A Web Based Optimization System Using Goal Programming for Supply Chain Network

Considering high competitive nature of todays industries,being on plan is very vital for supply chain network of an organization. Allthe flows of materials from initial suppliers to final customers need to besmooth. Hence, distribution network design is an important strategic decisionproblem for the supply chain managers. The aim of this research is to propose a web-based Decision Support System (DSS) foroptimizing fuzzy distribution network in the context of supply-chain management. A fuzzy goal-programming model has been designedfor the proposed DSS to consider the uncertain and imprecise data. Thisresearch focuses on four conflict fuzzy goals of (i). all demands must be covered by distribution center, (ii).investment goals for opening new sites considering fix costs, (iii). Investmentgoals for opening new distribution centers considering fix costs, (iv). Supplycosts goals, to meet the optimized results. Hence with those attributes ofmembership function of goals, the decision makers can apply this model toobtain the investment policy and the achieved level of each individual goal

TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content

BackgroundTNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.MethodsPrimary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.ResultsTRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.ConclusionsTRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization

Measurment of Ankle-Brachial Pressure Index, Homocystein Level, and Evaluation of Coronary Artery Disease Association with Other Macrovascular Diseases in Patients with Myocardial Infarction

We aimed to measure ankle-brachial pressure index (ABPI) and homocysteine levels, and to evaluate frequency of cerebrovascular disease (CVD) and/or peripheral arterial disease (PAD) combination of patients with myocardial infarction (MI). 39 patients (26 males, 13 females) with acute or subacute MI and 36 control cases (9 male, 27 female) were included in the study. ABPI and homocysteine levels were measured, and bilateral carotid-vertebral and bilateral lower extremity arterial Doppler ultrasonography, and coronary angiography were examined. Homocysteine was significantly higher in patient group than control group (p=0.0001). The ABPI was not significantly different in two groups (p=0.428). However the frequency of patients with lower ABPI (≤0.9) was significantly higher compared to the frequency of control patients with lower ABPI (25.6% and 3%, respectively; p=0.02). The combination of the atherosclerotic findings in the carotid artery and coronary artery disease (CAD) were found significantly higher compared to that of the bilateral lower extremity (59%, 25.6%). Screening of CVD should be done in patients with MI history. Determining carotid arterial lesions may be useful for the early diagnosis and treatment of any possible CVD in cases with CAD. Studies with larger numbers of cases are needed. [Med-Science 2013; 2(4.000): 896-906

CAN BE A PREFERABILITY BETWEEN INDUCTION ANESTHETIC AGENTS FOR FRACTURE SURGERY. HISTOPATHOLOGICAL AND BIOMECHANICAL APPROACH ON RATS

© 2023 World Scientific Publishing Company.As the effect of many medical agents such as nonsteroidal anti-inflammatory drugs or antibiotics were investigated on bone fracture healing, there is no study about the anesthetic agents when compared histopathologically and biomechanically. We asked the question that if a superiority can be between them since we operate many fractures and see the delayed or nonunions. Although different anesthetic agents are used in general anesthesia, the effects of these substances on bone fracture healing are not clear. Here, we intended to research different anesthetic agents on fracture union in rats. The study was done between January 2020 and November 2021 in a university animal research laboratory. Totally 48 male Wistar-Albino rats weighing 250-300g were seperated into 3 groups as Tiyopental Na in Group 1, Ketamin in Group 2 and Propofol in Group 3. For anesthesia; 40, 100, 100mg/kg of single dosages were injected intraperitoneally, respectively. A shaft fracture was created bilaterally to the tibia of all rats. Kirschner (K) wire is used for the fixation of fractures. Biomechanical and histopathological examination in bones is performed at the end of the first and second months in terms of fracture healing. It has been found that the fracture union in group 1 was statistically signifigant higher than group 3 at the end of the first and second months histopathologically (P = 0.006, P = 0.002). It is also found there is a statistically significant difference between groups 1 and 3 after the second month biomechanically (P = 0.013). Although the union was higher in group 1 than group 2 histopathologically and biomechanically after the first and second months, there was no statistically significant difference (P = 0.376, 0.039; P = 0.028, 0.867). There was a general trend in the decrease of union measurements starting from group 1 to 3 at the end of the first and second month both histopathologically and biomechanically. In this study, it is found that there was a positive consistency between histopathological and biomechanical results with respect to bone union. They supported each other. Fracture healing is stronger in rats that were anesthetized by using thiopental than those using ketamine and propofol, we think that this may affect the choice of anesthetic agent and further studies are needed

TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content

Background: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known. Methods: Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients. Results: TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content. Conclusions: TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization

Stereotactic radiotherapy for adrenal metastases: a multi-institutional review of patient characteristics and outcomes. Turkish Society for Radiation Oncology SBRT Group Study (TROD SBRT 10-004)

Introduction: This study aims to report the outcomes of SBRT for adrenal metastasis in a retrospective multi-institutional cohort. Methods: The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods.Results: The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median BED10 was 61 Gy. The overall LC rate was 83% and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival (LRFS), overall survival (OS) and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and = 8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity and late toxicity was observed in three patients, including one grade 5.Conclusion: A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients and systemic treatment options are needed to be improved