Comparison of prognosis between patients of pancreatic head cancer with and without obstructive jaundice at diagnosis

AbstractPurposeThe aim of this study was to elicit possible differences in prognoses and clinicopathological factors in pancreatic head cancer with and without obstructive jaundice at diagnosis.MethodsThe data from 169 patients with pancreatic head cancer were retrospectively analyzed.ResultsPatients were divided into two groups according to serum total bilirubin at diagnosis: ≥3 mg/dL for icteric group and <3 mg/dL for non-icteric group. In all cases, icteric group (n = 104) had a significantly worse prognosis than non-icteric group (n = 65) (median survival time (MST), 7.5 months (M) vs. 13.5 M, respectively; P = 0.049). In 84 resectable cases, icteric group had a significantly worse prognosis than non-icteric group (MST, 14.2 M vs. 20.9 M, respectively; P = 0.049) after almost equivalent treatment intensities. Icteric group had significantly larger T- and N-factors according to the UICC Classification compared to non-icteric group. The total number of lymph node metastases in icteric group was significantly larger than in non-icteric group (P = 0.008). The intrapancreatic nerve invasion in icteric group was significantly stronger than in non-icteric group (P = 0.016). There were no significant differences in the mortality and morbidity between icteric and non-icteric groups. In 85 unresectable cases, there was no significant difference between the survival periods of icteric and non-icteric groups (MST, 5.2 M vs. 5.3 M, respectively).ConclusionsThe presence of obstructive jaundice at diagnosis in patients with pancreatic head cancer may predict an unfavorable survival compared to such patients without obstructive jaundice

STUDIES ON THE CHLORIDE AND SULFATE CONTENT OF WELL WATERS AND THE AMOUNTS OF CHLORIDE A;\lD SULFATE FIXED TO THE SOIL IN THE MINERAL SPRING DISTRICTS (VIII) MATSUZAKI, TOGO AND ASOZU HOT SPRINGS, TOTTORI PREFECTURE, JAPAN

In Matsuzaki, Togo and Asozu Hot Springs which issue around the Pond Togo, the chloride and sulfate content and water temperatures of well waters and the amount of chloride and sufate fixed to the soil were determined with samples collected from various parts of the thermal spring districts and its neighborhood. The chloride and sulfate content and water temperatures of the well water samples collected from the thermal spring districts were higher than those from its neighbourhood, but for the amounts of chloride and sulfate fixed to the soil, no difference was detected. As the existence of other sources which would supply the chloride, sulfate and heat to the water is not expected, the difference in the chloride and sulfate content and water temperatures of well waters, between the samples collected from the thermal spring districts and its neighbourhood, seems to be due to the effects of thermal springs

Integrin Inhibitors as a Therapeutic Agent for Ovarian Cancer

Ovarian cancer is a deadly disease, with a cure rate of only 30%. Despite aggressive treatments, relapse remains almost inevitable in patients with advanced-stage disease. In recent years, great progress has been made towards targeting integrins in cancer treatment, and clinical studies with various integrin inhibitors have demonstrated their effectiveness in blocking cancer progression. Given that the initial critical step of ovarian cancer metastasis is the attachment of cancer cells onto the peritoneum or omentum, in addition to the proven positive clinical results of anti-angiogenic therapy, targeting integrins is likely to be one of the most feasible approaches. This paper summarizes the current understanding of the integrin biology in ovarian cancer metastasis and the various therapeutic approaches attempted with integrin inhibitors. Although no integrin inhibitors have shown favorable results so far, integrin-targeted therapies continue to be a promising approach to be explored for further clinical investigation

APPLICATION OF GENETIC ALGORITHMS IN SUPPLY MANAGEMENT DOI: 10.5585/rai.v7i2.328

Este artigo trata da aplicação do algoritmo genético como instrumento de tomada decisão para a gestão de suprimentos. O objetivo foi avaliar a sua utilização para a redução de estoques correntes. Para tanto, aplicou-se o método matemático à situação real de uma empresa brasileira de varejo de pneus. O resultado mostrou que a política de suprimentos simulada pelo algoritmo genético reduziu o estoque de pneus em cerca de 78%. Desse resultado pode-se concluir que o algoritmo genético proporciona importante contribuição para a gestão de suprimentos. Dada a natureza do estudo, exploratória do tipo estudo de caso, sugere-se otimizar a função objetivo com outras variáveis e simulá-las para diferentes índices de crossover e mutação bem como ampliar o uso do algoritmo genético para outros problemas de interesse prático.This article is about the application of genetic algorithm as a tool for decision making in supply management. The objective was to evaluate its use in current inventory reduction. To fulfill this objective, we used a mathematical method to study the supply management of a Brazilian retail tire company. The results showed that the supplies policy simulated by the genetic algorithm reduced the tire inventory by about 78%. With these results it was possible to conclude that the genetic algorithm provided an important contribution to supply management. Given the nature of the research results of this exploratory case study, we suggest optimizing the objective function with other variables and simulating them to different rates of crossover and mutation as well as expanding the use of genetic algorithm to other problems of practical interest

Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells

SummaryGerm cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome

miR-200b Precursor Can Ameliorate Renal Tubulointerstitial Fibrosis

Members of the miR-200 family of micro RNAs (miRNAs) have been shown to inhibit epithelial-mesenchymal transition (EMT). EMT of tubular epithelial cells is the mechanism by which renal fibroblasts are generated. Here we show that miR-200 family members inhibit transforming growth factor-beta (TGF-beta)-induced EMT of tubular cells. Unilateral ureter obstruction (UUO) is a common model of EMT of tubular cells and subsequent tubulointerstitial fibrosis. In order to examine the role of miR-200 family members in tubulointerstitial fibrosis, their expression was investigated in the kidneys of UUO mice. The expression of miR-200 family miRNAs was increased in a time-dependent manner, with induction of miR-200b most pronounced. To clarify the effect of miR-200b on tubulointerstitial fibrosis, we injected miR-200b precursor intravenously. A single injection of 0.5 nM miR-200b precursor was sufficient to inhibit the increase of collagen types I, III and fibronectin in obstructed kidneys, and amelioration of fibrosis was confirmed by observation of the kidneys with Azan staining. miR-200 family members have been previously shown to inhibit EMT by reducing the expression of ZEB-1 and ZEB-2 which are known repressors of E-cadherin. We demonstrated that expression of ZEB-1 and ZEB-2 was increased after ureter obstruction and that administration of the miR-200b precursor reversed this effect. In summary, these results indicate that miR-200 family is up-regulated after ureter obstruction, miR-200b being strongly induced, and that miR-200b ameliorates tubulointerstitial fibrosis in obstructed kidneys. We suggest that members of the miR-200 family, and miR-200b specifically, might constitute novel therapeutic targets in kidney disease

High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage.

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aβ species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aβ1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aβ1-42 were significantly greater than those of LMW-Aβ1-42. Therapeutic reduction of HMW-Aβ1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage