Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

Defects in Mating Behavior and Tail Morphology Are the Primary Cause of Sterility in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e Males at High Temperature

Reproduction is a fundamental imperative of all forms of life. For all the advantages sexual reproduction confers, it has a deeply conserved flaw: it is temperature sensitive. As temperatures rise, fertility decreases. Across species, male fertility is particularly sensitive to elevated temperature. Previously, we have shown in the model nematode Caenorhabditis elegans that all males are fertile at 20°C, but almost all males have lost fertility at 27°C. Male fertility is dependent on the production of functional sperm, successful mating and transfer of sperm, and successful fertilization post-mating. To determine how male fertility is impacted by elevated temperature, we analyzed these aspects of male reproduction at 27°C in three wild-type strains of C. elegans: JU1171, LKC34 and N2. We found no effect of elevated temperature on the number of immature non-motile spermatids formed. There was only a weak effect of elevated temperature on sperm activation. In stark contrast, there was a strong effect of elevated temperature on male mating behavior, male tail morphology and sperm transfer such that males very rarely completed mating successfully when exposed to 27°C. Therefore, we propose a model where elevated temperature reduces male fertility as a result of the negative impacts of temperature on the somatic tissues necessary for mating. Loss of successful mating at elevated temperature overrides any effects that temperature may have on the germline or sperm cells

An Atlas of Spectrophotometric Landolt Standard Stars

We present CCD observations of 102 Landolt standard stars obtained with the R-C spectrograph on the CTIO 1.5 m telescope. Using stellar atmosphere models we have extended the flux points to our six spectrophotometric secondary standards, in both the blue and the red, allowing us to produce flux-calibrated spectra that span a wavelength range from 3050 \AA to 1.1 \micron. Mean differences between UBVRI spectrophotometry computed using Bessell's standard passbands and Landolt's published photometry is found to be 1% or less. Observers in both hemispheres will find these spectra useful for flux-calibrating spectra and through the use of accurately constructed instrumental passbands be able to compute accurate corrections to bring instrumental magnitudes to any desired standard photometric system (S-corrections). In addition, by combining empirical and modeled spectra of the Sun, Sirius and Vega, we calculate and compare synthetic photometry to observed photometry taken from the literature for these three stars.Comment: Added referee's comments, minor corrections, replaced Table 1

Hygiene, Storage, and Waste Management for the Unsheltered Community: Gaps & Opportunities Analysis

This study, completed in early February 2022, included focus groups and interviews with 18 government employees and service providers, interviews with 19 people experiencing unsheltered homelessness, a review of research literature and news articles on the topic, and previous surveys and research from Portland State University to better understand gaps and opportunities in providing hygiene, storage and waste management to people living unsheltered

Differences in Breast Cancer Diagnosis and Treatment:Experiences of Insured and Uninsured Patients in a Safety Net Setting

To explore how well the safety net performs at eliminating differences in diagnosis and treatment of insured and uninsured women with breast cancer, we compared insured and uninsured women treated in a safety net setting. Controlling for socioeconomic characteristics, uninsured women are more likely to be diagnosed with advanced disease, requiring more extensive treatment relative to insured women, and also experience delays in initiating and completing treatment. The findings suggest that, despite the safety net system, uninsured women with breast cancer are likely to require more costly treatment and to have worse outcomes, relative to insured women with breast cancer.

Diabetes Insipidus in Mice with a Mutation in Aquaporin-2

Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2) gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2) gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI