD exercise groups performed one 60-min session per week for 12 weeks. Control group patients continued with their normal lives. All groups were assessed before and after the intervention., Main Outcome Measures: We used the Timed Up-and-Go Test (TUG) and Berg Balance Scale (BBS) to assess motor function, the Frontal Assessment Battery at bedside (FAB) and Mental Rotation Task (MRT) to assess cognitive function, and the Apathy Scale (AS) and Self-rating Depression Scale (SDS) to assess mental symptoms of PD. The Unified Parkinson's Disease Rating Scale (UPDRS) was used for general assessment of PD., Results: When comparing results before and after intervention, the dance group showed a large effect in TUG time (ES=0.65, p=0.006), TUG step number (ES=0.66, p=0.005), BBS (ES=0.75, p=0.001), FAB (ES=0.77, p=0.001), MRT response time (ES=0.79, p<0.001), AS (ES=0.78, p<0.001), SDS (ES=0.66, p=0.006) and UPDRS (ES=0.88, p<0.001)., Conclusions: Dance was effective in improving motor function, cognitive function, and mental symptoms in PD patients. General symptoms in PD also improved. Dance is an effective method for rehabilitation in PD patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A 52-year-old male visited a local clinic with a subjective complaint of pain in the left side of his abdomen. Abdominal CT revealed the presence of a pancreatic body tumor. On EUS, the tumor presented hypoechoic signals with an obscure boundary, which continued from the pancreatic parenchyma to the inside of the main pancreatic duct. Abdominal contrast CT revealed a hypervascular tumor with densely stained pancreatic parenchyma. ERP findings revealed that main pancreatic duct invasion was suspected based on partial radiolucency in the duct. Distal pancreatectomy was performed, and a definitive diagnosis of pancreatic neuroendocrine tumor (WHO class G1) was made histopathologically.