Generation and Control of Electrohydrodynamic Flows in Aqueous Electrolyte Solutions.

To drive electrohydrodynamic (EHD) flows in aqueous solutions, the separation of cation and anion transport pathways is essential because a directed electric body force has to be induced by ionic motions in liquid. On the other hand, positive and negative charges attract each other, and electroneutrality is maintained everywhere in equilibrium conditions. Furthermore, an increase in an applied voltage has to be suppressed to avoid water electrolysis, which causes the solutions to become unstable. Usually, EHD flows can be induced in non-aqueous solutions by applying extremely high voltages, such as tens of kV, to inject electrical charges. In this study, two methods are introduced to generate EHD flows induced by electrical charge separations in aqueous solutions, where two liquid phases are separated by an ion-exchange membrane. Due to a difference in the ionic mobility in the membrane, ion concentration polarization is induced between both sides of the membrane. In this study, we demonstrate two methods. (i) The relaxation of ion concentration gradients occurs via a flow channel that penetrates an ion-exchange membrane, where the transport of the slower species in the membrane selectively becomes dominant in the flow channel. This is a driving force to generate an EHD flow in the liquid. (ii) A long waiting time for the diffusion of ions passing through the ion-exchange membrane enables the generation of an ion-dragged flow by externally applying an electric field. Ions concentrated in a flow channel of a 1 x 1 mm2 cross-section determine the direction of the liquid flow, corresponding to the electrophoretic transport pathways. In both methods, the electric voltage difference required for an EHD flow generation is drastically reduced to near 2 V by rectifying the ion transport pathways.

Electrohydrodynamic flow through a 1 mm(2) cross-section pore placed in an ion-exchange membrane.

In recent years, the control of ionic currents has come to be recognized as one of the most important issues related to the efficient transport of single molecules and microparticles in aqueous solutions. However, the complicated liquid flows that are usually induced by applying electric potentials have made it difficult to address a number of unsolved problems in this area. In particular, the nonequilibrium phenomena that occur in electrically non-neutral fields must be more thoroughly understood. Herein, we report on the development of a theoretical model of liquid flows resulting from ion interactions while focusing on the so-called electrohydrodynamic (EHD) flow. We also discuss the development of an experimental system to optically and electrically observe EHD flows using a 1 mm(2) cross-section pore placed in an ion-exchange membrane where cation and anion flows can be separated without the use of a charged environment. Although micro/nanosized flow channels are usually applied to induce electric double layer overlaps to utilize strong electroosmotic effects, our system does not require such laborious fabrication processes. Instead, we visualize EHD flows by using a millimeter size pore immersed in an alkaline aqueous solution. In this setup, liquid flows passing through the pore along the direction of ion flow, whose velocity reaches on the order of 1 mm/s, can be clearly observed by applying a few volts of electric potential. Furthermore, the transient phenomena associated with ionic responses are theoretically elucidated.

Treatment when prognostic factors do not match St. Gallen recommendations: profiling of prognostic factors among HR(+) and HER2(-) breast cancer patients.

BACKGROUND: The St. Gallen consensus provides treatment recommendations for breast cancer based on prognostic factors. Although many patients' prognostic patterns are not easily matched with the prognostic patterns listed in the St. Gallen consensus, there has been no systematic investigation reporting the gap between treatment recommendations and actual postoperative treatment choices in clinical practice. METHODS: Four hundred seventy-one patients with hormone receptor-positive [HR(+)] and human epidermal growth factor receptor type 2-negative [HER2(-)] breast cancer were analyzed. These patients were classified into either the "crisp treatment group" or "fuzzy treatment group" based on the definitiveness of postoperative treatment selection based on St. Gallen treatment recommendations. The patients in the fuzzy treatment group were further classified into strata in which patients within each stratum shared the same prognostic factor patterns with similar recurrence rates. RESULTS: A total of 87.3% of HR(+)HER2(-) patients were designated to the fuzzy treatment group. Four prognostic strata were constructed according to the survival tree model, and revealed that patients with poor prognostic profiles tended to receive endocrine therapy with chemotherapy. This suggests that postoperative chemotherapy is useful, although there was no statistical significance. CONCLUSIONS: We constructed prognostic profiles of patients in the fuzzy treatment group and examined the recurrence rates associated with two treatment regimens within each prognostic profile. These findings are exploratory, but they may be useful for planning prospective studies of the effectiveness of postoperative treatment regimens among patients with a heterogeneous combination of prognostic factors.

Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer.

Neoadjuvant chemotherapy or preoperative systemic therapy is increasingly considered for patients with operable breast cancer. Patients with breast cancer were examined for pathologic factors predictive of response to neoadjuvant chemotherapy, using an anthracycline-based regimen. For clinical histomorphology and biomarkers, factors were compared among 16 pathologically complete responses and 52 nonpathologically complete responses, using univariate analysis and multivariate regression analysis of principal components, using preneoadjuvant chemotherapy needle biopsy samples as follows: degree of tumor-infiltrating lymphocytes, histologic grade, biology-based tumor type (hormone receptors and HER2 [human epidermal growth factor receptor type 2]), age, clinical TNM stage, and TNM staging. In univariate analysis, high tumor-infiltrating lymphocyte, high histologic grade, and hormone receptors(-)/HER2(+) were significantly associated with pathologically complete responses (93.7%, P < .0001; 81.3%, P = .0206; 43.7%, P = .014, respectively). In multivariate principal component regression analysis, high tumor-infiltrating lymphocytes were the best independent predictor for pathologically complete responses (odds ratio, 4.7; confidence interval, 2.2-10.06; P < .0001). Among tumor-infiltrating lymphocytes and biology-based tumor types, patients with high tumor-infiltrating lymphocytes had pathologically complete responses more than nonpathologically complete responses, especially in the hormone receptors(-)/HER2(+) group. Among high tumor-infiltrating lymphocyte cases, T lymphocytes showed more predominant tendency than B lymphocytes in the pathologically complete responses cases, compared with nonpathologically complete responses cases. These findings indicate that high tumor-infiltrating lymphocytes are important predictors of pathologically complete responses to neoadjuvant chemotherapy, especially in the hormone receptors(-)/HER2(+) group.

The differential effects of angiotensin II type 1 receptor blockers on microalbuminuria in relation to low-grade inflammation in metabolic hypertensive patients.

BACKGROUND: A dual angiotensin type 1 receptor blocker (ARB)/peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist telmisartan may be more useful for microalbuminuria reduction than ARBs with no PPARgamma agonistic action. We investigated whether there is a difference between the effects of telmisartan and valsartan with respect to microalbuminuria reduction, and the association with improvement of metabolic features or suppression of the inflammatory state. METHODS: Fifty-three patients who had metabolic syndrome and had been taking valsartan were recruited. All of these patients were randomly assigned to replace valsartan by telmisartan (telmisartan group; n = 30) or to keep taking valsartan (control group; n = 21). Various parameters were measured at baseline and 12 weeks after randomization. RESULTS: There were no significant changes in blood pressure (BP), glucose, and lipid parameters between baseline and 12 weeks after randomization in either group. There was a significant increase in high molecular weight adiponectin in the telmisartan group (4.6 v 5.0 microg/mL, P = .024), whereas there was no significant change in the control group. The reductions of microalbuminuria and high-sensitivity C-reactive protein (hs-CRP) were significant in the telmisartan group (28.1 v 18.9 mg/g.Cr and 0.77 v 0.60 mg/L, respectively, P = .001 and P = .022), whereas there was no significant change in the control group. The reductions of microalbuminuria and hs-CRP were significantly correlated with each other (gamma = 0.413, P = .003). CONCLUSIONS: The dual ARB/PPARgamma agonist telmisartan achieved more microalbuminuria reduction than an ARB with no PPARgamma agonistic action, possibly through suppression of the inflammatory state in metabolic hypertensive patients.