Human indoor climate preferences approximate specific geographies

Root mean square error analysis (between indoor and outdoor climates) and results for temperature and vapor pressur

Aminoglycosides Rapidly Inhibit NAD(P)H Metabolism Increasing Reactive Oxygen Species and Cochlear Cell Demise

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in all cell types. At the same time point, GM significantly increased manganese superoxide dismutase (MnSOD) levels while significantly decreasing copper/zinc superoxide dismutase (CuZnSOD) in cochlear sensory cells. This suggests (1) a rapid conversion of highly reactive O2·- to H2O2 during the acute stage of ototoxic antibiotic exposure and (2) that the endogenous antioxidant system is significantly altered by AGs. Fluorescence intensity-based measurements of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and mitochondrial membrane potential were measured to determine if increases in GM-induced ROS production were correlated with changes in mitochondrial metabolism. This project provides a basis for understanding the mechanisms of mitochondrial ROS production in cochlear cells exposed to ototoxic antibiotics. Understanding the nature of ototoxic antibiotic-induced changes in mitochondrial metabolism is critical for developing hearing loss treatment and prevention strategies

Gentamicin Differentially Alters Cellular Metabolism of Cochlear Hair Cells as Revealed by NAD(P)H Fluorescence Lifetime Imaging

Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs

eHealth Education and Support for Pediatric Hearing Aid Management: Parent Goals, Questions and Challenges

Purpose: To investigate parent goals, questions, and challenges that emerged during coaching phone calls in an eHealth program designed to provide education and support for hearing aid management. Methods: Coaching phone calls were audio-recorded, transcribed and qualitatively analyzed for emergent themes within the categories of goals, questions, and challenges. Results: Emergent themes revealed parent goals were focused on self-efficacy, routines, device care and child development. Emergent themes for questions revealed parents asked questions related to the device care, audiology appointments, confirmation of learning, and child development. For challenges emergent themes revealed parents’ own struggles (e.g., with emotions), issues related to working with their audiologist, child factors and anticipated challenges. Conclusion: The eHealth intervention allowed parents to raise questions and discuss their challenges in a supportive environment. Supportive accountability helped participants identify and address barriers to hearing aid management based on their priorities and current challenges. Providing supplemental learning support, in addition to routine audiology visits, can help parents develop more effective hearing aid management routines

Implementing Extended-Infusion Cefepime as Standard of Care in a Children’s Hospital: A Prospective Descriptive Study

Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children. Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population. Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children’s hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, operating, or emergency department areas. Demographic and clinical data for patients who received cefepime from April through August 2013, the period following EIC implementation, were extracted from the medical records. Results: A total of 150 patients were included in the study, with a median age (interquartile range [IQR]) of 6 years (2-12.3 years) and median weight (IQR) of 20.7 kg (13.2-42.8 kg); 143 patients received cefepime via extended infusions, and 10 (7.0%) of those were changed to a 30-minute infusion during treatment. The most common reasons for infusion time change were intravenous (IV) incompatibility and IV access concerns, responsible for 50% of changes. Dosing errors and reported incidents during therapy were sparse (n = 12, 8.0%) and were most commonly related to renal dosing errors and/or initial dose error by prescriber. Conclusions: Because 93.0% of the patients who initially received EIC remained on EIC, implementation of EIC as the standard dosing strategy was feasible in this pediatric hospital

Commercialisation and Impacts of Pasture Legumes in Southern Australia–Lessons Learnt

Forage legumes are a key feature of temperate grasslands in southern Australia, valued for their ability to increase animal production, improve soil fertility and fix atmospheric nitrogen. Of the 36 temperate annual legume and 11 temperate perennial legume species with registered cultivars introduced or domesticated in Australia over the last 100 years, a third have made a major contribution to agriculture, a third have modest use and a third have failed to make any commercial impact. Highly successful species include subterranean clover, barrel medic, white clover, lucerne, French serradella and balansa clover. Species were assessed on the scale of their application, ease of seed production and specific requirements for agronomic management to determine critical factors for maximising commercial success. Of fundamental importance is the need to understand the farming systems context for legume technologies, particularly as it relates to potential scale of application and impact on farm profitability. Other factors included a requirement for parallel investment in rhizobiology, implementing an adequate ‘duty of care’ problem-solving framework for each new plant product and the need to construct a commercialisation model that optimises the trade-off between rapid adoption by farmers and profitability of the seed industry. Our experience to date indicates that seed industry engagement is highest when they have exclusive rights to a cultivar, can exercise some control over seed production and can market seed for a premium price without having to carry over significant seed quantities from one season to the next. A capability for non-specialist seed production on-farm (with lower associated seed costs) is a disincentive for the seed industry, but may be an appropriate commercialisation model for some public cultivars

Do RARA/PML fusion gene deletions confer resistance to ATRA-based therapy in patients with acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) is characterized by the translocation t(15;17)(q22;q21), resulting in the promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) fusion protein in 95% cases whereas variant translocations involving PLZF (11q23), NPM (5q35), NUMA (11q13) and STAT5b (17q23) account for the rest. Leukemias with PML-RARA translocations respond well to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) therapy whereas those with PLZF-RARA fusions respond poorly. Although primary resistance to ATRA is rare, secondary or acquired resistance is frequently observed in patients treated with ATRA alone or in combination with other chemotherapy regimens. However, molecular abnormalities mediating resistance to ATRA therapy are underexplored. Here, we report two cases of APL with RARA-PML deletions on der(17) or der(15), which displayed clinical evidence of primary and secondary resistance to therapy, respectively

Ultrasmall Mixed Eu−Gd Oxide Nanoparticles for Multimodal Fluorescence and Magnetic Resonance Imaging of Passive Accumulation and Retention in TBI

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBI can have a long-term impact on the quality of life for survivors of all ages. However, there remains no approved treatment that improves outcomes following TBI, which is partially due to poor delivery of therapies into the brain. Therefore, there is a significant unmet need to develop more effective delivery strategies that increase the accumulation and retention of potentially efficacious treatments in the injured brain. Recent work has revealed that nanoparticles (NPs) may offer a promising approach for site-specific delivery; however, a detailed understanding of the specific NP properties that promote brain accumulation and retention are still being developed. Multimodal imaging plays a vital role in the understanding of physicochemical properties that initiate the uptake and accumulation of NPs in the brain at both high spatial (e.g., fluorescence imaging) and temporal (e.g., magnetic resonance imaging, MRI) frequency. However, many NP systems that are currently used in TBI only provide contrast in a single imaging modality limiting the imaging data that can be obtained, and those that offer multimodal imaging capabilities have complicated multistep synthesis methods. Therefore, the goal of this work was to develop an ultrasmall NP with simple fabrication capable of multimodal imaging. Here, we describe the development, characterization, accumulation, and retention of poly(ethylene glycol) (PEG)-coated europium−gadolinium (Eu−Gd) mixed magnetic NPs (MNPs) in a controlled cortical impact mouse model of TBI. We find that these NPs having an ultrasmall core size of 2 nm and a small hydrodynamic size of 13.5 nm can be detected in both fluorescence and MR imaging modalities and rapidly accumulate and are retained in injured brain parenchyma. These NPs should allow for further testing of NP physicochemical properties that promote accumulation and retention in TBI and other disease models