Field Evaluation of Novel Spatial Repellent Controlled Release Devices (CRDs) against Mosquitoes in an Outdoor Setting in the Northern Peruvian Amazon.

U.S. military troops are exposed to mosquito-borne pathogens when deployed to endemic regions. Personal protective measures such as permethrin-treated uniforms and dermal repellents are the cornerstones of mosquito-borne disease prevention for the U.S. military. These measures have limitations and additional personal protection tools, such as spatial repellent devices to decrease the risk of vector-borne pathogen transmission, are required. Novel spatial repellent controlled-release devices formulated with metofluthrin were evaluated in an outdoor setting in the northern Amazon of Peru to evaluate performance under field conditions. The metofluthrin emitting devices lowered the number of mosquitoes captured in protected human landing collections (HLC) compared to blank devices, although there were effect differences between Anopheles spp. and species in other mosquito genera. A computational-experimental model was developed to correlate HLC and active ingredient (AI) concentrations as a function of time and space. Results show a strong correlation between the released AI and the decrease in HLC. This model represents the first effort to obtain a predictive analytical tool on device performance using HLC as the entomological endpoint.

Retraction notice to "Proof of concept efficacy study of intranasal stabilized isoamyl nitrite (SIAN) in Rhesus monkeys against acute cyanide poisoning" [Regul. Toxicol. Pharmacol. 123 (2021) 104927].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief as the authors were unable to provide documentation of approval for the interinstitutional assurance/vertebrate animal section of the paper by the relevant authority, Public Health Service (PHS) Office of Laboratory Animal Welfare (OLAW) in the time that was provided.

RETRACTED: Proof of concept efficacy study of intranasal stabilized isoamyl nitrite (SIAN) in rhesus monkeys against acute cyanide poisoning.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief as the authors were unable to provide documentation of approval for the interinstitutional assurance /vertebrate animal section of the paper by the relevant authority, Public Health Service (PHS) Office of Laboratory Animal Welfare (OLAW) in the time that was provided.

Correction to: Rapid reconstitution packages (RRPs) for stable storage and delivery of glucagon.

Following are updated Figs. 1, 3, 5, and 7. The original article has also been updated: Fig. 1 a RRP. b RRP dimensions. c RRP inside of syringe. Fig. 3 RRP activation and fluid flow.

A combined experimental-computational approach for spatial protection efficacy assessment of controlled release devices against mosquitoes (Anopheles).

This work describes the use of entomological studies combined with in silico models (computer simulations derived from numerical models) to assess the efficacy of a novel device for controlled release of spatial repellents. Controlled Release Devices (CRDs) were tested with different concentrations of metofluthrin and tested against An. quadrimaculatus mosquitoes using arm-in cage, semi-field, and outdoor studies. Arm-in-cage trials showed an approximate mean values for mosquito knockdown of 40% and mosquito bite reduction of 80% for the optimal metofluthrin formulation for a 15-minute trial. Semi-field outdoor studies showed a mean mortality of a 50% for 24 hour trial and 75% for a 48 hour trial for optimal concentrations. Outdoors studies showed an approximate mean mortality rate of 50% for a 24 hour trial for optimal concentrations. Numerical simulations based on Computational Fluid Dynamics (CFD) were performed in order to obtain spatial concentration profiles for 24 hour and 48 hour periods. Experimental results were correlated with simulation results in order to obtain a functional model that linked mosquito mortality with the estimated spatial concentration for a given period of time. Such correlation provides a powerful insight in predicting the effectiveness of the CRDs as a vector-control tool. While CRDs represent an alternative to current spatial repellent delivery methods, such as coils, candles, electric repellents, and passive emanators based on impregnated strips, the presented method can be applied to any spatial vector control treatment by correlating entomological endpoints, i.e. mortality, with in-silico simulations to predict overall efficacy. The presented work therefore presents a new methodology for improving design, development and deployment of vector-control tools to reduce transmission of vector-borne diseases, including malaria and dengue.

Rapid reconstitution packages (RRPs) for stable storage and delivery of glucagon.

Current emergency injectors of glucagon require manual reconstitution, which involves several steps that may lead to dosage errors. Rapid reconstitution packages (RRPs) are new devices, designed using computational fluid dynamics (CFD) to optimize fluid mixing, integrating physical properties of active pharmaceutical ingredients (APIs), excipients and diluents. RRPs improve drug stability for long-term storage and ease of delivery. Device prototypes were manufactured using advanced stereolithography apparatus (SLA) 3D printing technology. Reconstitution of glucagon with RRPs was evaluated by high-performance liquid chromatography (HPLC) and optical spectroscopy methods. Enzyme-linked immunosorbent assays were performed to test in vitro activity. Experimental results showed that RRPs effectively reconstituted glucagon even after exposure to 60 °C for a 24-h period. RRPs exhibited improved performance at maintaining drug stability compared to lyophilized glucagon stored in a standard glass vial under the same temperature conditions. RRPs represent a portable platform for rapid reconstitution of lyophilized drugs, compatible with standard syringes available in any clinical setting. The RRP provides an alternative to manual reconstitution process, especially designed for medical emergencies.

Controlled release spatial repellent devices (CRDs) as novel tools against malaria transmission: a semi-field study in Macha, Zambia.

BACKGROUND: The emergence of mosquitoes that can avoid indoor-deployed interventions, such as treated bed nets and indoor residual spraying, threatens the mainstay of malaria control in Zambia. Furthermore, the requirement for high coverage of these tools poses operational challenges. Spatial repellents are being assessed to supplement these vector control tools, but limitations exist in the residual effect of the repellent and the need for external power or heat for diffusion of the volatiles. METHODS: A semi-field evaluation of a novel controlled release spatial repellent device (CRD) was conducted in Macha, Zambia. These devices emanate metofluthrin with no need for external power. Devices were deployed in huts within the semi-field system (SFS). Female Anopheles gambiae sensu stricto released within the SFS were trapped overnight by light traps and collected by aspiration the next morning inside and outside of huts to determine the extent of mosquito repellency and the impact on host-seeking and survival. Experiments studied the impact of number of devices as well as the presence of hut occupants. The study was complemented with numerical methods based on computational fluid dynamics to simulate spatial distribution of metofluthrin. RESULTS: Presence of CRDs was associated with significant reductions in indoor counts of mosquitoes, regardless of whether huts were occupied or not. Repellency ranged from 15 to 60% compared to huts with no devices. Reducing the number of devices from 16 to 4 had little impact on repellency. When huts were occupied, indoor mosquito host-seeking was higher in the presence of CRDs, whilst survival was significantly reduced. CONCLUSIONS: This study demonstrated that deployment of as few as four CRDs within a hut was associated with reduced indoor mosquito densities. As would be expected, presence of occupants within huts, resulted in greater indoor catches (both with and without devices). The increased indoor mosquito host-seeking and mortality in huts when devices were present may be explained by the excito-repellency activity of metofluthrin. These semi-field experiments provide preliminary data on the utility of CRD spatial repellents to reduce indoor densities of An. gambiae mosquitoes. Studies will further investigate the impact of CRDs on mosquito behaviour as well as epidemiological protective efficacy.

Biokinetics and tissue response to ultrananocrystalline diamond nanoparticles employed as coating for biomedical devices.

Although Ultrananocrystalline diamond (UNCD) has been proposed as a coating material for titanium biomedical implants, the biological effects and toxicity of UNCD particles that could eventually detach have not been studied to date. The biokinetics and biological effects of UNCD compared to titanium dioxide (TiO2 ) nanoparticles was evaluated in vivo using Wistar rats (n = 30) i.p. injected with TiO2 , UNCD or saline solution. After 6 months, blood, lung, liver, and kidney samples were histologically analyzed. Oxidative damage by membrane lipidperoxidation (thiobarbituric acid reactive substances-TBARS), generation of reactive oxygen species (superoxide anion- O2-), and antioxidant enzymes (superoxide dismutase-SOD, catalase-CAT) was evaluated in lung and liver. Histologic observation showed agglomerates of TiO2 or UNCD in the parenchyma of the studied organs, though there were fewer UNCD than TiO2 deposits. In addition, TiO2 caused areas compatibles with foci of necrosis in the liver and renal hyaline cylinders. Regarding UNCD, no membrane damage (TBARS) or mobilization of enzymatic antioxidants was observed either in lung or liver samples. No variations in O2- generation were observed in lung (Co: 35.1 ± 4.02 vs. UNCD: 48 ± 9.1, p > 0.05). Conversely, TiO2 exposure caused production of O2- in alveolar macrophages and consumption of catalase (p < 0.05). The studied parameters suggest that UNCD caused neither biochemical nor histological alterations, and therefore may prove useful as a surface coating for biomedical implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2408-2415, 2017.

