Cocktail of lipophilic and hydrophilic chemotherapeutics in high-load core@shell nanocarriers to treat pancreatic tumours.

ITC/Toc@Gd2(FLP)3 core@shell nanocarriers with a chemotherapeutic cocktail of lipophilic irinotecan (ITC) as the particle core and hydrophilic fludarabine phosphate (FLP) in the particle shell are realized. They are prepared via a microemulsion approach with ITC dissolved in tocopherol (Toc) as droplet phase and stabilized by water-insoluble Gd2(FLP)3. The synthesis can be followed by zeta-potential analysis. X-ray powder diffraction, infrared spectroscopy, elemental analysis, thermogravimetry, and photometry show a drug load of 49 µg per mL ITC and 317 µg per mL FLP at a nanocarrier concentration of 1.5 mg mL-1. Size and structure are evidenced by electron microscopy, resulting in a total diameter of 45 ± 16 nm, an inner core of 40 ± 17 nm, and a shell of 3-8 nm. In vitro studies with different cancer cell lines (i.e., human melanoma/SK-Mel-28, cervical cancer/HeLa, mouse pancreatic cancer/Panc02 and KPC as well as human pancreatic cancer/Capan-1 cells) prove efficient nanocarrier uptake and promising cytostatic efficacy. Specifically for KPC cells, ITC/Toc@Gd2(FLP)3 nanocarriers show an increased efficacy, with half maximal inhibitory concentration (IC50: 4.2 µM) > 10 times lower than the free drugs (IC50: ITC: 47.7 µM, FLP: 143 µM). This points to the synergistic effect of the ITC/FLP drug cocktail in the nanocarriers and may result in a promising strategy to treat pancreatic ductal adenocarcinoma (PDAC).

Risk Factors for Hospitalization and Effect of Immunosuppression on Clinical Outcomes Among an Urban Cohort of Patients With Mpox.

Background: During the 2022 mpox outbreak most patients were managed as outpatients, but some required hospitalization. Uncontrolled human immunodeficiency virus (HIV) has been identified as a risk factor for severe mpox. Methods: Patients with mpox diagnosed or treated within the Johns Hopkins Health System between 1 June and 15 December 2022 were included. The primary outcome of interest was risk of hospitalization. Demographic features, comorbid conditions, treatment, and clinical outcomes were determined. Results: A total of 353 patients were tested or treated for mpox; 100 had mpox diagnosed or treated (median age, 35.3 years; 97.0% male; 57.0% black and 10.0% Hispanic; 46.0% people with HIV [PWH]). Seventeen patients (17.0%) required hospitalization, 10 of whom were PWH. Age >40 years, race, ethnicity, HIV status, insurance status, and body mass index >30 (calculated as weight in kilograms divided by height in meters squared) were not associated with hospitalization. Eight of 9 patients (88.9%) with immunosuppression were hospitalized. Immunosuppression was associated with hospitalization in univariate (odds ratio, 69.3 [95% confidence interval, 7.8-619.7]) and adjusted analysis (adjusted odds ratio, 94.8 [8.5-1060.1]). Two patients (11.8%) who were hospitalized required intensive care unit admission and died; both had uncontrolled HIV infection and CD4 T-cell counts <50/µL. Median cycle threshold values for the first positive mpox virus sample did not differ between those who were hospitalized and those who were not. Conclusions: Immunosuppression was a significant risk factor for hospitalization with mpox. PWH with CD4 T-cell counts <50/µL are at high risk of death due to mpox infection. Patients who are immunosuppressed should be considered for early and aggressive treatment of mpox, given the increased risk of hospitalization.

Evaluation of Hydraulic Conductivity Estimates from Various Approaches with Groundwater Flow Models.

