Assessment of chronic wounds using in vivo diffuse near infrared spectroscopy

Chronic wounds are an increasing challenge as the population ages and the prevalence of obesity and diabetes increase in the U.S. and throughout the world. As the number and cost of treatments for chronic wounds increases, the importance of assessing the effectiveness of new therapies becomes critical. Current clinical methods for wound assessment rely on qualitative assessment of wound surface appearance and measurements of wound surface dimensions, but do not take the health of underlying tissue into account. The goal of this research is to develop a non-invasive method of assessing and predicting chronic wound healing using in vivo frequency-domain diffuse near infrared spectroscopy (DNIRS). The main hypothesis behind this research is that changes in blood vessel density and oxygen delivery beneath the surface of a wound can be measured using DNIRS. Furthermore, these changes could be used to quantitatively assess the healing status of a chronic wound and predict faster and more accurately than current clinical methods whether a wound treatment is working.The results of a study of twenty-eight human diabetic foot ulcers shows that changes in oxy- and total hemoglobin concentration measured with DNIRS can be used to differentiate healing from non-healing wounds, and the capability of DNIRS wound monitoring to predict healing in diabetic foot ulcers is examined. Additionally, data obtained from a study of impaired wound healing in obese rats demonstrate that DNIRS can be used to assess wound healing in an animal model, and a model for expected changes in DNIRS measurements of oxy- and deoxyhemoglobin concentration during wound healing is proposed. Wound size data obtained from this animal study show that obese rats may provide a better model of impaired healing than the chemically-induced diabetic rats which are often used by researchers when assessing novel wound therapies.Ph.D., Biomedical Engineering -- Drexel University, 201

Gene expression changes in therapeutic ultrasound-treated venous leg ulcers

IntroductionLow-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms.MethodsDebrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly differentially expressed between the ultrasound and sham groups using cut-off values of p < 0.05 and fold change of 2.Results and DiscussionThe top differentially expressed genes included those involved in regulation of cell metabolism, proliferation, and immune cell signaling. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cell-cell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as 1 week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life

Chitosan nanoparticles for nitric oxide delivery in human skin

The use of nanoparticle-based transdermal delivery systems is a promising approach to efficiently carry and deliver therapeutic agents for dermal and systemic administration. Nitric oxide (NO) is a key molecule that plays important roles in human skin such as the control of skin homeostasis, skin defense, control of dermal blood flow, and wound healing. In addition, human skin contains stores of NO derivatives that can be mobilized and release free NO upon UV irradiation with beneficial cardiovascular effects, for instance the control of blood pressure. In this work, the NO donor precursor glutathione (GSH) was encapsulated (encapsulation efficiency of 99.60%) into ultra-small chitosan nanoparticles (CS NPs) (hydrodynamic size of 30.65 +/- 11.90 nm). GSH-CS NPs have a core-shell structure, as revealed by atomic force microscopy and X-ray photoelectron spectroscopy, in which GSH is protected in the nanoparticle core. Nitrosation of GSH by nitrous acid led to the formation of the NO donor S-nitrosogluthathione (GSNO) into CS NPs. The GSNO release from the CS NPs followed a Fickian diffusion described by the Higuchi mathematical model. Topical application of GSNO-CS NPs in intact human skin significantly increased the levels of NO and its derivatives in the epidermis, as assayed by confocal microscopy, and this effect was further enhanced by skin irradiation with UV light. Therefore, NO-releasing CS NPs are suitable materials for transdermal NO delivery to local and/or systemic therapies.FAPESP [2015/00393-8, 2016/10347-6]Brazilian Network on Nanotoxicology (MCTI/CNPq) [552120/2011-1]Laboratory of Nanostructure Synthesis and Biosystem InteractionsNANOBIOSS (MCTI) [402280-2013]Newton Advanced Fellowship (The Royal Society) [NA140046]Univ Fed Sao Paulo, Exact & Earth Sci Dept, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilUniv Fed ABC, Ctr Nat & Human Sci, Av Estados 5001, BR-09210580 Santo Andre, SP, BrazilUniv Edinburgh, Queens Med Res Inst, MRC, Ctr Inflammat Res, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, ScotlandNatl Ctr Energy & Mat CNPEM, Natl Nanotechnol Lab LNNano, Rua Giuseppe Maximo Scolfaro 10-000, BR-13083970 Campinas, SP, BrazilUniv Fed Sao Paulo, Exact & Earth Sci Dept, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilWeb of Scienc

Software engineering basics: a primer for the project manager

A key to any software development project is the presence of technically proficient management. The discipline of software Engineering offers many different tools and techniques to aid the project manager in the development of quality software. This thesis provides an overview of this discipline, including its goals and underlying theoretical concepts. A discussion of specific tools and techniques that are applicable throughout the life cycle is included. Recognizing that the maintainability of the software is a primary consideration of any development project, two methods of measuring software for this important attribute are examined. Among the conclusions is that there exists a need for further research necessary in order to validate the utility of the tools and techniques of Software Engineering in large scale applications.http://archive.org/details/softwareengineer00artzLieutenant, United States NavyApproved for public release; distribution is unlimited

Prostate Cryosurgery with Various Numbers of Probes

No access to the full paper due to lack of a FERPA release.Cryosurgery is an increasingly popular way to treat prostate cancer. This process includes inserting one or more probes directly into the prostate to freeze the whole tissue and kill the cancer cells. The number of probes is a determining factor for the effectiveness of the procedure. In our project, we varied the number of probes to see how much of the prostate is frozen in twenty minutes. We used an argon cryogen system with probe temperature of -150oC. Using FIDAP to model the freezing of the prostate, we looked at the temperature data of nodes 2 cm away from the center of the prostate after 20 minutes. For the 1 probe model, the average temperature of the tissue was 25.76 deg C, for the 3 probe the average was 1.05 deg C and for the 5 probe, -16.97 deg C. From these results, it is evident that 1 probe is insufficient for prostate freezing since the temperature only went from 35oC to 25oC in twenty minutes, a mere 10 degree change. Even three probes will be inefficient for prostate freezing since it was twenty degrees away from reaching the optimal temperature of -20oC. We recommend using 5 probes for prostate freezing and looking into using even more probes for more time-efficient freezing. A colder cryogen would also lead to faster cooling. Our model used an argon system; liquid nitrogen with temperature -196oC could be a better alternative