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The wettabilities of nanoscale porous surfaces play important roles in the context of molecular and fluid transport or oil-water separation. The wettability pattern along a nanopore strongly influences fluid distribution throughout the membrane. Mesoporous silica thin films with gradually adjusted wettabilities were fabricated via cocondensation. With consecutive mesoporous layer depositions, double-layer mesoporous silica films with asymmetric or so-called Janus wettability patterns were generated. The effects of these wetting gradients on mass transport, water imbibition, and water vapor condensation were investigated with ellipsometry, cyclic voltammetry (CV), drop friction force instrument (DoFFIs), fluorescence microscopy and interferometry. By increasing the film thickness of the hydrophobic mesoporous silica top layer deposited on a hydrophilic mesoporous silica layer up to 205 nm, molecular transport through both the layers was prevented. However, water was observed to condense onto the bottom layer, and transport occurred for thinner top layers.

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For miniaturization, as well as for improving artificial nanopore performance, precise local polymer functionalization and the combination of different functionalities are required. Imagining data driven nanopore design automated nanopore functionalization would be beneficial. Using direct laser writing as one option of automated nanopore polymer functionalization visible light induced polymerizations are beneficial. Here, we demonstrate the functionalization of mesoporous silicafilms with two different polymers using automated laser writing. For this we developed a visible light (400-700 nm and 405 nm) N,N(diethylamino)dithiocarbamoylbenzyl(trimethoxy)silane (SBDC) inifierter initiated polymerization. While transferring this visible light induced polymerization using SBDC to a commercially available microscope, direct, automated laser writing, as well as polymer re-initiation was demonstrated. Thereby, polymer spots of 37 and 40 µm in diameter were achieved using 1-5 seconds for each irradiated spot.

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For high throughput applications, e.g., in the context of sensing especially when being combined with machine learning, large sample numbers in acceptable production time are required. This needs automated synthesis and material functionalization concepts ideally combined with high precision. To automate sensing relevant mesopore polymer functionalization while being highly precise in polymer placement, polymer amount control, and polymer sequence design, a process for polymer writing in mesoporous silica films with pore diameter in the range of 13 nm is developed. Mesoporous films are functionalized with different polymers in adjustable polymer amount including block-copolymer functionalization in an automated process using a visible-light induced, controlled photo electron/energy transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization. While transferring this PET-RAFT to a commercially available microscope, direct, automated laser writing of three different polymers, as well as polymer re-initiation is demonstrated. Using a laser diameter of ≈72 µm, significantly smaller polymer spots of ≈7 µm in diameter are realized. Micrometerscale resolved polymer images including block-copolymers are written into mesoporous layers covering millimeter scale areas requiring a writing time in the range of one second per polymer spot.

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Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose-effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0-2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source.

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The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as "cell-adhesion-mediated-radio-resistance" (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments. As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signalling towards chromatin remodelling in response to a cell's microenvironment. We aimed to investigate this molecular origin that leads to CAM-RR by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin ß1 in clusters and maintain a less defined cluster status than 3D cultured cells. Upon X-irradiation this nanoscale distribution of integrin ß1 is disturbed at much lower dosages in 2D versus 3D cultured cells. Radioresistance is thus linked to the ability to maintain a well defined organization of integrins in clusters, making integrin distribution a potential drug target for radiosensitization.

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Although needleless connectors (NC) are frequently used in the perioperative setting, the potential of modern NCs to slow delivery of IV fluids has not been thoroughly studied. We examined flow characteristics of 5 NC models during pressurized delivery of crystalloid and banked red blood cells from a Level 1 warmer through various IV catheters. Crystalloid flow rates were reduced by 29% to 85% from control in catheters >18 gauge, while red blood cell flow reductions ranged from 22% to 76% in these catheters (all P < 0.0050). We suggest that practitioners consider eliminating NCs when large IV catheters are inserted for rapid fluid administration.