Significant efforts have been expended for improved characterization of hydraulic conductivity (K) and specific storage (Ss ) to better understand groundwater flow and contaminant transport processes. Conventional methods including grain size analyses (GSA), permeameter, slug, and pumping tests have been utilized extensively, while Direct Push-based Hydraulic Profiling Tool (HPT) surveys have been developed to obtain high-resolution K estimates. Moreover, inverse modeling approaches based on geology-based zonations, and highly parameterized Hydraulic Tomography (HT) have also been advanced to map spatial variations of K and Ss between and beyond boreholes. While different methods are available, it is unclear which one yields K estimates that are most useful for high resolution predictions of groundwater flow. Therefore, the main objective of this study is to evaluate various K estimates at a highly heterogeneous field site obtained with three categories of characterization techniques including: (1) conventional methods (GSA, permeameter, and slug tests); (2) HPT surveys; and (3) inverse modeling based on geology-based zonations and highly parameterized approaches. The performance of each approach is first qualitatively analyzed by comparing K estimates to site geology. Then, steady-state and transient groundwater flow models are employed to quantitatively assess various K estimates by simulating pumping tests not used for parameter estimation. Results reveal that inverse modeling approaches yield the best drawdown predictions under both steady and transient conditions. In contrast, conventional methods and HPT surveys yield biased predictions. Based on our research, it appears that inverse modeling and data fusion are necessary steps in predicting accurate groundwater flow behavior.

Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis.

Tuberculosis (TB) is one of the most prevalent infectious diseases. The global TB situation is further complicated by increasing patient numbers infected with Mycobacterium tuberculosis (M.tb.) strains resistant to either one or two of the first-line therapeutics, promoted by insufficient treatment length and/or drug levels due to adverse reactions and reduced patient compliance. An intriguing approach to improve anti-TB therapy relates to nanocarrier-based drug-delivery systems, which enhance local drug concentrations at infection sites without systemic toxicity. Recently developed anti-TB antibiotics, however, are lipophilic and difficult to transport in aqueous systems. Here, the very lipophilic TB-antibiotics bedaquiline (BDQ) and BTZ (1,3-benzothiazin-4-one 043) are prepared as high-dose, amorphous nanoparticles via a solvent-antisolvent technique. The nanoparticles exhibit mean diameters of 60 ± 13 nm (BDQ) and 62 ± 44 nm (BTZ) and have an extraordinarily high drug load with 69% BDQ and >99% BTZ of total nanoparticle mass plus a certain amount of surfactant (31% for BDQ, <1% for BTZ) to make the lipophilic drugs water-dispersible. Suspensions with high drug load (4.1 mg/mL BDQ, 4.2 mg/mL BTZ) are stable for several weeks. In vitro and in vivo studies employing M.tb.-infected macrophages and susceptible C3HeB/FeJ mice show promising activity, which outperforms conventional BDQ/BTZ solutions (in DMF or DMSO) with an up to 50% higher efficacy upon pulmonary delivery. In vitro, the BDQ/BTZ nanoparticles demonstrate their ability to cross the different biological barriers and to reach the site of the intracellular mycobacteria. In vivo, high amounts of the BDQ/BTZ nanoparticles are found in the lung and specifically inside granulomas, whereas only low BDQ/BTZ-nanoparticle levels are observed in spleen or liver. Thus, pulmonary delivered BDQ/BTZ nanoparticles are promising formulations to improve antituberculosis treatment.

SMART RHESINs-Superparamagnetic Magnetite Architecture Made of Phenolic Resin Hollow Spheres Coated with Eu(III) Containing Silica Nanoparticles for Future Quantitative Magnetic Particle Imaging Applications.

Magnetic particle imaging (MPI) is a powerful and rapidly growing tomographic imaging technique that allows for the non-invasive visualization of superparamagnetic nanoparticles (NPs) in living matter. Despite its potential for a wide range of applications, the intrinsic quantitative nature of MPI has not been fully exploited in biological environments. In this study, a novel NP architecture that overcomes this limitation by maintaining a virtually unchanged effective relaxation (Brownian plus Néel) even when immobilized is presented. This superparamagnetic magnetite architecture made of phenolic resin hollow spheres coated with Eu(III) containing silica nanoparticles (SMART RHESINs) was synthesized and studied. Magnetic particle spectroscopy (MPS) measurements confirm their suitability for potential MPI applications. Photobleaching studies show an unexpected photodynamic due to the fluorescence emission peak of the europium ion in combination with the phenol formaldehyde resin (PFR). Cell metabolic activity and proliferation behavior are not affected. Colocalization experiments reveal the distinct accumulation of SMART RHESINs near the Golgi apparatus. Overall, SMART RHESINs show superparamagnetic behavior and special luminescent properties without acute cytotoxicity, making them suitable for bimodal imaging probes for medical use like cancer diagnosis and treatment. SMART RHESINs have the potential to enable quantitative MPS and MPI measurements both in mobile and immobilized environments.

Subsurface mobility of land applied greenhouse nutrient feed water and environmental implications.

Greenhouse nutrient feedwater (GNF) discharge is considered a potential contributor to eutrophication issues in Lake Erie, Ontario. Land application of GNF is an accepted legislated management response to mitigate the impact of such nutrient loads. To assess the potential environmental impacts of this management practice, field infiltration experiments were conducted at four different greenhouse operations near Leamington, Ontario. Over a three-year study, GNF was applied on agricultural land adjacent to the greenhouse operations in the fall during the first year, and along with a bromide tracer in the summer and fall in Years 2 and 3, respectively. The GNF was applied at the maximum allowable rates as defined in legislation. Chemical constituents (nutrients, metals and the conservative tracer bromide) were monitored within the soil profile matrix and pore water above the water table. The results showed that, even with the GNF being applied at the highest permissible rates, the species of interest remained within the unsaturated soil zone at low concentrations over three to six months sampling intervals. The bromide tracer test demonstrated that highly mobile species could move through permeable soils to the water table depth in a potential worst-case application scenario. However, considering the low initial concentrations, long vadose zone residence time and the low mass flux, it would appear that land application of GNF, when applied in accordance with Ontario's Regulations, is a feasible and environmentally reasonable treatment option for managing GNF.

Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals.

Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers' characteristics influenced the MPs' sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying.

An Electron-Balance Based Approach to Predict the Decreasing Denitrification Potential of an Aquifer.

Numerical models for reactive transport can be used to estimate the breakthrough of a contaminant in a pumping well or at other receptors. However, as natural aquifers are highly heterogeneous with unknown spatial details, reactive transport predictions on the aquifer scale require a stochastic framework for uncertainty analysis. The high computational demand of spatially explicit reactive-transport models hampers such analysis, thus motivating the search for simplified estimation tools. We suggest performing an electron balance between the reactants in the infiltrating solution and in the aquifer matrix to obtain the hypothetical time of dissolved-reactant breakthrough at a receptor if the reaction with the matrix was instantaneous. This time we denote as the advective breakthrough time for instantaneous reaction (τinst ). It depends on the amount of the reaction partner present in the matrix, the mass flux of the dissolved reactant, and the stoichiometry. While the shape of the reactive-species breakthrough curve depends on various kinetic parameters, the overall timing scales with τinst . We calculate the latter by particle tracking. The effort of computing τinst is so low that stochastic calculations become feasible. We apply the concept to a two-dimensional test case of aerobic respiration and denitrification. A detailed spatially explicit reactive-transport model includes microbial dynamics. Scaling the time of local breakthrough curves observed at individual points by τinst decreased the variability of electron-donor breakthrough curves significantly. We conclude that the advective breakthrough time for instantaneous reaction is efficient in estimating the time over which an aquifer retains its degradation potential.

Delineating baseflow contribution areas for streams - A model and methods comparison.

This study addresses the delineation of areas that contribute baseflow to a stream reach, also known as stream capture zones. Such areas can be delineated using standard well capture zone delineation methods, with three important differences: (1) natural gradients are smaller compared to those produced by supply wells and are therefore subject to greater numerical errors, (2) stream discharge varies seasonally, and (3) stream discharge varies spatially. This study focuses on model-related uncertainties due to model characteristics, discretization schemes, delineation methods, and particle tracking algorithms. The methodology is applied to the Alder Creek watershed in southwestern Ontario. Four different model codes are compared: HydroGeoSphere, WATFLOW, MODFLOW, and FEFLOW. In addition, two delineation methods are compared: reverse particle tracking and reverse transport, where the latter considers local-scale parameter uncertainty by using a macrodispersion term to produce a capture probability plume. The results from this study indicate that different models can calibrate acceptably well to the same data and produce very similar distributions of hydraulic head, but can produce different capture zones. The stream capture zone is found to be highly sensitive to the particle tracking algorithm. It was also found that particle tracking by itself, if applied to complex systems such as the Alder Creek watershed, would require considerable subjective judgement in the delineation of stream capture zones. Reverse transport is an alternative and more reliable approach that provides probability intervals for the baseflow contribution areas, taking uncertainty into account. The two approaches can be used together to enhance the confidence in the final outcome.

Drug delivery of zinc to Barrett's metaplasia by oral administration to Barrett's esophagus patients.

BACKGROUND: Delivery of a pharmacologically effective drug dosage to a target tissue is critical. Barrett's epithelia are a unique challenge for drug delivery of orally administered zinc due to rapid transit down the esophageal lumen, incomplete absorptive differentiation of these epithelia, and the use of proton-pump inhibitor drugs abrogating intestinal uptake of supplemental zinc. METHODS: Barrett's esophagus patients were administered oral zinc gluconate (26 mg zinc twice daily) for 14 days prior to biopsy procurement. Barrett's biopsies were analyzed for total zinc content by atomic absorption spectroscopy and by western immunoblot for cellular proteins known to be regulated by zinc. RESULTS: Cellular levels of both the Znt-1 transport protein and the alpha isoform of PKC were over 50% lower in the zinc treatment group. CONCLUSION: Oral zinc administration can result in effective delivery of zinc to Barrett's epithelia with resulting effects on intracellular signal transduction.

An integrated approach for addressing uncertainty in the delineation of groundwater management areas.

Uncertainty is a pervasive but often poorly understood factor in the delineation of wellhead protection areas (WHPAs), which can discourage water managers and practitioners from relying on model results. To make uncertainty more understandable and thereby remove a barrier to the acceptance of models in the WHPA context, we present a simple approach for dealing with uncertainty. The approach considers two spatial scales for representing uncertainty: local and global. At the local scale, uncertainties are assumed to be due to heterogeneities, and a capture zone is expressed in terms of a capture probability plume. At the global scale, uncertainties are expressed through scenario analysis, using a limited number of physically realistic scenarios. The two scales are integrated by using the precautionary principle to merge the individual capture probability plumes corresponding to the different scenarios. The approach applies to both wellhead protection and the mitigation of contaminated aquifers, or in general, to groundwater management areas. An example relates to the WHPA for a supply well located in a complex glacial aquifer system in southwestern Ontario, where we focus on uncertainty due to the spatial distributions of recharge. While different recharge scenarios calibrate equally well to the same data, they result in different capture probability plumes. Using the precautionary approach, the different plumes are merged into two types of maps delineating groundwater management areas for either wellhead protection or aquifer mitigation. The study shows that calibrations may be non-unique, and that finding a "best" model on the basis of the calibration fit may not be possible.

A simple method to assess unsaturated zone time lag in the travel time from ground surface to receptor.

In contaminant travel from ground surface to groundwater receptors, the time taken in travelling through the unsaturated zone is known as the unsaturated zone time lag. Depending on the situation, this time lag may or may not be significant within the context of the overall problem. A method is presented for assessing the importance of the unsaturated zone in the travel time from source to receptor in terms of estimates of both the absolute and the relative advective times. A choice of different techniques for both unsaturated and saturated travel time estimation is provided. This method may be useful for practitioners to decide whether to incorporate unsaturated processes in conceptual and numerical models and can also be used to roughly estimate the total travel time between points near ground surface and a groundwater receptor. This method was applied to a field site located in a glacial aquifer system in Ontario, Canada. Advective travel times were estimated using techniques with different levels of sophistication. The application of the proposed method indicates that the time lag in the unsaturated zone is significant at this field site and should be taken into account. For this case, sophisticated and simplified techniques lead to similar assessments when the same knowledge of the hydraulic conductivity field is assumed. When there is significant uncertainty regarding the hydraulic conductivity, simplified calculations did not lead to a conclusive decision.

Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis.

Inflammatory Bowel Disease--comprised of Crohn's Disease and Ulcerative Colitis (UC)--is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals. Through Significance Analysis of Microarrays, a signature of 31 differentially expressed platelet-derived miRNAs has been identified and biomarker performance estimated through a non-probabilistic binary linear classification using Support Vector Machines. Through this approach, classifier measurements reveal a predictive score of 92.8% accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients from normal individuals. Additionally, the platelet-derived biomarker signature can be validated at 88% accuracy through qPCR assays, and a majority of the miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated intensity based clusters. Analysis of predicted targets of these biomarkers reveal an enrichment of pathways associated with cytoskeleton assembly, transport, membrane permeability and regulation of transcription factors engaged in a variety of regulatory cascades that are consistent with a cell-mediated immune response model of intestinal inflammation. Interestingly, comparison of the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide association studies identifies a physical linkage between hsa-miR-941 and a UC susceptibility loci located on Chr 20. Taken together, analysis of these expression maps outlines a promising catalog of novel platelet-derived miRNA biomarkers of clinical utility and provides insight into the potential biological function of these candidates in disease pathogenesis.

Nitrate controls methyl mercury production in a streambed bioreactor.

Organic carbon bioreactors provide low-cost, passive treatment of a variety of environmental contaminants but can have undesirable side effects in some cases. This study examines the production of methyl mercury (MeHg) in a streambed bioreactor consisting of 40 m³ of wood chips and designed to treat nitrate (NO3) in an agricultural drainage ditch in southern Ontario (Avon site). The reactor provides 30 to 100% removal of NO3-N concentrations of 0.6 to 4.4 mg L(-1), but sulfate (SO4(2-)) reducing conditions develop when NO3 removal is complete. Sulfate reducing conditions are known to stimulation the production of MeHg in natural wetlands. Over one seasonal cycle, effluent MeHg ranged from 0.01 to 0.76 ng L(-1) and total Hg ranged from 1.3 to 3.4 ng L(-1). During all sampling events when reducing conditions were only sufficient to promote NO3(-) reduction (or denitrification) ( = 5, late fall 2009, winter 2010), MeHg concentrations decreased in the reactor and it was a net sink for MeHg (mean flux of -5.1 µg m(-2) yr(-1)). During all sampling events when SO4(2-) reducing conditions were present ( = 6, early fall 2009, spring 2010), MeHg concentrations increased in the reactor and it was a strong source of MeHg to the stream (mean flux of 15.2 µg m(-2) yr(-1)). Total Hg was consistently removed in the reactor (10 of 11 sampling events) and was correlated to the total suspended sediment load ( r² = 0.69), which was removed in the reactor by physical filtration. This study shows that organic carbon bioreactors can be a strong source of MeHg production when SO4(2-) reducing conditions develop; however, maintaining NO3-N concentrations > 0.5 mg L suppresses the production of MeHg.

Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores.

BACKGROUND: Proton pump inhibitors (PPIs) cause a sharp elevation of gastro-duodenal luminal pH which in turn has resulted in reports of reduced absorption of magnesium and certain other nutrients. METHODS: Gastroesophageal reflux disease (GERD) patients on long-term PPI therapy (> 6 months) or healthy test subjects (not on any acid preventive or neutralizing medication) were administered oral doses of zinc gluconate (26.2 mg zinc, twice daily) for 14 days followed by 5 cc venous blood samples. Plasma was analyzed for total zinc content by atomic absorption spectrophotometry. Baseline plasma and red blood cell zinc levels were also measured in these two groups when not taking any zinc supplementation. RESULTS: Plasma zinc levels of healthy controls increased by 126% during the period of zinc supplementation compared to only a 37% increase for individuals on long-term PPI therapy. On their normal diet (with no zinc supplementation), PPI-users had a 28% lower plasma zinc level than healthy controls (P < 0.005). CONCLUSIONS: PPI use dramatically reduces supplemental zinc uptake and can result in decreased zinc body stores. Certain individuals on long-term PPI therapy, such as infants being treated for colic, may be at risk for decreased systemic levels of trace metals needed for developmental, regenerative and immunological requirements.

