Background.Outpatient therapies for urinary tract infections (UTIs) are becoming limited due to antimicrobial resistance. The purpose of this paper is to report how the incidence of hospitalizations for UTIs have varied over time in both men and women and across age groups. We also explore how the severity for UTI hospitalizations has changed and describe the seasonality of UTI hospitalizations.Methods.Using the Nationwide Inpatient Sample, we compute a time-series of UTI incidence and subdivide the series by age and sex. We fit a collection of time-series models to explore how the trend and seasonal intensity varies by age and sex. We modeled changes in severity using regression with available confounders.Results.In 2011, there were approximately 400000 hospitalizations for UTIs with an estimated cost of $2.8 billion. Incidence increased by 52% between 1998 and 2011. The rate of increase was larger among both women and older patients. We found that the seasonal intensity (summer peaks and winter troughs) increased over time among women while decreasing among men. For both men and women, seasonality decreased with advancing age. Relative to controls and adjusted for demographics, we found that costs among UTI patients grew more slowly, patients left the hospital earlier, and patients had lower odds of death.Conclusions.Incidence of UTI hospitalization is increasing and is seasonal, peaking in the summer. However, the severity of UTI admissions seems to be decreasing, indicating that patients previously treated as outpatients may now be admitted to the hospital due to increasing antimicrobial resistance.

Paraquat, as one of the most widely used herbicides globally, is highly toxic to humans, and chronic exposure and acute ingestion leads to high morbidity and mortality rates. Here, we report user-friendly, photo-responsive paraquat-loaded supramolecular vesicles, prepared via one-pot self-assembly of amphiphilic, ternary host-guest complexes between cucurbit[8]uril, paraquat, and an azobenzene derivative. In this vesicle formulation, paraquat is only released upon UV or sunlight irradiation that converts the azobenzene derivative from its trans- to its cis- form, which in turn dissociates the ternary host-guest complexations and the vesicles. The cytotoxicity evaluation of this vesicle formulation of paraquat on in vitro cell models, in vivo zebrafish models, and mouse models demonstrates an enhanced safety profile. Additionally, the PQ-loaded vesicles’ herbicidal activity against a model of invasive weed is nearly identical to that of free paraquat under natural sunlight. This study provides a safe yet effective herbicide formulation.

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Edited by Tamas DalmayKeywords: MicroRNAs Glioma Eph tyrosine kinase receptor A8 Migration Invasion Epithelial-mesenchymal transition a b s t r a c t MicroRNAs (miRNAs) play a critical role in the development of cancers. However, the role of miRNAs in glioma is still poorly understood. In this study, we demonstrate that microRNA-10a (miR-10a) promotes cell migration and invasion by negatively regulating the expression of Eph tyrosine kinase receptor A8 (EphA8). Ectopic expression of EphA8 counteracts the promotion of migration and invasion induced by miR-10a. We further demonstrate that miR-10a and EphA8 regulate epithelial-mesenchymal transition (EMT) to affect cell migration and invasion. Collectively, we unveil a branch of the miR-10a/EphA8 pathway that regulates the progression of glioma.

In order to realize a combination of chemotherapy and selective drug release into tumor cells, novel pH-sensitive prodrugnanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for the selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells. Additionally, a second chemotherapeutic agent, Cur, was encapsulated in the core of nanoparticles (Cur-Dox-NPs) via hydrophobic effects, with a significant drug loading capacity. Cur-Dox-NPs exhibited an efficient release of both Dox and Cur in acidic media and further studies of their intracellular uptake and drug release confirmed that Dox-NPs were easily taken up by cells and selectively released the drug into the human breast cancer cell line MCF-7. In vitro cytotoxicity studies of the NPs showed a remarkable efficacy against MCF-7 cell lines, whereas an improved safety profile was observed in the human breast epithelial cell line MCF-10A. Furthermore, in vivo studies in zebrafish further confirmed an efficient absorption of Dox-NPs. In vivo cardiotoxicity experiments on a zebrafish model showed that Dox-NPs exhibited an improved cardiotoxicity profile in comparison with free Dox. This study demonstrated that this novel pH-sensitive prodrug-nanoparticle system may provide a simple and efficient platform for the selective co-delivery of multiple drugs to tumor cells.