Large-scale first-principles molecular dynamics for electrochemical systems with O(N) methods

A method for large-scale first-principles molecular dynamics (MD) simulations on electrochemical systems has been developed by combining the effective screening medium (ESM) method with O(N) density functional theory (DFT). This implementation has been significantly simplified by the introduction of neutral atom potentials, which minimizes the modifications to existing DFT code. In order to demonstrate ability of this implementation, it has been applied to an electrochemical system consisting of a H-Si(111) electrode, which is a candidate anode for high-capacity Li-ion secondary batteries, and a propylene carbonate (PC) solvent to simulate how PC molecules in the vicinity of the electrode surface respond to an imposed electric field. The large-scale MD simulation clearly demonstrates that the combination of the ESM and O(N) DFT methods provides a useful tool for first-principles investigation of complicated electrochemical systems such as high-capacity batteries

Dienogest does not augment the gene expression of adhesion molecules, MCP-1, and monocyte adherence in human endothelial cells

AbstractObjective Medroxyprogesterone acetate (MPA) may increase the risk of atherosclerosis during hormone replacement therapy (HRT); therefore, the effect of progestogens other than MPA on atherosclerotic lesions requires evaluation. Adhesion of monocytes to vascular endothelial cells is an important early step in atherosclerosis progression. MCP-1 is a key chemokine that promotes monocyte migration and adhesion to vascular endothelial cells. In this study, we investigated the effects of dienogest (DNG), an alternative progestogen, on monocyte adhesion and cytokine expression in human umbilical vein endothelial cells (HUVECs).Study Design HUVECs were treated with DNG, natural progesterone, or MPA, followed by interleukin (IL)-1β stimulation. The mRNA expression of adhesion molecules (E-selectin and ICAM-1) and cytokines (MCP-1 and IL-6) was examined using real-time PCR. A flow chamber system was used to examine the effect of DNG on the adhesion of U937 monocytic cells to monolayer HUVECs.Results Unlike MPA, DNG did not alter the mRNA expression of E-selectin, ICAM-1, MCP-1, and IL-6 in HUVECs. Moreover, it did not increase the number of monocytes adhering to HUVECs in the flow chamber system. However, MPA treatment significantly enhanced monocyte adhesion to HUVECs (p < 0.05).Conclusions DNG had no effect on the mRNA expression of adhesion molecules and cytokines in HUVECs, as well as the monocyte adhesion to HUVECs, suggesting that DNG can be explored as an alternative to MPA for HRT

Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels &le;17 ng/mL, suggesting deficiency for bone health, but not in those &gt;17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18&ndash;28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25&ndash;0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (&le;17 ng/mL) or with high (&ge;29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers

Dienogest does not augment the gene expression of adhesion molecules, MCP-1, and monocyte adherence in human endothelial cells

Medroxyprogesterone acetate (MPA) may increase the risk of atherosclerosis during hormone replacement therapy (HRT); therefore, the effect of progestogens other than MPA on atherosclerotic lesions requires evaluation. Adhesion of monocytes to vascular endothelial cells is an important early step in atherosclerosis progression. MCP-1 is a key chemokine that promotes monocyte migration and adhesion to vascular endothelial cells. In this study, we investigated the effects of dienogest (DNG), an alternative progestogen, on monocyte adhesion and cytokine expression in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with DNG, natural progesterone, or MPA, followed by interleukin (IL)-1β stimulation. The mRNA expression of adhesion molecules (E-selectin and ICAM-1) and cytokines (MCP-1 and IL-6) was examined using real-time PCR. A flow chamber system was used to examine the effect of DNG on the adhesion of U937 monocytic cells to monolayer HUVECs. Unlike MPA, DNG did not alter the mRNA expression of E-selectin, ICAM-1, MCP-1, and IL-6 in HUVECs. Moreover, it did not increase the number of monocytes adhering to HUVECs in the flow chamber system. However, MPA treatment significantly enhanced monocyte adhesion to HUVECs (p  DNG had no effect on the mRNA expression of adhesion molecules and cytokines in HUVECs, as well as the monocyte adhesion to HUVECs, suggesting that DNG can be explored as an alternative to MPA for HRT.</p

化学療法が有効であった乳房外Paget癌の1例

乳房外Paget病は長期間表皮内にとどまっていることが多く,外科的切除により比較的予後良好な疾患である.しかし自覚症状に乏しく,かつ発症部位の特殊性により早期発見が困難なこともある.さらに一旦Paget癌へ進行すると有効な治療法がなく,一転して予後不良とされている.今回われわれは,化学療法により病巣の縮小と明らかな生存期間の延長を認めた乳房外Paget癌の1例を経験したので報告する.症例は72歳,女性.1984年頃より陰部に掻痒感を伴う紅色皮疹を自覚し,近医で処方された外用薬で軽決と増悪を繰り返していた.その後1994年に他院でPaget病と診断され,当院皮膚科で広範囲皮膚切除術を施行された.病理組織学的所見では真皮へ浸潤するPaget癌と診断された.補助化学療法として5-FUの経口投与を受けていたが,1996年4月にCEAの上昇を認め,局所およびリンパ節再発と診断された.手術目的で当科に転科となったが,その際左鼠径部から総腸骨動脈周囲のリンパ節に転移を認め,鼠径リンパ節の生検で低分化腺癌と診断された.そのため予後不良と判断し,患者のQOLを考慮してCDDP・Leucovorin・5-FUによる多剤併用療法を開始した.3クール施行後CEA値は低下し,局所再発巣およびリンパ節転移も著明に縮小し,PRと判定した(PR継続期間53ヵ月).1999年3月,再び左鼠径リンパ節が著明に腫大し皮膚潰瘍を伴うため,Virchowに転移を認めたが左鼠径リンパ節摘除術を施行した.このリンパ節摘除によりCEA値は著明に低下した.その後再発巣は徐々に増悪し,化学療法開始から4年3ヵ月後の2000年10月に死亡した.しかしその間他臓器への浸潤・転移はなく,本人の希望通り最後まで外来での加療が施行され,高度なQOLが得られた.We herein report a patient who presented with extramammary Paget\u27 s carcinoma (EPC) with local and lymph-node recurrences and demonstrated a good response to biochemical modulation chemotherapy. Biochemical modulation chemotherapy seems to be beneficial for patients with EPC with lymph-node metastasis. In August 1994, under a diagnosis of EPC, the patient underwent an extensive skin resection including subcutaneous fatty tissue along a line 3 cm outside the border of the dermatitis. In January 1996, she was diagnosed to have local recurrence and lymph-node metastasis of EPC. As a result, cisplatin (CDDP) + leucovorin (LV) + 5-fluorouracil (5FU) chemotherapy was started according to the patient\u27 s wishes and from the standpoint of the patient\u27 s age and quality of life. After three courses of this therapy, the patient was judged to show a partial response (PR). After six courses, the regimen was changed due to grade 3 leucopenia. Thereafter, the disease progressed. However, she continued the chemotherapy. On October 13, 2000, four years and three months after bigining the chemotherapy, she died. In this case, the chemotherapy was judged to be effective based on: the degree of reduction of tumor size, the long survival period of 4 years 3 months from the start of chemotherapy, the absence of any severe side effects, and the high quality of life, which was defined as a normal daily life without admission to the hospital. It is concluded that low-dose CDDP/LV/5-FU therapy may therefore be a useful chemotherapeutic regimen for advanced EPC