Chemically Stable Styrenic Electrospun Membranes with Tailorable Surface Chemistry.

Membranes with tailorable surface chemistry have applications in a wide range of industries. Synthesizing membranes from poly(chloromethyl styrene) directly incorporates an alkyl halide surface-bound initiator which can be used to install functional groups via SN2 chemistry or graft polymerization techniques. In this work, poly(chloromethyl styrene) membranes were synthesized through electrospinning. After fabrication, membranes were crosslinked with a diamine, and the chemical resistance of the membranes was evaluated by exposure to 10 M nitric acid, ethanol, or tetrahydrofuran for 24 h. The resulting membranes had diameters on the order of 2-5 microns, porosities of >80%, and permeance on the order of 10,000 L/m2/h/bar. Crosslinking the membranes generally increased the chemical stability. The degree of crosslinking was approximated using elemental analysis for nitrogen and ranged from 0.5 to 0.9 N%. The poly(chloromethyl styrene) membrane with the highest degree of crosslinking did not dissolve in THF after 24 h and retained its high permeance after solvent exposure. The presented chemically resistant membranes can serve as a platform technology due to their versatile surface chemistry and can be used in membrane manufacturing techniques that require the membrane to be contacted with organic solvents or monomers. They can also serve as a platform for separations that are performed in strong acids.

Comparison of Two Place-Based Mapping Procedures on Masked Sentence Recognition as a Function of Electrode Array Angular Insertion Depth and Presence of Acoustic Low-Frequency Information: A Simulation Study.

INTRODUCTION: Cochlear implant (CI) and electric-acoustic stimulation (EAS) users may experience better performance with maps that align the electric filter frequencies to the cochlear place frequencies, known as place-based maps, than with maps that present spectrally shifted information. Individual place-based mapping procedures differ in the frequency content that is aligned to cochlear tonotopicity versus discarded or spectrally shifted. The performance benefit with different place-based maps may vary due to individual differences in angular insertion depth (AID) of the electrode array and whether functional acoustic low-frequency information is available in the implanted ear. The present study compared masked speech recognition with two types of place-based maps as a function of AID and presence of acoustic low-frequency information. METHODS: Sixty adults with normal hearing listened acutely to CI or EAS simulations of two types of place-based maps for one of three cases of electrode arrays at shallow AIDs. The strict place-based (Strict-PB) map aligned the low- and mid-frequency information to cochlear tonotopicity and discarded information below the frequency associated with the most apical electrode contact. The alternative place-based map (LFshift-PB) aligned the mid-frequency information to cochlear tonotopicity and provided more of the speech spectrum by compressing low-frequency information on the apical electrode contacts (i.e., <1 kHz). Three actual cases of a 12-channel, 24-mm electrode array were simulated by assigning the carrier frequency for an individual channel as the cochlear place frequency of the associated electrode contact. The AID and cochlear place frequency for the most apical electrode contact were 460° and 498 Hz for case 1, 389° and 728 Hz for case 2, and 335° and 987 Hz for case 3, respectively. RESULTS: Generally, better performance was observed with the Strict-PB maps for cases 1 and 2, where mismatches were 2-4 octaves for the most apical channel with the LFshift-PB map. Similar performance was observed between maps for case 3. For the CI simulations, performance with the Strict-PB map declined with decreases in AID, while performance with the LFshift-PB map remained stable across cases. For the EAS simulations, performance with the Strict-PB map remained stable across cases, while performance with the LFshift-PB map improved with decreases in AID. CONCLUSIONS: Listeners demonstrated differences with the Strict-PB versus LFshift-PB maps as a function of AID and whether acoustic low-frequency information was available (CI vs. EAS). These data support the use of the Strict-PB mapping procedure for AIDs ≥335°, though further study including time for acclimatization in CI and EAS users is warranted.

iPSC-derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function.

Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases. Metabolomic surveys of patient populations and GWAS have linked MacTel to decreased circulating levels of serine and elevated levels of neurotoxic 1-deoxysphingolipids (1-dSLs). However, retina-specific, disease-contributing factors have yet to be identified. Here, we used iPSC-differentiated retinal pigmented epithelial (iRPE) cells derived from donors with or without MacTel to screen for novel cell-intrinsic pathological mechanisms. We show that MacTel iRPE cells mimicked the low serine levels observed in serum from patients with MacTel. Through RNA-Seq and gene set enrichment pathway analysis, we determined that MacTel iRPE cells are enriched in cellular stress pathways and dysregulation of central carbon metabolism. Using respirometry and mitochondrial stress testing, we functionally validated that MacTel iRPE cells had a reduction in mitochondrial function that was independent of defects in serine biosynthesis and 1-dSL accumulation. Thus, we identified phenotypes that may constitute alternative disease mechanisms beyond the known serine/sphingolipid pathway.

Sphingomonas paucimobilis Bacteremia in a Patient With Retropharyngeal Abscess.

Sphingomonas p aucimobilis is a nonfermenting gram-negative bacillus that is widely distributed in both community environments and hospitals. Various infections have been identified in humans, but most have been limited to case reports. When reported, it is most commonly nosocomial infections associated with contaminated hospital equipment such as indwelling catheters, ventilators, hemodialysis devices, and very rarely upper respiratory tract infections. We report an unusual presentation of S . paucimobilis infection. This case report describes a 59-year-old immunocompetent man who presented with a retropharyngeal abscess. Blood culture was positive for S . paucimobilis. The patient was treated for a total of 21 days of intravenous (IV) cefepime and oral (PO) metronidazole. He showed significant improvement and was discharged home with no medical sequelae.

A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis.

Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.