Fishers' perception of the interaction between the South American sea lions and the Chinook salmon fishery in southern Chile.

We studied how the South American sea lion (SASL, Otaria flavescens) interacts with the operation of an artisanal fishery of Chinook salmon, a non-native species in Chile, using a combination of biological and social approaches, including a valuation by fishers about this interaction. During austral summer of 2019, an observer onboard artisanal fishing boats characterized the attack behavior of SASLs to gillnet-captured Chinook salmon during 33 hauls and analyzed which factors may affect the intensity of attacks. To analyze the relationship between fishers and SASLs, a Likert scale about the perception and views about nature was applied. A total of 23 interviews-including 35 open and 16 closed questions-with fishers were conducted to describe how they perceived the interactions with SASLs. Interactions with SASLs were recorded in 35% of the fishing events and varied depending on both operational factors, such as the number of boats, as well as environmental factors, such as moon's luminosity. Even though SASL interactions resulted in seven fish (~ 70 kg) damaged of a total catch of 2815 kg (2.5%) during the survey, boats with a damaged catch by SASL lost up to 11% of their revenue. This is consistent with 87% of the interviewed fishers who considered that the conflict with the SASL negatively impacts their activity and results in economic losses. A negative perception towards SASLs likely results from personal experience and revenue loss, even though impacts of SASL interactions at the scale of the entire fishery may be less important. While older fishers with less formal education have a productivist and instrumental focus, younger fishers with a more sustainable and conservationist view of fishing offer an opportunity to lead an improved local understanding of the relationship between salmon, SASLs, and humans.

Oral management with polaprezinc solution reduces adverse events in haematopoietic stem cell transplantation patients.

The aim of this study was to analyse the effects of gargling with and then swallowing PPAA (polaprezinc in polyacrylic acid solution), in addition to regular oral management, on patients with a haematopoietic neoplasm scheduled for haematopoietic stem cell transplantation (HSCT). A total of 120 patients scheduled for HSCT during the years 2006-2016 were recruited. Patient background, oral adverse events, the incidence and severity of systemic adverse events (sepsis/septic shock, acute graft-versus-host disease (GVHD) after transplantation), and outcomes (survival/death) were compared between groups treated with and without PPAA. The severities of oral adverse events (oral mucositis, oral pain, and dysgeusia) were significantly lower in patients treated with PPAA. There was no significant difference in the incidence of febrile neutropenia (P=0.622) or sepsis/septic shock (P=0.665) as systemic adverse events. The severity of allograft-induced acute graft-versus-host disease (GVHD) was significantly lower in the PPAA group (P=0.011). There was no significant difference in outcome between the two groups (P=0.285). Within the limitations of the study design, it may be concluded that oral management with PPAA reduces adverse events in HSCT. Oral management with concomitant use of PPAA decreased oral adverse events and reduced the systemic complication of GVHD.

Oral squamous cell carcinoma arising in a patient with Werner syndrome.

Werner syndrome (WS) is an autosomal recessive disorder characterized by physical signs and symptoms, including premature aging and scleroderma-like skin changes. The gene responsible for WS is the WRN gene. A significant proportion of WS-related malignant tumours are non-epithelial types, and the incidence of oral squamous cell carcinoma (SCC) is rare. A case of oral SCC of the lower alveolus and gingiva arising in a 63-year-old woman with WS is reported here. Biopsy confirmed moderately differentiated SCC. Surgical resection was performed and there was no recurrence or metastasis at the 3-year follow-up. Mutation analysis using next-generation sequencing, detected no mutations in the genes encoding the molecules strongly involved in the development of oral SCC, such as TP53 or PIK3CA. No obvious mutations were detected. Based on the results of the study, the results of mutation analysis suggest that this case might be genetically different from the common mechanisms of SCC in the oral cavity.

Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer.

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pancreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied. Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

An integrated linkage map reveals candidate genes underlying adaptive variation in Chinook salmon (Oncorhynchus tshawytscha).

Salmonids are an important cultural and ecological resource exhibiting near worldwide distribution between their native and introduced range. Previous research has generated linkage maps and genomic resources for several species as well as genome assemblies for two species. We first leveraged improvements in mapping and genotyping methods to create a dense linkage map for Chinook salmon Oncorhynchus tshawytscha by assembling family data from different sources. We successfully mapped 14 620 SNP loci including 2336 paralogs in subtelomeric regions. This improved map was then used as a foundation to integrate genomic resources for gene annotation and population genomic analyses. We anchored a total of 286 scaffolds from the Atlantic salmon genome to the linkage map to provide a framework for the placement 11 728 Chinook salmon ESTs. Previously identified thermotolerance QTL were found to colocalize with several candidate genes including HSP70, a gene known to be involved in thermal response, as well as its inhibitor. Multiple regions of the genome with elevated divergence between populations were also identified, and annotation of ESTs in these regions identified candidate genes for fitness related traits such as stress response, growth and behaviour. Collectively, these results demonstrate the utility of combining genomic resources with linkage maps to enhance evolutionary inferences.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with α-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial.

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Secondary contact and changes in coastal habitat availability influence the nonequilibrium population structure of a salmonid (Oncorhynchus keta).

Numerous empirical studies have reported lack of migration-drift equilibrium in wild populations. Determining the causes of nonequilibrium population structure is challenging because different evolutionary processes acting at a variety of spatiotemporal scales can produce similar patterns. Studies of contemporary populations in northern latitudes suggest that nonequilibrium population structure is probably caused by recent colonization of the region after the last Pleistocene ice age ended ~13,000 years ago. The chum salmon's (Oncorhynchus keta) range was fragmented by dramatic environmental changes during the Pleistocene. We investigated the population structure of chum salmon on the North Alaska Peninsula (NAP) and, using both empirical data and simulations, evaluated the effects of colonization timing and founder population heterogeneity on patterns of genetic differentiation. We screened 161 single nucleotide polymorphisms and found evidence of nonequilibrium population structure when the slope of the isolation-by-distance relationship was examined at incremental spatial scales. In addition, simulations suggested that this pattern closely matched models of recent colonization of the NAP by secondary contact. Our results agree with geological and archaeological data indicating that the NAP was a dynamic landscape that may have been more recently colonized than during the last deglaciation because of dramatic changes in coastal hydrology over the last several thousand years.

Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan.

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy. RESULTS: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41-0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001). CONCLUSION: For advanced HCC, HAIC is considered to be an effective treatment.

[Three cases of spontaneous mediastinal emphysema].

We report 3 cases of spontaneous mediastinal emphysema. All patients were young males, and had predisposing episodes for development of spontaneous mediastinal emphysema; sports in 2, loud voice in 1. The each chief complaint was dyspnea, throat pain, and epigastric pain. Two patients were admitted, but 1 rejected admission despite sufficient informed consent. All patients became asymptomatic with mediastinal air reabsorption within a week. We should recognize spontaneous mediastinal emphysema as one cause of chest, back, neck and epigastric pain.

[Removal of infected pacemaker leads under extracorporeal circulation].

We report 3 cases of removal of infected pacemaker leads under extracorporeal circulation. The infections occurred 12, 29, and 58 months after the implantations. A skin ulcer was at first formed over the pacemaker; then the pacemaker itself became infected. The right atrium was incised, and the infected leads were pulled out. The ventricular leads adhered to the tricuspid valve, the chordae tendineae and the endocardia. A lead tip could easily be extirpated with sharp scissors. Two cases underwent implantation of myocardial electrodes; the new generators were implanted below the fascia of the rectus abdominis muscle. In the other case, a pacemaker was implanted transvenously because an appropriate epicardial pacing site could not be found. Case infected by methicillin-resistant Staphylococcus aureus (MRSA) died from mediastinitis a month after the operation. The others did not have a recrudescence of their infections. Removal of the leads under extracorporeal circulation is an invasive but sure procedure to extirpate.

Basal cell adenoma of the parotid gland: MR imaging findings with pathologic correlation.

BACKGROUND AND PURPOSE: Basal cell adenomas (BCAs) are rare tumors of the parotid gland. Only a few case reports describing MR imaging features of BCA have been published. The aim of this study was to describe and characterize the MR findings of BCAs of the parotid gland. MATERIALS AND METHODS: We retrospectively reviewed MR images of BCA with pathologic correlation in 8 cases (2 men and 6 women; age range, 52-82 years) collected between January 1992 and August 2004 from our pathologic data base. All MR images were retrospectively evaluated with respect to the marginal morphology, signal intensity (SI), and enhancement behavior by 2 experienced radiologists. RESULTS: On pathologic examination, 5 tumors were solid type, 2 were trabecular type, and 1 was membranous type. All of the tumors were well circumscribed with smooth contours. Cystic changes were seen in 4 cases. On T1-weighted images (T1WI), 7 tumors showed homogeneously low SI equal to muscle and one showed heterogeneously low SI. On T2-weighted images (T2WI), all of them showed slightly lower SI than that of surrounding parotid tissue. On gadolinium-enhanced T1WI, 6 tumors demonstrated moderate enhancement and one demonstrated strong enhancement (membranous type). Dynamic studies were performed in 4 cases. All showed rapid and prolonged enhancement. CONCLUSION: MR imaging findings of BCA were well-defined and smooth marginal morphologies, relatively low SI on both T11W and T2WI, and rapid and prolonged enhancement on dynamic study. Although BCAs are rare, they should be suspected when a tumor shows all of the characteristics noted here.

Frequent downregulation of 14-3-3 sigma protein and hypermethylation of 14-3-3 sigma gene in salivary gland adenoid cystic carcinoma.

14-3-3 sigma:, a target gene of the p53 tumour suppressor protein, has been shown to regulate the cell cycle at the G2/M checkpoint. Recent studies have demonstrated that 14-3-3 sigma is downregulated by hypermethylation of the CpG island in several types of cancer. In this study, we investigated the expression and methylation status of 14-3-3 sigma in human salivary gland adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed that the positive expression rate of 14-3-3 sigma in ACC (one out of 14) was markedly lower than that in MEC (ten out of 10). Since most of the ACCs carried the wild-type p53 protein, downregulation of 14-3-3 sigma in ACC may not be due to the dysfunction of p53 pathway. Microdissection-methylation-specific PCR revealed that frequent hypermethylation of the 14-3-3 sigma gene was observed in ACC when compared to that in MEC. In cultured-ACC cells, we confirmed the downregulation of 14-3-3 sigma via hemimethylation of the gene by sequencing analysis after sodium bisulphite treatment. Furthermore, re-expression of 14-3-3 sigma in the ACC cells was induced by the treatment with DNA demethylating agent, 5-aza-2'-deoxycytidine. Irradiation apparently induced the enhanced expression of 14-3-3 sigma and G2/M arrest in normal salivary gland cells; however, in the ACC cells, neither induction of 14-3-3 sigma nor G2/M arrest was induced by irradiation. These results suggest that downregulation of 14-3-3 sigma might play critical roles in the neoplastic development and radiosensitivity of ACC.

Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line.

Recently, a new concept for cancer therapy termed "tumor dormancy therapy" has been proposed. The concept of this therapy is to prolong the survival time of cancer patients while maintaining their quality of life. We have been developing a differentiation-inducing therapy, which is included in the tumor dormancy therapy, for salivary gland cancer. In this study, we examined the effect of a differentiation-inducing drug, Vesnarinone on the growth of several cancer cells, and examined the molecular mechanism by which Vesnarinone induces the cyclin dependent kinase inhibitor, p21waf1 in the cancer cells. Vesnarinone significantly suppressed the growth of TYS (salivary gland cancer cells), PC3 (prostate cancer cells), and A431 (squamous cell cancer cells). Furthermore, Vesnarinone dose-dependently enhanced the expression of p21waf1 mRNA in TYS cells. Using the luciferase reporter assay it was found that the enhancement of p21waf1 mRNA expression by Vesnarinone was through direct transcriptional activation of the p21waf1 promoter. Thus, analyzing the molecular mechanisms of differentiation inducing drugs may lead to the development of a new therapeutic strategy for several human malignancies, including salivary gland cancer.

Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line.

We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21(waf1) gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of p21(waf1) gene by vesnarinone in TYS cells. We constructed several reporter plasmids containing the p21(waf1) promoter, and attempted to identify vesnarinone-responsive elements in the p21(waf1) promoter. By the luciferase reporter assay, we identified the minimal vesnarinone-responsive element in the p21(waf1) promoter at -124 to -61 relative to the transcription start site. Moreover, we demonstrated by electrophoretic mobility shift assay that Sp1 and Sp3 transcription factors bound to the vesnarinone-responsive element. Furthermore, we found that vesnarinone induced the histone hyperacetylation in TYS cells. These results suggest that vesnarinone directly activates p21(waf1) promoter via the activation of Sp1 and Sp3 transcription factors and the histone hyperacetylation in TYS cells.

Dihydropyrimidine dehydrogenase mRNA level correlates with the response to 5-fluorouracil-based chemo-immuno-radiation therapy in human oral squamous cell cancer.

The measurement of the intra-tumoral level of thymidylate synthetase (TS), and dihydropyrimidine dehydrogenase (DPD), may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). In this study, we examined the mRNA levels of DPD and TS in 28 oral squamous cell carcinomas (SCC), and 22 salivary gland tumors by semi-quantitative reverse transcription polymerase chain reaction. Then we examined the correlation of the responsiveness of the patients with oral SCC to 5-FU with the intra-tumoral levels of DPD and TS mRNA. All specimens were obtained at the biopsy before treatment, and then the patients were treated by oral administration of a 5-FU compound (UFT), the irradiation of cobalt-60 (upto 60 Gy) and injection of an immuno-potentiator (OK-432). Intra-tumoral levels of DPD mRNA in the patients who showed CR (complete response) and PR (partial response) were significantly lower than those in the patients who showed NC (no change). However, intra-tumoral levels of DPD mRNA did not correlate with the local recurrence of the tumor during the observation period after initial treatment with or without surgical resection of the residual tumors. On the other hand, TS mRNA levels in the tumors did not correlate with any clinico-pathological parameters. These observations suggest that intra-tumoral levels of DPD mRNA may predict the tumor response to 5-FU-based chemo-immuno-radiation therapy in the patients with oral SCC.

Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cells in vitro and its clinical significance.

We examined the role of the hepatocyte growth factor (HGF)/c-met system on invasion and metastasis of oral squamous cell carcinoma (SCC) cells. In monolayer culture, exogenous HGF marginally affected the growth of oral SCC cells (BHY, HN, IH) and human gingival epithelial cells (GE). In type I collagen matrix, however, HGF significantly enhanced the invasive growth of the cancer cells (p < 0.05). We detected the expression of c-met (HGF receptor) mRNA in all of the cancer cells, but not in human gingival fibroblasts (GF). Oral SCC cells did not secret HGF protein into the medium, but GF secreted a large amount of HGF protein (15 ng/ml). Furthermore, HGF markedly enhanced the migration of cancer cells in a Transwell invasion chamber. Then, we examined the serum levels of HGF in oral SCC patients, or HGF concentrations in oral cancer tissues. Serum levels of HGF in the patients were significantly higher than those in healthy volunteers (p < 0.05). After initial treatment, all of the tumor-free survivors showed a marked decline in the serum HGF levels. Furthermore, HGF concentrations in metastatic cancer tissues were significantly higher than those of non-metastatic cancer tissues and normal gingiva (p < 0.01). These results suggest that HGF plays an important role in invasion and metastasis of oral SCC cells as a paracrine factor, and an elevated HGF level in the cancer tissue can be a predictive marker for metastasis formation in patients with oral SCC.