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BACKGROUND: Iron administration has been implicated as a cause of poor clinical outcome in maintenance hemodialysis (MHD) patients. However, the role of low iron levels in the clinical outcome of MHD patients is not clear. METHODS: We examined the predicting value of baseline serum iron level on prospective mortality and hospitalization in a cohort of all 1,283 MHD patients from 10 DaVita dialysis facilities in Los Angeles County, CA. RESULTS: Patients aged 57.8 +/- 15.2 years included 49% men, 45% Hispanics, 25% African Americans, and 53% patients with diabetes. During the first 3 months of the cohort, 97% of patients were administered erythropoietin (EPO) and 60% were administered intravenous iron (gluconate and/or dextran) at least once. During a 12-month follow-up, mortality was significantly greater (23%) in the lowest serum iron quartile (<45.3 microg/dL [<8.1 micromol/L]) compared with other quartiles (10% to 12%). Multivariate Poisson and Cox models adjusted for demographic features, dialysis dose and vintage, serum albumin and ferritin and blood hemoglobin concentrations, and administered EPO and iron doses showed that both serum iron level and iron saturation ratio had significant, but inverse, associations with prospective mortality and hospitalization. There was a statistically significant trend toward greater rates of mortality and hospitalization with lower serum iron levels. This reverse association remained significant in a subcohort of 322 MHD patients after additional adjustments for comorbid conditions and serum C-reactive protein level to reflect inflammation. CONCLUSION: Low baseline serum iron indicators are associated with increased mortality and hospitalization in MHD patients independent of hemoglobin level, EPO and iron doses, indicators of nutrition and inflammation, and comorbid conditions. Clinical trials to examine the role of iron administration in improving morbidity and mortality by increasing serum iron levels in MHD patients are required.

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BACKGROUND: Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). METHODS: The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. RESULTS: A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. CONCLUSION: The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

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OBJECTIVES: Normalized protein nitrogen appearance (nPNA), also known as protein catabolic rate (nPCR), reflects the daily protein intake in maintenance hemodialysis (MHD) patients. Several studies indicate that nPNA and Kt/V correlate with clinical outcome and also with each other. Thus, the relationship between low nPNA and poor outcome could be due to uremia, low Kt/V or due to reported mathematical coupling between nPNA and Kt/V. We therefore investigated whether nPNA is associated with outcome in patients who have adequate or high Kt/V. DESIGN: Prospective cohort. SETTINGS: Outpatient dialysis unit affiliated with a tertiary-care community medical center. PATIENTS: From a pool of 135 MHD outpatients in one dialysis unit, 122 patients with a delivered, Kt/V(sp)>1.20, independent of their residual renal function, were evaluated. Patients (61 women, 61 men), aged from 23 to 89 years (53.4+/-14.0 years)(+/-SD), had been undergoing MHD for one month to 17 years. INTERVENTION: Review of laboratory values and clinical outcome. MAIN OUTCOME MEASURES: Twelve-month mortality and hospitalization. RESULTS: Delivered Kt/V(sp) ranged from 1.23 to 2.71 (1.77+/-0.34), nPNA from 0.5 to 2.15 (1.13+/-0.29 g/kg/day), and serum albumin, from 1.9 to 4.6 (3.76+/-0.37 g/dL). During the 12-month follow-up, 55 patients were hospitalized overnight at least once; 12 patients died; 5 patients underwent renal transplantation, and 6 patients left the study. The nPNA and Kt/V(sp) did not correlate significantly (r=.09) except when analysis was limited to Kt/V values < 1.5 (r=.54). Serum nPNA and albumin were the only variables with statistically significant correlations with both mortality and 3 measures of hospitalization (H): total days of H (H(D)), total number of H (H(F)), and time to first H (H(T)). The case-mix adjusted correlations for serum albumin and nPNA versus total days (r(HD)) and frequency of H (r(HF)) were significant, and Cox analysis based on H(T) and time to death resulted in significant odds ratios for each standard deviation decrement for both serum albumin and nPNA. Serum total iron binding capacity (TIBC) and creatinine concentrations also correlated with some but not all outcome measures: lower serum concentrations of these values were each significantly associated with poor clinical outcomes. CONCLUSIONS: Both nPNA and serum albumin predict prospective hospitalization and mortality in MHD patients with Kt/V > 1.20. Serum TIBC and creatinine concentrations appear to have association with some outcome measures as well. These data are consistent with the possibility that protein intake affects the clinical course even in the setting of an adequate to high hemodialysis dose. Studies based on randomized assignments to different protein intakes would be helpful to confirm these conclusions.

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