The utility of microspheres as surrogates for the transport of E. coli RS2g in partially saturated agricultural soil.

Polystyrene latex microspheres are widely used as surrogates for biocolloid transport in porous media; however, relatively few studies directly compare microsphere transport with that of the microorganism it is intended to represent, particularly at the field scale. Here, we compared the transport behaviour of a bacterium (Escherichia coli RS2g; 1.2 microm in diameter) and three different sized microspheres (1.1, 3.9, and 4.8 microm in diameter) within undisturbed agricultural field soil following infiltration under partially saturated conditions. The soil contained significant macroporosity. A tension infiltrometer was used to control the application of a transport solution containing Brilliant Blue FCF dye to two plots. A >2 log reduction in the concentration of all colloids was observed from the soil surface to 5 cm depth in both plots. The concentration of colloids in the soil was generally proportional to the intensity of soil dye staining; however, both the E. coli RS2g bacterium and the 1.1 microm microspheres appeared to be transported deeper than the other colloids and the visible dye along root holes at the bottom of the profile in both plots. The similarities in size and zeta potential of the 1.1 microm microspheres and the E. coli RS2g likely contributed to that outcome. Colloid concentrations in dyed soil by depth were similar between the two plots, despite differences in soil properties and infiltration patterns. The properties of the colloids and macropore density were the most important factors affecting colloid transport. These results suggest that microspheres with size and surface properties similar to the microbe of interest are useful surrogates to trace potential pathways of transport in the subsurface.

Influence of macroporosity on preferential solute and colloid transport in unsaturated field soils.

Transport of solutes and colloids in soils, particularly those subject to preferential flow along macropores, is important for assessing the vulnerability of shallow groundwater to contamination. The objective of this study was to investigate flow and transport phenomena for dissolved and colloid tracers during large infiltration events in partially saturated, macroporous soils. Controlled tracer infiltration tests were completed at two field sites in southern Ontario. A tension infiltrometer (TI) was used to infiltrate water with dissolved Brilliant Blue FCF dye simultaneously with 3.7 microm and 0.53 microm diameter fluorescent microspheres. Infiltration was conducted under maximum infiltration pressure heads ranging from -5.2 to -0.4 cm. All infiltration test sites were excavated to examine and photograph dye-stained flow patterns, map soil features, and collect samples for microsphere enumeration. Results indicated that preferential transport of dye and microspheres via macropores occurred when maximum pressure heads were greater than -3.0 cm, and the corresponding infiltration rates exceeded 2.0 cm h(-1). Dye and microspheres were detected at depths greater than 70 cm under the highest infiltration rates from both sites. Microsphere concentrations in the top 5-10 cm of soil decreased by more than two orders of magnitude relative to input concentrations, yet remained relatively constant with depth thereafter. There was some evidence for increased retention of the 3.7 microm microspheres relative to the 0.53 microm microspheres, particularly at lower infiltration pressures where straining and attachment mechanisms are most prevalent. Microspheres were observed within dye stained soil matrix surrounding individual macropores, illustrating the significance of capillary pressures in controlling the vertical migration of both tracers in the vicinity of the macropores. Overall, microsphere distributions closely followed the dye patterns, with microsphere concentrations at all depths directly related to the intensity (or concentration) of dye staining. It is concluded that the flow system influenced transport to a much greater degree than differences between dissolved and colloidal species, and hence a dye tracer could serve as a reasonable surrogate for colloid distributions in the vadose zone following individual infiltration events.

Proton pump inhibitors: actions and reactions.

Proton pump inhibitors are the second most commonly prescribed drug class in the United States. The increased utilization of PPIs parallels the rising incidence of reflux disease. Owing to their clinical efficacy and relative lack of tachyphylaxis, PPIs have largely displaced H-2 receptor antagonists in the treatment of acid peptic disorders. The elevation of intragastric pH and subsequent alterations of gastric physiology induced by PPIs may yield undesired effects within the upper GI tract. The ubiquity of the various types of H(+), K(+)-ATPase could also contribute to non-gastric effects. PPIs may influence physiology in other ways, such as inducing transepithelial leak.