The use of micro-electro mechanical systems in vascular monitoring: implications for clinical use.

INTRODUCTION: BioMEMS relates to the implementation of Micro-Electro-Mechanical Systems (MEMS), in the biological and medical sphere. BioMEMS sensors are being utilized for many clinical applications, including a wireless urinary pressure system, right heart pressure sensor, and measurements on shearing force on the vascular system An important application of BioMEMS is on Heart failure (HF), a common disease, with a prevalence of 10% or more in persons 70 years of age or older, associated with high morbidity and mortality. HF affects over 5 million people and contributes to over 200,000 deaths a year in the United States alone. AREAS COVERED: The purpose of this paper is to provide a short overview on the successful implementation of BioMEMS sensors in heart failure and vascular medicine. Expert commentary: BioMEMS devices have overcome current limitations in pharmacotherapies for resistant hypertension by electrical modulation of the baroreceeptors. This represents a step towards the development of biomedical micro-devices for those conditions in which pharmacotherapies result poorly effective or elicit unacceptable toxicity.

The Use of Microdispensers with Spatial Repellents for Personal Protection Against Mosquito Biting.

Mosquito-borne pathogens affect millions of people worldwide. This work describes a new method to deliver spatial repellents. Functional microdispensers (FMDs) were designed to deliver spatial repellents against mosquitoes. In vivo trials showed that FMDs protect human subjects against mosquitoes by reducing 70­90% of bites received, with a protection that lasted up to 4 weeks. FMDs can be cost-effectively implemented as wearable or field-dispensed devices for local area protection, defined as a confined geographical region.

Functional Micro-Dispensers based on Micro-Electro-Mechanical-Systems (MEMS) integrated with fabrics as functional materials to protect humans from mosquito feeding.

Functional Micro-Dispensers (FMDs) based on Micro-Electro-Mechanical-Systems (MEMS) were designed to deliver spatial repellents that reduce the ability of mosquitoes to feed on humans. FMDs were integrated with fabrics as functional materials for protection against mosquito bites. The use of MEMS devices provides an unprecedented control over the release kinetics by means of integration with electronics for selective and timely activation of each device to perform controlled release of pesticides in air. In addition, because MEMS manufacturing techniques evolved from the microelectronic industry, FMDs can be mass produced at very low cost. Trials using FMDs that contained transfluthrin improved protection against mosquito feeding in human subjects above that of permethrin-treated uniform fabric worn on the arm of the volunteer. The overall reduction in feeding was approximately 90% compared to the untreated fabric control, and about 50% reduction compared to the permethrin-treated fabric control. The devices were efficacious over course of 32 days. FMDs have the potential for a simple and cost-effective implementation for mass adoption as wearable devices integrated in fabrics as active functional materials.

Clinical applications of biomedical microdevices for controlled drug delivery.

Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.

Prefilled devices for parenteral applications.

Current parenteral administration of drugs suffers from several drawbacks including the requirement of healthcare personnel to administer the drug, the risk of needle stick injuries that may result in the transmission of blood borne pathogens, and patient discomfort. Prefilled devices have emerged as powerful tools to improve parenteral administration of drugs. There are a number of clinical conditions including treatment of endocrine diseases, neurological disorders, autoimmune diseases and emergency medicine where prefilled devices have made major improvements to patient care. Prefilled devices have become an important set of tools for the medical practitioner due to their ease of use and safety, cost effectiveness and patient convenience. This review provides a comprehensive summary of existing prefilled devices, their current clinical uses and corresponding regulatory processes.