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Droplet microarray technology is of great interest in biology and chemistry as it allows for significant reactant savings and massive parallelization of experiments. Upon scaling down the footprint of each droplet in an array, it becomes increasingly challenging to produce the array drop‐by‐drop. Therefore, techniques for parallelized droplet production are developed, e.g., dip‐coating of biphilic substrates. However, it is in general difficult to tailor the characteristics of individual droplets, such as size and content, without updating the substrate. Here, the method of dip‐coating of uniformly patterned biphilic substrates in so‐called "acceleration‐mode" to produce droplet arrays featuring gradients in droplet height for fixed droplet footprint is developed. The results herein present this method applied to produce drops with base diameters varying over orders of magnitude, from as high as 6 mm to as small as 50 µm; importantly, the experimentally measured power‐law‐dependency of volume on capillary‐number matches analytical theory for droplet formation on heterogenous substrates though the precise quantitative values likely differ due to 2D substrate patterning. Gradient characteristics, including average droplet volume, steepness of the gradient, and its monotonicity, can all be tuned by changing the dip‐coating parameters, thus providing a robust method for high‐throughput screening applications and experiments. [ABSTRACT FROM AUTHOR]

SUMMARY: In most plant tissues, threads of cytoplasm, or plasmodesmata, connect the protoplasts via pores in the cell walls. This enables symplasmic transport, for instance in phloem loading, transport and unloading. Importantly, the geometry of the wall pore limits the size of the particles that may be transported, and also (co‐)defines plasmodesmal resistance to diffusion and convective flow. However, quantitative information on transport through plasmodesmata in non‐cylindrical cell wall pores is scarce. We have found conical, funnel‐shaped cell wall pores in the phloem‐unloading zone in growing root tips of five eudicot and two monocot species, specifically between protophloem sieve elements and phloem pole pericycle cells. 3D reconstructions by electron tomography suggested that funnel plasmodesmata possess a desmotubule but lack tethers to fix it in a central position. Model calculations showed that both diffusive and hydraulic resistance decrease drastically in conical and trumpet‐shaped cell wall pores compared with cylindrical channels, even at very small opening angles. Notably, the effect on hydraulic resistance was relatively larger. We conclude that funnel plasmodesmata generally are present in specific cell–cell interfaces in angiosperm roots, where they appear to facilitate symplasmic phloem unloading. Interestingly, cytosolic sleeves of most plasmodesmata reported in the literature do not resemble annuli of constant diameter but possess variously shaped widenings. Our evaluations suggest that widenings too small for unambiguous identification on electron micrographs may drastically reduce the hydraulic and diffusional resistance of these pores. Consequently, theoretical models assuming cylindrical symmetries will underestimate plasmodesmal conductivities. Significance Statement: Plasmodesmata enable the exchange of materials between neighboring cells in plant tissues. In seven plant species, we found the plasmodesmata between terminal sieve elements and adjacent pericycle cells, which mediate phloem unloading in root growth zones, to be irregularly funnel‐shaped. Modeling approaches demonstrated much reduced hydraulic and diffusive resistances for such funnel plasmodesmata compared with cylindrical ones of similar minimum widths. Consequently, currently favoured models may dramatically underestimate plasmodesmal fluxes in phloem unloading. [ABSTRACT FROM AUTHOR]

Penicillin G is frequently used to treat infective endocarditis ( IE) caused by streptococci, penicillin-susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined penicillin G plasma concentration [p-penicillin] once weekly in 46 IE patients. The aim was to evaluate whether penicillin G 3 g every 6 hr (q6 h) resulted in therapeutic concentrations and to analyse potential factors that influence inter- and intra-individual variability, using linear regression and a random coefficient model. [P-penicillin] at 3 hr and at 6 hr was compared with the minimal inhibitory concentration ( MIC) of the bacteria isolated from blood cultures to evaluate the following PK/ PD targets: 50% fT > MIC and 100% fT > MIC. [P-penicillin] varied notably between patients and was associated with age, weight, p-creatinine and estimated creatinine clearance (eCLcr). Additionally, an increase in [p-penicillin] during the treatment period showed strong correlation with age, a low eCLcr, a low weight and a low p-albumin. Of the 46 patients, 96% had [p-penicillin] that resulted in 50% fT > MIC, while 71% had [p-penicillin] resulting in 100% fT > MIC. The majority of patients not achieving the 100% fT > MIC target were infected with enterococci. Streptococci and staphylococci isolated from blood cultures were highly susceptible to penicillin G. Our results suggest that penicillin G 3 g q6 h is suitable to treat IE caused by streptococci and penicillin-susceptible staphylococci, but caution must be taken when the infection is caused by enterococci. When treating enterococci, therapeutic drug monitoring should be applied to optimize penicillin G dosing and exposure. [ABSTRACT FROM AUTHOR]

Background: The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy. Aim: We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference. Methods and results: A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF. Conclusions: In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy. [Copyright &y& Elsevier]