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines.

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARalpha, beta, gamma, and RXRalpha) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARbeta, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10(-6)and 10(-7)M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10(-8)M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA.

Involvement of cathepsin B- and L-like proteinases in silk gland histolysis during metamorphosis of Bombyx mori.

To identify proteinases involved in programmed cell death of the silk glands of Bombyx mori, we measured enzyme activities in silk gland homogenates. Several peptidyl-4-methylcoumaryl-7-amides (MCAs) and bovine hemoglobin were used as substrates in the presence and absence of proteinase inhibitors. The hydrolysis of t-butyloxycarbonyl-Phe-Ser-Arg-MCA (Boc-FSR-MCA), benzyloxy-carbonyl-Phe-Arg-MCA (Z-FR-MCA), and Z-Arg-Arg-MCA (Z-RR-MCA) was optimal at pH 5.5, 5.0, and 5.5, respectively. It was stimulated by the sulfhydryl compounds or EDTA and inhibited by both cysteine proteinase inhibitors and a cathepsin B-specific inhibitor, l-3-trans-(propyl-carbamoyl)oxirane-2-carbonyl)-L-isoleucyl-L-prolin (CA-074). The hemoglobin hydrolysis at the optimum pH 3.5 was inactivated by cysteine proteinase inhibitors, but stimulated slightly by pepstatin. The cleavage of Arg-MCA (R-MCA) and Leu-MCA (L-MCA) at optimum pH of 7.0 was strongly inhibited by an aminopeptidase inhibitor, puromycin, and by sulfhydryl compounds. The Boc-FSR-MCA, Z-FR-MCA, Z-RR-MCA, and hemoglobin hydrolyzing activities increased in the silk glands dramatically after cocoon formation, while the R-MCA and L-MCA cleaving activities declined. The results strongly suggest the involvement of cathepsin B- and cathepsin L-like proteinases in the histolysis of the silk gland during metamorphosis.

Involvement of PACAP receptor in primary afferent fibre-evoked responses of ventral roots in the neonatal rat spinal cord.

The role of PACAP receptor in nociceptive transmission was investigated in vitro using maxadilan, a PACAP receptor selective agonist and max.d.4, a PACAP receptor selective antagonist. Potentials, from a ventral root (L3 - L5) of an isolated spinal cord preparation or a spinal cord - saphenous nerve - skin preparation from 0 - 3-day-old rats, were recorded extracellularly. In the isolated spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of max. d.4 (0.01 - 3 microM) inhibited the slow VRP in a concentration-dependent manner. In the spinal cord - saphenous nerve - skin preparation, application of capsaicin (0.1 microM) to the skin evoked a depolarization of the ventral root. This response was also depressed by max.d.4 (1 microM). Application of maxadilan evoked a long-lasting depolarization in a concentration-dependent manner in the spinal cord preparation. In the presence of max.d.4 (0.3 microM), the concentration response curve of maxadilan was shifted to the right. Reverse transcription-polymerase chain reaction (RT - PCR) experiments demonstrated the existence of PACAP receptor and VPAC(2) receptor in the neonatal rat spinal cord and [(125)I]-PACAP27 binding was displaced almost completely by maxadilan and max.d.4, but not by vasoactive intestinal peptide (VIP). These data indicate that PACAP receptor is dominantly distributed in the neonatal rat spinal cord. The present study suggests that PACAP receptor may play an excitatory role in nociceptive transmission in the neonatal rat spinal cord.