Emergency egress for the elderly in care home fire situations

Practitioners are continuing to develop egress modelling software for the design of the built environment. These models require data about human behaviour and factors for calibration, validation and verification. This study aims to address the specific data and knowledge gap: emergency egress of the elderly. Such data are difficult to collect given privacy and consent concerns, with strong relationships generally being required between residences and researchers. Through the observation of nine fire drills at six Canadian long-term care (LTC) and retirement homes, specific evacuation actions and behaviour were observed for 37 staff members and information about the evacuation of 56 residents was collected. These drills demonstrated that emergency egress in LTC and retirement homes is highly staff dependent with 72% of residents recorded requiring full assistance at all stages of movement in evacuation, and that the type of announced/unannounced drill and level of resident care will affect the type of data collected. The development of travel speed and pre-movement is discussed subject to limitation with qualitative behavioural insights of residents that were observed. This study provides valuable methodological discussion on how to conduct behavioural studies in similar highly restricted research environments. Specific attention is given to understanding the considerations that must be made when using fire drills as data sources, and the impact that these can have on using such data for modelling. This study may inform the initial setup and programming of evacuation models from an actions and behavioural perspectives of staff members and residents.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Despite the approval of oncolytic virus (OV) therapy for advanced melanoma, its intrinsic limitations that include the risk of persistent viral infection and cost‐intensive manufacturing motivate the development of analogous approaches that are free from the disadvantages of virus‐based therapies. Herein, reported is a nanoassembly comprised of multivalent host–guest interactions between polymerized paclitaxel (pPTX) and nitric oxide‐incorporated polymerized β‐cyclodextrin (pCD‐pSNO) that through its bioactive components and when used locoregionally recapitulates the therapeutic effects of OV. The resultant pPTX/pCD‐pSNO exhibits significantly enhanced cytotoxicity, immunogenic cell death, dendritic cell (DC) activation, and T cell expansion in vitro compared to free agents alone or in combination. In vivo, intratumoral administration of pPTX/pCD‐pSNO results in activation and expansion of DCs systemically, but with a corresponding expansion of myeloid‐derived suppressor cells and suppression of CD8⁺ T cell expansion. When combined with antibody targeting cytotoxic T lymphocyte antigen‐4 that blunts this molecule's signaling effects on T cells, intratumoral pPTX/pCD‐pSNO treatment elicits potent anticancer effects that significantly prolong animal survival. This formulation thus leverages the chemo‐ and immunotherapeutic synergies of PTX and nitric oxide and suggests the potential for virus‐free nanoformulations to mimic the therapeutic action and benefits of OVs.     

Utilizing TiO2 amorphous precursors for polymorph selection: An in situ TEM study of phase formation and kinetics

Selective synthesis of metastable polymorphs requires a fundamental understanding of the complex energy landscapes in which these phases form. Recently, the development of in situ high temperature and controlled atmosphere transmission electron microscopy has enabled the direct observation of nucleation, growth, and phase transformations with near atomic resolution. In this work, we directly observe the crystallization behavior of amorphous TiO₂ thin films grown under different pulsed laser deposition conditions and quantify the mechanisms behind metastable crystalline polymorph stabilization. Films deposited at 10 mTorr chamber oxygen pressure crystallize into nanocrystalline Anatase at 325°C, whereas films deposited at 2 mTorr crystallize into significantly larger needle-like grains of Brookite and Anatase at 270°C. Increasing film deposition rate by a factor of 4 results in a 10× increase in the crystalline growth front velocity as well as a decrease in crystallization temperature from 270°C to 225°C. Engineering the amorphous precursor state through deposition conditions therefore provides routes to microstructure control and the accessibility of higher energy metastable phases.     

Field Performance of High Oleic Soybeans with Mutant FAD2-1A and FAD2-1B Genes in Tennessee

Soybean [Glycine max (L.) Merr.] oil with high oleic acid (>75%) has increased oxidative stability and health benefits that are valuable for food, fuel, and industrial products. It has been determined that two naturally occurring mutations in genes FAD2-1A and FAD2-1B can combine to produce high oleic soybeans. The objective of this study was to test the effect of these mutant alleles on seed yield and oil and protein concentration. Molecular markers assisted in the creation of a population of 48 BC₃F_2:4 lines (93.75% expected genome commonality). Each line was classified into one of four genotypic groups where both FAD2-1A and FAD2-1B genes were either homozygous wild type or mutant, respectively. Twelve lines for each genotypic group were evaluated in three replications at six locations across Tennessee. There was no seed yield difference between the high oleic genotypic group and the other groups (P < 0.05). On the other hand, there were differences in fatty acid profiles and oil and protein concentrations. In combination, the mutant FAD2-1A and FAD2-1B alleles produced a mean of 803.1 g kg⁻¹ oleic acid. This is, on average, approximately 500 g kg⁻¹ more oleic acid compared to soybean lines with only one mutant FAD2-1 allele. The high oleic double mutant group had more total oil (228.0 g kg⁻¹) and protein (401.0 g kg⁻¹) compared to all other genotypic groups (P < 0.05). Overall, this specific combination of mutant FAD2-1A and FAD2-1B alleles appears to generate conventional high oleic soybeans without a yield drag.     

Design Principles for Cationic,Astrocyte-Targeted Probes

The brain's astrocytes play key roles in normal and pathological brain processes. Targeting small molecules to astrocytes in the presence of the many other cell types in the brain will provide useful tools for their visualization and manipulation. Herein, we explore the functional consequences of synthetic modifications to a recently described astrocyte marker composed of a bright rhodamine-based fluorophore and an astrocyte-targeting moiety. We altered the nature of the targeting moiety to probe the dependence of astrocyte targeting on hydrophobicity, charge, and pK_a when exposed to astrocytes and neurons isolated from the mouse cortex. We found that an overall molecular charge of +2 and a targeting moiety with a heterocyclic aromatic amine are important requirements for specific and robust astrocyte labeling. These results provide a basis for engineering astrocyte-targeted molecular tools with unique properties, including metabolite sensing or optogenetic control.     

Biocompatible electrospun tactic poly(methyl methacrylate) blend fibers

Uniform and beads free fibers of pristine syndiotactic PMMA (s-PMMA), isotactic PMMA (i-PMMA), and their blends in the ratio of s:i = 3:1, 1:1 and 1:3 were successfully prepared using the electrospinning technique. The tactic PMMA blend fibers showed unique thermal stability and glass transition temperatures compared to their pristine counterparts. An interesting endotherm peak was observed for the s:i = 1:3 electrospun fibers, which might indicate a complex formation between the two tactic PMMAs. Systematic surface functionalities study by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) revealed the interactions between these two tactic PMMAs. Biocompatibility of tactic PMMA and their blend fibers was first time comparably investigated using HeLa as the model mammalian cell line; an intriguing observance was first revealed that the blend fibers showed better biocompatibility than both pristine ones, though the behind mechanism is not well understood yet.