Golden Sails

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Liposomal Encapsulation of Amoxicillin via Microfluidics with Subsequent Investigation of the Significance of PEGylated Therapeutics

With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications. Particle sizes of circa. 130 nm, with viable short-term (28-day) physical stability were obtained, using two different non-cytotoxic liposomal formulations, both of which displayed suitable antibacterial efficacy. The microfluidic method allowed for high encapsulation efficiencies (≈77 %) and the subsequent in vitro release profile suggested high limits of antibiotic dissociation from the nanovessels, achieving 90% release within 72 h. In addition to the experimental data, the growing use of poly(ethylene) glycol (PEG) within lipid-based formulations is discussed in relation to anti-PEG antibodies, highlighting the key pharmacological differences between PEGylated and non-PEGylated formulations and their respective advantages and drawbacks. It's surmised that in the case of the formulations used in this study, the addition of PEG upon the liposomal membrane would still be a beneficial feature to possess owing to beneficial features such as stability, antibiotic efficacy and the capacity to further modify the liposomal membrane.</p

What motivates farmers to apply phosphorus at the “right” time? Survey evidence from the Western Lake Erie Basin

Phosphorus loadings from the Maumee River watershed have significantly compromised the Lake Erie ecosystem, as evidenced by the most severe harmful algal bloom in Lake Erie in 2015 and the shut-down of Toledo drinking water supply in 2014. Despite government payments for adoption of voluntary conservation practices, excess nutrient runoff from agricultural production remains a substantial challenge. The right timing of nutrient application is a critical best management practice (BMP). Using a unique survey of 2540 farmer respondents in the Maumee River watershed, this paper analyzes how socio-psychological, socio-demographic, and field-based spatial characteristics impact farmers\u27 adoption of timing-related best practices for nutrient management, including delaying broadcast application before a storm event, avoiding winter application of nutrients, and avoiding fall application of nutrients. Results reveal three unique classes of farmers for each of the timing-related management decisions. While the significance of most farmer and field characteristics varies across the three BMP adoption decisions, perceived efficacy—the belief that the particular practice will actually reduce dissolved phosphorus runoff from farm fields—is positively correlated with a higher likelihood of adopting each of the BMPs across almost all classes of farmers. For example, results from the ordered logit model suggest that a 20% increase in perceived efficacy would result in the likelihood of actual adoption of delaying broadcast from 35% to 48%. An implication is that policies and outreach efforts aimed at increasing farmers\u27 perceived efficacy of practices could lead to higher adoption levels, but the effectiveness may vary across different classes of farmers

How Americans Feel About Terrorism And Security: Two Years After 9/11

Understanding attitudes, concerns and reactions of individuals and families is critical to emergency planning efforts on all levels. In order to have effective implementation of a disaster plan, people need to be confident in (a) the reliability of information from official sources, (b) the capacity of government to perform effectively in a crisis and (c) the capability of response systems, particularly the health systems and first responders. Absence of confidence in response systems or leadership may undermine the best of crisis plans, leading to unnecessary panic and potential excess loss of life. In August 2003, The National Center for Disaster Preparedness at Columbia University's Mailman School of Public Health, in collaboration with The Children's Health Fund, commissioned the Marist Institute for Public Opinion to conduct a survey of adults nearly two years after the multiple terrorist attacks on New York, Washington, D.C. and Pennsylvania. The survey included both a national and a New York City representative sample of households contacted by telephone. Questions covered a wide range of issues including people's concern about potential new additional acts of terrorism in the U.S., the government's ability to protect citizens, and the health system's capacity to respond. Throughout, specific questions were asked of a subset of parents of children from four to eighteen years of age. To the extent possible, specific questions were replicated from four previous surveys commissioned by The Children's Health Fund since September 11, 2001 to identify trends in public attitudes and perceptions

<i>In vivo</i> gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation

AbstractTherapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis — the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available “self-delivery” modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and “self-delivery” siRNAs. Remarkably, a sustained >40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use

International Society for the Study of Women's Sexual Health (ISSWSH) review of epidemiology and pathophysiology, and a consensus nomenclature and process of care for the management of persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD)

Background Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. Aim To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. Methods A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. Outcomes The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed