The Art and Science of Learning, Teaching, and Delivering Feedback in Psychosomatic Medicine.

PubMed

Lokko, Hermioni N; Gatchel, Jennifer R; Becker, Madeleine A; Stern, Theodore A

2016-01-01

The teaching and learning of psychosomatic medicine has evolved with the better understanding of effective teaching methods and feedback delivery in medicine and psychiatry. We sought to review the variety of teaching methods used in psychosomatic medicine, to present principles of adult learning (and how these theories can be applied to students of psychosomatic medicine), and to discuss the role of effective feedback delivery in the process of teaching and learning psychosomatic medicine. In addition to drawing on the clinical and teaching experiences of the authors of the paper, we reviewed the literature on teaching methods, adult learning theories, and effective feedback delivery methods in medicine to draw parallels for psychosomatic medicine education. We provide a review of teaching methods that have been employed to teach psychosomatic medicine over the past few decades. We outline examples of educational methods using the affective, behavioral, and cognitive domains. We provide examples of learning styles together with the principles of adult learning theory and how they can be applied to psychosomatic medicine learners. We discuss barriers to feedback delivery and offer suggestions as to how to give feedback to trainees on a psychosomatic medicine service. The art of teaching psychosomatic medicine is dynamic and will continue to evolve with advances in the field. Psychosomatic medicine educators must familiarize themselves with learning domains, learning styles, and principles of adult learning in order to be impactful. Effective feedback delivery methods are critical to fostering a robust learning environment for psychosomatic medicine. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Advances in fish vaccine delivery.

PubMed

Plant, Karen P; Lapatra, Scott E

2011-12-01

Disease prevention is essential to the continued development of aquaculture around the world. Vaccination is the most effective method of combating disease and currently there are a number of vaccines commercially available for use in fish. The majority of aquatic vaccines are delivered by injection, which is by far the most effective method when compared to oral or immersion deliveries. However it is labor intensive, costly and not feasible for large numbers of fish under 20 g. Attempts to develop novel oral and immersion delivery methods have resulted in varying degrees of success but may have great potential for the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing.

PubMed

Lu, Ruirui; Schmidtko, Achim

2013-01-01

Intrathecal delivery of drugs is an important method in pain research in order to investigate pain-relevant effects in the spinal cord in vivo. Here, we describe a method of intrathecal drug delivery by direct lumbar puncture in mice. The procedure does not require surgery, is rapidly performed, and does not produce neurological deficits. If cGMP analogs are injected, a state of transient hindpaw hypersensitivity can be induced which is quantifiable by measurement of hindpaw withdrawal latency in response to mechanical stimulation.

Synthesis of PLGA-Lipid Hybrid Nanoparticles for siRNA Delivery Using the Emulsion Method PLGA-PEG-Lipid Nanoparticles for siRNA Delivery.

PubMed

Wang, Lei; Griffel, Benjamin; Xu, Xiaoyang

2017-01-01

The effective delivery of small interfering RNA (siRNA) to tumor cells remains a challenge for applications in cancer therapy. The development of polymeric nanoparticles with high siRNA loading efficacy has shown great potential for cancer targets. Double emulsion solvent evaporation technique is a useful tool for encapsulation of hydrophilic molecules (e.g., siRNA). Here we describe a versatile platform for siRNA delivery based on PLGA-PEG-cationic lipid nanoparticles by using the double emulsion method. The resulting nanoparticles show high encapsulation efficiency for siRNA (up to 90%) and demonstrate effective downregulation of the target genes in vitro and vivo.

The Effects of Consequence Manipulation during Functional Analysis of Problem Behavior Maintained by Negative Reinforcement

ERIC Educational Resources Information Center

Potoczak, Kathryn; Carr, James E.; Michael, Jack

2007-01-01

Two distinct analytic methods have been used to identify the function of problem behavior. The antecedent-behavior-consequence (ABC) method (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) includes the delivery of consequences for problem behavior. The AB method (Carr & Durand, 1985) does not include consequence delivery, instead relying…

Development of a modified in vitro skin absorption method to study the epidermal/dermal disposition of a contact allergen in human skin.

PubMed

Pendlington, Ruth U; Minter, Helen J; Stupart, Leanne; MacKay, Cameron; Roper, Clive S; Sanders, David J; Pease, Camilla K

2008-01-01

In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

PubMed Central

Vieira, Débora B; Gamarra, Lionel F

2016-01-01

This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered. PMID:27799765

Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier.

PubMed

Vieira, Débora B; Gamarra, Lionel F

This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

Effects of Cesarean delivery and formula supplementation on the intestinal microbiome of six-week old infants

PubMed Central

Madan, Juliette C.; Hoen, Anne G.; Lundgren, Sara N.; Farzan, Shohreh F.; Cottingham, Kathryn L.; Morrison, Hilary G.; Sogin, Mitchell L.; Li, Hongzhe; Moore, Jason H.; Karagas, Margaret R.

2016-01-01

Importance The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breastmilk vs. formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula fed infants, with little consideration given to combination feeding of both breastmilk and formula. Objectives To examine the relative effects of delivery mode and feeding method on infant intestinal microbiome composition at approximately six weeks of life. Design, Setting and Participants Prospective observational study of 102 infants followed as part of a US pregnancy cohort study. Exposures Delivery mode was abstracted from delivery medical records and feeding method prior to the time of stool collection was ascertained through detailed questionnaires. Main Outcomes and Measures Stool microbiome composition was characterized using next-generation sequencing of the 16S rRNA gene. Results We identified independent associations between microbial community composition and both delivery mode and feeding method. Differences in microbial community composition between vaginally and infants delivered by Cesarean section were equivalent to or significantly larger than those between feeding groups. Bacterial communities associated with combination feeding were more similar to those associated with exclusive formula feeding than exclusive breastfeeding. We identified individual bacterial genera that were differentially abundant between delivery mode and feeding groups. Conclusions and Relevance The infant intestinal microbiome at approximately six weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breastmilk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities. PMID:26752321

Latent cytokines for targeted therapy of inflammatory disorders.

PubMed

Mullen, Lisa; Adams, Gill; Layward, Lorna; Vessillier, Sandrine; Annenkov, Alex; Mittal, Gayatri; Rigby, Anne; Sclanders, Michelle; Baker, David; Gould, David; Chernajovsky, Yuti

2014-01-01

The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules. A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed. Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas.

PubMed

Saito, Ryuta; Tominaga, Teiji

2017-01-15

Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future.

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas

PubMed Central

SAITO, Ryuta; TOMINAGA, Teiji

2017-01-01

Convection-enhanced delivery (CED) circumvents the blood–brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future. PMID:27980285

A Comparison of Vaginal Pressures and Abdominal Muscle Thickness According to Childbirth Delivery Method during the Valsalva Maneuver

PubMed Central

Kim, Haroo; Kak, Hwang-Bo; Kim, Boin

2014-01-01

[Purpose] The purpose of this study was to compare the effect of childbirth delivery method on vaginal pressure and abdominal thickness during the Valsalva maneuver (VAL). [Subjects] Thirty healthy female volunteers (26–39 years of age) were selected for this research. Their delivery histories were: nulliparous 10, vaginal delivery 10, and Cesarean delivery 10. None of the participants had a history of incontinence. [Methods] In the crook-lying position, a perineometer probe was inserted into the vagina and the transducer was placed transversely on the right side of the body during the Valsalva maneuver. [Results] There were significant differences in the thickness of the transverses abdominis (TrA) between in all the groups rest and the Valsalva maneuver, and there were significant differences in the internus oblique (IO) in the nulliparous group. During the Valsalva maneuver, there were significant differences in the TrA between the nulliparous group and the vaginal delivery group, and there were significant differences in the IO between the nulliparous delivery group and the vaginal delivery group, and between the nulliparous group and the Cesarean section group. Delivery history changed vaginal pressure, and there were significant differences between the nulliparous group and the vaginal delivery group, and between the nulliparous group and the Cesarean delivery group. [Conclusion] Pregnancy and delivery method may affect pelvic floor and abdominal muscles during the Valsalva maneuver. PMID:24707104

Liposome-based drug co-delivery systems in cancer cells.

PubMed

Zununi Vahed, Sepideh; Salehi, Roya; Davaran, Soodabeh; Sharifi, Simin

2017-02-01

Combination therapy and nanotechnology offer a promising therapeutic method in cancer treatment. By improving drug's pharmacokinetics, nanoparticulate systems increase the drug's therapeutic effects while decreasing its adverse side effects related to high dosage. Liposomes are extensively used as drug delivery systems and several liposomal nanomedicines have been approved for clinical applications. In this regard, liposome-based combination chemotherapy (LCC) opens a novel avenue in drug delivery research and has increasingly become a significant approach in clinical cancer treatment. This review paper focuses on LCC strategies including co-delivery of: two chemotherapeutic drugs, chemotherapeutic agent with anti-cancer metals, and chemotherapeutic agent with gene agents and ligand-targeted liposome for co-delivery of chemotherapeutic agents. Definitely, the multidisciplinary method may help improve the efficacy of cancer therapy. An extensive literature review was performed mainly using PubMed. Copyright © 2016 Elsevier B.V. All rights reserved.

Determining the Effectiveness of Various Delivery Methods in an Information Technology/Information Systems Curriculum

ERIC Educational Resources Information Center

Davis, Gary Alan; Kovacs, Paul J.; Scarpino, John; Turchek, John C.

2010-01-01

The emergence of increasingly sophisticated communication technologies and the media-rich extensions of the World Wide Web have prompted universities to use alternatives to the traditional classroom teaching and learning methods. This demand for alternative delivery methods has led to the development of a wide range of eLearning techniques.…

Pharmacokinetics of orally administered DL-α-lipoic acid in dogs.

PubMed

Zicker, Steven C; Avila, Albert; Joshi, Dinesh K; Gross, Kathy L

2010-11-01

To determine the pharmacokinetics of DL-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. 27 clinically normal Beagles. In a 3 × 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. Values for pharmacokinetic parameters of orally administered DL-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status.

Transdermal Delivery of Functional Collagen Via Polyvinylpyrrolidone Microneedles

PubMed Central

Sun, Wenchao; Inayathullah, Mohammed; Manoukian, Martin A. C.; Malkovskiy, Andrey V.; Manickam, Sathish; Marinkovich, M. Peter; Lane, Alfred T.; Tayebi, Lobat; Seifalian, Alexander M.; Rajadas, Jayakumar

2017-01-01

Collagen makes up a large proportion of the human body, particularly the skin. As the body ages, collagen content decreases, resulting in wrinkled skin and decreased wound healing capabilities. This paper presents a method of delivering type I collagen into porcine and human skin utilizing a polyvinylpyrrolidone microneedle delivery system. The microneedle patches were made with concentrations of 1, 2, 4, and 8% type I collagen (w/w). Microneedle structures and the distribution of collagen were characterized using scanning electron microscopy and confocal microscopy. Patches were then applied on the porcine and human skin, and their effectiveness was examined using fluorescence microscopy. The results illustrate that this microneedle delivery system is effective in delivering collagen I into the epidermis and dermis of porcine and human skin. Since the technique presented in this paper is quick, safe, effective and easy, it can be considered as a new collagen delivery method for cosmetic and therapeutic applications. PMID:26066056

Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

PubMed

Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

2015-01-01

Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

Introduction strategies raise key questions.

PubMed

Finger, W R; Keller, S

1995-09-01

Key issues that must be considered before a new contraceptive is introduced center on the need for a trained provider to begin or terminate the method, its side effects, duration of use, method's ability to meet users' needs and preferences, and extra training or staff requirements. Logistics and economic issues to consider are identifying a dependable way of effectively supplying commodities, planning extra services needed for the method, and cost of providing the method. Each contraceptive method presents a different side effect pattern and burdens the service delivery setting differently. The strategy developed to introduce or expand the 3-month injectable Depo-Provera (DMPA) can be used for any method. It includes a needs assessment and addresses regulatory issues, service delivery policies and procedures, information and training, evaluation, and other concerns. Viet Nam's needs assessment showed that Norplant should not be introduced until the service delivery system becomes stronger. Any needs assessment for expansion of contraceptive services should cover sexually transmitted disease/HIV issues. A World Health Organization strategy helps officials identify the best method mix for local situations. Introductory strategies must aim to improve the quality of family planning programs and expand choices. Many begin by examining existing data and conducting interviews with policymakers, users, providers, and women's health advocates. Introductory programs for Norplant focus on provider training, adequate counseling and informed consent for users, and ready access to removal. They need a well-prepared service delivery infrastructure. The first phase of the DMPA introductory strategy for the Philippines comprised a social marketing campaign and DMPA introduction at public clinics in 10 pilot areas with strong service delivery. Successful AIDS prevention programs show that people tend to use barrier methods when they are available. USAID is currently studying whether or not women in developing countries will use the female condom.

Constructive Student Feedback: Online vs. Traditional Course Evaluations

ERIC Educational Resources Information Center

Donovan, Judy; Mader, Cynthia E.; Shinsky, John

2010-01-01

Substantial efforts have been made recently to compare the effectiveness of traditional course formats to alternative formats (most often, online delivery compared to traditional on-site delivery). This study examines, not the delivery format but rather the evaluation format. It compares traditional paper and pencil methods for course evaluation…

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis.

PubMed

Zha, Lisha; He, Lichun; Xie, Weidong; Cheng, Jin; Li, Tong; Mohsen, Mona O; Lei, Fan; Storni, Federico; Bachmann, Martin; Chen, Hongquan; Zhang, Yaou

2017-01-01

Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo.

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis

PubMed Central

Xie, Weidong; Cheng, Jin; Li, Tong; Mohsen, Mona O.; Lei, Fan; Storni, Federico; Bachmann, Martin; Chen, Hongquan; Zhang, Yaou

2017-01-01

Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo. PMID:28562667

Delivery by Cesarean Section is not Associated With Decreased at-Birth Fracture Rates in Osteogenesis Imperfecta

PubMed Central

Bellur, S; Jain, M; Cuthbertson, D; Krakow, D; Shapiro, JR; Steiner, RD; Smith, PA; Bober, MB; Hart, T; Krischer, J; Mullins, M; Byers, PH; Pepin, M; Durigova, M; Glorieux, FH; Rauch, F; Sutton, VR; Lee, B; Nagamani, SC

2015-01-01

Purpose Osteogenesis imperfecta (OI) predisposes to recurrent fractures. The moderate-to-severe forms of OI present with antenatal fractures and the mode of delivery that would be safest for the fetus is not known. Methods We conducted systematic analyses on the largest cohort of individuals (n=540) with OI enrolled to-date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared in individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates including method of delivery on fracture-related outcomes. Results When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean section (CS). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CS for delivery. Conclusion Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI shows that delivery by CS is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CS should be performed only for other maternal or fetal indications, but not for the sole purpose of fracture prevention in OI. PMID:26426884

Ultraviolet, visible, and infrared laser delivery using laser-to-fiber coupling via a grazing-incidence-based hollow taper

NASA Astrophysics Data System (ADS)

Ilev, Ilko K.; Waynant, Ronald W.

2001-01-01

We present a novel all-optical-waveguide method for ultraviolet (UV), visible (VIS) and infrared (IR) laser delivery including a lens-free method of laser-to-fiber coupling using a simple uncoated glass hollow taper. Based on the grazing incidence effect, the hollow taper provides a way of direct launching, without any intermediate focusing elements, high power laser radiation into delivery fibers. Because of the mutual action of the nearly parallel laser excitation, the mode coupling process, and mode filtering effect, the hollow taper serves as a mode converter that transforms the highly multimode profile of the input laser emission into a high-quality Gaussian-shaped profile at the taper output. When the grazing incidence effect of the taper is applied to laser delivery, the maintenance of high reflectance coefficients in a wide spectral region allows to utilize the same uncoated hollow taper for laser radiation in the UV, VIS and IR ranges. Applying the experimental hollow-taper based delivery systems, we obtain high laser- to-taper and taper-to-fiber coupling efficiencies.

Design strategies and applications of circulating cell-mediated drug delivery systems.

PubMed

Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

2015-01-01

Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

Mathematics Achievement: Traditional Instruction and Technology-Assisted Course Delivery Methods

ERIC Educational Resources Information Center

Vilardi, Robert

2013-01-01

The purpose of this study was to analyze technology-assisted course delivery methods to determine their overall effectiveness as it pertains to mathematics courses. This study analyzed both current and historical data in mathematics classes in the areas of achievement, retention, and grade distribution. The goal of this study was to determine if…

Mathematics Achievement: Traditional Instruction and Technology-Assisted Course Delivery Methods

ERIC Educational Resources Information Center

Vilardi, Robert; Rice, Margaret L.

2014-01-01

The purpose of this study was to analyze technology-assisted course delivery methods to determine their overall effectiveness as it pertains to mathematics courses. This study analyzed both current and historical data in the areas of achievement, retention, and grade distribution for mathematics classes. The study included 14,562 students enrolled…

Web Conference vs Webcast: The Perceived Effectiveness of Training Sessions at a Southeastern Community College

ERIC Educational Resources Information Center

Jones, Jenny Bailey

2017-01-01

Professional development is a lifelong learning process and technology has provided and will continue to provide new and different delivery methods. Regardless of the delivery method, the intention of professional development is to increase teacher knowledge, which in turn, increases student achievement. At a southeastern community college,…

Effectiveness of a Hybrid Classroom in the Delivery of Medical Terminology Course Content

ERIC Educational Resources Information Center

Martin, Jeffrey S.; Kreiger, Joan E.; Apicerno, Amy L

2015-01-01

Hybrid courses are emerging as a viable option for content delivery across college campuses. In an attempt to maximize learning outcomes while leveraging resources, one institution used several sections of a Medical Terminology course as a pilot. Traditional and hybrid course delivery were compared utilizing a quantitative research method to…

Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers

PubMed Central

Xi, Jinxiang; Zhang, Ze; Si, Xiuhua A

2015-01-01

Background Although direct nose-to-brain drug delivery has multiple advantages, its application is limited by the extremely low delivery efficiency (<1%) to the olfactory region where drugs can enter the brain. It is crucial to developing new methods that can deliver drug particles more effectively to the olfactory region. Materials and methods We introduced a delivery method that used magnetophoresis to improve olfactory delivery efficiency. The performance of the proposed method was assessed numerically in an image-based human nose model. Influences of the magnet layout, magnet strength, drug-release position, and particle diameter on the olfactory dosage were examined. Results and discussion Results showed that particle diameter was a critical factor in controlling the motion of nasally inhaled ferromagnetic drug particles. The optimal particle size was found to be approximately 15 μm for effective magnetophoretic guidance while avoiding loss of particles to the walls in the anterior nose. Olfactory delivery efficiency was shown to be sensitive to the position and strength of magnets and the release position of drug particles. The results of this study showed that clinically significant olfactory doses (up to 45%) were feasible using the optimal combination of magnet layout, selective drug release, and microsphere-carrier diameter. A 64-fold-higher delivery of dosage was predicted in the magnetized nose compared to the control case, which did not have a magnetic field. However, the sensitivity of olfactory dosage to operating conditions and the unstable nature of magnetophoresis make controlled guidance of nasally inhaled aerosols still highly challenging. PMID:25709443

Localized Cell and Drug Delivery for Auditory Prostheses

PubMed Central

Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

2011-01-01

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

Parenting Interventions Implementation Science: How Delivery Format Impacts the Parenting Wisely Program

ERIC Educational Resources Information Center

Cotter, Katie L.; Bacallao, Martica; Smokowski, Paul R.; Robertson, Caroline I. B.

2013-01-01

Objectives: This study examines the implementation and effectiveness of Parenting Wisely, an Internet-based parenting skills intervention. The study assesses whether parents benefit from Parenting Wisely participation and whether the delivery format influences program effectiveness. Method: This study uses a quasi-experimental design.…

Meta-analysis of the role of delivery mode in postpartum depression (Iran 1997-2011)

PubMed Central

Bahadoran, Parvin; Oreizi, Hamid Reza; Safari, Saeideh

2014-01-01

Background: Postpartum period is the riskiest time for mood disorders and psychosis. Postpartum depression is the most important mood disorder after delivery, which can be accompanied by mother-child and family relationship disorders. Meta-analysis with the integration of research results demonstrates to investigate the association between the mode of delivery and postpartum depression. Materials and Methods: This meta-analysis uses the Rosenthal and Robin approach. For this purpose, 18 studies which were acceptable in terms of methodology were selected and meta-analysis was conducted on them. Research instrument was a checklist of meta-analysis. After summarizing the results of the studies, effect sizes were calculated manually and combined based on meta-analysis method. Results: The findings showed that the amount of effect size (in term of Cohen d) of delivery mode on postpartum depression was 0/30 (P < 0.001). Conclusion: Delivery mode on maternal mental health is assessed medium. Meta analysis also indicates moderator variables role, and researcher must focus in these variables. PMID:25540791

Evaluation of Oregon Department of Transportation project delivery.

DOT National Transportation Integrated Search

2007-08-01

This report summarizes analysis of Oregon Department of Transportation (ODOT) methods of insourced and outsourced project delivery using data obtained from ODOT reporting systems, ratings of project effectiveness by ODOT Area Managers and by construc...

Using mobile electronic devices to deliver educational resources in developing countries.

PubMed

Mazal, Jonathan Robert; Ludwig, Rebecca

2015-01-01

Developing countries have far fewer trained radiography professionals than developed countries, which exacerbates the limited access to imaging services. The lack of trained radiographers reflects, in part, limited availability of radiographer-specific educational resources. Historically, organizations that provided such resources in the developing world faced challenges related to the limited stock of current materials as well as expenses associated with shipping and delivery. Four mobile electronic devices (MEDs) were loaded with educational content (e-books, PDFs, and digital applications) spanning major radiography topics. The MEDs were distributed to 4 imaging departments in Ghana, India, Nepal, and Nigeria based on evidence of need for radiography-specific resources, as revealed by survey responses. A cost comparison of postal delivery vs digital delivery of educational content was performed. The effectiveness of delivering additional content via Wi-Fi transmission also was evaluated. Feedback was solicited on users' experience with the MEDs as a delivery tool for educational content. An initial average per e-book expense of $30.05, which included the cost of the device, was calculated for the MED delivery method compared with $15.56 for postal delivery of printed materials. The cost of the MED delivery method was reduced to an average of $10.05 for subsequent e-book deliveries. Additional content was successfully delivered via Wi-Fi transmission to all recipients during the 3-month follow-up period. Overall user feedback on the experience was positive, and ideas for enhancing the MED-based method were identified. Using MEDs to deliver radiography-specific educational content appears to be more cost effective than postal delivery of printed materials on a long-term basis. MEDs are more efficient for providing updates to educational materials. Customization of content to department needs, and using projector devices could enhance the usefulness of MEDs for radiographer training.

The effects of perineal management techniques on labor complications

PubMed Central

Fahami, Fariba; Shokoohi, Zohreh; Kianpour, Mariam

2012-01-01

Background: Many women suffer from perineal trauma during the normal vaginal delivery. Perineal trauma is mainly associated with pain and complications after the childbirth. Perineal management techniques can play a significant role in perineal trauma reduction. This study aimed to compare the effects of perineal management techniques (hands-off technique, Ritgen maneuver and perineal massage using a lubricant during delivery) on the labor complications. Materials and Methods: This quasi-experimental clinical trial was conducted on 99 primiparous women who referred to Daran Hospital, Isfahan, Iran for normal vaginal delivery in 2009. The subjects were selected using a convenient method and randomly assigned to three groups of Ritgen maneuver, hands-off technique and perineal massage with lubricant. A questionnaire was used to determine the demographic characteristics of the participants and complications after birth. The short form of McGill Pain Questionnaire and the visual analogue scale for pain were also employed. The incidence and degree of perineal tears were evaluated immediately after delivery. Moreover, the incidence and severity of perineal pain were assessed 24 hours and also 6 weeks after delivery. Findings: In the Ritgen maneuver group, the frequency of tears, the relative frequency of tear degrees, the severity of perineal pain 24 hours after delivery and the frequency of pain and perineal pain severity 6 weeks after delivery were significantly different from the other two methods. Conclusions: Hands-off technique during parturition of the neonate's head was associated with fewer complications after delivery. It was even better than perineal massage during the parturition. PMID:23493441

Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

PubMed

Ozeki, Tetsuya; Tagami, Tatsuaki

2013-01-01

The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

Anterior eye segment drug delivery systems: current treatments and future challenges.

PubMed

Molokhia, Sarah A; Thomas, Samuel C; Garff, Kevin J; Mandell, Kenneth J; Wirostko, Barbara M

2013-03-01

New technologies for delivery of drugs, such as small molecules and biologics, are of growing interest among clinical and pharmaceutical researchers for use in treating anterior segment eye disease. The challenge is to deliver effective drugs at therapeutic concentrations to the targeted ocular tissue with minimal side effects. To achieve this, a better understanding of the unmet needs, what is required of the various methods of delivery to achieve successful delivery, and the potential challenges of anterior segment drug delivery is necessary and the primarily aim of this review. This review covers the various physiological and anatomical barriers that exist for effective delivery to the targeted tissue of the eye, the pathological conditions of the anterior segment, and the unmet needs for treatment of these ocular diseases. Second, it reviews the novel delivery technologies that have the potential to maintain and/or improve the drug's therapeutic index and improving both patient adherence for chronic therapy and potential patient outcomes. This review bridges the pharmaceutical and clinical research/challenges and provides a detailed overview of anterior segment drug delivery accomplishments thus far, for researchers and clinicians.

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia

PubMed Central

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

Background A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Methods Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998–2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Findings Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. Conclusions The content of care may fulfill the women’s need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery. PMID:28742809

Delivery of cardiopulmonary resuscitation in the microgravity environment

NASA Technical Reports Server (NTRS)

Barratt, M. R.; Billica, R. D.

1992-01-01

The microgravity environment presents several challenges for delivering effective cardiopulmonary resuscitation (CPR). Chest compressions must be driven by muscular force rather than by the weight of the rescuer's upper torso. Airway stabilization is influenced by the neutral body posture. Rescuers will consist of crew members of varying sizes and degrees of physical deconditioning from space flight. Several methods of CPR designed to accommodate these factors were tested in the one G environment, in parabolic flight, and on a recent shuttle flight. Methods: Utilizing study participants of varying sizes, different techniques of CPR delivery were evaluated using a recording CPR manikin to assess adequacy of compressive force and frequency. Under conditions of parabolic flight, methods tested included conventional positioning of rescuer and victim, free floating 'Heimlich type' compressions, straddling the patient with active and passive restraints, and utilizing a mechanical cardiac compression assist device (CCAD). Multiple restrain systems and ventilation methods were also assessed. Results: Delivery of effective CPR was possible in all configurations tested. Reliance on muscular force alone was quickly fatiguing to the rescuer. Effectiveness of CPR was dependent on technique, adequate restraint of the rescuer and patient, and rescuer size and preference. Free floating CPR was adequate but rapidly fatiguing. The CCAD was able to provide adequate compressive force but positioning was problematic. Conclusions: Delivery of effective CPR in microgravity will be dependent on adequate resuer and patient restraint, technique, and rescuer size and preference. Free floating CPR may be employed as a stop gap method until patient restraint is available. Development of an adequate CCAD would be desirable to compensate for the effects of deconditioning.

Nonviral siRNA delivery for gene silencing in neurodegenerative diseases.

PubMed

Prakash, Satya; Malhotra, Meenakshi; Rengaswamy, Venkatesh

2010-01-01

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington's disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

Co-Teaching as an Effective Instructional Delivery Model in Secondary Schools

ERIC Educational Resources Information Center

Beachum, Laura Maree

2016-01-01

School districts across North Carolina are implementing co-teaching practices as a part of inclusive education. This study analyzed the effectiveness of co-teaching as an instructional delivery method and the components needed for success. This study also examined the defined roles needed between the general education teacher and the special…

Engaging Participants without Leaving the Office: Planning and Conducting Effective Webinars

ERIC Educational Resources Information Center

Robinson, Julie; Poling, Mary

2017-01-01

The University of Arkansas System Division of Agriculture Cooperative Extension Service has been developing and refining webinar delivery practices since 2012. On the basis of a review of existing literature and our own experiences, we have established methods for necessary planning, organization of content and people, and effective delivery of…

The efficacy of an intraosseous injection system of delivering local anesthetic.

PubMed

Leonard, M S

1995-01-01

This article describes the clinical testing of a new system for the intraosseous delivery of local anesthesia. The author concluded that the system delivered local anesthetic very effectively (in some situations more effectively than the traditional delivery method), thus offering a great potential advantage to both dentists and patients.

Progress and perspective of inorganic nanoparticles based siRNA delivery system

PubMed Central

Jiang, Ying; Huo, Shuaidong; Hardie, Joseph; Liang, Xing-Jie; Rotello, Vincent M.

2016-01-01

Introduction Small interfering RNA (siRNA) is an effective method for regulating the expression of proteins, even “undruggable” ones that are nearly impossible to target through traditional small molecule therapeutics. Delivery to the cell and then to the cytosol is the primary requirement for realization of therapeutic potential of siRNA. Areas covered We summarize recent advances in the design of inorganic nanoparticle with surface functionality and physicochemical properties engineered for siRNA delivery. Specifically, we discuss the main approaches developed so far to load siRNA into/onto NPs, and NP surface chemistry engineered for enhanced intracellular siRNA delivery, endosomal escape, and targeted delivery of siRNA to disease cells and tissues. Expert Opinion Several challenges remain in developing inorganic NPs for efficient and effective siRNA delivery. Getting the material to the chosen site is important, however the greatest hurdle may well be delivery into the cytosol, either through efficient endosomal escape or by direct cytosolic siRNA delivery. Effective delivery at the organismic and cellular level coupled with biocompatible vehicles with low immunogenic response will facilitate the clinical translation of RNAi for the treatment of genetic diseases. PMID:26735861

Controlling subcellular delivery to optimize therapeutic effect

PubMed Central

Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

2010-01-01

This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

Unmet Demand for Highly Effective Postpartum Contraception in Texas

PubMed Central

Potter, Joseph E.; Hopkins, Kristine; Aiken, Abigail R. A.; Lopez, Celia Hubert; Stevenson, Amanda J.; White, Kari; Grossman, Daniel

2014-01-01

Objectives We aimed to assess women's contraceptive preferences and use in the first 6 months after delivery. The postpartum period represents a key opportunity for women to learn about and obtain effective contraception, especially since 50% of unintended pregnancies to parous women occur within 2 years of a previous birth. Methods We conducted a prospective cohort study of 800 postpartum women recruited from three hospitals in Austin and El Paso, TX. Women aged 18–44 who wanted to delay childbearing for at least 24 months were eligible for the study and completed interviews following delivery and at 3 and 6 months postpartum. Participants were asked about the contraceptive method they were currently using and the method they would prefer to use at 6 months after delivery. Results At 6 months postpartum, 13% of women were using an IUD or implant, and 17% were sterilized or had a partner who had had a vasectomy. Twenty-four percent were using hormonal methods, and 45% relied on less effective methods, mainly condoms and withdrawal. Yet 44% reported that they would prefer to be using sterilization, and 34% would prefer to be using LARC. Conclusions This study shows a considerable preference for LARC and permanent methods at six months postpartum. However, there is a marked discordance between women's method preference and actual use, indicating substantial unmet demand for highly effective methods of contraception. PMID:25129329

The effect of water immersion delivery on the strength of pelvic floor muscle and pelvic floor disorders during postpartum period

PubMed Central

Zhao, Yun; Xiao, Mei; Tang, Fei; Tang, Wan; Yin, Heng; Sun, Guo-Qiang; Lin, Yin; Zhou, Yong; Luo, Yan; Li, Lu-Man; Tan, Zhi-Hua

2017-01-01

Abstract Background: Water immersion delivery is a non-pharmacological approach to ease labor pain. This paper aims to investigate the effect of water immersion delivery on increasing strength of pelvic floor muscle (PFM) and relieving pelvic floor disorders (PFDs) during postpartum period. Methods: A total of 2749 vaginal-delivery primiparas in postpartum 6-8 weeks were selected as research objects. Based on the modes of delivery, 600 patients were assigned into water immersion delivery group, 2149 were assigned into conventional delivery group. The scales of PFM strength and pelvic organ prolapsed (POP) were determined by specially trained personnel using digital palpation, and the symptoms of stress urinary incontinence (SUI) were investigated by questionnaire survey. The weak PFM strength was improved by doing Kegel exercise at home for 6-8 weeks. Results: We found that ①The rate of episiotomy in water immersion delivery group was 77.50% (465/600), which was lower than that in conventional delivery group (84.69%, 1820/2149) (P < .01); The primiparas without having an episiotomy have higher PFM strength than those having an episiotomy for both groups (P < .01). ②There was a negative correlation between the scale of PFM strength and SUI or POP, wherein the r-values were −0.135 and −0.435, respectively (P < .01). ③The rate of SUI was 6.50% (39/600) in water immersion delivery group and 6.89% (148/2149) in the conventional delivery group, wherein the intergroup difference was not significant (P > .05); ④The rates of vaginal wall prolapsed and uterus prolapsed were 29.83% (179/600) and 2.83% (17/600) in water immersion delivery group and 30.95% (665/2149) and 4.37% (94/2149) in the conventional delivery group, wherein the intergroup difference was not significant (P > .05). ⑤After Kegel exercise, the strength of PFM was promoted (P < .01). Conclusion: Water immersion delivery has been proved to a beneficial alternative method for conventional delivery method. This delivery mode is associated with fewer episiotomy rate, and avoiding episiotomy is beneficial for maintaining PFM strength of women in postpartum 6-8 weeks. The strength of PFM during postpartum period can be improved by doing Kegel exercise at home. PMID:29019880

Effects of different data-editing methods on trends in race-specific preterm delivery rates, United States, 1990-2002.

PubMed

Qin, Cheng; Dietz, Patricia M; England, Lucinda J; Martin, Joyce A; Callaghan, William M

2007-09-01

In recent years, national vital statistics data indicate that the US preterm delivery rate has decreased among African Americans and increased among whites. These trends in preterm delivery rates may have been affected, in part, by improvements in the accuracy of gestational age reporting on birth certificates. Several data-editing methods have been developed with the intention of reducing the percentage of records with misclassified gestational age. We explored whether three data-editing methods yielded different trends in preterm delivery for years 1990-2002 among US non-Hispanic white and non-Hispanic African American singleton livebirths. Using National Center for Health Statistics (NCHS) public-use data, we assessed two published methods for editing gestational age, one by Alexander et al. and the other by Zhang and Bowes (Zhang/Bowes). We also assessed a third method that substitutes the clinical estimate (CE) of gestational age when the NCHS last menstrual period (LMP)-based estimate differs from the CE by more than 2 weeks (the LMP/CE method). The percentage of records excluded and/or reclassified by each method was calculated for years 1990, 1996 and 2002. Gestational age-specific birthweight distributions were plotted by race for each method. Preterm delivery rates were calculated and compared by method of editing over time. The percentage of records excluded or reclassified declined from 1990 to 2002 regardless of the method applied. For infants at 28-33 weeks' gestation using the NCHS edited data, birthweight distributions were bimodal, with the second (right-sided) mode showing a mean birthweight consistent with that of term infants. The second mode was less pronounced using the Alexander et al. and the Zhang/Bowes methods, and was not present when the LMP/CE method was used. From 1990 to 2002, preterm delivery rates increased for non-Hispanic whites regardless of method (range 21.3-31.3%). Preterm delivery rates increased slightly for non-Hispanic African Americans with the LMP/CE method (1.8%), and decreased with the other methods (range 6.7-10.8%). Different approaches to editing gestational age from vital records can result in variation in preterm delivery rates and trends. Uncertainty persists around the true trends in preterm delivery, especially among African Americans. Additional research is needed to identify the approach that results in the most accurate classification of gestational age.

A Delphi Method Study on Triggering Transactional Distance to Improve Students' Learning: The Instructor's Rubric

ERIC Educational Resources Information Center

Maston, Heidi L.

2011-01-01

The 21st century ushered in change with the increased use of technology in educational delivery methods and opened doors for a new generation of students. While the debate over pedagogy, content design and overall effectiveness of this delivery format continues, scholars have not attended to the lessons of earlier theorists. This study examined a…

Synthesis of Poly(N-isopropylacrylamide) Microcapsules for Drug Delivery Applications via UV Aerosol Photopolymerization

NASA Astrophysics Data System (ADS)

Roberson, Nicole; Denmark, Daniel; Witanachchi, Sarath

Hybrid drug delivery systems composed of thermoresponsive polymers and magnetic nanoparticles have been developed using chemical methods to deliver controlled amounts of a biotherapeutic to target tissue. These methods can be expensive, time intensive, and produce impure composites due to the use of surfactants during polymer synthesis. In this study, UV aerosol photopolymerization is used to synthesize N-isoplopylacrylamide (NIPAM) monomers, N,N-methylenebisacrylamide (MBA) crosslinker, and irgacure 2959 photoinitiator into the transporting microcapsule for drug delivery. The method of UV aerosol photopolymerization allows for the continuous, cost effective, and time efficient synthesis of a high concentration of pure polymers in a short amount of time; toxic surfactants are not necessary. Optimal NIPAM monomer, MBA crosslinker, and irgacure 2959 photoinitiator concentrations were tested and analyzed to synthesize a microcapsule with optimal conditions for controlled drug delivery. Scanning Electron Microscope (SEM) imaging reveals that synthesis of polymer microcapsules of about 30 micrometers in size is effective through UV aerosol photopolymerization. Findings will contribute greatly to the field of emergency medicine. This work was supported by the United States Army (Grant No. W81XWH1020101/3349).

Methods and metrics challenges of delivery-system research

PubMed Central

2012-01-01

Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011. The opinions in the paper are those of the author and do not represent the views or recommendations of AHRQ or the US Department of Health and Human Services.1 PMID:22409885

Collaborative Course Syllabus Construction: Impact on Consultative Competency of Graduate Students in School Psychology

ERIC Educational Resources Information Center

Camilli, Andrea Lauren

2009-01-01

Consultation has emerged as an effective alternative to traditional methods of service delivery in schools. Additionally, current research and recent changes in legislation (e.g., reauthorization of IDEA) indicate that not only is consultation an effective approach to service delivery, but it is a preferred activity of school psychologists and an…

Ultrasound-mediated drug delivery for cardiovascular disease

PubMed Central

Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail; Holland, Christy K

2014-01-01

Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments. PMID:23448121

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

PubMed Central

Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

2009-01-01

Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment

PubMed Central

2016-01-01

Background Intrathecal drug delivery systems can be used to manage refractory or persistent cancer pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain due owing to cancer. Methods We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, National Health Service's Economic Evaluation Database, and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs. Results We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year. Conclusions Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in adults. Publicly funding intrathecal drug delivery systems for cancer pain would result in a budget impact of several hundred thousand dollars per year. PMID:27026796

Gene Delivery Strategies to Promote Spinal Cord Repair

PubMed Central

Walthers, Christopher M; Seidlits, Stephanie K

2015-01-01

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

PubMed Central

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

2015-01-01

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

Evaluation on Collaborative Satisfaction for Project Management Team in Integrated Project Delivery Mode

NASA Astrophysics Data System (ADS)

Zhang, L.; Li, Y.; Wu, Q.

2013-05-01

Integrated Project Delivery (IPD) is a newly-developed project delivery approach for construction projects, and the level of collaboration of project management team is crucial to the success of its implementation. Existing research has shown that collaborative satisfaction is one of the key indicators of team collaboration. By reviewing the literature on team collaborative satisfaction and taking into consideration the characteristics of IPD projects, this paper summarizes the factors that influence collaborative satisfaction of IPD project management team. Based on these factors, this research develops a fuzzy linguistic method to effectively evaluate the level of team collaborative satisfaction, in which the authors adopted the 2-tuple linguistic variables and 2-tuple linguistic hybrid average operators to enhance the objectivity and accuracy of the evaluation. The paper demonstrates the practicality and effectiveness of the method through carrying out a case study with the method.

Magnetic resonance imaging: A tool to monitor and optimize enzyme distribution during porcine pancreas distention for islet isolation

PubMed Central

Scott, WE; Weegman, BP; Balamurugan, AN; Ferrer-Fabrega, J; Anazawa, T; Karatzas, T; Jie, T; Hammer, BE; Matsumoto, S; Avgoustiniatos, ES; Maynard, KS; Sutherland, DER; Hering, BJ; Papas, KK

2014-01-01

Background Porcine islet xenotransplantation is emerging as a potential alternative for allogeneic clinical islet transplantation. Optimization of porcine islet isolation in terms of yield and quality is critical for the success and cost effectiveness of this approach. Incomplete pancreas distension and inhomogeneous enzyme distribution have been identified as key factors for limiting viable islet yield per porcine pancreas. The aim of this study was to explore the utility of Magnetic Resonance Imaging (MRI) as a tool to investigate the homogeneity of enzyme delivery in porcine pancreata. Traditional and novel methods for enzyme delivery aimed at optimizing enzyme distribution were examined. Methods Pancreata were procured from Landrace pigs via en bloc viscerectomy. The main pancreatic duct was then cannulated with an 18g winged catheter and MRI performed at 1.5 T. Images were collected before and after ductal infusion of chilled MRI contrast agent (gadolinium) in physiological saline. Results Regions of the distal aspect of the splenic lobe and portions of the connecting lobe and bridge exhibited reduced delivery of solution when traditional methods of distension were utilized. Use of alternative methods of delivery (such as selective re-cannulation and distension of identified problem regions) resolved these issues and MRI was successfully utilized as a guide and assessment tool for improved delivery. Conclusion Current methods of porcine pancreas distension do not consistently deliver enzyme uniformly or adequately to all regions of the pancreas. Novel methods of enzyme delivery should be investigated and implemented for improved enzyme distribution. MRI serves as a valuable tool to visualize and evaluate the efficacy of current and prospective methods of pancreas distension and enzyme delivery. PMID:24986758

The effect of primary delivery of the anterior compared with the posterior shoulder on perineal trauma: a study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Approximately 85% of vaginal deliveries are accompanied by perineal trauma. The objective of this trial is to compare the incidence and degree of perineal trauma after primary delivery of the anterior compared with the posterior shoulder during vaginal birth. The hypothesis is that primary delivery of the posterior shoulder reduces the rate and degree of perineal trauma. Methods/design This is a single-centre, randomized controlled trial, with computer-generated randomization in a 1:1 allocation ratio. Women planning their first vaginal delivery (n = 650) are randomized to primary delivery of either the anterior or posterior shoulder. The primary outcome is any perineal trauma. Additional outcomes are the perineal injury subtypes, postpartum bleeding, umbilical artery pH, Apgar score at 5 minutes and any neonatal birth trauma. Perineal trauma is assessed by a midwife or doctor blinded to the method of shoulder delivery. All midwives are trained in the two methods of shoulder delivery and in the grading of perineal tears. The trial is being undertaken at a Danish community hospital with 1,600 yearly deliveries. Data will be analyzed according to the intention-to-treat principle. Recruitment started in January 2013 and the trial is planned to proceed for 24 months. Discussion Most delivery assistance techniques are based on tradition and heritage and lack objective evidence. This trial provides an example of how vaginal delivery techniques can be evaluated in a randomized controlled trial. The results of this trial will clarify the role that delivery of the shoulders has on perineal trauma and thereby provide knowledge to recommendations on birthing technique. Trial registration ClinicalTrials.gov: NCT01937546. PMID:25047001

Dance Online: Can the Students Still Follow the Steps? A Rationale for Online Delivery Methods in Dance.0

ERIC Educational Resources Information Center

Zimmerly, Lauralee C.

2012-01-01

The purpose of this study was to design an online section of a university level general education dance course, and to determine if the effectiveness of the online delivery was at least equal to that of the face-to-face delivery as measured by student achievement on examinations. To accomplish this, the goals were: (1) to present evidence that the…

Status and future directions in the management of pancreatic cancer: potential impact of nanotechnology.

PubMed

Sielaff, Catherine M; Mousa, Shaker A

2018-07-01

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity. In addition, PDAC tumor tissue is dense and highly resistant to many traditional chemotherapeutic applications, making the disease difficult to treat and impeding options for palliative care. New developments in nanotechnology may offer innovative options for targeted PDAC therapeutic drug delivery. Nanotechnology can be implemented using multimodality methods that offer increased opportunities for earlier diagnosis, precision enhanced imaging, targeted long-term tumor surveillance, and controlled drug delivery, as well as improved palliative care and patient comfort. Nanoscale delivery methods have demonstrated the capacity to infiltrate the dense, fibrous tumor tissue associated with PDAC, increasing delivery and effectiveness of chemotherapeutic agents and reducing toxicity through the loading of multiple drug therapies on a single nano delivery vehicle. This review presents an overview of nanoscale drug delivery systems and multimodality carriers at the forefront of new PDAC treatments.

[Effects of penetration enhancers on curcumin transdermal drug delivery].

PubMed

Gao, Zhen-Shen; Wang, Lan; Zhang, Mei

2012-01-01

To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. The HP-beta-CD has the most potent enhancing effect.

Magnetic resonance imaging: a tool to monitor and optimize enzyme distribution during porcine pancreas distention for islet isolation.

PubMed

Scott, William E; Weegman, Bradley P; Balamurugan, Appakalai N; Ferrer-Fabrega, Joana; Anazawa, Takayuki; Karatzas, Theodore; Jie, Tun; Hammer, Bruce E; Matsumoto, Shuchiro; Avgoustiniatos, Efstathios S; Maynard, Kristen S; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2014-01-01

Porcine islet xenotransplantation is emerging as a potential alternative for allogeneic clinical islet transplantation. Optimization of porcine islet isolation in terms of yield and quality is critical for the success and cost-effectiveness of this approach. Incomplete pancreas distention and inhomogeneous enzyme distribution have been identified as key factors for limiting viable islet yield per porcine pancreas. The aim of this study was to explore the utility of magnetic resonance imaging (MRI) as a tool to investigate the homogeneity of enzyme delivery in porcine pancreata. Traditional and novel methods for enzyme delivery aimed at optimizing enzyme distribution were examined. Pancreata were procured from Landrace pigs via en bloc viscerectomy. The main pancreatic duct was then cannulated with an 18-g winged catheter and MRI performed at 1.5-T. Images were collected before and after ductal infusion of chilled MRI contrast agent (gadolinium) in physiological saline. Regions of the distal aspect of the splenic lobe and portions of the connecting lobe and bridge exhibited reduced delivery of solution when traditional methods of distention were utilized. Use of alternative methods of delivery (such as selective re-cannulation and distention of identified problem regions) resolved these issues, and MRI was successfully utilized as a guide and assessment tool for improved delivery. Current methods of porcine pancreas distention do not consistently deliver enzyme uniformly or adequately to all regions of the pancreas. Novel methods of enzyme delivery should be investigated and implemented for improved enzyme distribution. MRI serves as a valuable tool to visualize and evaluate the efficacy of current and prospective methods of pancreas distention and enzyme delivery. © 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

The Effectiveness of Streaming Video on Medical Student Learning: A Case Study

PubMed Central

Bridge, Patrick D.; Jackson, Matt; Robinson, Leah

2009-01-01

Information technology helps meet today's medical students’ needs by providing multiple curriculum delivery methods. Video streaming is an e-learning technology that uses the Internet to deliver curriculum while giving the student control of the content's delivery. There have been few studies conducted on the effectiveness of streaming video in medical schools. A 5-year retrospective study was conducted using three groups of students (n = 1736) to determine if the availability of streaming video in Years 1–2 of the basic science curriculum affected overall Step 1 scores for first-time test-takers. The results demonstrated a positive effect on program outcomes as streaming video became more readily available to students. Based on these findings, streaming video technology seems to be a viable tool to complement in-class delivery methods, to accommodate the needs of medical students, and to provide options for meeting the challenges of delivering the undergraduate medical curriculum. Further studies need to be conducted to continue validating the effectiveness of streaming video technology. PMID:20165525

Bystander programs addressing sexual violence on college campuses: A systematic review and meta-analysis of program outcomes and delivery methods.

PubMed

Jouriles, Ernest N; Krauss, Alison; Vu, Nicole L; Banyard, Victoria L; McDonald, Renee

2018-02-06

This systematic review and meta-analysis evaluates the effectiveness of bystander programs that address sexual violence on college campuses. Program effects on student attitudes/beliefs and bystander behavior were examined. Durability of program outcomes and the influence of program-delivery methods (e.g., facilitator-led programs vs. video, online or poster campaign programs) and program-parameters (e.g., program length) were also evaluated. Twenty-four studies met criteria for inclusion in the meta-analysis, and 207 separate results from these studies were coded. Students who participated in a bystander program, compared to those who had not, had more pro-social attitudes/beliefs about sexual violence and intervening to prevent it, and engaged in more bystander behavior. Program effects diminished over time, but meaningful changes persisted for at least three months following program delivery. Longer programs had greater effects than shorter programs on attitudes/beliefs. Bystander programs can be a valuable addition to colleges' violence prevention efforts.

The effectiveness of streaming video on medical student learning: a case study.

PubMed

Bridge, Patrick D; Jackson, Matt; Robinson, Leah

2009-08-19

Information technology helps meet today's medical students' needs by providing multiple curriculum delivery methods. Video streaming is an e-learning technology that uses the Internet to deliver curriculum while giving the student control of the content's delivery. There have been few studies conducted on the effectiveness of streaming video in medical schools. A 5-year retrospective study was conducted using three groups of students (n = 1736) to determine if the availability of streaming video in Years 1-2 of the basic science curriculum affected overall Step 1 scores for first-time test-takers. The results demonstrated a positive effect on program outcomes as streaming video became more readily available to students. Based on these findings, streaming video technology seems to be a viable tool to complement in-class delivery methods, to accommodate the needs of medical students, and to provide options for meeting the challenges of delivering the undergraduate medical curriculum. Further studies need to be conducted to continue validating the effectiveness of streaming video technology.

Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis

PubMed Central

Mishanina, Ekaterina; Rogozinska, Ewelina; Thatthi, Tej; Uddin-Khan, Rehan; Khan, Khalid S.; Meads, Catherine

2014-01-01

Background: Induction of labour is common, and cesarean delivery is regarded as its major complication. We conducted a systematic review and meta-analysis to investigate whether the risk of cesarean delivery is higher or lower following labour induction compared with expectant management. Methods: We searched 6 electronic databases for relevant articles published through April 2012 to identify randomized controlled trials (RCTs) in which labour induction was compared with placebo or expectant management among women with a viable singleton pregnancy. We assessed risk of bias and obtained data on rates of cesarean delivery. We used regression analysis techniques to explore the effect of patient characteristics, induction methods and study quality on risk of cesarean delivery. Results: We identified 157 eligible RCTs (n = 31 085). Overall, the risk of cesarean delivery was 12% lower with labour induction than with expectant management (pooled relative risk [RR] 0.88, 95% confidence interval [CI] 0.84–0.93; I2 = 0%). The effect was significant in term and post-term gestations but not in preterm gestations. Meta-regression analysis showed that initial cervical score, indication for induction and method of induction did not alter the main result. There was a reduced risk of fetal death (RR 0.50, 95% CI 0.25–0.99; I2 = 0%) and admission to a neonatal intensive care unit (RR 0.86, 95% CI 0.79–0.94), and no impact on maternal death (RR 1.00, 95% CI 0.10–9.57; I2 = 0%) with labour induction. Interpretation: The risk of cesarean delivery was lower among women whose labour was induced than among those managed expectantly in term and post-term gestations. There were benefits for the fetus and no increased risk of maternal death. PMID:24778358

Comparing two instructional methods of role playing and lecture on primigravida females, decision about type of delivery.

PubMed

Abedian, Zahra; Navaee, Maryam; Sani, Hossein Jafari; Ebrahimzadeh, Saeed

2017-01-01

Each mother has the legal right to decide about her delivery, but this decision should be made based on scientific knowledge. Instructions during pregnancy help to choose the proper type of delivery. This study conducted aimed to compare two instructional methods of role playing and lecture on primigravida decision about type of delivery. In this single-blind clinical trial 67 primigravida, 34-36 week were selected using multi-stage sampling and assigned into two groups randomly. Decision-making (before, 2-week after, and at admission in maternity department) was tested by a questionnaire. In role-playing group, advantages and disadvantages of two type delivery were presented by role-playing in 90-min by three scenarios. In lecture group, it was also presented in a 90-min lecture. Data were analyzed by mean difference test, Fisher test, independent and paired t -test. Two groups showed a significant difference in terms of decision at admission to maternity department ( P = 0.000). 75% of lecture group and 100% of role-playing group selected normal delivery. Postintervention knowledge score in lecture group was 18 ± 5.3 and in role-playing group 17.1 ± 4.0. Percent of change in knowledge scores in two groups was significant ( P = 0.001). Participants' attitude, before and after the intervention, in both groups was significant ( P < 0.05). Mean difference of pre- and post-test in relation to two groups' knowledge and attitude scores was not significant ( P > 0.05). In this research, lecture was more effective in raising knowledge level, and role playing was more effective in raising decision to vaginal delivery and reducing elective caesarean section. It is therefore suggested to use both teaching methods altogether for pregnant women to decrease the rate of unnecessary cesarean.

Going the Distance Part 2: Five Ways of Teaching an Extension Course: Elive, Blackboard, Teleconference, Correspondence, and Face-to-Face

ERIC Educational Resources Information Center

Rader, Heidi B.; Hanna, Virgene; Spiers, Kent; Kienenberger, Donavan

2014-01-01

Remote and widely dispersed clientele in Alaska create a need for effective distance-delivery programs. Extension agents often travel via small airplane, snow machine, or boat to teach face-to-face classes in off-road communities. Effective and more cost-efficient delivery methods are needed. We taught a course for beginning farmers residing…

Molecular Cardiac Surgery with Recirculating Delivery (MCARD): Procedure and Vector Transfer.

PubMed

Katz, Michael G; Fargnoli, Anthony S; Kendle, Andrew P; Bridges, Charles R

2017-01-01

Despite progress in clinical treatment, cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Therefore, novel therapeutic approaches are needed, targeting the underlying molecular mechanisms of disease with improved outcomes for patients. Gene therapy is one of the most promising fields for the development of new treatments for the advanced stages of cardiovascular diseases. The establishment of clinically relevant methods of gene transfer remains one of the principal limitations on the effectiveness of gene therapy. Recently, there have been significant advances in direct and transvascular gene delivery methods. The ideal gene transfer method should be explored in clinically relevant large animal models of heart disease to evaluate the roles of specific molecular pathways in disease pathogenesis. Characteristics of the optimal technique for gene delivery include low morbidity, an increased myocardial transcapillary gradient, esxtended vector residence time in the myocytes, and the exclusion of residual vector from the systemic circulation after delivery to minimize collateral expression and immune response. Here we describe myocardial gene transfer techniques with molecular cardiac surgery with recirculating delivery in a large animal model of post ischemic heart failure.

Comparing two instructional methods of role playing and lecture on primigravida females, decision about type of delivery

PubMed Central

Abedian, Zahra; Navaee, Maryam; Sani, Hossein Jafari; Ebrahimzadeh, Saeed

2017-01-01

INTRODUCTION: Each mother has the legal right to decide about her delivery, but this decision should be made based on scientific knowledge. Instructions during pregnancy help to choose the proper type of delivery. This study conducted aimed to compare two instructional methods of role playing and lecture on primigravida decision about type of delivery. SUBJECTS AND METHODS: In this single-blind clinical trial 67 primigravida, 34–36 week were selected using multi-stage sampling and assigned into two groups randomly. Decision-making (before, 2-week after, and at admission in maternity department) was tested by a questionnaire. In role-playing group, advantages and disadvantages of two type delivery were presented by role-playing in 90-min by three scenarios. In lecture group, it was also presented in a 90-min lecture. Data were analyzed by mean difference test, Fisher test, independent and paired t-test. RESULTS: Two groups showed a significant difference in terms of decision at admission to maternity department (P = 0.000). 75% of lecture group and 100% of role-playing group selected normal delivery. Postintervention knowledge score in lecture group was 18 ± 5.3 and in role-playing group 17.1 ± 4.0. Percent of change in knowledge scores in two groups was significant (P = 0.001). Participants’ attitude, before and after the intervention, in both groups was significant (P < 0.05). Mean difference of pre- and post-test in relation to two groups’ knowledge and attitude scores was not significant (P > 0.05). CONCLUSION: In this research, lecture was more effective in raising knowledge level, and role playing was more effective in raising decision to vaginal delivery and reducing elective caesarean section. It is therefore suggested to use both teaching methods altogether for pregnant women to decrease the rate of unnecessary cesarean. PMID:28584829

Double-stranded RNA Oral Delivery Methods to Induce RNA Interference in Phloem and Plant-sap-feeding Hemipteran Insects.

PubMed

Ghosh, Saikat Kumar B; Hunter, Wayne B; Park, Alexis L; Gundersen-Rindal, Dawn E

2018-05-04

Phloem and plant sap feeding insects invade the integrity of crops and fruits to retrieve nutrients, in the process damaging food crops. Hemipteran insects account for a number of economically substantial pests of plants that cause damage to crops by feeding on phloem sap. The brown marmorated stink bug (BMSB), Halyomorpha halys (Heteroptera: Pentatomidae) and the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae) are hemipteran insect pests introduced in North America, where they are an invasive agricultural pest of high-value specialty, row, and staple crops and citrus fruits, as well as a nuisance pest when they aggregate indoors. Insecticide resistance in many species has led to the development of alternate methods of pest management strategies. Double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) is a gene silencing mechanism for functional genomic studies that has potential applications as a tool for the management of insect pests. Exogenously synthesized dsRNA or small interfering RNA (siRNA) can trigger highly efficient gene silencing through the degradation of endogenous RNA, which is homologous to that presented. Effective and environmental use of RNAi as molecular biopesticides for biocontrol of hemipteran insects requires the in vivo delivery of dsRNAs through feeding. Here we demonstrate methods for delivery of dsRNA to insects: loading of dsRNA into green beans by immersion, and absorbing of gene-specific dsRNA with oral delivery through ingestion. We have also outlined non-transgenic plant delivery approaches using foliar sprays, root drench, trunk injections as well as clay granules, all of which may be essential for sustained release of dsRNA. Efficient delivery by orally ingested dsRNA was confirmed as an effective dosage to induce a significant decrease in expression of targeted genes, such as juvenile hormone acid O-methyltransferase (JHAMT) and vitellogenin (Vg). These innovative methods represent strategies for delivery of dsRNA to use in crop protection and overcome environmental challenges for pest management.

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

PubMed Central

2010-01-01

Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery. PMID:20085661

The relationship between quality of life and methods of delivery: A systematic review and meta-analysis.

PubMed

Rezaei, Nazanin; Tavalaee, Zahra; Sayehmiri, Kourosh; Sharifi, Nasibeh; Daliri, Salman

2018-04-01

Some physical, emotional and social changes arise in mothers during the postpartum periods which can affect the quality of life (QOL) of the mother and family. Given the importance of the quality of life in the postpartum period and its influencing factors such as method of delivery, the present study aimed at investigating the relationship between the quality of life and methods of delivery in the world, using a systematic review and meta-analysis method. The present study is a systematic review and meta-analysis on the relationship between aspects of quality of life and method of delivery in the world conducted in Persian and English language articles published by the end of 2015. For this purpose, the databases of Medlib, SID, Scopus, ISI Web of Science, PubMed, Google scholar, Irandoc, Magiran and Iranmedex were searched using key words and their compounds. The results of studies were combined using the random effects model in the meta-analysis. Heterogeneity of studies was assessed using I2 index and Cochran test and data were analyzed using STATA Version 11.1 and SPSS Version 16. Based on the results of the meta-analysis of studies, the aspect of physical functioning had the highest quality of life mean score in women with vaginal delivery: 74.37 (95% CI: 67.7-81) and mental health had the highest QOL mean score in women with cesarean delivery: 65.8 (95% CI: 62.7-69). Also, based on the time elapsed since delivery, mental health had the highest mean score in less than 1 month, 2 months and 4 months' postpartum. Physical pain had the highest mean score 6 months after giving birth, and mental functioning in 8 months after giving birth. The results of the present meta-analysis showed that the mean scores for most dimensions of quality of life in women with vaginal delivery were higher than in women with cesarean delivery.

Parent-Based Adolescent Sexual Health Interventions And Effect on Communication Outcomes: A Systematic Review and Meta-Analyses

PubMed Central

Maria, Diane Santa; Markham, Christine; Mullen, Patricia Dolan; Bluethmann, Shirley

2016-01-01

Context Parent-based adolescent sexual health interventions aim to reduce sexual risk behaviors by bolstering parental protective behaviors. Few studies of theory use, methods, applications, delivery and outcomes of parent-based interventions have been conducted. Methods A systematic search of databases for the period 1998–2013 identified 28 published trials of U.S. parent-based interventions to examine theory use, setting, reach, delivery mode, dose and effects on parent-child communication. Established coding schemes were used to assess use of theory and describe methods employed to achieve behavioral change; intervention effects were explored in meta-analyses. Results Most interventions were conducted with minority parents in group sessions or via self-paced activities; interventions averaged seven hours, and most used theory extensively. Meta-analyses found improvements in sexual health communication: Analysis of 11 controlled trials indicated a medium effect on increasing communication (Cohen's d, 0.5), and analysis of nine trials found a large effect on increasing parental comfort with communication (0.7); effects were positive regardless of delivery mode or intervention dose. Intervention participants were 68% more likely than controls to report increased communication and 75% more likely to report increased comfort. Conclusions These findings point to gaps in the range of programs examined in published trials—for example, interventions for parents of sexual minority youth, programs for custodial grandparents and faith-based services. Yet they provide support for the effectiveness of parent-based interventions in improving communication. Innovative delivery approaches could extend programs' reach, and further research on sexual health outcomes would facilitate the meta-analysis of intervention effectiveness in improving adolescent sexual health behaviors. PMID:25639664

Private vs. Public Care for Juvenile Offenders: A Qualitative Examination.

ERIC Educational Resources Information Center

Kronick, Robert F.

1993-01-01

Examined effectiveness of methods used by public and private institutions' handling of incarcerated delinquents. Concluded that organizational culture is key concept in delivery of services to incarcerated children and youth; that private sector provides alternative to public in delivery of services; that alcohol and drug treatment programs are…

Double strand RNA delivery system for plant-sap-feeding insects

PubMed Central

Ghosh, Saikat Kumar B.; Hunter, Wayne B.; Park, Alexis L.; Gundersen-Rindal, Dawn E.

2017-01-01

Double-stranded RNA (dsRNA)-mediated gene silencing, also known as RNA interference (RNAi), has been a breakthrough technology for functional genomic studies and represents a potential tool for the management of insect pests. Since the inception of RNAi numerous studies documented successful introduction of exogenously synthesized dsRNA or siRNA into an organism triggering highly efficient gene silencing through the degradation of endogenous RNA homologous to the presented siRNA. Managing hemipteran insect pests, especially Halyomorpha halys (Stål) (Heteroptera: Pentatomidae), the brown marmorated stink bug (BMSB), is critical to food productivity. BMSB was recently introduced into North America where it is both an invasive agricultural pest of high value specialty, row, and staple crops, as well as an indoor nuisance pest. RNAi technology may serve as a viable tool to manage this voracious pest, but delivery of dsRNA to piercing-sucking insects has posed a tremendous challenge. Effective and practical use of RNAi as molecular biopesticides for biocontrol of insects like BMSB in the environment requires that dsRNAs be delivered in vivo through ingestion. Therefore, the key challenge for molecular biologists in developing insect-specific molecular biopesticides is to find effective and reliable methods for practical delivery of stable dsRNAs such as through oral ingestion. Here demonstrated is a reliable delivery system of effective insect-specific dsRNAs through oral feeding through a new delivery system to induce a significant decrease in expression of targeted genes such as JHAMT and Vg. This state-of-the-art delivery method overcomes environmental delivery challenges so that RNAi is induced through insect-specific dsRNAs orally delivered to hemipteran and other insect pests. PMID:28182760

The effect of perineal control with hands-on and hand-poised methods on perineal trauma and delivery outcome

PubMed Central

Foroughipour, Azam; Firuzeh, Farah; Ghahiri, Ataolah; Norbakhsh, Vajihe; Heidari, Tayebeh

2011-01-01

BACKGROUND: The objective of the present study was to evaluate the effect of the two methods of delivery, “hands-on” vs. “hands poised”, on perineal trauma and delivery outcome in primiparous women referred to Shariati Hospital of Isfahan during 2007-2008. METHODS: In a clinical trial study, 100 low risk primiparous pregnant women were randomly assigned to two hands-on and hand-poised (hands-off) groups. In the hands-on group, this method was used to control fetal head in the second stage of labor. It means that the fingers of one hand supported fetal occiput and the other hand applied slight pressure on the head to control the delivery of the head during the crowning process. In the hands-poised group, midwife observed the parturient woman and do not touch perineum during the second labor stage while fetal head was delivering. Then, the two groups were compared in terms of perineal trauma, as well as neonatal and delivery outcome. RESULTS: Demographic characteristics of all studied women were similar in two groups. The rate of episiotomy was higher in hands-on group (84% vs. 40%, p = 0.001). The rate of postpartum hemorrhage (4th stage) was higher in hands-on group (12% vs. 4%, p = 0.04). The rate of mild and moderate postpartum pain in hands-on group was higher than hands-off group (70% vs. 58% and 29% vs. 10%, p < 0.001) but sever pain was not different in two groups. CONCLUSIONS: It seems that hands-poised method is associated with less perineal trauma, particularly regarding the lower need for episiotomy and postpartum hemorrhage. PMID:22279480

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

PubMed

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret

PubMed Central

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

2016-01-01

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs. PMID:27822034

Novel Strategies for Anterior Segment Ocular Drug Delivery

PubMed Central

Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

2013-01-01

Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

Performance Analysis of Cyber Security Awareness Delivery Methods

NASA Astrophysics Data System (ADS)

Abawajy, Jemal; Kim, Tai-Hoon

In order to decrease information security threats caused by human-related vulnerabilities, an increased concentration on information security awareness and training is necessary. There are numerous information security awareness training delivery methods. The purpose of this study was to determine what delivery method is most successful in providing security awareness training. We conducted security awareness training using various delivery methods such as text based, game based and a short video presentation with the aim of determining user preference delivery methods. Our study suggests that a combined delvery methods are better than individual secrity awareness delivery method.

Coated microneedle arrays for transcutaneous delivery of live virus vaccines

PubMed Central

Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

2016-01-01

Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

Coated microneedle arrays for transcutaneous delivery of live virus vaccines.

PubMed

Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C

2012-04-10

Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

PubMed

Hani, Umme; Shivakumar, H G

2014-01-01

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

Targeted Drug Delivery Based on Gold Nanoparticle Derivatives.

PubMed

Gholipourmalekabadi, Mazaher; Mobaraki, Mohammadmahdi; Ghaffari, Maryam; Zarebkohan, Amir; Omrani, Vahid Fallah; Urbanska, Aleksandra M; Seifalian, Alexander

2017-01-01

Drug delivery systems are effective and attractive methods which allow therapeutic substances to be introduced into the body more effectively and safe by having tunable delivery rate and release target site. Gold nanoparticles (AuNPs) have a myriad of favorable physical, chemical, optical, thermal and biological properties that make them highly suitable candidates as non-toxic carriers for drug and gene delivery. The surface modifications of AuNPs profoundly improve their circulation, minimize aggregation rates, enhance attachment to therapeutic molecules and target agents due to their nano range size which further increases their ability to cross cell membranes and reduce overall cytotoxicity. This comprehensive article reviews the applications of the AuNPs in drug delivery systems along with their corresponding surface modifications. The highlighting results obtained from the preclinical trial are promising and next five years have huge possibility move to the clinical setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimization of gene delivery methods in Xenopus laevis kidney (A6) and Chinese hamster ovary (CHO) cell lines for heterologous expression of Xenopus inner ear genes

PubMed Central

Ramirez-Gordillo, Daniel; Trujillo-Provencio, Casilda; Knight, V. Bleu; Serrano, Elba E.

2014-01-01

The Xenopus inner ear provides a useful model for studies of hearing and balance because it shares features with the mammalian inner ear, and because amphibians are capable of regenerating damaged mechanosensory hair cells. The structure and function of many proteins necessary for inner ear function have yet to be elucidated and require methods for analysis. To this end, we seek to characterize Xenopus inner ear genes outside of the animal model through heterologous expression in cell lines. As part of this effort, we aimed to optimize physical (electroporation), chemical (lipid-mediated; Lipofectamine™ 2000, Metafectene® Pro), and biological (viral-mediated; BacMam virus Cellular Lights™ Tubulin-RFP) gene delivery methods in amphibian (Xenopus; A6) cells and mammalian (Chinese hamster ovary (CHO)) cells. We successfully introduced the commercially available pEGFP-N3, pmCherry-N1, pEYFP-Tubulin, and Cellular Lights™ Tubulin-RFP fluorescent constructs to cells and evaluated their transfection or transduction efficiencies using the three gene delivery methods. In addition, we analyzed the transfection efficiency of a novel construct synthesized in our laboratory by cloning the Xenopus inner ear calcium-activated potassium channel β1 subunit, then subcloning the subunit into the pmCherry-N1 vector. Every gene delivery method was significantly more effective in CHO cells. Although results for the A6 cell line were not statistically significant, both cell lines illustrate a trend towards more efficient gene delivery using viral-mediated methods; however the cost of viral transduction is also much higher. Our findings demonstrate the need to improve gene delivery methods for amphibian cells and underscore the necessity for a greater understanding of amphibian cell biology. PMID:21959846

Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

PubMed Central

Kim, Jean; Schlesinger, Erica B; Desai, Tejal A

2015-01-01

Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered. PMID:26652282

Unmet demand for highly effective postpartum contraception in Texas.

PubMed

Potter, Joseph E; Hopkins, Kristine; Aiken, Abigail R A; Hubert, Celia; Stevenson, Amanda J; White, Kari; Grossman, Daniel

2014-11-01

We aimed to assess women's contraceptive preferences and use in the first 6 months after delivery. The postpartum period represents a key opportunity for women to learn about and obtain effective contraception, especially since 50% of unintended pregnancies to parous women occur within 2 years of a previous birth. We conducted a prospective cohort study of 800 postpartum women recruited from three hospitals in Austin and El Paso, TX. Women aged 18-44 who wanted to delay childbearing for at least 24 months were eligible for the study and completed interviews following delivery and at 3 and 6 months postpartum. Participants were asked about the contraceptive method they were currently using and the method they would prefer to use at 6 months after delivery. At 6 months postpartum, 13% of women were using an intrauterine device or implant, and 17% were sterilized or had a partner who had had a vasectomy. Twenty-four percent were using hormonal methods, and 45% relied on less effective methods, mainly condoms and withdrawal. Yet 44% reported that they would prefer to be using sterilization, and 34% would prefer to be using long-acting reversible contraception (LARC). This study shows a considerable preference for LARC and permanent methods at 6 months postpartum. However, there is a marked discordance between women's method preference and actual use, indicating substantial unmet demand for highly effective methods of contraception. In two Texas cities, many more women preferred long-acting and permanent contraceptive methods (LAPM) than were able to access these methods at 6 months postpartum. Women's contraceptive needs could be better met by counseling about all methods, by reducing cost barriers and by making LAPM available at more sites. Copyright © 2014 Elsevier Inc. All rights reserved.

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells.

PubMed

Schmidt, Christian; Yokaichiya, Fabiano; Doğangüzel, Nurdan; Dias Franco, Margareth K K; Cavalcanti, Leide P; Brown, Mark A; Alkschbirs, Melissa I; de Araujo, Daniele R; Kumpugdee-Vollrath, Mont; Storsberg, Joachim

2016-09-15

An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.

Traversing the Skin Barrier with Nano-emulsions.

PubMed

Burger, Cornel; Shahzad, Yasser; Brummer, Alicia; Gerber, Minja; du Plessis, Jeanetta

2017-01-01

In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes. This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed. Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs. This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

PubMed

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-02-23

Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

Health maintenance organizations, independent practice associations, and cesarean section rates.

PubMed

Tussing, A D; Wojtowycz, M A

1994-04-01

This study tests two hypotheses: that a given delivery is less likely to be by cesarean section (c-section) in an HMO (closed-panel health maintenance organization) or IPA (independent practice association), than in other settings; and that where HMO and IPA penetration is high, the probability of a c-section will be reduced for all deliveries, whether in prepaid groups or not. A data set consisting of 104,595 obstetric deliveries in New York state in 1986 is analyzed. A series of probit regressions is estimated, in which the dependent variable is either the probability that a given delivery is by c-section, or that a given delivery will result in a c-section for dystocia or fetal distress. The Live Birth File is linked with SPARCS hospital discharge data and other variables. HMO setting reduces the probability of a cesarean section by 2.5 to 3.0 percentage points. However, this result is likely to be partly an artifact of offsetting diagnostic labeling and of choice of method of delivery, given diagnosis; a better estimate of the effect of HMO setting is -1.3 percentage points. IPA setting appears to affect the probability of a cesarean section even less, perhaps not at all. And HMO and IPA penetration in a region, as measured by HMO and IPA deliveries, respectively, as a percent of all deliveries, has relatively large depressing effects on the probability of a cesarean section. Ceteris paribus, the probability of a c-section is lower for an HMO delivery than for a fee-for-service delivery; however, HMO effects are smaller than previously reported in the literature for other types of inpatient care. For IPA deliveries, the effects are still smaller, perhaps nil. However, HMO and IPA penetration, possibly measuring the degree of competition in obstetrics markets, have important effects on c-section rates, not only in HMO/IPA settings, but throughout an area. These results appear to have important implications for public policy.

Dermal and transdermal delivery of pharmaceutically relevant macromolecules.

PubMed

Münch, S; Wohlrab, J; Neubert, R H H

2017-10-01

The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin. This effect can be achieved using physical and chemical methods, as well as biological peptides. The most popular physical method is the use of microneedles to create micropores in the skin and release the active agent in different sections. But also, other methods have been tested. Microjets, lasers, electroporation, sonophoresis and iontophoresis are also promising methods to successfully deliver dermal and transdermal macromolecules. Additionally, there are different penetration enhancer groups and biological peptides, which are also considered to be interesting approaches of enabling macromolecules to travel along the skin. All these methods will be described and evaluated in this review article. Copyright © 2017 Elsevier B.V. All rights reserved.

Delivering Vitamin A Supplements to Children Aged 6 to 59 Months: Comparing Delivery Through Mass Campaign and Through Routine Health Services in Ethiopia.

PubMed

Gatobu, Sospeter; Horton, Susan; Kiflie Aleyamehu, Yibeltal; Abraham, Gelila; Birhanu, Negalign; Greig, Alison

2017-12-01

The delivery of vitamin A supplements in Ethiopia has been shifting from Child Health Days (campaigns) to routine delivery via the community health services. The objective of this study was to compare the cost and effectiveness of these 2 delivery methods. No previous studies have done this. A mixed method approach was used. Quantitative data on costs were collected from interviews with key staff and coverage data from health facility records. Qualitative data on the 2 modalities were collected from key informants and community members from purposefully sampled communities using the 2 modalities. Communities appreciated the provision of vitamin A supplements to their under 5-year-old children. The small drop in coverage that occurred as a result of the change in modality can be attributed to normal changes that occur with any system change. Advantages of campaigns included greater ease of mobilization and better coverage of older children from more remote communities. Advantages of routine delivery included not omitting children who happened to miss the 1 day per round that supplementation occurred and not disrupting the availability of other health services for the 5 to 6 days each campaign requires. The cost of routine delivery is not easy to measure nor is the cost of disruption to normal services entailed by campaigns. Cost-effectiveness likely depends more on effectiveness than on cost. Overall, the routine approach can achieve good coverage and is sustainable in the long run, as long as the transition is well planned and implemented.

Enhancing and targeting nucleic acid delivery by magnetic force.

PubMed

Plank, Christian; Anton, Martina; Rudolph, Carsten; Rosenecker, Joseph; Krötz, Florian

2003-08-01

Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.

Enhancement of transdermal protein delivery by photothermal effect of gold nanorods coated on polysaccharide-based hydrogel.

PubMed

Haine, Aung Thu; Koga, Yuki; Hashimoto, Yuta; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Niidome, Takuro

2017-10-01

Transdermal protein delivery is a useful and attractive method for protein therapy and dermal vaccination. However, this delivery method is restricted by the low permeability of the stratum corneum. The purpose of this study was to develop a transdermal delivery system for enhancement of protein permeability into the skin. First, we prepared a transparent gel patch made of polysaccharides with gold nanorods on the gel surface and fluorescein isothiocyanate-modified ovalbumin (FITC-OVA) inside. Next, the gel patch was placed on mouse skin to allow contact with the coated gold nanorods, and irradiated by a continuous-wave laser. The laser irradiation heated the gold nanorods and the skin temperature increased to 43°C, resulting in enhanced translocation of FITC-OVA into the skin. These results confirmed the capability of the transdermal protein delivery system to perforate the stratum corneum and thus facilitate the passage of proteins across the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Delivery Skills Instruction on Speech Anxiety.

ERIC Educational Resources Information Center

Neer, Michael R.; Kircher, W. Faye

A study tested a delivery skills method of instruction for reducing public speaking anxiety. Subjects were 59 male and 71 female undergraduates (ranging in age from 17-49) enrolled in a basic public speaking course at a midwestern university during the 1986-87 academic year. The Personal Report of Public Speaking Apprehension (PRPSA) which…

The effect of water immersion delivery on the strength of pelvic floor muscle and pelvic floor disorders during postpartum period: An experimental study.

PubMed

Zhao, Yun; Xiao, Mei; Tang, Fei; Tang, Wan; Yin, Heng; Sun, Guo-Qiang; Lin, Yin; Zhou, Yong; Luo, Yan; Li, Lu-Man; Tan, Zhi-Hua

2017-10-01

Water immersion delivery is a non-pharmacological approach to ease labor pain. This paper aims to investigate the effect of water immersion delivery on increasing strength of pelvic floor muscle (PFM) and relieving pelvic floor disorders (PFDs) during postpartum period. A total of 2749 vaginal-delivery primiparas in postpartum 6-8 weeks were selected as research objects. Based on the modes of delivery, 600 patients were assigned into water immersion delivery group, 2149 were assigned into conventional delivery group. The scales of PFM strength and pelvic organ prolapsed (POP) were determined by specially trained personnel using digital palpation, and the symptoms of stress urinary incontinence (SUI) were investigated by questionnaire survey. The weak PFM strength was improved by doing Kegel exercise at home for 6-8 weeks. We found that ①The rate of episiotomy in water immersion delivery group was 77.50% (465/600), which was lower than that in conventional delivery group (84.69%, 1820/2149) (P < .01); The primiparas without having an episiotomy have higher PFM strength than those having an episiotomy for both groups (P < .01). ②There was a negative correlation between the scale of PFM strength and SUI or POP, wherein the r-values were -0.135 and -0.435, respectively (P < .01). ③The rate of SUI was 6.50% (39/600) in water immersion delivery group and 6.89% (148/2149) in the conventional delivery group, wherein the intergroup difference was not significant (P > .05); ④The rates of vaginal wall prolapsed and uterus prolapsed were 29.83% (179/600) and 2.83% (17/600) in water immersion delivery group and 30.95% (665/2149) and 4.37% (94/2149) in the conventional delivery group, wherein the intergroup difference was not significant (P > .05). ⑤After Kegel exercise, the strength of PFM was promoted (P < .01). Water immersion delivery has been proved to a beneficial alternative method for conventional delivery method. This delivery mode is associated with fewer episiotomy rate, and avoiding episiotomy is beneficial for maintaining PFM strength of women in postpartum 6-8 weeks. The strength of PFM during postpartum period can be improved by doing Kegel exercise at home.

Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

PubMed Central

Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

2014-01-01

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

The generation of NGF-secreting primary rat monocytes: a comparison of different transfer methods.

PubMed

Hohsfield, Lindsay A; Geley, Stephan; Reindl, Markus; Humpel, Christian

2013-05-31

Nerve growth factor (NGF), a member of the neurotrophin family, is responsible for the maintenance and survival of cholinergic neurons in the basal forebrain. The degeneration of cholinergic neurons and reduced acetycholine levels are hallmarks of Alzheimer's disease (AD) as well as associated with learning and memory deficits. Thus far, NGF has proven the most potent neuroprotective molecule against cholinergic neurodegeneration. However, delivery of this factor into the brain remains difficult. Recent studies have begun to elucidate the potential use of monocytes as vehicles for therapeutic delivery into the brain. In this study, we employed different transfection and transduction methods to generate NGF-secreting primary rat monocytes. Specifically, we compared five methods for generating NGF-secreting monocytes: (1) cationic lipid-mediated transfection (Effectene and FuGene), (2) classical electroporation, (3) nucleofection, (4) protein delivery (Bioporter) and (5) lentiviral vectors. Here, we report that classical transfection methods (lipid-mediated transfection, electroporation, nucleofection) are inefficient tools for proper gene transfer into primary rat monocytes. We demonstrate that lentiviral infection and Bioporter can successfully transduce/load primary rat monocytes and produce effective NGF secretion. Furthermore, our results indicate that NGF is bioactive and that Bioporter-loaded monocytes do not appear to exhibit any functional disruptions (i.e. in their ability to differentiate and phagocytose beta-amyloid). Taken together, our results show that primary monocytes can be effectively loaded or transduced with NGF and provides information on the most effective method for generating NGF-secreting primary rat monocytes. This study also provides a basis for further development of primary monocytes as therapeutic delivery vehicles to the diseased AD brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Intrathecal Drug Delivery Systems for Noncancer Pain: A Health Technology Assessment.

PubMed

2016-01-01

Intrathecal drug delivery systems can be used to manage refractory or persistent chronic nonmalignant (noncancer) pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain owing to nonmalignant conditions. We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library, and the National Health Service's Economic Evaluation Database and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and also searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. We found comparative evidence of effectiveness and harms in one cohort study at high risk of bias (≥ 3-year follow-up, N = 130). Four economic evaluations of low to very low quality were also included. Compared with oral opioid analgesia alone or a program of analgesia plus rehabilitation, intrathecal drug delivery systems significantly reduced pain (27% additional improvement) and morphine consumption. Despite these reductions, intrathecal drug delivery systems were not superior in patient-reported well-being or quality of life. There is no evidence of superiority of intrathecal drug delivery systems over oral opioids in global pain improvement and global treatment satisfaction. Comparative evidence of harms was not found. Cost-effectiveness evidence is of insufficient quality to assess the appropriateness of funding intrathecal drug delivery systems. Evidence comparing intrathecal drug delivery systems with standard care was of very low quality. Current evidence does not establish (or rule out) superiority or cost-effectiveness of intrathecal drug delivery systems for managing chronic refractory nonmalignant pain. The budget impact of funding intrathecal drug delivery systems would be between $1.5 and $5.0 million per year.

A randomised study of three different informational AIDS prior to coronary angiography, measuring patient recall, satisfaction and anxiety.

PubMed

Astley, Carolyn M; Chew, Derek P; Aylward, Philip E; Molloy, Danielle A; De Pasquale, Carmine G

2008-02-01

Informed consent is a basic standard of care for all patients undergoing medical procedures, but recall of information has been shown to be poor. We sought to compare verbal, written and animated audiovisual information delivery, during consent for coronary angiography, by measuring improvement in recall. A sample population of 99 cardiac patients at Flinders Medical Centre was randomised (1:1:1) to receive one of three information delivery methods. The information content was standardised by a risk proforma, which explained the procedure and defined 12 specific risks. Recall, satisfaction and anxiety were assessed by a questionnaire administered at three different time points: post-consent, post-procedure and at 30 days. Effect of delivery method on satisfaction and anxiety was rated on a self-reported scale from 1-5, with 5 representing very satisfied or very anxious. Groups were compared by non-parametric testing and a p-value of <0.05 was considered statistically significant. Patients were a median age of 64 (i.q.r. 56, 72) years. Information delivery method had no effect on recall of risks at any time-point (p=0.2, 0.7, 0.5, respectively) and the average recall score across the population was 3-4 out of 12. There was no significant effect on median satisfaction scores: verbal; 5 (i.q.r.4, 5) versus written/audiovisual; 4 (i.q.r.4, 5) (p=ns), or on median anxiety scores: verbal; 3 (i.q.r.2, 4) versus written/audiovisual; 3 (i.q.r.2, 4) (p=ns). Despite careful design of an innovative audiovisual delivery technique aimed at optimising comprehension and aiding memory, recall of information was poor and informational aids showed no improvement. Modes of information delivery are not the key to patient assimilation of complex medical information.

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

PubMed

Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, K-N; Park, S-J; Bhandari, D R; Lee, K-H; An, G-H; Beck, G R; Cho, M-H

2007-03-01

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

Heat effects on drug delivery across human skin

PubMed Central

Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.

2016-01-01

Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472

In vivo investigation of temporal effects and drug delivery induced by transdermal microneedles with optical coherence tomography

PubMed Central

Tsai, Meng-Tsan; Lee, I-Chi; Lee, Zhung-Fu; Liu, Hao-Li; Wang, Chun-Chieh; Choia, Yo-Chun; Chou, Hsin-Yi; Lee, Jiann-Der

2016-01-01

Transdermal drug-delivery systems (TDDS) have been a growing field in drug delivery because of their advantages over parenteral and oral administration. Recent studies illustrate that microneedles (MNs) can effectively penetrate through the stratum corneum barrier to facilitate drug delivery. However, the temporal effects on skin and drug diffusion are difficult to investigate in vivo. In this study, we used optical coherence tomography (OCT) to observe the process by which MNs dissolve and to investigate the temporal effects on mouse skin induced by MNs, including the morphological and vascular changes. Moreover, the recovery process of the skin was observed with OCT. Additionally, we proposed a method to observe drug delivery by estimation of cross-correlation relationship between sequential 2D OCT images obtained at the same location, reflecting the variation in the backscattered intensity due to the diffusion of the rhodamine molecules encapsulated in MNs. Our observations supported the hypothesis that the temporal effects on skin due to MNs, the dissolution of MNs, and the drug diffusion process can be quantitatively evaluated with OCT. The results showed that OCT can be a potential tool for in vivo monitoring of effects and outcomes when MNs are used as a TDDS. PMID:27231627

[Combined spinal and epidural anaesthesia in abdominal delivery].

PubMed

Matlubov, M M; Rakhimov, A U; Semenikhin, A A

2010-01-01

The purpose of this work is to estimate the efficacy and safety of balanced two-segmental spinal-epidural anaesthesia (SEA) as well as application of this technique in conditions of extended operative delivery. The method has been used in 69 pregnant patients aged 23-42 years, with gestation period ranging from 36 to 40 weeks. It was found out that SEA is highly effective and safe technique, therefore it can be recommended as suitable method of anaesthesia in surgery with an extension possibility.

Frank Gilbreth and health care delivery method study driven learning.

PubMed

Towill, Denis R

2009-01-01

The purpose of this article is to look at method study, as devised by the Gilbreths at the beginning of the twentieth century, which found early application in hospital quality assurance and surgical "best practice". It has since become a core activity in all modern methods, as applied to healthcare delivery improvement programmes. The article traces the origin of what is now currently and variously called "business process re-engineering", "business process improvement" and "lean healthcare" etc., by different management gurus back to the century-old pioneering work of Frank Gilbreth. The outcome is a consistent framework involving "width", "length" and "depth" dimensions within which healthcare delivery systems can be analysed, designed and successfully implemented to achieve better and more consistent performance. Healthcare method (saving time plus saving motion) study is best practised as co-joint action learning activity "owned" by all "players" involved in the re-engineering process. However, although process mapping is a key step forward, in itself it is no guarantee of effective re-engineering. It is not even the beginning of the end of the change challenge, although it should be the end of the beginning. What is needed is innovative exploitation of method study within a healthcare organisational learning culture accelerated via the Gilbreth Knowledge Flywheel. It is shown that effective healthcare delivery pipeline improvement is anchored into a team approach involving all "players" in the system especially physicians. A comprehensive process study, constructive dialogue, proper and highly professional re-engineering plus managed implementation are essential components. Experience suggests "learning" is thereby achieved via "natural groups" actively involved in healthcare processes. The article provides a proven method for exploiting Gilbreths' outputs and their many successors in enabling more productive evidence-based healthcare delivery as summarised in the "learn-do-learn-do" feedback loop in the Gilbreth Knowledge Flywheel.

Bovine adenovirus-3 as a vaccine delivery vehicle.

PubMed

Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

2015-01-15

The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

PubMed Central

Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

2014-01-01

Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

Contaminated water delivery as a simple and effective method of experimental Salmonella infection

PubMed Central

O’Donnell, Hope; Pham, Oanh H.; Benoun, Joseph M.; Ravesloot-Chávez, Marietta M.; McSorley, Stephen J.

2016-01-01

Aims In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the gastrointestinal tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. Materials and Methods C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. Results We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 hours allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Conclusions Together, these data question the need for gavage delivery for infection with oral pathogens. PMID:26439708

Thiolated polymers as mucoadhesive drug delivery systems.

PubMed

Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

2017-03-30

Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Placental Abruption and Perinatal Mortality With Preterm Delivery as a Mediator: Disentangling Direct and Indirect Effects

PubMed Central

Ananth, Cande V.; VanderWeele, Tyler J.

2011-01-01

The authors use recent methodology in causal inference to disentangle the direct and indirect effects that operate through a mediator in an exposure-response association paradigm. They demonstrate how total effects can be partitioned into direct and indirect effects even when the exposure and mediator interact. The impact of bias due to unmeasured confounding on the exposure-response association is assessed through a series of sensitivity analyses. These methods are applied to a problem in perinatal epidemiology to examine the extent to which the effect of abruption on perinatal mortality is mediated through preterm delivery. Data on over 26 million US singleton births (1995–2002) were utilized. Risks of mortality among abruption and nonabruption births were 102.7 and 6.2 per 1,000 births, respectively. Risk ratios of the natural direct and indirect (preterm delivery-mediated) effects of abruption on mortality were 10.18 (95% confidence interval: 9.80, 10.58) and 1.35 (95% confidence interval: 1.33, 1.38), respectively. The proportion of increased mortality risk mediated through preterm delivery was 28.1%, with even higher proportions associated with deliveries at earlier gestational ages. Sensitivity analyses underscore that the qualitative conclusions of some mediated effects and substantial direct effects are reasonably robust to unmeasured confounding of a fairly considerable magnitude. PMID:21430195

Effects of Emulsion Composition on Pulmonary Tobramycin Delivery During Antibacterial Perfluorocarbon Ventilation

PubMed Central

Orizondo, Ryan A.; Fabiilli, Mario L.; Morales, Marissa A.

2016-01-01

Abstract Background: The effectiveness of inhaled aerosolized antibiotics is limited by poor ventilation of infected airways. Pulmonary delivery of antibiotics emulsified within liquid perfluorocarbon [antibacterial perfluorocarbon ventilation (APV)] may solve this problem through better airway penetration and improved spatial uniformity. However, little work has been done to explore emulsion formulation and the corresponding effects on drug delivery during APV. This study investigated the effects of emulsion formulation on emulsion stability and the pharmacokinetics of antibiotic delivery via APV. Methods: Gravity-driven phase separation was examined in vitro by measuring emulsion tobramycin concentrations at varying heights within a column of emulsion over 4 hours for varying values of fluorosurfactant concentration (Cfs = 5–48 mg/mL H2O). Serum and pulmonary tobramycin concentrations in rats were then evaluated following pulmonary tobramycin delivery via aerosol or APV utilizing sufficiently stable emulsions of varying aqueous volume percentage (Vaq = 1%–5%), aqueous tobramycin concentration (Ct = 20–100 mg/mL), and Cfs (15 and 48 mg/mL H2O). Results: In vitro assessment showed sufficient spatial and temporal uniformity of tobramycin dispersion within emulsion for Cfs ≥15 mg/mL H2O, while lower Cfs values showed insufficient emulsification even immediately following preparation. APV with stable emulsion formulations resulted in 5–22 times greater pulmonary tobramycin concentrations at 4 hours post-delivery relative to aerosolized delivery. Concentrations increased with emulsion formulations utilizing increased Vaq (with decreased Ct) and, to a lesser extent, increased Cfs. Conclusions: The emulsion stability necessary for effective delivery is retained at Cfs values as low as 15 mg/mL H2O. Additionally, the pulmonary retention of antibiotic delivered via APV is significantly greater than that of aerosolized delivery and can be most effectively increased by increasing Vaq and decreasing Ct. APV has been further proven as an effective means of pulmonary drug delivery with the potential to significantly improve antibiotic therapy for lung disease patients. PMID:26741303

Innovative Technology for the Assisted Delivery of Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson Disease

ERIC Educational Resources Information Center

Halpern, Angela E.; Ramig, Lorraine O.; Matos, Carlos E. C.; Petska-Cable, Jill A.; Spielman, Jennifer L.; Pogoda, Janice M.; Gilley, Phillip M.; Sapir, Shimon; Bennett, John K.; McFarland, David H.

2012-01-01

Purpose: To assess the feasibility and effectiveness of a newly developed assistive technology system, Lee Silverman Voice Treatment Companion (LSVT[R] Companion[TM], hereafter referred to as "Companion"), to support the delivery of LSVT[R]LOUD, an efficacious speech intervention for individuals with Parkinson disease (PD). Method: Sixteen…

The delivery of medical services in a retail shopping mall: a strategy for growth.

PubMed

Hayden, K R

1989-01-01

The successful medical practice of the future will continually search for growth strategies. This writer believes the location of a primary care medical clinic in a retail shopping mall, with a full menu of primary services, is one strategy for growth. It is an effective method of health care delivery to a community.

Mitigating the risk of food handling in the home-delivered meal program.

PubMed

Namkung, Young; Ismail, Joseph A; Almanza, Barbara A; Nelson, Douglas C

2007-02-01

The purpose of this cross-sectional study was to examine the length of time between packing and delivery of home-delivered meals, and the extent of foodborne illness risk to the elderly. Procedures to mitigate that risk were also evaluated. Researchers surveyed 95 drivers from home-delivered meal preparation sites in six states across the United States to determine the average length of time that passed during packing, loading, leaving, and delivery. The efficiency of various risk mitigation methods were evaluated and used to adjust the actual delivery time. Total average delivery time from packing to last delivery was 1.92 hours. This study suggests that the risk associated with the actual 1.92 hours of total delivery time could be mitigated to represent approximately 1.55 hours of effective time with proper packing and holding conditions. This methodology proposes a single measure for evaluating the effectiveness of various handling procedures associated with distributing home-delivered meals, which can be utilized to evaluate overall risk when combined with in-house preparation and client-handling behaviors.

Method of hyperthermia and tumor size influence effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors.

PubMed

Willerding, Linus; Limmer, Simone; Hossann, Martin; Zengerle, Anja; Wachholz, Kirsten; Ten Hagen, Timo L M; Koning, Gerben A; Sroka, Ronald; Lindner, Lars H; Peller, Michael

2016-01-28

Systemic chemotherapy of solid tumors could be enhanced by local hyperthermia (HT) in combination with thermosensitive liposomes (TSL) as drug carriers. In such an approach, effective HT of the tumor is considered essential for successful triggering local drug release and targeting of the drug to the tumor. To investigate the effect of HT method on the effectiveness of drug delivery, a novel laser-based HT device designed for the use in magnetic resonance imaging (MRI) was compared systematically with the frequently used cold light lamp and water bath HT. Long circulating phosphatidyldiglycerol-based TSL (DPPG2-TSL) with encapsulated doxorubicin (DOX) were used as drug carrier enabling intravascular drug release. Experiments were performed in male Brown Norway rats with a syngeneic soft tissue sarcoma (BN 175) located on both hind legs. One tumor was heated while the second tumor remained unheated as a reference. Six animals were investigated per HT method. DPPG2-TSL were injected i.v. at a stable tumor temperature above 40°C. Thereafter, temperature was maintained for 60min. Total DOX concentration in plasma, tumor tissue and muscle was determined post therapy by HPLC. Finally, the new laser-based device was tested in a MRI environment at 3T using DPPG2-TSL with encapsulated Gd-based contrast agent. All methods showed effective DOX delivery by TSL with 4.5-23.1ng/mg found in the heated tumors. In contrast, DOX concentration in the non-heated tumors was 0.5±0.1ng/mg. Independent of used HT methods, higher DOX levels were found in the smaller tumors. In comparison water bath induced lowest DOX delivery but still showing fourfold higher DOX concentrations compared to the non-heated tumors. With the laser-based applicator, a 13 fold higher DOX deposition was possible for large tumors and a 15 fold higher for the small tumors, respectively. Temperature gradients in the tumor tissue were higher with the laser and cold light lamp (-0.3°C/mm to -0.5°C/mm) compared to the water bath (-0.1°C/mm and -0.2°C/mm). Visualization of HT in the MRI demonstrated successful localized heating throughout the entire tumor volume by contrast agent release from DPPG2-TSL. In conclusion, HT triggered drug delivery by using DPPG2-TSL is a promising tool in chemotherapy but effectiveness markedly depended on the method of heating and also on tumor size. Local HT using a cold light lamp or the new laser applicator allowed more efficient drug delivery than using a regional water bath heating. MR-compatibility of the new applicator gives the opportunity for future experiments investing drug delivery in more detail by MRI at low technical efforts. Copyright © 2015 Elsevier B.V. All rights reserved.

Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

PubMed Central

Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

2009-01-01

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

Quadratus Lumborum Block Versus Transversus Abdominis Plane Block for Postoperative Pain After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Blanco, Rafael; Ansari, Tarek; Riad, Waleed; Shetty, Nanda

Effective postoperative analgesia after cesarean delivery enhances early recovery, ambulation, and breastfeeding. In a previous study, we established the effectiveness of the quadratus lumborum block in providing pain relief after cesarean delivery compared with patient-controlled analgesia (morphine). In the current study, we hypothesized that this method would be equal to or better than the transversus abdominis plane block with regard to pain relief and its duration of action after cesarean delivery. Between April 2015 and August 2015, we randomized 76 patients scheduled for elective cesarean delivery under spinal anesthesia to receive the quadratus lumborum block or the transversus abdominis plane block for postoperative pain relief. This trial was registered prospectively (NCT 02489851) [corrected]. Patients in the quadratus lumborum block group used significantly less morphine than the transversus abdominis plane block group (P < 0.05) at 12, 24, and 48 hours but not at 4 and 6 hours after cesarean delivery. This group also had significantly fewer morphine demands than the control group (P < 0.05) at 6, 12, 24, and 48 hours after cesarean delivery. No significant differences in visual analog scale results were shown between the 2 groups at rest or with movement. Calculated total pain relief at rest and with movement were similar (P < 0.001) in both groups. The quadratus lumborum block was more effective in reducing morphine consumption and demands than transversus abdominis plane blocks after cesarean section. This effect was observed up to 48 hours postoperatively.

Non-Viral Transfection Methods Optimized for Gene Delivery to a Lung Cancer Cell Line

PubMed Central

Salimzadeh, Loghman; Jaberipour, Mansooreh; Hosseini, Ahmad; Ghaderi, Abbas

2013-01-01

Background Mehr-80 is a newly established adherent human large cell lung cancer cell line that has not been transfected until now. This study aims to define the optimal transfection conditions and effects of some critical elements for enhancing gene delivery to this cell line by utilizing different non-viral transfection Procedures. Methods In the current study, calcium phosphate (CaP), DEAE-dextran, superfect, electroporation and lipofection transfection methods were used to optimize delivery of a plasmid construct that expressed Green Fluorescent Protein (GFP). Transgene expression was detected by fluorescent microscopy and flowcytometry. Toxicities of the methods were estimated by trypan blue staining. In order to evaluate the density of the transfected gene, we used a plasmid construct that expressed the Stromal cell-Derived Factor-1 (SDF-1) gene and measured its expression by real-time PCR. Results Mean levels of GFP-expressing cells 48 hr after transfection were 8.4% (CaP), 8.2% (DEAE-dextran), 4.9% (superfect), 34.1% (electroporation), and 40.1% (lipofection). Lipofection had the highest intense SDF-1 expression of the analyzed methods. Conclusion This study has shown that the lipofection and electroporation methods were more efficient at gene delivery to Mehr-80 cells. The quantity of DNA per transfection, reagent concentration, and incubation time were identified as essential factors for successful transfection in all of the studied methods. PMID:23799175

Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

PubMed Central

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-01-01

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

PubMed

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

PubMed Central

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-01-01

Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems. PMID:29473914

Microfabrication for Drug Delivery

PubMed Central

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

Intravenous Delivery of pDNA and siRNA into Muscle with Bubble Liposomes and Ultrasound

NASA Astrophysics Data System (ADS)

Negishi, Yoichi; Sekine, Shohko; Endo, Yoko; Nishijima, Nobuaki; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

2010-03-01

Skeletal muscle is an attractive target tissue for numerous gene therapy strategies. Gene delivery into muscle has been extensively studied. Of the strategies, intravascular delivery of naked pDNA is desirable. Muscle has a high density of capillaries that are in close contact with myofibers. Previously, we developed polyethylene glycol (PEG)-modified liposomes entrapping echo-contrast gas, known as ultrasound (US) imaging gas. We called the liposomes "Bubble liposomes" (BLs). It has been reported that BLs improve the tissue permeability by cavitation on US exposure. Here, we modified the naked pDNA or siRNA transfer method into hind limb muscle through blood vessels using BLs and US. The intravenous delivery of pDNA into muscle can be markedly enhanced when the pDNA is delivered in combination with BLs and US. In addition, the expression of pDNA is high in the US-focused site. Moreover, efficient gene delivery can be achieved by the intravenous delivery of pDNA into muscle with BLs and US. Expression is also down-regulated by delivering siRNA with BLs and US. Thus, this US-mediated BL technique involving veins may be an effective method for gene therapy.

Synthetic mRNA is a more reliable tool for the delivery of DNA-targeting proteins into the cell nucleus than fusion with a protein transduction domain.

PubMed

Leontovyc, Ivan; Habart, David; Loukotova, Sarka; Kosinova, Lucie; Kriz, Jan; Saudek, Frantisek; Koblas, Tomas

2017-01-01

Cell reprogramming requires efficient delivery of reprogramming transcription factors into the cell nucleus. Here, we compared the robustness and workload of two protein delivery methods that avoid the risk of genomic integration. The first method is based on fusion of the protein of interest to a protein transduction domain (PTD) for delivery across the membranes of target cells. The second method relies on de novo synthesis of the protein of interest inside the target cells utilizing synthetic mRNA (syn-mRNA) as a template. We established a Cre/lox reporter system in three different cell types derived from human (PANC-1, HEK293) and rat (BRIN-BD11) tissues and used Cre recombinase to model a protein of interest. The system allowed constitutive expression of red fluorescence protein (RFP), while green fluorescence protein (GFP) was expressed only after the genomic action of Cre recombinase. The efficiency of protein delivery into cell nuclei was quantified as the frequency of GFP+ cells in the total cell number. The PTD method showed good efficiency only in BRIN-BD11 cells (68%), whereas it failed in PANC-1 and HEK293 cells. By contrast, the syn-mRNA method was highly effective in all three cell types (29-71%). We conclude that using synthetic mRNA is a more robust and less labor-intensive approach than using the PTD-fusion alternative.

Delivery of dsRNA through topical feeding for RNA interference in the citrus sap piercing-sucking hemipteran, Diaphorina citri.

PubMed

Killiny, Nabil; Kishk, Abdelaziz

2017-06-01

RNA interference (RNAi) is a powerful means to study functional genomics in insects. The delivery of dsRNA is a challenging step in the development of RNAi assay. Here, we describe a new delivery method to increase the effectiveness of RNAi in the Asian citrus psyllid Diaphorina citri. Bromophenol blue droplets were topically applied to fifth instar nymphs and adults on the ventral side of the thorax between the three pairs of legs. In addition to video recordings that showed sucking of the bromophenol blue by the stylets, dissected guts turned blue indicating that the uptake was through feeding. Thus, we called the method topical feeding. We targeted the abnormal wing disc gene (awd), also called nucleoside diphosphate kinase (NDPK), as a reporter gene to prove the uptake of dsRNA via this method of delivery. Our results showed that dsRNA-awd caused reduction of awd expression and nymph mortality. Survival and lifespan of adults emerged from treated nymphs and treated adults were affected. Silencing awd caused wing malformation in the adults emerged from treated nymphs. Topical feeding as a delivery of dsRNA is highly efficient for both nymphs and adults. The described method could be used to increase the efficiency of RNAi in D. citri and other sap piercing-sucking hemipterans. © 2017 Wiley Periodicals, Inc.

Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

PubMed Central

Li, Bo; Wang, Hai; Qiu, Guixing; Su, Xinlin

2016-01-01

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs), as key mediators in angiogenesis and osteogenesis, are used in a combined delivery manner as a novel strategy in bone tissue engineering. VEGF has the potential to enhance BMPs induced bone formation. Both gene delivery and material-based delivery systems were incorporated in previous studies to investigate the synergistic effects of VEGF and BMPs. However, their results were controversial due to variation of methods incorporated in different studies. Factors influencing the synergistic effects of VEGF on BMPs induced bone formation were identified and analyzed in this review to reduce confusion on this issue. The potential mechanisms and directions of future studies were also proposed here. Further investigating mechanisms of the synergistic effects and optimizing these influencing factors will help to generate more effective bone regeneration. PMID:28070506

Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth

PubMed Central

Walenga, Ross L.; Kaviratna, Anubhav; Hindle, Michael

2017-01-01

Abstract Background: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. Materials and Methods: A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Results: Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%–134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%–17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%–90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. Conclusions: The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration. PMID:28075194

How to Select a Project Delivery Method for School Facilities

ERIC Educational Resources Information Center

Kalina, David

2007-01-01

In this article, the author discusses and explains three project delivery methods that are commonly used today in the United States. The first project delivery method mentioned is the design-bid-build, which is still the predominant method of project delivery for public works and school construction in the United States. The second is the…

Boosting facility deliveries with results-based financing: a mixed-methods evaluation of the government midwifery incentive scheme in Cambodia.

PubMed

Ir, Por; Korachais, Catherine; Chheng, Kannarath; Horemans, Dirk; Van Damme, Wim; Meessen, Bruno

2015-08-15

Increasing the coverage of skilled attendance at births in a health facility (facility delivery) is crucial for saving the lives of mothers and achieving Millennium Development Goal five. Cambodia has significantly increased the coverage of facility deliveries and reduced the maternal mortality ratio in the last decade. The introduction of a nationwide government implemented and funded results-based financing initiative, known as the Government Midwifery Incentive Scheme (GMIS), is considered one of the most important contributors to this. We evaluated GMIS to explore its effects on facility deliveries and the health system. We used a mixed-methods design. An interrupted time series model was applied, using routine longitudinal data on reported deliveries between 2006 and 2011 that were extracted from the health information system. In addition, we interviewed 56 key informants and performed 12 focus group discussions with 124 women who had given birth (once or more) since 2006. Findings from the quantitative data were carefully interpreted and triangulated with those from qualitative data. We found that facility deliveries have tripled from 19% of the estimated number of births in 2006 to 57% in 2011 and this increase was more substantial at health centres as compared to hospitals. Segmented linear regressions showed that the introduction of GMIS in October 2007 made the increase in facility deliveries and deliveries with skilled attendants significantly jump by 18 and 10% respectively. Results from qualitative data also suggest that the introduction of GMIS together with other interventions that aimed to improve access to essential maternal health services led to considerable improvements in public health facilities and a steep increase in facility deliveries. Home deliveries attended by traditional birth attendants decreased concomitantly. We also outline several operational issues and limitations of GMIS. The available evidence strongly suggests that GMIS is an effective mechanism to complement other interventions to improve health system performance and boost facility deliveries as well as skilled birth attendance; thereby contributing to the reduction of maternal mortality. Our findings provide useful lessons for Cambodia to further improve GMIS and for other low-income countries to implement similar results-based financing mechanisms.

Real-time evaluation of two light delivery systems for photodynamic disinfection of Candida albicans biofilm in curved root canals.

PubMed

Sabino, C P; Garcez, A S; Núñez, S C; Ribeiro, M S; Hamblin, M R

2015-08-01

Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has been recognized as an alternative approach to complement conventional root canal disinfection methods on bacterial biofilms. We developed an in  vitro model of bioluminescent Candida albicans biofilm inside curved dental root canals and investigated the microbial reduction produced when different light delivery methods are employed. Each light delivery method was evaluated in respect to the light distribution provided inside curved root canals. After conventional endodontic preparation, teeth were sterilized before canals were contaminated by a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 μM) was introduced into the canals and then irradiated (λ = 660 nm, P = 100 mW, beam diameter = 2 mm) with laser tip either in contact with pulp chamber or within the canal using an optical diffuser fiber. Light distribution was evaluated by CCD camera, and microbial reduction was monitored through bioluminescence imaging. Our findings demonstrated that the bioluminescent C. albicans biofilm model had good reproducibility and uniformity. Light distribution in dental tissue was markedly dependent on the light delivery system, and this strategy was directly related to microbial destruction. Both light delivery systems performed significant fungal inactivation. However, when irradiation was performed with optical diffuser fiber, microbial burden reduction was nearly 100 times more effective. Bioluminescence is an interesting real-time analysis to endodontic C. albicans biofilm inactivation. APDT showed to be an effective way to inactivate C. albicans biofilms. Diffuser fibers provided optimized light distribution inside curved root canals and significantly increased APDT efficiency.

Real-time evaluation of two light delivery systems for photodynamic disinfection of Candida albicans biofilm in curved root canals

PubMed Central

Sabino, C. P.; Garcez, A. S.; Núñez, S. C.; Ribeiro, M. S.; Hamblin, M. R.

2014-01-01

Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has been recognized as an alternative approach to complement conventional root canal disinfection methods on bacterial biofilms. We developed an in vitro model of bioluminescent Candida albicans biofilm inside curved dental root canals and investigated the microbial reduction produced when different light delivery methods are employed. Each light delivery method was evaluated in respect to the light distribution provided inside curved root canals. After conventional endodontic preparation, teeth were sterilized before canals were contaminated by a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 µM) was introduced into the canals and then irradiated (λ=660 nm, P=100 mW, beam diameter=2 mm) with laser tip either in contact with pulp chamber or within the canal using an optical diffuser fiber. Light distribution was evaluated by CCD camera, and microbial reduction was monitored through bioluminescence imaging. Our findings demonstrated that the bioluminescent C. albicans biofilm model had good reproducibility and uniformity. Light distribution in dental tissue was markedly dependent on the light delivery system, and this strategy was directly related to microbial destruction. Both light delivery systems performed significant fungal inactivation. However, when irradiation was performed with optical diffuser fiber, microbial burden reduction was nearly 100 times more effective. Bioluminescence is an interesting real-time analysis to endodontic C. albicans biofilm inactivation. APDT showed to be an effective way to inactivate C. albicans biofilms. Diffuser fibers provided optimized light distribution inside curved root canals and significantly increased APDT efficiency. PMID:25060900

A bacterial type III secretion-based protein delivery tool for broad applications in cell biology.

PubMed

Ittig, Simon J; Schmutz, Christoph; Kasper, Christoph A; Amstutz, Marlise; Schmidt, Alexander; Sauteur, Loïc; Vigano, M Alessandra; Low, Shyan Huey; Affolter, Markus; Cornelis, Guy R; Nigg, Erich A; Arrieumerlou, Cécile

2015-11-23

Methods enabling the delivery of proteins into eukaryotic cells are essential to address protein functions. Here we propose broad applications to cell biology for a protein delivery tool based on bacterial type III secretion (T3S). We show that bacterial, viral, and human proteins, fused to the N-terminal fragment of the Yersinia enterocolitica T3S substrate YopE, are effectively delivered into target cells in a fast and controllable manner via the injectisome of extracellular bacteria. This method enables functional interaction studies by the simultaneous injection of multiple proteins and allows the targeting of proteins to different subcellular locations by use of nanobody-fusion proteins. After delivery, proteins can be freed from the YopE fragment by a T3S-translocated viral protease or fusion to ubiquitin and cleavage by endogenous ubiquitin proteases. Finally, we show that this delivery tool is suitable to inject proteins in living animals and combine it with phosphoproteomics to characterize the systems-level impact of proapoptotic human truncated BID on the cellular network. © 2015 Ittig et al.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

PubMed Central

Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

2016-01-01

Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

Delivery Pain Anxiety/Fear Control between Midwives among Women in Cross River State, Nigeria

ERIC Educational Resources Information Center

Oyira, Emilia James; Mgbekem, Mary; Osuchukwu, Easther Chukwudi; Affiong, Ekpenyong Onoyom; Lukpata, Felicia E.; Ojong-Alasia, Mary Manyo

2016-01-01

Objective: To examine background of midwives the effectiveness in delivery pain and anxiety/fear control of expectant mothers in Nigeria. Methods: Two null hypotheses were formulated. The survey design with sample of 360 post-natal women was selected from a population of 78,814 through the polio immunization registers of selected health center in…

Leadership training design, delivery, and implementation: A meta-analysis.

PubMed

Lacerenza, Christina N; Reyes, Denise L; Marlow, Shannon L; Joseph, Dana L; Salas, Eduardo

2017-12-01

Recent estimates suggest that although a majority of funds in organizational training budgets tend to be allocated to leadership training (Ho, 2016; O'Leonard, 2014), only a small minority of organizations believe their leadership training programs are highly effective (Schwartz, Bersin, & Pelster, 2014), calling into question the effectiveness of current leadership development initiatives. To help address this issue, this meta-analysis estimates the extent to which leadership training is effective and identifies the conditions under which these programs are most effective. In doing so, we estimate the effectiveness of leadership training across four criteria (reactions, learning, transfer, and results; Kirkpatrick, 1959) using only employee data and we examine 15 moderators of training design and delivery to determine which elements are associated with the most effective leadership training interventions. Data from 335 independent samples suggest that leadership training is substantially more effective than previously thought, leading to improvements in reactions (δ = .63), learning (δ = .73), transfer (δ = .82), and results (δ = .72), the strength of these effects differs based on various design, delivery, and implementation characteristics. Moderator analyses support the use of needs analysis, feedback, multiple delivery methods (especially practice), spaced training sessions, a location that is on-site, and face-to-face delivery that is not self-administered. Results also suggest that the content of training, attendance policy, and duration influence the effectiveness of the training program. Practical implications for training development and theoretical implications for leadership and training literatures are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

PubMed Central

Sun, Shaoping; Liang, Na; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

2015-01-01

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery. PMID:25999713

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin.

PubMed

Sun, Shaoping; Liang, Na; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

2015-01-01

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin-sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit(®) FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.

23 CFR 635.104 - Method of construction.

Code of Federal Regulations, 2010 CFR

2010-04-01

... effectiveness is necessary in selecting projects for the design-build delivery method. [56 FR 37004, Aug. 2... 23 Highways 1 2010-04-01 2010-04-01 false Method of construction. 635.104 Section 635.104 Highways... CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.104 Method of construction. (a) Actual construction work...

Future therapeutic directions; new medications and insulin delivery in a changing world for effective diabetes management.

PubMed

Modi, Pankaj

2009-09-01

Insulin remains a key to the management of diabetes. The early addition of insulin to oral therapy in type-2 patients is recognized as an effective option that can help improve glycemic control and reduces the complications and contribute to more favorable outcomes. Controlling blood glucose levels within acceptable limits is crucial to the long-term health of patients with diabetes. The benefits of patient education and chronic disease management tools cannot be underestimated as many patients will require education and help in initiation of insulin therapy to achieve glycemic targets. The wide choice of insulin formulations and the ever-expanding range of delivery methods are now available. These methods made insulin administration easier, less painful, more discreet, and more accurate than ever before thus providing important tools to overcome barriers to insulin initiation and improve achievement of glycemic goals. In addition, exciting developments in newer therapeutics have increased the potential for optimal glycemic control. This review discusses how these approaches can help patients manage their diabetes effectively by considering new insulin formulations and delivery devices and newer therapeutics.

Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery

NASA Astrophysics Data System (ADS)

Wu, Zhi Min; Ling, Li; Zhou, Li Ying; Guo, Xin Dong; Jiang, Wei; Qian, Yu; Luo, Kathy Qian; Zhang, Li Juan

2012-06-01

The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia.

PubMed

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998-2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. The content of care may fulfill the women's need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery.

At What Price? A Cost-Effectiveness Analysis Comparing Trial of Labour after Previous Caesarean versus Elective Repeat Caesarean Delivery

PubMed Central

Fawsitt, Christopher G.; Bourke, Jane; Greene, Richard A.; Everard, Claire M.; Murphy, Aileen; Lutomski, Jennifer E.

2013-01-01

Background Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland. Methods Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both “bottom-up” and “top-down” costing estimations. Results Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD (€1,835.06 versus €4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis. Conclusions Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model. PMID:23484038

A Panel Analysis of the Strategic Association Between Information and Communication Technology and Public Health Delivery

PubMed Central

Wu, Sarah Jinhui

2012-01-01

Background In this exploratory research, we use panel data analysis to examine the correlation between Information and Communication Technology (ICTs) and public health delivery at the country level. Objective The goal of this exploratory research is to examine the strategic association over time between ICTs and country-level public health. Methods Using data from the World Development Indicators, we construct a panel data set of countries of five different income levels and look closely at the period from 2000 to 2008. The panel data analysis allows us to explore this dynamic relationship under the control for unobserved country-specific effects by using a fixed-effects estimation method. In particular,, we examine the association of five ICT factors with five public health indicators: adolescent fertility rate, child immunization coverage, tuberculosis case detected, life expectancy, and adult mortality rate. Results First, overall ICTs’ factors substantially improve a country’s public health delivery on the top of wealth effect. Second, among all the ICTs’ factors, accessibility is the only one that is associated with improvements in all aspects of public health delivery, while the contributions from the usage, quality, and applications are negligible. ICTs’ accessibility factor is associated with a considerable extension to life expectancy and reduced adult mortality rate. Third, all entity-specific factors are significant in each model, indicating that countries’ economic development level does influence their public health delivery. Conclusions Our results indicate that ICT accessibility has a strong association with effective delivery of public health. There are others, but the key strategic applications are eHealth and mHealth. The findings of this study will help government officials and public health policy makers to formulate strategic decisions regarding the best ICT investments and deployment. For example, the study shows that providing accessibility should be a critical focus. PMID:23089193

Effective Parenting Interventions to Reduce Youth Substance Use: A Systematic Review

PubMed Central

Garcia-Huidobro, Diego; Porta, Carolyn; Curran, Dorothy; Patel, Roma; Miller, Jonathan; Borowsky, Iris

2016-01-01

CONTEXT: Parenting interventions may prevent adolescent substance use; however, questions remain regarding the effectiveness of interventions across substances and delivery qualities contributing to successful intervention outcomes. OBJECTIVE: To describe the effectiveness of parent-focused interventions in reducing or preventing adolescent tobacco, alcohol, and illicit substance use and to identify optimal intervention targeted participants, dosage, settings, and delivery methods. DATA SOURCES: PubMed, PsycINFO, ERIC, and CINAHL. STUDY SELECTION: Randomized controlled trials reporting adolescent substance use outcomes, focusing on imparting parenting knowledge, skills, practices, or behaviors. DATA EXTRACTION: Trained researchers extracted data from each article using a standardized, prepiloted form. Because of study heterogeneity, a qualitative technique known as harvest plots was used to summarize findings. RESULTS: A total of 42 studies represented by 66 articles met inclusion criteria. Results indicate that parenting interventions are effective at preventing and decreasing adolescent tobacco, alcohol, and illicit substance use over the short and long term. The majority of effective interventions required ≤12 contact hours and were implemented through in-person sessions including parents and youth. Evidence for computer-based delivery was strong only for alcohol use prevention. Few interventions were delivered outside of school or home settings. LIMITATIONS: Overall risk of bias is high. CONCLUSIONS: This review suggests that relatively low-intensity group parenting interventions are effective at reducing or preventing adolescent substance use and that protection may persist for multiple years. There is a need for additional evidence in clinical and other community settings using an expanded set of delivery methods. PMID:27443357

Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

PubMed Central

Dinarvand, R; Sepehri, N; Manoochehri, S; Rouhani, H; Atyabi, F

2011-01-01

The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA), a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects. PMID:21720501

Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

NASA Astrophysics Data System (ADS)

Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

2016-08-01

We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

Biomimetics in drug delivery systems: A critical review.

PubMed

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation on Physicochemical Characteristics of a Nanoliposome-Based System for Dual Drug Delivery

NASA Astrophysics Data System (ADS)

Nam, Jae Hyun; Kim, So-Yeon; Seong, Hasoo

2018-04-01

Synergistic effects of multiple drugs with different modes of action are utilized for combinatorial chemotherapy of intractable cancers. Translation of in vitro synergistic effects into the clinic can be realized using an efficient delivery system of the drugs. Despite a few studies on nano-sized liposomes containing erlotinib (ERL) and doxorubicin (DOX) in a single liposome vesicle, reliable and reproducible preparation methods as well as physicochemical characteristics of a non-PEGylated nanoliposome co-encapsulated with ERL and DOX have not been yet elucidated. In this study, ERL-encapsulated nanoliposomes were prepared using the lipid film-hydration method. By ultrasonication using a probe sonicator, the liposome diameter was reduced to less than 200 nm. DOX was loaded into the ERL-encapsulated nanoliposomes using ammonium sulfate (AS)-gradient or pH-gradient method. Effects of DOX-loading conditions on encapsulation efficiency (EE) of the DOX were investigated to determine an efficient drug-loading method. In the EE of DOX, AS-gradient method was more effective than pH gradient. The dual drug-encapsulated nanoliposomes had more than 90% EE of DOX and 30% EE of ERL, respectively. Transmission electron microscopy and selected area electron diffraction analyses of the dual drug-encapsulated nanoliposomes verified the highly oriented DOX-sulfate crystals inside the liposome as well as the less oriented small crystals of ERL in the outermost region of the nanoliposome. The nanoliposomes were stable at different temperatures without an increase of the nanoliposome diameter. The dual drug-encapsulated nanoliposomes showed a time-differential release of ERL and DOX, implying proper sequential releases for their synergism. The preparation methods and the physicochemical characteristics of the dual drug delivery system contribute to the development of the optimal process and more advanced systems for translational researches.

Parent-based adolescent sexual health interventions and effect on communication outcomes: a systematic review and meta-analyses.

PubMed

Santa Maria, Diane; Markham, Christine; Bluethmann, Shirley; Mullen, Patricia Dolan

2015-03-01

Parent-based adolescent sexual health interventions aim to reduce sexual risk behaviors by bolstering parental protective behaviors. Few studies of theory use, methods, applications, delivery and outcomes of parent-based interventions have been conducted. A systematic search of databases for the period 1998-2013 identified 28 published trials of U.S. parent-based interventions to examine theory use, setting, reach, delivery mode, dose and effects on parent-child communication. Established coding schemes were used to assess use of theory and describe methods employed to achieve behavioral change; intervention effects were explored in meta-analyses. Most interventions were conducted with minority parents in group sessions or via self-paced activities; interventions averaged seven hours, and most used theory extensively. Meta-analyses found improvements in sexual health communication: Analysis of 11 controlled trials indicated a medium effect on increasing communication (Cohen's d, 0.5), and analysis of nine trials found a large effect on increasing parental comfort with communication (0.7); effects were positive regardless of delivery mode or intervention dose. Intervention participants were 68% more likely than controls to report increased communication and 75% more likely to report increased comfort. These findings point to gaps in the range of programs examined in published trials-for example, interventions for parents of sexual minority youth, programs for custodial grandparents and faith-based services. Yet they provide support for the effectiveness of parent-based interventions in improving communication. Innovative delivery approaches could extend programs' reach, and further research on sexual health outcomes would facilitate the meta-analysis of intervention effectiveness in improving adolescent sexual health behaviors. Copyright © 2015 by the Guttmacher Institute.

4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

NASA Astrophysics Data System (ADS)

Zhao, Qingya

2011-12-01

Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery mechanism. These three steps provide an innovative integrated framework for accurate 4D proton dose calculation and treatment planning for a moving tumor, which extends the functionalities of existing 3D planning systems. In short, this dissertation work addresses a few important problems for effective proton radiotherapy to a moving target. The outcomes of the dissertation are very useful for motion compensation with advanced image guided proton treatment.

Navigating change: how outreach facilitators can help clinicians improve patient outcomes.

PubMed

Laferriere, Dianne; Liddy, Clare; Nash, Kate; Hogg, William

2012-01-01

The objective of this study was to describe outreach facilitation as an effective method of assisting and supporting primary care practices to improve processes and delivery of care. We spent 4 years working with 83 practices in Eastern Ontario, Canada, on the Improved Delivery of Cardiovascular Care through the Outreach Facilitation program. Primary care practices, even if highly motivated, face multiple challenges when providing quality patient care. Outreach facilitation can be an effective method of assisting and supporting practices to make the changes necessary to improve processes and delivery of care. Multiple jurisdictions use outreach facilitation for system redesign, improved efficiencies, and advanced access. The development and implementation of quality improvement programs using practice facilitation can be challenging. Our research team has learned valuable lessons in developing tools, finding resources, and assisting practices to reach their quality improvement goals. These lessons can lead to improved experiences for the practices and overall improved outcomes for the patients they serve.

Text messaging versus email for emergency medicine residents’ knowledge retention: a pilot comparison in the United States

PubMed Central

2016-01-01

We evaluated the effectiveness of text messaging versus email, as a delivery method to enhance knowledge retention of emergency medicine (EM) content in EM residents. We performed a multi-centered, prospective, randomized study consisting of postgraduate year (PGY) 1 to PGY 3 & 4 residents in three United States EM residency programs in 2014. Fifty eight residents were randomized into one delivery group: text message or email. Participants completed a 40 question pre- and post-intervention exam. Primary outcomes were the means of pre- and post-intervention exam score differences. Data were analyzed using descriptive statistics, paired t-test, and multiple linear regressions. No significant difference was found between the primary outcomes of the two groups (P=0.51). PGY 2 status had a significant negative effect (P=0.01) on predicted exam score difference. Neither delivery method enhanced resident knowledge retention. Further research on implementation of mobile technology in residency education is required. PMID:27780350

Text messaging versus email for emergency medicine residents' knowledge retention: a pilot comparison in the United States.

PubMed

Hoonpongsimanont, Wirachin; Kulkarni, Miriam; Tomas-Domingo, Pedro; Anderson, Craig; McCormack, Denise; Tu, Khoa; Chakravarthy, Bharath; Lotfipour, Shahram

2016-01-01

We evaluated the effectiveness of text messaging versus email, as a delivery method to enhance knowledge retention of emergency medicine (EM) content in EM residents. We performed a multi-centered, prospective, randomized study consisting of postgraduate year (PGY) 1 to PGY 3 & 4 residents in three United States EM residency programs in 2014. Fifty eight residents were randomized into one delivery group: text message or email. Participants completed a 40 question pre- and post-intervention exam. Primary outcomes were the means of pre- and post-intervention exam score differences. Data were analyzed using descriptive statistics, paired t-test, and multiple linear regressions. No significant difference was found between the primary outcomes of the two groups (P=0.51). PGY 2 status had a significant negative effect (P=0.01) on predicted exam score difference. Neither delivery method enhanced resident knowledge retention. Further research on implementation of mobile technology in residency education is required.

Methods for the economic evaluation of changes to the organisation and delivery of health services: principal challenges and recommendations.

PubMed

Meacock, Rachel

2018-04-20

There is a requirement for economic evaluation of health technologies seeking public funding across Europe. Changes to the organisation and delivery of health services, including changes to health policy, are not covered by such appraisals. These changes also have consequences for National Health Service (NHS) funds, yet undergo no mandatory cost-effectiveness assessment. The focus on health technologies may have occurred because larger-scale service changes pose more complex challenges to evaluators. This paper discusses the principal challenges faced when performing economic evaluations of changes to the organisation and delivery of health services and provides recommendations for overcoming them. The five principal challenges identified are as follows: undertaking ex-ante evaluation; evaluating impacts in terms of quality-adjusted life years; assessing costs and opportunity costs; accounting for spillover effects; and generalisability. Of these challenges, methods for estimating the impact on costs and quality-adjusted life years are those most in need of development. Methods are available for ex-ante evaluation, assessing opportunity costs and examining generalisability. However, these are rarely applied in practice. The general principles of assessing the cost-effectiveness of interventions should be applied to all NHS spending, not just that involving health technologies. Advancements in this area have the potential to improve the allocation of scarce NHS resources.

A robust interrupted time series model for analyzing complex health care intervention data.

PubMed

Cruz, Maricela; Bender, Miriam; Ombao, Hernando

2017-12-20

Current health policy calls for greater use of evidence-based care delivery services to improve patient quality and safety outcomes. Care delivery is complex, with interacting and interdependent components that challenge traditional statistical analytic techniques, in particular, when modeling a time series of outcomes data that might be "interrupted" by a change in a particular method of health care delivery. Interrupted time series (ITS) is a robust quasi-experimental design with the ability to infer the effectiveness of an intervention that accounts for data dependency. Current standardized methods for analyzing ITS data do not model changes in variation and correlation following the intervention. This is a key limitation since it is plausible for data variability and dependency to change because of the intervention. Moreover, present methodology either assumes a prespecified interruption time point with an instantaneous effect or removes data for which the effect of intervention is not fully realized. In this paper, we describe and develop a novel robust interrupted time series (robust-ITS) model that overcomes these omissions and limitations. The robust-ITS model formally performs inference on (1) identifying the change point; (2) differences in preintervention and postintervention correlation; (3) differences in the outcome variance preintervention and postintervention; and (4) differences in the mean preintervention and postintervention. We illustrate the proposed method by analyzing patient satisfaction data from a hospital that implemented and evaluated a new nursing care delivery model as the intervention of interest. The robust-ITS model is implemented in an R Shiny toolbox, which is freely available to the community. Copyright © 2017 John Wiley & Sons, Ltd.

Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

PubMed

Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

2015-01-01

Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

Nanochanneled Device and Related Methods

NASA Technical Reports Server (NTRS)

Grattoni, Alessandro (Inventor); Fine, Daniel (Inventor); Goodall, Randy (Inventor); Hosali, Sharath (Inventor); Ferrari, Mauro (Inventor); Liu, Xuewu (Inventor); Medema, Ryan (Inventor); Hudson, Lee (Inventor)

2016-01-01

A nanochannel delivery device and method of manufacturing and use. The nanochannel delivery device comprises an inlet, an outlet, and a nanochannel. The nanochannel may be oriented parallel to the primary plane of the nanochannel delivery device. The inlet and outlet may be in direct fluid communication with the nanochannel. Considerable advances have been made in the field oftherapeutic agent (e.g. drug) delivery technology over thelast three decades, resulting in many breakthroughs in clinicalmedicine. The creation of therapeutic agent deliverydevices that are capable of delivering therapeutic agents incontrolled ways is still a challenge. One of the majorrequirements for an implantable drug delivery device iscontrolled release of therapeutic agents, ranging from smalldrug molecules to larger biological molecules. It is particularlydesirable to achieve a continuous passive drug releaseprofile consistent with zero order kinetics whereby theconcentration of drug in the bloodstream remains constantthroughout an extended delivery period.These devices have the potential to improve therapeuticefficacy, diminish potentially life-threatening side effects,improve patient compliance, minimize the intervention ofhealthcare personnel, reduce the duration of hospital stays,and decrease the diversion of regulated drugs to abusiveuses.Nanochannel delivery devices may be used in drug deliveryproducts for the effective administration of drugs. Inaddition, nanochannel delivery devices can be used in otherapplications where controlled release of a substance overtime is needed. Embodiments of this invention comprise a nanochanneldelivery device having nanochannels within a structureconfigured to yield high mechanical strength and high flowrates. Various fabrication protocols may be used to form thenanochannel delivery device. Embodiments of the fabricateddevices feature horizontal nanochannel lay-out (e.g., thenanochannel is parallel to the primary plane of the device),high molecule transport rate, high mechanical strength,optional multilayered lay-out, amenability to select channellining materials, and possible transparent top cover. Basedon silicon microfabrication technology, the dimensions ofthe nanochannel area as well as concomitant microchannelareas can be precisely controlled, thus providing a predictable,reliable, constant release rate of drug (or other) moleculesover an extended time period. In certain embodiments,the nanochannel delivery device can be used to builda multilayered nanochannel structure.

The effects of the mode of delivery on oxidative-antioxidative balance.

PubMed

Mutlu, Birgul; Aksoy, Nurten; Cakir, Hale; Celik, Hakim; Erel, Ozcan

2011-11-01

The purpose of this study was to investigate the effects of the mode of delivery on the oxidant and antioxidant systems in mothers and infants and to demonstrate which mode leads more oxidative stress. The participants were divided into two groups according to the mode of their labour and delivery: group 1 (n = 33) women with normal labour and delivery and group 2 (n = 33) with scheduled caesarean section (C/S) and delivery. The maternal, cord, and infant blood samples in both groups were collected. The serum total antioxidant capacity (TAC) and the total oxidant status (TOS) were evaluated by using an automated colorimetric measurement method. The parameters indicating oxidative stress (TOS, oxidative stress index, and lipid hydroperoxide) in maternal, cord, and newborn blood samples were higher in patients delivering with C/S than those normal spontaneous vaginal deliveries (NSVD) patient group, while it was vice versa for TAC. It may be concluded that both the mothers and neonates in C/S group are exposed to higher oxidative stress as compared with those in NSVD group and the antioxidant mechanisms are insufficient to cope with this stress during C/S. This result indicates that the normal delivery through the physiological route is healthier for the bodies of mothers and infants.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

PubMed

Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

2016-01-01

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p < 0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM-Glu20 in MDA-MB231 cells, 173.56 ± 1.37%, was significantly higher than that of MCF7 cells, 65.00 ± 1.73% (p < 0.05). The results indicated that hPAMAM-Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM-glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

Intra Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

DTIC Science & Technology

2016-10-01

method. Our central hypotheses are that joint retention time and therapeutic efficacy will be influenced by amniotic membrane particle size ...three Specific Aims: Aim 1: Evaluate the effects of human amniotic membrane (AM) particle size distribution on particle retention and progression of OA...following trauma. Factors we hypothesized would impact therapeutic efficacy of dHACM included particle size , timing of treatment, and frequency of delivery

An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler.

PubMed

Holmes, Martin S; Seheult, Jansen N; O'Connell, Peter; D'Arcy, Shona; Ehrhardt, Carsten; Healy, Anne Marie; Costello, Richard W; Reilly, Richard B

2015-08-01

Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods. An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files. All exhalation factors had a statistically significant effect on drug delivery (p<0.05); distance from the inhaler mouthpiece had the largest effect size. Humid air exhalations were found to reduce the fine particle fraction (FPF) compared to dry air. In a dataset of 110 audio files from 22 asthmatic patients, the acoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%. Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

Effectiveness of respiratory-gated radiotherapy with audio-visual biofeedback for synchrotron-based scanned heavy-ion beam delivery

NASA Astrophysics Data System (ADS)

He, Pengbo; Li, Qiang; Zhao, Ting; Liu, Xinguo; Dai, Zhongying; Ma, Yuanyuan

2016-12-01

A synchrotron-based heavy-ion accelerator operates in pulse mode at a low repetition rate that is comparable to a patient’s breathing rate. To overcome inefficiencies and interplay effects between the residual motion of the target and the scanned heavy-ion beam delivery process for conventional free breathing (FB)-based gating therapy, a novel respiratory guidance method was developed to help patients synchronize their breathing patterns with the synchrotron excitation patterns by performing short breath holds with the aid of personalized audio-visual biofeedback (BFB) system. The purpose of this study was to evaluate the treatment precision, efficiency and reproducibility of the respiratory guidance method in scanned heavy-ion beam delivery mode. Using 96 breathing traces from eight healthy volunteers who were asked to breathe freely and guided to perform short breath holds with the aid of BFB, a series of dedicated four-dimensional dose calculations (4DDC) were performed on a geometric model which was developed assuming a linear relationship between external surrogate and internal tumor motions. The outcome of the 4DDCs was quantified in terms of the treatment time, dose-volume histograms (DVH) and dose homogeneity index. Our results show that with the respiratory guidance method the treatment efficiency increased by a factor of 2.23-3.94 compared with FB gating, depending on the duty cycle settings. The magnitude of dose inhomogeneity for the respiratory guidance methods was 7.5 times less than that of the non-gated irradiation, and good reproducibility of breathing guidance among different fractions was achieved. Thus, our study indicates that the respiratory guidance method not only improved the overall treatment efficiency of respiratory-gated scanned heavy-ion beam delivery, but also had the advantages of lower dose uncertainty and better reproducibility among fractions.

Silk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus

PubMed Central

Price, Daniel L.; Li, Pingdong; Chen, Chun-Hao; Wong, Danni; Yu, Zhenkun; Chen, Nanhai G.; Yu, Yong A.; Szalay, Aladar A.; Cappello, Joseph; Fong, Yuman; Wong, Richard J.

2016-01-01

Background Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Methods Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. Conclusion The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. PMID:25244076

Innovations and issues in the delivery of continuing education to nurse practitioners in rural and northern communities.

PubMed

Tilleczek, Kate; Pong, Raymond; Caty, Suzanne

2005-03-01

This paper addresses the need to provide rural nurse practitioners (NPs) with the distance education that is considered vital to the upgrading of their professional skills. The method of delivering the courses is a critical aspect of their success. The authors trace and describe the innovative delivery of the Rural Ontario Nurse Practitioner Continuing Education Initiative, from the initial needs assessment study through to the implementation and evaluation study. In each study, a multi-method action research model was used. The respondents showed a preference for face-to-face modalities that were perceived to be constrained by barriers. These barriers were subsequently addressed by the pilot project. Those living in rural areas recognized the benefits of information technologies. Implementation was effectively weighted on multiple modes of online course delivery and the use of constructivist pedagogy. The findings suggest that the delivery of continuing education to rural and remote NPs is still wrought with challenges.

Photoacoustic microscopy imaging for microneedle drug delivery

NASA Astrophysics Data System (ADS)

Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

2018-02-01

The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

Evaluating the potential of poly(beta-amino ester) nanoparticles for reprogramming human fibroblasts to become induced pluripotent stem cells.

PubMed

Bhise, Nupura S; Wahlin, Karl J; Zack, Donald J; Green, Jordan J

2013-01-01

Gene delivery can potentially be used as a therapeutic for treating genetic diseases, including neurodegenerative diseases, as well as an enabling technology for regenerative medicine. A central challenge in many gene delivery applications is having a safe and effective delivery method. We evaluated the use of a biodegradable poly(beta-amino ester) nanoparticle-based nonviral protocol and compared this with an electroporation-based approach to deliver episomal plasmids encoding reprogramming factors for generation of human induced pluripotent stem cells (hiPSCs) from human fibroblasts. A polymer library was screened to identify the polymers most promising for gene delivery to human fibroblasts. Feeder-independent culturing protocols were developed for nanoparticle-based and electroporation-based reprogramming. The cells reprogrammed by both polymeric nanoparticle-based and electroporation-based nonviral methods were characterized by analysis of pluripotency markers and karyotypic stability. The hiPSC-like cells were further differentiated toward the neural lineage to test their potential for neurodegenerative retinal disease modeling. 1-(3-aminopropyl)-4-methylpiperazine end-terminated poly(1,4-butanediol diacry-late-co-4-amino-1-butanol) polymer (B4S4E7) self-assembled with plasmid DNA to form nanoparticles that were more effective than leading commercially available reagents, including Lipofectamine® 2000, FuGENE® HD, and 25 kDa branched polyethylenimine, for nonviral gene transfer. B4S4E7 nanoparticles showed effective gene delivery to IMR-90 human primary fibroblasts and to dermal fibroblasts derived from a patient with retinitis pigmentosa, and enabled coexpression of exogenously delivered genes, as is needed for reprogramming. The karyotypically normal hiPSC-like cells generated by conventional electroporation, but not by poly(beta-amino ester) reprogramming, could be differentiated toward the neuronal lineage, specifically pseudostratified optic cups. This study shows that certain nonviral reprogramming methods may not necessarily be safer than viral approaches and that maximizing exogenous gene expression of reprogramming factors is not sufficient to ensure successful reprogramming.

Physical Methods for Intracellular Delivery: Practical Aspects from Laboratory Use to Industrial-Scale Processing

PubMed Central

Meacham, J. Mark; Durvasula, Kiranmai; Degertekin, F. Levent; Fedorov, Andrei G.

2015-01-01

Effective intracellular delivery is a significant impediment to research and therapeutic applications at all processing scales. Physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus, and the mechanisms underlying the most common approaches (microinjection, electroporation, and sonoporation) have been extensively investigated. In this review, we discuss established approaches, as well as emerging techniques (magnetofection, optoinjection, and combined modalities). In addition to operating principles and implementation strategies, we address applicability and limitations of various in vitro, ex vivo, and in vivo platforms. Importantly, we perform critical assessments regarding (1) treatment efficacy with diverse cell types and delivered cargo molecules, (2) suitability to different processing scales (from single cell to large populations), (3) suitability for automation/integration with existing workflows, and (4) multiplexing potential and flexibility/adaptability to enable rapid changeover between treatments of varied cell types. Existing techniques typically fall short in one or more of these criteria; however, introduction of micro-/nanotechnology concepts, as well as synergistic coupling of complementary method(s), can improve performance and applicability of a particular approach, overcoming barriers to practical implementation. For this reason, we emphasize these strategies in examining recent advances in development of delivery systems. PMID:23813915

Comet Assay: A Method to Evaluate Genotoxicity of Nano-Drug Delivery System

PubMed Central

Vandghanooni, Somayeh; Eskandani, Morteza

2011-01-01

Introduction Drug delivery systems could induce cellular toxicity as side effect of nanomaterials. The mechanism of toxicity usually involves DNA damage. The comet assay or single cell gel electrophoresis (SCGE) is a sensitive method for detecting strand damages in the DNA of a cell with applications in genotoxicity testing and molecular epidemiology as well as fundamental research in DNA damage and repair. Methods In the current study, we reviewed recent drug delivery researches related to SCGE. Results We found that one preference for choosing the assay is that comet images may result from apoptosis-mediated nuclear fragmentation. This method has been widely used over the last decade in several different areas. Overall cells, such as cultured cells are embedded in agarose on a microscope slide, lysed with detergent, and treated with high salt. Nucleoids are supercoiled DNA form. When the slide is faced to alkaline electrophoresis any breakages present in the DNA cause the supercoiling to relax locally and loops of DNA extend toward the anode as a ‘‘comet tail’’. Conclusion This article provides a relatively comprehensive review upon potentiality of the comet assay for assessment of DNA damage and accordingly it can be used as an informative platform in genotoxicity studies of drug delivery systems. PMID:23678412

[Methods of pushing at vaginal delivery and pelvi-perineal consequences. Review].

PubMed

Ratier, N; Balenbois, E; Letouzey, V; Marès, P; de Tayrac, R

2015-03-01

The main objective of that review was to evaluate the pelvi-perineal consequences of the different methods of pushing at vaginal delivery. A review on PubMed, the Cochrane Library and EM-Premium was performed from 1984 to 2014. Among 29 manuscripts analysed, only nine randomised controlled trials (including one meta-analysis of three trials) comparing Valsalva and spontaneous pushing were selected. A 10 th study, secondary analysis of a randomized controlled trial comparing different methods of perineal protection (warm compresses, massage and manual protection), was also selected. Two trials have shown that spontaneous pushing reduces the risk of perineal tears, but studies were heterogeneous and discordant results do not allowed definitive conclusions. Results on the duration of the second stage of labour are conflicting. The method of pushing does not seem to affect the rate of episiotomy, instrumental delivery and cesarean section. Maternal satisfaction seems to be better after spontaneous pushing. It seems that there is no negative effect of spontaneous pushing on neonate well-being, and one study has shown a significant improvement of prenatal fetal parameters during the expulsive phase. According to current knowledge, both techniques of pushing during the expulsive phase at delivery seem comparable in terms of duration, risk of perineal tears and neonatal outcome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

PubMed

Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

2015-09-15

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved

PubMed Central

Inrig, Stephen J.; Tiro, Jasmin A.; Melhado, Trisha V.; Argenbright, Keith E.; Craddock Lee, Simon J.

2017-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. Objectives To better understand how to implement a decentralized regional delivery “hub & spoke” model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow’s RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Methods and Design The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow’s RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. Discussion This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting. PMID:28713882

Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Able, Charles M., E-mail: cable@wfubmc.edu; Bright, Megan; Frizzell, Bart

Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles withmore » 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.« less

Creating Effective Media Messaging for Rural Smoke-free Policy.

PubMed

Riker, Carol A; Butler, Karen M; Ricks, JaNelle M; Record, Rachael A; Begley, Kathy; Anderson, Debra Gay; Hahn, Ellen J

2015-01-01

Objectives were to (1) explore perceived effectiveness of existing smoke-free print advertisements in rural communities and (2) generate message content, characteristics, and media delivery channels that resonate with residents. Qualitative methods design. Thirty-nine rural adults recruited by community partners. Content analysis of findings from individuals in four focus groups who participated in general discussion and reviewed eight print ads related to secondhand smoke (SHS) and smoke-free policy. Six content themes were identified: smoking/SHS dangers, worker health, analogies, economic impact, rights, and nostalgia. Seven message characteristics were recognized: short/to the point, large enough to read, graphic images, poignant stories, statistics/charts/graphs, message sender, and messages targeting different groups. Four media delivery channels were considered most effective: local media, technology, billboard messages, and print materials. Seeking input from key informants is essential to reaching rural residents. Use of analogies in media messaging is a distinct contribution to the literature on effective smoke-free campaigns. Other findings support previous studies of effective messaging and delivery channels. Further research is needed to examine effectiveness of themes related to message content in smoke-free ads and delivery strategies. Effective media messaging can lead to policy change in rural communities to reduce exposure to SHS. © 2015 Wiley Periodicals, Inc.

Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment.

PubMed

2016-01-01

Intrathecal drug delivery systems can be used to manage refractory or persistent cancer pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain due owing to cancer. We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, National Health Service's Economic Evaluation Database, and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs. We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year. Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in adults. Publicly funding intrathecal drug delivery systems for cancer pain would result in a budget impact of several hundred thousand dollars per year.

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

PubMed Central

LaPelle, Nancy R; Luckmann, Roger; Simpson, E Hatheway; Martin, Elaine R

2006-01-01

Background Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. Methods Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. Results Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. Conclusion Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners. PMID:16597331

Applying dynamic simulation modeling methods in health care delivery research-the SIMULATE checklist: report of the ISPOR simulation modeling emerging good practices task force.

PubMed

Marshall, Deborah A; Burgos-Liz, Lina; IJzerman, Maarten J; Osgood, Nathaniel D; Padula, William V; Higashi, Mitchell K; Wong, Peter K; Pasupathy, Kalyan S; Crown, William

2015-01-01

Health care delivery systems are inherently complex, consisting of multiple tiers of interdependent subsystems and processes that are adaptive to changes in the environment and behave in a nonlinear fashion. Traditional health technology assessment and modeling methods often neglect the wider health system impacts that can be critical for achieving desired health system goals and are often of limited usefulness when applied to complex health systems. Researchers and health care decision makers can either underestimate or fail to consider the interactions among the people, processes, technology, and facility designs. Health care delivery system interventions need to incorporate the dynamics and complexities of the health care system context in which the intervention is delivered. This report provides an overview of common dynamic simulation modeling methods and examples of health care system interventions in which such methods could be useful. Three dynamic simulation modeling methods are presented to evaluate system interventions for health care delivery: system dynamics, discrete event simulation, and agent-based modeling. In contrast to conventional evaluations, a dynamic systems approach incorporates the complexity of the system and anticipates the upstream and downstream consequences of changes in complex health care delivery systems. This report assists researchers and decision makers in deciding whether these simulation methods are appropriate to address specific health system problems through an eight-point checklist referred to as the SIMULATE (System, Interactions, Multilevel, Understanding, Loops, Agents, Time, Emergence) tool. It is a primer for researchers and decision makers working in health care delivery and implementation sciences who face complex challenges in delivering effective and efficient care that can be addressed with system interventions. On reviewing this report, the readers should be able to identify whether these simulation modeling methods are appropriate to answer the problem they are addressing and to recognize the differences of these methods from other modeling approaches used typically in health technology assessment applications. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

NASA Astrophysics Data System (ADS)

Zhao, Shuting; Xu, Zhaobin; Wang, Hai; Reese, Benjamin E.; Gushchina, Liubov V.; Jiang, Meng; Agarwal, Pranay; Xu, Jiangsheng; Zhang, Mingjun; Shen, Rulong; Liu, Zhenguo; Weisleder, Noah; He, Xiaoming

2016-10-01

It is difficult to achieve minimally invasive injectable cell delivery while maintaining high cell retention and animal survival for in vivo stem cell therapy of myocardial infarction. Here we show that pluripotent stem cell aggregates pre-differentiated into the early cardiac lineage and encapsulated in a biocompatible and biodegradable micromatrix, are suitable for injectable delivery. This method significantly improves the survival of the injected cells by more than six-fold compared with the conventional practice of injecting single cells, and effectively prevents teratoma formation. Moreover, this method significantly enhances cardiac function and survival of animals after myocardial infarction, as a result of a localized immunosuppression effect of the micromatrix and the in situ cardiac regeneration by the injected cells.

From nose to brain: understanding transport capacity and transport rate of drugs.

PubMed

Wu, Hongbing; Hu, Kaili; Jiang, Xinguo

2008-10-01

The unique relationship between nasal cavity and cranial cavity tissues in anatomy and physiology makes intranasal delivery to the brain feasible. An intranasal delivery provides some drugs with short channels to bypass the blood-brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. In the past two decades, a good number of encouraging outcomes have been reported in the treatment of diseases of the brain or central nervous system (CNS) through nasal administration. In spite of the significant merit of bypassing the BBB, direct nose-to-brain delivery still bears the problems of low efficiency and volume for capacity due to the limited volume of the nasal cavity, the small area ratio of olfactory mucosa to nasal mucosa and the limitations of low dose and short retention time of drug absorption. It is crucial that selective distribution and retention time of drugs or preparations on olfactory mucosa should be enhanced so as to increase the direct delivery efficiency. In this article, we first briefly review the nose-to-brain transport pathways, before detailing the impacts on them, followed by a comprehensive summary of effective methods, including formulation modification, agglutinant-mediated transport and a brain-homing, peptide-mediated delivery based on phage display screening technique, with a view to providing a theoretic reference for elevating the therapeutic effects on brain diseases.

Aerosol delivery and humidification with the Boussignac continuous positive airway pressure device.

PubMed

Thille, Arnaud W; Bertholon, Jean-François; Becquemin, Marie-Hélène; Roy, Monique; Lyazidi, Aissam; Lellouche, François; Pertusini, Esther; Boussignac, Georges; Maître, Bernard; Brochard, Laurent

2011-10-01

A simple method for effective bronchodilator aerosol delivery while administering continuing continuous positive airway pressure (CPAP) would be useful in patients with severe bronchial obstruction. To assess the effectiveness of bronchodilator aerosol delivery during CPAP generated by the Boussignac CPAP system and its optimal humidification system. First we assessed the relationship between flow and pressure generated in the mask with the Boussignac CPAP system. Next we measured the inspired-gas humidity during CPAP, with several humidification strategies, in 9 healthy volunteers. We then measured the bronchodilator aerosol particle size during CPAP, with and without heat-and-moisture exchanger, in a bench study. Finally, in 7 patients with acute respiratory failure and airway obstruction, we measured work of breathing and gas exchange after a β(2)-agonist bronchodilator aerosol (terbutaline) delivered during CPAP or via standard nebulization. Optimal humidity was obtained only with the heat-and-moisture exchanger or heated humidifier. The heat-and-moisture exchanger had no influence on bronchodilator aerosol particle size. Work of breathing decreased similarly after bronchodilator via either standard nebulization or CPAP, but P(aO(2)) increased significantly only after CPAP aerosol delivery. CPAP bronchodilator delivery decreases the work of breathing as effectively as does standard nebulization, but produces a greater oxygenation improvement in patients with airway obstruction. To optimize airway humidification, a heat-and-moisture exchanger could be used with the Boussignac CPAP system, without modifying aerosol delivery.

The effect of midwifery continuing care on childbirth outcomes

PubMed Central

Sehhatie, Fahimeh; Najjarzadeh, Maryam; Zamanzadeh, Vahid; Seyyedrasooli, Alehe

2014-01-01

Background: Continuation of delivery care by a midwife, and establishing a relationship between the midwife and the delivering woman, is so important for women, and preserving such relationship increases woman's calmness and self-confidence. The current research aims at studying the effect of midwifery continuing care during delivery on delivery outcomes. Materials and Methods: This study was a quasi-experimental research conducted on childbearing women referring to Tabriz 29 Bahman Hospital. One hundred women were randomly assigned to either experimental (n = 50) or control (n = 50) group. In the experimental group, the women were cared exclusively with a midwife from the active phase continuously, while in the control group, women were cared with several midwifes conventionally. The birth outcomes were recorded in both valid and reliable groups (checklists). Data were analyzed using SPSS version 13.0. Results: Type of delivery was the same in both the groups (P = 0.051). In the experimental group, grade of the perineal lacerations was lower (P = 0.001); also, in this group, less oxytocin was used in the labor stage (P = 0.001). Conclusions: The results showed that providing one-to-one delivery care and continuous attendance of the midwife on the bedside of delivering woman had positive effect on improvement of birth outcomes. So, providing the choice of one-to-one care for women in delivery rooms must be considered where it is logistically possible. PMID:24949059

Graduate Student Services: A Study of the Delivery of Services at the Location Where Students Matriculate

ERIC Educational Resources Information Center

Burlison, John G.

2010-01-01

This dissertation investigates and explores the best method for the delivery of graduate student services. Essentially, there are two methods for delivery of these services. They can be delivered by virtue of centralization or decentralization. Decentralized delivery, for the purpose of this dissertation is the delivery of graduate student…

Ultrasound mediated nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Mullin, Lee B.

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems. Ultrasound parameters are optimized to achieve maximum cell internalization of molecules and increased nanoparticle delivery to a cell layer on a coverslip. In-vivo studies demonstrate the possibility of using a lower dose of paclitaxel to slow tumor growth rates, increase doxorubicin concentration in tumor tissue, and enhance tumor delivery of fluorescent molecules through treatments that combine nanoparticles with ultrasound and microbubbles.

Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution

PubMed Central

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J.; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F.; Yock, Paul; March, Keith L.

2012-01-01

Objectives To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous or arterial delivery. Background Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. Methods In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either intracoronary (IC) or retrograde coronary venous (RCV) infusion of 107 111Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hours after cell delivery. Results IC delivery of porcine ASCs to normal myocardium was well-tolerated up to a cumulative dose of 14×106 cells (approximately 0.5×106 cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50×106 ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, while at 10×106 ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hour with IC delivery compared to RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, p=0.037) but this initial difference was not apparent at 24 hours (22.6 ± 5.5% vs. 18.7 ± 8.6%; p= 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hours post-delivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Conclusions Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. Intracoronary arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. PMID:22972685

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism of the polymeric coating. It also reviews other rumen stable delivery systems and methods for evaluating their in vitro and in vivo performance.

Amylose-Based Cationic Star Polymers for siRNA Delivery.

PubMed

Nishimura, Tomoki; Umezaki, Kaori; Mukai, Sada-atsu; Sawada, Shin-ichi; Akiyoshi, Kazunari

2015-01-01

A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials.

Effectiveness of a Grief Intervention for Caregivers of People With Dementia.

PubMed

MacCourt, Penny; McLennan, Marianne; Somers, Sandie; Krawczyk, Marian

2017-08-01

In this article, we report on the structure and effectiveness of a grief management coaching intervention with caregivers of individuals with dementia. The intervention was informed by Marwit and Meuser's Caregiver Grief Model and considered levels of grief, sense of empowerment, coping, and resilience using five methods of delivery. Results indicate that the intervention had significant positive effects on caregivers' levels of grief and increased their levels of empowerment, coping, and resilience. The intervention was found to be effective across caregivers' characteristics as well as across five delivery modalities. Through description of this intervention, as well as outcome, this research contributes to the body of knowledge about caregivers' disenfranchised grief and ways to effectively address it.

Colloidal micelles of block copolymers as nanoreactors, templates for gold nanoparticles, and vehicles for biomedical applications.

PubMed

Bakshi, Mandeep Singh

2014-11-01

Target drug delivery methodology is becoming increasingly important to overcome the shortcomings of conventional drug delivery absorption method. It improves the action time with uniform distribution and poses minimum side effects, but is usually difficult to design to achieve the desire results. Economically favorable, environment friendly, multifunctional, and easy to design, hybrid nanomaterials have demonstrated their enormous potential as target drug delivery vehicles. A combination of both micelles and nanoparticles makes them fine target delivery vehicles in a variety of biological applications where precision is primarily required to achieve the desired results as in the case of cytotoxicity of cancer cells, chemotherapy, and computed tomography guided radiation therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanobiotechnology-based drug delivery in brain targeting.

PubMed

Dinda, Subas C; Pattnaik, Gurudutta

2013-01-01

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeutics. The current challenges are to design and develop the drug delivery careers, which must be able to deliver the drug across the BBB at a safe and effective manner. Nanoparticles are found to be effective careers in delivery of conventional drugs, recombinant proteins, vaccines as well as nucleotides. Nanoparticlulate drug delivery systems are found to be improving in the pharmacokinetic strategies of the drug molecules such as biodistribution, bioavailability and drug release characteristics in a controlled and effective manner with site specific drug delivery targeting to tissue or cell with reduction in toxic manifestation. Therefore, the use of nanotechnology in the field of pharmaceutical biotechnology helps in improving the drug delivery strategy including the kinetics and therapeutic index to solve the delivery problems of some biotech drugs including the recombinant proteins and oligonucleotides. This review is made to provide an insight to the role of nanobiotechnology in drug delivery and drug targeting to brain and its recent advances in the field of drug delivery systems.

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

Drug delivery across the blood-brain barrier using focused ultrasound

PubMed Central

Burgess, Alison; Hynynen, Kullervo H.

2015-01-01

Introduction The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a non-invasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. Areas Covered The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. Expert Opinion The introduction of MRI guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient, and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development. PMID:24650132

Drug delivery across the blood-brain barrier using focused ultrasound.

PubMed

Burgess, Alison; Hynynen, Kullervo

2014-05-01

The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a noninvasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. The introduction of magnetic resonance imaging guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development.

Improving Quality and Reducing Waste in Allied Health Workplace Education Programs: A Pragmatic Operational Education Framework Approach.

PubMed

Golder, Janet; Farlie, Melanie K; Sevenhuysen, Samantha

2016-01-01

Efficient utilisation of education resources is required for the delivery of effective learning opportunities for allied health professionals. This study aimed to develop an education framework to support delivery of high-quality education within existing education resources. This study was conducted in a large metropolitan health service. Homogenous and purposive sampling methods were utilised in Phase 1 (n=43) and 2 (n=14) consultation stages. Participants included 25 allied health professionals, 22 managers, 1 educator, and 3 executives. Field notes taken during 43 semi-structured interviews and 4 focus groups were member-checked, and semantic thematic analysis methods were utilised. Framework design was informed by existing published framework development guides. The framework model contains governance, planning, delivery, and evaluation and research elements and identifies performance indicators, practice examples, and support tools for a range of stakeholders. Themes integrated into framework content include improving quality of education and training provided and delivery efficiency, greater understanding of education role requirements, and workforce support for education-specific knowledge and skill development. This framework supports efficient delivery of allied health workforce education and training to the highest standard, whilst pragmatically considering current allied health education workforce demands.

Long-Term Delivery of Protein Therapeutics

PubMed Central

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-01-01

Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics. PMID:25251334

Long-term delivery of protein therapeutics.

PubMed

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-03-01

Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

What Are We Going to Do about a Problem Like Polymer Chemistry? Develop New Methods of Delivery to Improve Understanding of a Demanding Interdisciplinary Topic

ERIC Educational Resources Information Center

Cavalli, G.; Hamerton, I.; Lygo-Baker, S.

2015-01-01

Following collaboration between two chemistry lecturers and an academic developer an attempt was made to enhance the learning of students within a chemistry module through the adaptation of the delivery of content material. This paper reports a piece of practitioner led research which considered how effective the approach developed was upon the…

Delivery of RNAi reagents in murine models of obesity and diabetes.

PubMed

Wilcox, Denise M; Yang, Ruojing; Morgan, Sherry J; Nguyen, Phong T; Voorbach, Martin J; Jung, Paul M; Haasch, Deanna L; Lin, Emily; Bush, Eugene N; Opgenorth, Terry J; Jacobson, Peer B; Collins, Christine A; Rondinone, Cristina M; Surowy, Terry; Landschulz, Katherine T

2006-11-29

RNA interference (RNAi) is an exciting new tool to effect acute in vivo knockdown of genes for pharmacological target validation. Testing the application of this technology to metabolic disease targets, three RNAi delivery methods were compared in two frequently utilized preclinical models of obesity and diabetes, the diet-induced obese (DIO) and B6.V-Lep/J (ob/ob) mouse. Intraperitoneal (i.p.) and high pressure hydrodynamic intravenous (i.v.) administration of naked siRNA, and low pressure i.v. administration of shRNA-expressing adenovirus were assessed for both safety and gene knockdown efficacy using constructs targeting cJun N-terminal kinase 1 (JNK1). Hydrodynamic delivery of siRNA lowered liver JNK1 protein levels 40% in DIO mice, but was accompanied by iatrogenic liver damage. The ob/ob model proved even more intolerant of this technique, with hydrodynamic delivery resulting in severe liver damage and death of most animals. While well-tolerated, i.p. injections of siRNA in DIO mice did not result in any knockdown or phenotypic changes in the mice. On the other hand, i.v. injected adenovirus expressing shRNA potently reduced expression of JNK1 in vivo by 95% without liver toxicity. In conclusion, i.p. and hydrodynamic injections of siRNA were ineffective and/or inappropriate for in vivo gene targeting in DIO and ob/ob mice, while adenovirus-mediated delivery of shRNA provided a relatively benign and effective method for exploring liver target silencing.

Building of Reusable Reverse Logistics Model and its Optimization Considering the Decision of Backorder or Next Arrival of Goods

NASA Astrophysics Data System (ADS)

Lee, Jeong-Eun; Gen, Mitsuo; Rhee, Kyong-Gu; Lee, Hee-Hyol

This paper deals with the building of the reusable reverse logistics model considering the decision of the backorder or the next arrival of goods. The optimization method to minimize the transportation cost and to minimize the volume of the backorder or the next arrival of goods occurred by the Just in Time delivery of the final delivery stage between the manufacturer and the processing center is proposed. Through the optimization algorithms using the priority-based genetic algorithm and the hybrid genetic algorithm, the sub-optimal delivery routes are determined. Based on the case study of a distilling and sale company in Busan in Korea, the new model of the reusable reverse logistics of empty bottles is built and the effectiveness of the proposed method is verified.

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

PubMed Central

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-01-01

Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system. PMID:16930490

New strategies for providing hormonal contraception in developing countries.

PubMed

Townsend, John W; Sitruk-Ware, Regine; Williams, Katherine; Askew, Ian; Brill, Klaus

2011-05-01

Even with progress in increasing access to effective contraception over the past decades, and the growing range of contraceptive methods available on the market, women in developing countries continue to report an unmet need for family planning. This constraint continues to challenge reproductive health policies and programs, while the momentum of population growth and the young age structure in developing countries leads to larger numbers of potential contraceptive users and increasing global demand in contraceptive markets. Of late, there is a renewed focus on increasing access to long-acting hormonal methods to effectively meet this need, establishing and effectively implementing new service delivery strategies. A number of processes have profoundly affected the procurement and use of hormonal contraceptive methods in developing countries: a supportive policy environment, evidence-based practices and an increasing diversity of delivery strategies play a significant part in increasing number of contraceptive users and the demand for hormonal contraception. Copyright © 2011 Elsevier Inc. All rights reserved.

Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial

PubMed Central

Levine, Lisa D.; Downes, Katheryne L.; Elovitz, Michal A.; Parry, Samuel; Sammel, Mary D.; Srinivas, Sindhu K

2016-01-01

Objective To evaluate the effectiveness of four commonly used induction methods. Methods This randomized trial compared four induction methods: Misoprostol alone, Foley alone, Misoprostol–cervical Foley concurrently, and Foley–oxytocin concurrently,. Women undergoing labor induction with full term (≥37 weeks), singleton, vertex presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score ≤6, and cervical dilation ≤2cm were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor providers were blinded to assigned treatment group since examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (N=492) was planned to compare the four groups pairwise (P≤.008), with a 4-hour reduction in delivery time considered clinically meaningful. Results From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods, (misoprostol–Foley: 13.1 hours, Foley–oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, p<0.001). When censored for cesarean and adjusting for parity, women who received misoprostol–Foley delivered almost twice as likely to deliver before women who received misoprostol alone (hazard ratio (HR, 95% CI) 1.92 [1.42–2.59]) or Foley alone (HR, 95%CI: 1.87 [1.39–2.52]), whereas Foley–oxytocin was not statistically different from single-agent methods. Conclusion After censoring for cesarean and adjusting for parity, misoprostol–cervical Foley resulted in twice the chance of delivering before either single-agent method. PMID:27824758

Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models.

PubMed

Kumar, K; Rai, A K

2012-10-01

Curcumin, the active ingredient of the spice turmeric, has a long history as an herbal remedy for a variety of diseases. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol, and formulation PA2. They were characterized by scanning electron microscopy, revealing vesicular structures, and assessed for stability and effect on in vitro skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of formulation PA2 and PB1 were compared with a standard market product containing indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud's adjuvant (CFA) induced arthritis in rats. Further histopathological and radiographic evaluation was performed. The investigated curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin products.

Understanding causal pathways within health systems policy evaluation through mediation analysis: an application to payment for performance (P4P) in Tanzania.

PubMed

Anselmi, Laura; Binyaruka, Peter; Borghi, Josephine

2017-02-02

The evaluation of payment for performance (P4P) programmes has focused mainly on understanding contributions to health service coverage, without unpacking causal mechanisms. The overall aim of the paper is to test the causal pathways through which P4P schemes may (or may not) influence maternal care outcomes. We used data from an evaluation of a P4P programme in Tanzania. Data were collected from a sample of 3000 women who delivered in the 12 months prior to interview and 200 health workers at 150 health facilities from seven intervention and four comparison districts in Tanzania in January 2012 and in February 2013. We applied causal mediation analysis using a linear structural equation model to identify direct and indirect effects of P4P on institutional delivery rates and on the uptake of two doses of an antimalarial drug during pregnancy. We first ran a series of linear difference-in-difference regression models to test the effect of P4P on potential mediators, which we then included in a linear difference-in-difference model evaluating the impact of P4P on the outcome. We tested the robustness of our results to unmeasured confounding using semi-parametric methods. P4P reduced the probability of women paying for delivery care (-4.5 percentage points) which mediates the total effect of P4P on institutional deliveries (by 48%) and on deliveries in a public health facility (by 78%). P4P reduced the stock-out rate for some essential drugs, specifically oxytocin (-36 percentage points), which mediated the total effect of P4P on institutional deliveries (by 22%) and deliveries in a public health facility (by 30%). P4P increased kindness at delivery (5 percentage points), which mediated the effect of P4P on institutional deliveries (by 48%) and on deliveries in a public health facility (by 49%). P4P increased the likelihood of supervision visits taking place within the last 90 days (18 percentage points), which mediated 15% of the total P4P effect on the uptake of two antimalarial doses during antenatal care (IPT2). Kindness during deliveries and the probability of paying out of pocket for delivery care were the mediators most robust to unmeasured confounding. The effect of P4P on institutional deliveries is mediated by financing and human resources factors, while uptake of antimalarials in pregnancy is mediated by governance factors. Further research is required to explore additional and more complex causal pathways.

Physical non-viral gene delivery methods for tissue engineering.

PubMed

Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

2013-03-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

Physical non-viral gene delivery methods for tissue engineering

PubMed Central

Mellott, Adam J.; Forrest, M. Laird; Detamore, Michael S.

2016-01-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications. PMID:23099792

Technical Aspects of Fecal Microbial Transplantation (FMT).

PubMed

Bhutiani, N; Schucht, J E; Miller, K R; McClave, Stephen A

2018-06-09

Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice. FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.

Recent Updates on Novel Approaches in Insulin Drug Delivery: A Review of Challenges and Pharmaceutical Implications.

PubMed

Pandey, Manisha; Choudhury, Hira; Yi, Cheah Xiao; Mun, Chen Wei; Ping, Goh Khang; Rou, Guee Xin; Singh, Bhalqish Jeet Kaur A/P Ambar Jeet; Jhee, Angel Ng Ann; Chin, Lee Kai; Kesharwani, Prashant; Gorain, Bapi; Hussain, Zahid

2018-05-22

Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major researches are ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non-compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance pharmaceutical performance of the insulin therapy. Despite of facing substantial challenges in developing efficient delivery systems for insulin, vast researches have been carried out for the development of smart delivery systems to delivery insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessing learning outcomes and cost effectiveness of an online sleep curriculum for medical students.

PubMed

Bandla, Hari; Franco, Rose A; Simpson, Deborah; Brennan, Kimberly; McKanry, Jennifer; Bragg, Dawn

2012-08-15

Sleep disorders are highly prevalent across all age groups but often remain undiagnosed and untreated, resulting in significant health consequences. To overcome an inadequacy of available curricula and learner and instructor time constraints, this study sought to determine if an online sleep medicine curriculum would achieve equivalent learner outcomes when compared with traditional, classroom-based, face-to-face instruction at equivalent costs. Medical students rotating on a required clinical clerkship received instruction in 4 core clinical sleep-medicine competency domains in 1 of 2 delivery formats: a single 2.5-hour face-to-face workshop or 4 asynchronous e-learning modules. Immediate learning outcomes were assessed in a subsequent clerkship using a multiple-choice examination and standardized patient station, with long-term outcomes assessed through analysis of students' patient write-ups for inclusion of sleep complaints and diagnoses before and after the intervention. Instructional costs by delivery format were tracked. Descriptive and inferential statistical analyses compared learning outcomes and costs by instructional delivery method (face-to-face versus e-learning). Face-to-face learners, compared with online learners, were more satisfied with instruction. Learning outcomes (i.e., multiple-choice examination, standardized patient encounter, patient write-up), as measured by short-term and long-term assessments, were roughly equivalent. Design, delivery, and learner-assessment costs by format were equivalent at the end of 1 year, due to higher ongoing teaching costs associated with face-to-face learning offsetting online development and delivery costs. Because short-term and long-term learner performance outcomes were roughly equivalent, based on delivery method, the cost effectiveness of online learning is an economically and educationally viable instruction platform for clinical clerkships.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Mesoporous carbon nanomaterials in drug delivery and biomedical application.

PubMed

Zhao, Qinfu; Lin, Yuanzhe; Han, Ning; Li, Xian; Geng, Hongjian; Wang, Xiudan; Cui, Yu; Wang, Siling

2017-01-01

Recent development of nano-technology provides highly efficient and versatile treatment methods to achieve better therapeutic efficacy and lower side effects of malignant cancer. The exploration of drug delivery systems (DDSs) based on nano-material shows great promise in translating nano-technology to clinical use to benefit patients. As an emerging inorganic nanomaterial, mesoporous carbon nanomaterials (MCNs) possess both the mesoporous structure and the carbonaceous composition, endowing them with superior nature compared with mesoporous silica nanomaterials and other carbon-based materials, such as carbon nanotube, graphene and fullerene. In this review, we highlighted the cutting-edge progress of carbon nanomaterials as drug delivery systems (DDSs), including immediate/sustained drug delivery systems and controlled/targeted drug delivery systems. In addition, several representative biomedical applications of mesoporous carbon such as (1) photo-chemo synergistic therapy; (2) delivery of therapeutic biomolecule and (3) in vivo bioimaging are discussed and integrated. Finally, potential challenges and outlook for future development of mesoporous carbon in biomedical fields have been discussed in detail.

Nanomedicine in pulmonary delivery

PubMed Central

Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

2009-01-01

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

PubMed Central

Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

2011-01-01

Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

Cryogen spray cooling: Effects of droplet size and spray density on heat removal.

PubMed

Pikkula, B M; Torres, J H; Tunnell, J W; Anvari, B

2001-01-01

Cryogen spray cooling (CSC) is an effective method to reduce or eliminate non-specific injury to the epidermis during laser treatment of various dermatological disorders. In previous CSC investigations, fuel injectors have been used to deliver the cryogen onto the skin surface. The objective of this study was to examine cryogen atomization and heat removal characteristics of various cryogen delivery devices. Various cryogen delivery device types including fuel injectors, atomizers, and a device currently used in clinical settings were investigated. Cryogen mass was measured at the delivery device output orifice. Cryogen droplet size profiling for various cryogen delivery devices was estimated by optically imaging the droplets in flight. Heat removal for various cryogen delivery devices was estimated over a range of spraying distances by temperature measurements in an skin phantom used in conjunction with an inverse heat conduction model. A substantial range of mass outputs were measured for the cryogen delivery devices while heat removal varied by less than a factor of two. Droplet profiling demonstrated differences in droplet size and spray density. Results of this study show that variation in heat removal by different cryogen delivery devices is modest despite the relatively large difference in cryogen mass output and droplet size. A non-linear relationship between heat removal by various devices and droplet size and spray density was observed. Copyright 2001 Wiley-Liss, Inc.

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

PubMed

Chen, Yang; Wang, Manli; Fang, Liang

2013-01-01

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

Gene delivery for periodontal tissue engineering: current knowledge - future possibilities.

PubMed

Chen, Fa-Ming; Ma, Zhi-Wei; Wang, Qin-Tao; Wu, Zhi-Fen

2009-08-01

The cellular and molecular events of periodontal healing are coordinated and regulated by an elaborate system of signaling molecules, pointing to a primary strategy for functional periodontal compartment regeneration to replicate components of the natural cellular microenvironment by providing an artificial extracellular matrix (ECM) and by delivering growth factors. However, even with optimal carriers, the localized delivery of growth factors often requires a large amount of protein to stimulate significant effects in vivo, which increases the risk and unwanted side effects. A simple and relatively new approach to bypassing this dilemma involves converting cells into protein producing factories. This is done by a so-called gene delivery method, where therapeutic agents to be delivered are DNA plasmids that include the gene encoding desired growth factors instead of recombinant proteins. As localized depots of genes, novel gene delivery systems have the potential to release their cargo in a sustained and controlled manner and finally provide time- and space- dependent levels of encoded proteins during all stages of tissue regrowth, offering great versatility in their application and prompting new tissue engineering strategy in periodontal regenerative medicine. However, gene therapy in Periodontology is clearly in its infancy. Significant efforts still need to be made in developing safe and effective delivery platforms and clarifying how gene delivery, in combination with tissue engineering, may mimic the critical aspects of natural biological processes occurring in periodontal development and repair. The aim of this review is to trace an outline of the state-of-the-art in the application of gene delivery and tissue engineering strategies for periodontal healing and regeneration.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

PubMed

Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli

2016-01-01

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.

Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery.

PubMed

Chaudhary, Mirnal A; Guo, Lian-Wang; Shi, Xudong; Chen, Guojun; Gong, Shaoqin; Liu, Bo; Kent, K Craig

2016-07-10

Intimal hyperplasia (IH) remains a major cause of poor patient outcomes after surgical revascularization to treat atherosclerosis. A multitude of drugs have been shown to prevent the development of IH. Moreover, endovascular drug delivery following angioplasty and stenting has been achieved with a marked diminution in the incidence of restenosis. Despite advances in endovascular drug delivery, there is currently no clinically available method of periadventitial drug delivery suitable for open vascular reconstructions. Herein we provide an overview of the recent literature regarding innovative polymer platforms for periadventitial drug delivery in preclinical models of IH as well as insights about barriers to clinical translation. A comprehensive PubMed search confined to the past 15years was performed for studies of periadventitial drug delivery. Additional searches were performed for relevant clinical trials, patents, meeting abstracts, and awards of NIH funding. Most of the research involving direct periadventitial delivery without a drug carrier was published prior to 2000. Over the past 15years there have been a surge of reports utilizing periadventitial drug-releasing polymer platforms, most commonly bioresorbable hydrogels and wraps. These methods proved to be effective for the inhibition of IH in various animal models (e.g. balloon angioplasty, wire injury, and vein graft), but very few have advanced to clinical trials. There are a number of barriers that may account for this lack of translation. Promising new approaches including the use of nanoparticles will be described. No periadventitial drug delivery system has reached clinical application. For periadventitial delivery, polymer hydrogels, wraps, and nanoparticles exhibit overlapping and complementary properties. The ideal periadventitial delivery platform would allow for sustained drug release yet exert minimal mechanical and inflammatory stresses to the vessel wall. A clinically applicable strategy for periadventitial drug delivery would benefit thousands of patients undergoing open vascular reconstruction each year. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuous corticosterone delivery via the drinking water or pellet implantation: A comparative study in mice.

PubMed

Gasparini, Sylvia J; Weber, Marie-Christin; Henneicke, Holger; Kim, Sarah; Zhou, Hong; Seibel, Markus J

2016-12-01

In order to investigate the effects of glucocorticoid excess in rodent models, reliable methods of continuous glucocorticoid delivery are essential. The current study compares two methods of corticosterone (CS) delivery in regards to their ability to induce typical adverse outcomes such as fat accrual, insulin resistance, sarcopenia and bone loss. Eight-week-old mice received CS for 4weeks either via the drinking water (25-100μgCS/mL) or through weekly surgical implantation of slow release pellets containing 1.5mg CS. Both methods induced abnormal fat mass accrual, inhibited lean mass accretion and bone expansion, suppressed serum osteocalcin levels and induced severe insulin resistance. There was a clear dose dependant relationship between the CS concentrations in the drinking water and the severity of the phenotype, with a concentration of 50μg CS/mL drinking water most closely matching the metabolic changes induced by weekly pellet implantations. In contrast to pellets, however, delivery of CS via the drinking water resulted in a consistent diurnal exposure pattern, closely mimicking the kinetics of clinical glucocorticoid therapy. In addition, the method is safe, inexpensive, easily adjustable, non-invasive and avoids operative stress to the animals. Our data demonstrate that delivery of CS via the drinking water has advantages over weekly implantations of slow-release pellets. A dose of 50μg CS/mL drinking water is appropriate for the investigation of chronic glucocorticoid excess in mice. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

A Review of Analytical Methods for p-Coumaric Acid in Plant-Based Products, Beverages, and Biological Matrices.

PubMed

Ferreira, Paula Scanavez; Victorelli, Francesca Damiani; Fonseca-Santos, Bruno; Chorilli, Marlus

2018-05-14

p-Coumaric acid (p-CA), also known as 4-hydroxycinnamic acid, is a phenolic acid, which has been widely studied due to its beneficial effects against several diseases and its wide distribution in the plant kingdom. This phenolic compound can be found in the free form or conjugated with other molecules; therefore, its bioavailability and the pathways via which it is metabolized change according to its chemical structure. p-CA has potential pharmacological effects because it has high free radical scavenging, anti-inflammatory, antineoplastic, and antimicrobial activities, among other biological properties. It is therefore essential to choose the most appropriate and effective analytical method for qualitative and quantitative determination of p-CA in different matrices, such as plasma, urine, plant extracts, and drug delivery systems. The most-reported analytical method for this purpose is high-performance liquid chromatography, which is mostly coupled with some type of detectors, such as UV/Vis detector. However, other analytical techniques are also used to evaluate this compound. This review presents a summary of p-CA in terms of its chemical and pharmacokinetic properties, pharmacological effects, drug delivery systems, and the analytical methods described in the literature that are suitable for its quantification.

Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins.

PubMed

Ryou, Sang-Mi; Yeom, Ji-Hyun; Kang, Hyo Jung; Won, Miae; Kim, Jin-Sik; Lee, Boeun; Seong, Maeng-Je; Ha, Nam-Chul; Bae, Jeehyeon; Lee, Kangseok

2014-12-28

Although the delivery of biologically functional protein(s) into mammalian cells could be of tremendous value to biomedical research, the development of such technology has been hindered by the lack of a safe and effective delivery method. Here, we present a simple, efficient, and versatile gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system, with nanoblock-like properties, that allows any recombinant protein to be loaded without additional modifications and delivered into mammalian living systems. AuNP-Apt-based protein delivery system was able to deliver various proteins into variety of cell types in vitro without showing cytotoxicity. This AuNP-Apt system was also effective for the local and systemic targeted delivery of proteins in vivo. A local injection of the AuNP-Apt loaded with the apoptosis-inducing BIM protein efficiently inhibited the growth of xenograft tumors in mice. Furthermore, an intravenous injection of AuNP-Apt loaded with both epidermal growth factor (EGF) and BIM resulted in the targeted delivery of BIM into a xenograft tumor derived from EGF receptor-overexpressing cancer cells with no detectable systemic toxicity. Our findings show that this system can serve as an innovative platform for the development of protein-based biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Transepidermal drug delivery: a new treatment option for areata alopecia?

PubMed

Issa, Maria Claudia Almeida; Pires, Marianna; Silveira, Priscilla; Xavier de Brito, Esther; Sasajima, Cristiane

2015-02-01

Transepidermal drug delivery (TED) is a new potential method in dermatology. Permeability alterations induced by ablative fractional resurfacing have been described with the aim to increasing the delivery of different substances into the skin. To evaluate clinical response and side effects of TED in areata alopecia (AA) treatment using ablative fractional methods associated with acoustic pressure ultrasound (US) to deliver triamcinolone solution into the skin. Five cases of AA underwent treatment which comprised of 3 steps: 1) Ablative fractioned RF or CO2 laser 2) topical application of triamcinolone 3) acoustic pressure wave US. The number of sessions varied according to the clinical response, ranging from one to six sessions. All patients had complete recovery of the area treated. Two of them treated with ablative fractional RF + triamcinolone + US had complete response after three and six sessions. The other two treated with ablative fractional CO2 + triamcinolone + US had complete response after one session. Fractioned ablative resurfacing associated with acoustic pressure wave US is a new option to areata alopecia treatment with good clinical result and low incidence of side effects.

The Effect of Psychosocial Factors on Acute and Persistent Pain Following Childbirth

DTIC Science & Technology

2015-10-14

longitudinal study. Methods: Baseline measures of psychosocial variables were obtained during the last 8 weeks of pregnancy . Delivery and acute pain...low income by the US Census Bureau???s definition. Routine assessment of depression during pregnancy may identify those at risk of developing...were obtained during the last 8 weeks of pregnancy . Delivery and acute pain data were collected from the electronic medical record. Follow-up data were

Trans-Dermal Fentanyl Patches are a Cost-Effective Method of Long-Term Analgesic Delivery Following Corneal Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2012-01-01

SM) exposure in rabbits involves delivery of the opioid receptor agonist buprenorphine using subcutaneously implanted osmotic pumps. The...significantly lower than the costs of purchasing and loading an osmotic pump with buprenorphine . Pump implantation took approximately 10 min per...general distress than did the buprenorphine cohort. The elevated behavioral changes exhibited by the rabbits with implanted pumps were likely a

Introduction for Design of Nanoparticle Based Drug Delivery Systems.

PubMed

Edgar, Jun Yan Chan; Wang, Hui

2017-01-01

Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, watersoluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy. In particular for cancer therapy, antineoplastic drugs are taking advantage of nanoparticulate drug carriers to improve the cure efficacy. Nanoparticle based drug carriers are capable of improving the therapeutic effectiveness of the drugs by using active targeting for the site-specific delivery, passive targeting mechanisms such as enhanced permeability and retention (EPR), de novo synthesis and uptake of low density liposome in cancer cells or by being water-soluble to improve the suboptimal pharmacokinetics in limited water-soluble delivery methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of Breast Crawl Between Infants Delivered by Vaginal Delivery and Cesarean Section.

PubMed

Heidarzadeh, Mohammad; Hakimi, Sevil; Habibelahi, Abbas; Mohammadi, Marzieh; Shahrak, Shakiba Pourasad

2016-05-12

Exclusive breastfeeding is the single most cost-effective intervention to reduce infant mortality. Breast crawl (BC) is deemed a natural way for the baby to behave immediately after delivery. BC is the method that may help initiation of breastfeeding in the most natural way. The aim of this study is to compare successful BC between neonates born through vaginal delivery and those born through cesarean section (CS) and factors associated with a positive outcome. Participants were mothers who delivered their babies during the period of October 2012 to December 2013 in Alzahra Hospital in Tabriz, through cesarean or vaginal delivery. Infants were placed prone on their mothers' abdomen after delivery. Data show that babies delivered through vaginal delivery had significantly more success in BC than babies born through the cesarean delivery (88.01% versus 11.21%). Moreover, babies in the CS group used significantly less time to achieve BC (45 versus 28 minutes). There is a remarkable difference in completion and length of time used to achieve BC between infants with regard to the delivery mode. Encouraging BC in all dyads, especially in cesarean births, may unduly delay the infant's first breastfeed.

Selecting a dynamic simulation modeling method for health care delivery research-part 2: report of the ISPOR Dynamic Simulation Modeling Emerging Good Practices Task Force.

PubMed

Marshall, Deborah A; Burgos-Liz, Lina; IJzerman, Maarten J; Crown, William; Padula, William V; Wong, Peter K; Pasupathy, Kalyan S; Higashi, Mitchell K; Osgood, Nathaniel D

2015-03-01

In a previous report, the ISPOR Task Force on Dynamic Simulation Modeling Applications in Health Care Delivery Research Emerging Good Practices introduced the fundamentals of dynamic simulation modeling and identified the types of health care delivery problems for which dynamic simulation modeling can be used more effectively than other modeling methods. The hierarchical relationship between the health care delivery system, providers, patients, and other stakeholders exhibits a level of complexity that ought to be captured using dynamic simulation modeling methods. As a tool to help researchers decide whether dynamic simulation modeling is an appropriate method for modeling the effects of an intervention on a health care system, we presented the System, Interactions, Multilevel, Understanding, Loops, Agents, Time, Emergence (SIMULATE) checklist consisting of eight elements. This report builds on the previous work, systematically comparing each of the three most commonly used dynamic simulation modeling methods-system dynamics, discrete-event simulation, and agent-based modeling. We review criteria for selecting the most suitable method depending on 1) the purpose-type of problem and research questions being investigated, 2) the object-scope of the model, and 3) the method to model the object to achieve the purpose. Finally, we provide guidance for emerging good practices for dynamic simulation modeling in the health sector, covering all aspects, from the engagement of decision makers in the model design through model maintenance and upkeep. We conclude by providing some recommendations about the application of these methods to add value to informed decision making, with an emphasis on stakeholder engagement, starting with the problem definition. Finally, we identify areas in which further methodological development will likely occur given the growing "volume, velocity and variety" and availability of "big data" to provide empirical evidence and techniques such as machine learning for parameter estimation in dynamic simulation models. Upon reviewing this report in addition to using the SIMULATE checklist, the readers should be able to identify whether dynamic simulation modeling methods are appropriate to address the problem at hand and to recognize the differences of these methods from those of other, more traditional modeling approaches such as Markov models and decision trees. This report provides an overview of these modeling methods and examples of health care system problems in which such methods have been useful. The primary aim of the report was to aid decisions as to whether these simulation methods are appropriate to address specific health systems problems. The report directs readers to other resources for further education on these individual modeling methods for system interventions in the emerging field of health care delivery science and implementation. Copyright © 2015. Published by Elsevier Inc.

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

PubMed Central

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

Cost effectiveness and efficiency in assistive technology service delivery.

PubMed

Warren, C G

1993-01-01

In order to develop and maintain a viable service delivery program, the realities of cost effectiveness and cost efficiency in providing assistive technology must be addressed. Cost effectiveness relates to value of the outcome compared to the expenditures. Cost efficiency analyzes how a provider uses available resources to supply goods and services. This paper describes how basic business principles of benefit/cost analysis can be used to determine cost effectiveness. In addition, basic accounting principles are used to illustrate methods of evaluating a program's cost efficiency. Service providers are encouraged to measure their own program's effectiveness and efficiency (and potential viability) in light of current trends. This paper is meant to serve as a catalyst for continued dialogue on this topic.

Modes of information delivery in radiologic anatomy education: Impact on student performance.

PubMed

Ketelsen, Dominik; Schrödl, Falk; Knickenberg, Inés; Heckemann, Rolf A; Hothorn, Torsten; Neuhuber, Winfried; Bautz, Werner A L; Grunewald, Markus

2007-01-01

This study provides a systematic assessment of different methods of delivering radiologic teaching content (lecture, printed text, and digital content delivery) under standard conditions, enabling comparison of the effectiveness of these methods. A printed atlas of sectional anatomy was used as a standard. Digital content was developed on the basis of the printed atlas. Lecturers used both the printed and the digital content to prepare lectures. Standardized teaching material thus created was presented to second-term undergraduate students who had attended the school's anatomy course, but had not received any radiology teaching. Multiple choice examinations were used to assess the students' ability to recognize anatomical structures in known as well as unknown images. In a survey, the students' subjective experience of the learning process was assessed. No difference was seen between the groups regarding examination results. Students preferred a combination of digital media and lectures by enthusiastic teachers. The shortage of teachers requires a compromise concerning the delivery of radiologic anatomy content in a medical school setting. Based on our results, we recommend a combined approach of lecture and digital content delivery.

Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

PubMed

Barua, Neil U; Gill, Steven S; Love, Seth

2014-03-01

Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

NASA Astrophysics Data System (ADS)

Camacho, Kathryn Militar

Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly applied to various agents. Findings from our research can potentially widen the therapeutic window of chemotherapy combinations by emphasizing investigations of optimal drug ratios rather than maximum drug doses and by identifying appropriate nanoparticles for their delivery. Application of these concepts can ultimately help capture the full therapeutic potential of combination regimens.

Exploring the first delay: a qualitative study of home deliveries in Makwanpur district Nepal

PubMed Central

2014-01-01

Background In many low-income countries women tend to deliver at home, and delays in receiving appropriate maternal care can be fatal. A contextual understanding of these delays is important if countries are to meet development targets for maternal health. We present qualitative research with women who delivered at home in rural Nepal, to gain a contemporary understanding of the context where we are testing the effectiveness of an intervention to increase institutional deliveries. Methods We purposively sampled women who had recently delivered at home and interviewed them to explore their reasons for home delivery. Interviews were recorded, transcribed and analysed using thematic content analysis. We used the ‘delays’ model discussed in the literature to frame our analysis. Results Usually a combination of factors prevented women from delivering in health institutions. Many women were aware of the benefits of institutional delivery yet their status in the home restricted their access to health facilities. Often they did not wish to bring shame on their family by going against their wishes, or through showing their body in a health institution. They often felt unable to demand the organisation of transportation because this may cause financial problems for their family. Some felt that government incentives were insufficient. Often, a lack of family support at the time of delivery meant that women delivered at home. Past bad experience, and poor quality health services, also prevented women from having an institutional delivery. Conclusions Formative research is important to develop an understanding of local context. Sociocultural issues, perceived accessibility of health services, and perceived quality of care were all important barriers preventing institutional delivery. Targeting one factor alone may not be effective in increasing institutional deliveries. Our intervention encourages communities to develop local responses to address the factors preventing institutional delivery through women’s groups and improved health facility management. We will monitor perceptions of health services over time to help us understand the effectiveness of the intervention. PMID:24576187

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery.

PubMed

Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo; Lamberti, Gaetano

2013-01-01

The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract. All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.

Microneedle and mucosal delivery of influenza vaccines

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

2017-01-01

In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

Amylose-Based Cationic Star Polymers for siRNA Delivery

PubMed Central

Nishimura, Tomoki; Umezaki, Kaori; Mukai, Sada-atsu; Sawada, Shin-ichi; Akiyoshi, Kazunari

2015-01-01

A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials. PMID:26539548

Measurement of laser power for photo-triggered drug delivery in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, R.; Zhang, X. L.; Liu, F.

Thus far, despite many investigations have been carried out for photo-triggered drug delivery systems, most of them suffer from an intrinsic drawback of without real-time monitoring mechanism. Incident intensity of light is a feasible parameter to monitor the drug release profiles. However, it is difficult to measure the incident laser power irradiated onto the photo-triggered carriers in drug delivery systems during in vivo therapy. We design an online measurement method based on the fluorescence intensity ratio (FIR) technique through upconversion nanoparticles. FIR value varies with temperature of sample due to the thermal effect induced by the incident laser, which validatesmore » the laser power measurement. Effects of rare earth doping concentration, as well as experimental conditions including laser spots and wavelengths on the measurement behavior were also investigated.« less

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.

PubMed

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi

2006-03-01

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.

Targeting Future Customers: An Introductory Biobanking Course for Undergraduate Students of Life Sciences.

PubMed

Abdelhafiz, Ahmed Samir; Fouda, Merhan Ahmed; El-Jaafary, Shaimaa Ibrahim; Farghly, Maysa Ibrahim; Salem, Mazen; Tammam, Ahmed; Gabr, Hala

2017-08-01

Biobanking is a relatively new concept in the Arab region. Targeting different stakeholders to introduce the concept of biobanking and develop an acceptance of it among them is important for the growth of biobanking in the region. Undergraduate students of life sciences represent an important segment of stakeholders, since they constitute potential future biobank customers. Limited funding, lack of awareness of the existence of the term "biobanking" itself among these students, and questions regarding best marketing strategies presented challenges to planning for the most effective message delivery to this target group. A specific course was designed for undergraduate students of life sciences, which was conducted at the Faculty of Medicine, Cairo University, Egypt. The course was conducted twice in 2016 and included lectures covering biobanking, quality, ethics, information technology, and translational research. Facebook and word-of-mouth were used for marketing and advertising. A total number of 125 participants attended both courses cumulatively. Facebook appeared to have been an effective marketing outlet, especially when paid advertisements were used. Evaluation of knowledge, measured using a pretest and posttest, demonstrated some improvement in knowledge of participants. Evaluation forms filled after the course showed positive attitude toward content and message delivery by a majority of participants. Facebook was also used as an evaluation method through analysis of engagement with posts created after course completion. Biobanking education can be carried out effectively with limited resources. Understanding the needs of the target group and using appropriate methods of communication are essential prerequisites to a well-tailored curriculum and effective message delivery. Using Facebook appears to be an effective and affordable method of communication and advertising. Targeting undergraduate students of life sciences interested in research is a good investment and can be very effective in increasing awareness about biobanking inside the research community.

Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo study

PubMed Central

2014-01-01

Background The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye. Methods An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm2 and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor samples, collected 90 min after the treatment, was determined using chromatography methods. Light microscopy observations were done to determine the structural changes in the cornea as a result of ultrasound application. Results An increase in drug concentration in aqueous humor samples of 2.8 times (p < 0.05) with ultrasound application at 400 kHz and 2.4 times (p < 0.01) with ultrasound application at 600 kHz was observed as compared to sham-treated samples. Histological analysis showed that the structural changes in the corneas exposed to ultrasound predominantly consisted of minor epithelial disorganization. Conclusions Ultrasound application enhanced the delivery of an anti-inflammatory ocular drug, dexamethasone sodium phosphate, through the cornea in vivo. Ultrasound-enhanced ocular drug delivery appears to be a promising area of research with a potential future application in a clinical setting. PMID:24921047

Localized delivery of chemotherapy to the cervix for radiosensitization.

PubMed

Hodge, Lucy S; Downs, Levi S; Chura, Justin C; Thomas, Sajeena G; Callery, Patrick S; Soisson, A Patrick; Kramer, Paul; Wolfe, Stephen S; Tracy, Timothy S

2012-10-01

Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of radiosensitizing agents. However, administration of radiosensitizing chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of radiosensitizing chemotherapeutics to the cervix while limiting systemic toxicities. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CerviPrep™). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite 2',2'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/g tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/g tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for radiosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Atlanto-occipital catheterization of young rats for long-term drug delivery into the lumbar subarachnoid space combined with in vivo testing and electrophysiology in situ.

PubMed

Kopach, Olga; Krotov, Volodymyr; Voitenko, Nana

2017-10-01

Catheterization has been widely used in neuroscience and pain research for local drug delivery. Though different modifications were developed, the use of young animals for spinal catheterization remains limited because of a little success rate. A reliable technique is needed to catheterize young animals aimed for in vivo testing combined with spinal cord electrophysiology, often limited by animal age, to facilitate pain research. We describe intrathecal catheterization of young rats (3-week-old) through atlanto-occipical approach for long-lasting drug delivery into the lumbar subarachnoid space. The technique represents a surgical approach of minimized invasiveness that requires PE-10 catheter and few equipment of standard laboratory use. Behavioral assessments revealed that spinal catheterization does not change peripheral sensitivity of different modalities (thermal and mechanical) and gives no rise to locomotive deficit or anxiety-like behavior in young rats. The long-term administration of genetic material (oligodeoxynucleotides given up to 4days), examined both in vivo and in situ, produced no adverse effects on basal peripheral sensitivity, but changed the AMPA receptor-mediated currents in sensory interneurons of the spinal cord. Dissimilar to already described methods, the method is designed for the use of young rats for behavioral testing in vivo and/or spinal cord electrophysiology in situ. A practical method for spinal catheterization of young animals designed for studies in vivo and in situ is proposed. The method is rapid and effective and should facilitate investigation of therapeutic effects on both systemic and subcellular levels, as an advantage over the existing methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

Effectiveness of Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) Methods in Medicaid-Supported Prenatal Care: Trial III

ERIC Educational Resources Information Center

Windsor, Richard; Woodby, Lesa; Miller, Thomas; Hardin, Michael

2011-01-01

This two-phase evaluation documented the delivery and effectiveness of evidence-based health education methods by regular staff to pregnant smokers. During Phase 1, a total of 436 Medicaid patients were screened and 416 (95%) gave consent: 334 nonsmokers and 102 smokers. This historical Comparison (C) group was assessed to document the "normal"…

Ethosomes and Transfersomes: Principles, Perspectives and Practices.

PubMed

Garg, Varun; Singh, Harmanpreet; Bimbrawh, Sneha; Singh, Sachin Kumar; Gulati, Monica; Vaidya, Yogyata; Kaur, Prabhjot

2017-01-01

The success story of liposomes in the treatment of systemic infectious diseases and various carcinomas lead the scientists to the innovation of elastic vesicles to achieve similar success through transdermal route. In this direction, ethosomes and transfersomes were developed with the objective to design the vesicles that could pass through the skin. However, there is a lack of systematic review outlining the principles, method of preparation, latest advancement and applications of ethosomes and transfersomes. This review covers various aspects that would be helpful to scientists in understanding advantages of these vesicular systems and designing a unique nano vesicular delivery system. Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of principle of these vesicular delivery systems, composition, mechanism of actions, preparation techniques, methods for their characterization and their application. A total of 182 papers including both, research and review articles, were included in this review in order to make the article comprehensive and readily understandable. The mechanism of action and composition of ethosomes and transfersomes was extensively discussed. Various methods of preparation such as, rotary film evaporation method, reverse phase evaporation method, vortex/ sonication method, ethanol injection method, freeze thaw methods, along with their advantages has been discussed. It was also discussed that both these elastic nanocarriers offer unique advantages of ferrying the drug across membranes, sustaining drug release as well as protecting the encapsulated bio actives from external environment. The enhanced bioavailability and skin penetration of ethosomes as compared to conventional vesicular delivery systems is attributed to the presence of ethanol in the bilayers while that for transfersomes accrues due to their elasticity along with their ability to retain their shape because of the presence of edge activators. Successful delivery of synthetic drugs as well as phytomedicines has been extensively reported through these vesicles. Though these vesicular systems offer a good potential for rational drug delivery, a thoughtfully designed process is required to optimize the process variables involved. Industrial scale production of efficacious, safe, cost effective and stable formulations of both these delivery systems appears to be a pre-requisite to ensure their utility as the trans-dermal vehicles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

PubMed Central

Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

1996-01-01

BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811

CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

PubMed

Dal Monte, Olga; Noble, Pamela L; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B

2014-01-01

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

Inadequacy of Plasma Acyclovir Levels at Delivery in Patients with Genital Herpes Receiving Oral Acyclovir Suppressive Therapy in Late Pregnancy

PubMed Central

Leung, Daniel T.; Henning, Paul A.; Wagner, Emily C.; Blasig, Audrey; Wald, Anna; Sacks, Stephen L.; Corey, Lawrence; Money, Deborah M.

2009-01-01

Objective: Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for caesarean delivery. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal data suggests that low levels of HSV replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labor and delivery is warranted. Our objectives were to determine actual acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour and time since last acyclovir dose. Methods: Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour and time since last acyclovir dose with acyclovir blood levels were calculated. Results: Acyclovir levels were below the published mean steady-state trough value (180 ng/ml) in 52% of venous cord, 55% of arterial cord, and 36% of maternal samples. There was a significant inverse correlation between time since last dose and venous cord (rs19=−0.57, p<0.015), arterial cord (rs16=−0.63, p<0.01), and maternal acyclovir levels (r10=−0.69, p<0.03). Conclusions: Oral dosing of acyclovir in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches should evaluate dosing through labor, perhaps intravenously, and its effect on viral shedding. PMID:20085679

Factors involved in selecting the birth type among primiparous women

PubMed Central

Safari-Moradabadi, Ali; Alavi, Azin; Pormehr-Yabandeh, Asiyeh; Eftekhaari, Tasnim Eghbal; Dadipoor, Sakineh

2018-01-01

BACKGROUND: Mortality and disability rates were reported to be respectively 2-3 and 5-10 times higher in C-sections compared to Vaginal delivery. OBJECTIVES: This study was aimed to explore the factors involved in selecting the birth type among primiparous women. METHODS: The present cross-sectional research was conducted on 220 primiparous women, who visited the health-care centers of Bandar Abbas. They were recruited in their first trimester of pregnancy with a simple randomized clustering method. Data were collected in a researcher-designed questionnaire. Its validity was confirmed by a panel of experts and reliability was tested and approved through the test–retest method. Mean, standard deviation, independent sample t-test, and Chi-squared tests for data analysis were done by SPSS 16. P < 0.05 was considered statistically significant. RESULTS: The mean age of the participants was 27.40 ± 6.07 years. The main barriers to the choice of vaginal delivery were the fear of pain and fear of vaginal area tears and ruptures, fear of injury to fetus, and doctor's recommendation. A statistically significant correlation was observed between the age, education, employment, income, awareness, and the reasons for preferring surgical childbirth. CONCLUSIONS: To reduce the rate of unnecessary cesarean sections (C-section), the following recommendations are suggested: Reducing fear of pain in expectant mothers, modifying wrong beliefs about the culture of natural childbirth, increasing awareness of fewer adverse effects of vaginal delivery including the vaginal tears if the mother abides by all midwife(s) instructions during the delivery procedure, providing educational courses for the necessary movements during the delivery, decreasing surgeons’ payment for C-section, and increasing payment for natural childbirth and implementing barriers for optional delivery to reduce the C-section. PMID:29693036

Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.

PubMed

Démoulins, Thomas; Milona, Panagiota; Englezou, Pavlos C; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth C

2016-04-01

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effect of the Removal of User Fees for Delivery at Public Health Facilities on Institutional Delivery in Urban Kenya.

PubMed

Calhoun, Lisa M; Speizer, Ilene S; Guilkey, David; Bukusi, Elizabeth

2018-03-01

Objectives In 2013, Kenya removed delivery fees at public health facilities in an effort to promote equity in access to health services and address high maternal mortality. This study determines the effect of the policy to remove user fees on institutional delivery in a population-based sample of women from urban Kenya. Methods Longitudinal data were collected from a representative sample of 8500 women from five cities in Kenya in 2010 with a follow-up interview in 2014 (response rate 58.9%). Respondents were asked about their most recent birth since 2008 at baseline and 2012 at endline, including the delivery location. Multinomial logistic regression is used, controlling for the temporal time trend and background characteristics, to determine if births which occurred after the national policy change were more likely to occur at a public facility than at home or a private facility. Results Multivariate findings show that women were significantly more likely to deliver at a public facility as compared to a private facility after the policy. Among the poor, the results show that poor women were significantly more likely to deliver in a public facility compared to home or a private facility after policy change. Conclusions for Practice These findings show Kenya's progress towards achieving universal access to delivery services and meeting its national development targets. The removal of delivery fees in the public sector is leading to increased use of facilities for delivery among the urban poor; this is an important first step in reducing maternal death.

A comparative evaluation of the effect of internet-based CME delivery format on satisfaction, knowledge and confidence

PubMed Central

2010-01-01

Background Internet-based instruction in continuing medical education (CME) has been associated with favorable outcomes. However, more direct comparative studies of different Internet-based interventions, instructional methods, presentation formats, and approaches to implementation are needed. The purpose of this study was to conduct a comparative evaluation of two Internet-based CME delivery formats and the effect on satisfaction, knowledge and confidence outcomes. Methods Evaluative outcomes of two differing formats of an Internet-based CME course with identical subject matter were compared. A Scheduled Group Learning format involved case-based asynchronous discussions with peers and a facilitator over a scheduled 3-week delivery period. An eCME On Demand format did not include facilitated discussion and was not based on a schedule; participants could start and finish at any time. A retrospective, pre-post evaluation study design comparing identical satisfaction, knowledge and confidence outcome measures was conducted. Results Participants in the Scheduled Group Learning format reported significantly higher mean satisfaction ratings in some areas, performed significantly higher on a post-knowledge assessment and reported significantly higher post-confidence scores than participants in the eCME On Demand format that was not scheduled and did not include facilitated discussion activity. Conclusions The findings support the instructional benefits of a scheduled delivery format and facilitated asynchronous discussion in Internet-based CME. PMID:20113493

Restenosis Inhibition and Re-differentiation of TGFβ/Smad3-activated Smooth Muscle Cells by Resveratrol

PubMed Central

Zhu, Yichen; Takayama, Toshio; Wang, Bowen; Kent, Alycia; Zhang, Mengxue; Binder, Bernard Y.K.; Urabe, Go; Shi, Yatao; DiRenzo, Daniel; Goel, Shakti A.; Zhou, Yifan; Little, Christopher; Roenneburg, Drew A.; Shi, Xu Dong; Li, Lingjun; Murphy, William L.; Kent, K. Craig; Ke, Jianjuan; Guo, Lian-Wang

2017-01-01

To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. In a rat carotid injury model, periadventitial delivery of resveratrol either via Pluronic gel (2-week), or polymer sheath (3-month), effectively reduced IH without causing endothelium impairment and vessel shrinkage. In an in vitro model, primary smooth muscle cells (SMCs) were stimulated with elevated transforming growth factor (TGFβ) and its signaling protein Smad3, known contributors to IH. TGFβ/Smad3 up-regulated Kruppel-like factor (KLF5) protein, and SMC de-differentiation which was reversed by KLF5 siRNA. Furthermore, TGFβ/Smad3-stimulated KLF5 production and SMC de-differentiation were blocked by resveratrol via its inhibition of the Akt-mTOR pathway. Concordantly, resveratrol attenuated Akt phosphorylation in injured arteries. Taken together, periadventitial delivery of resveratrol produces durable inhibition of all three pro-restenotic pathologies — a rare feat among existing anti-restenotic methods. Our study suggests a potential anti-restenotic modality of resveratrol application suitable for open surgery. PMID:28165488

MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, D; Li, X; Li, H

2014-06-15

Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beammore » segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart review.« less

College Instructors' Experiences Transitioning to Inverted Classroom Instruction

ERIC Educational Resources Information Center

Brown, Glenda Maria

2017-01-01

Lecture methods in higher education continue to be the most often used form of lesson delivery, although they seem to be less effective in promoting adult students' learning and engagement. Many higher education instructors have incorporated inverted classroom (IC) methods to increase student engagement and learning. The purpose of this…

An Architecture for a Problem-Solving Assessment Authoring and Delivery System

DTIC Science & Technology

2006-06-01

know it works? In J. Willis (Series Ed.) & W. F. Heinecke & L. Blasi (Vol. Eds.), Research methods for educational technology: Vol. 1. Methods of...use of formal assessment in the classroom. In W. Hawley (Ed.) (with D. L. Rollie), The keys to effective schools: Educational reform as continuous

SU-F-T-242: A Method for Collision Avoidance in External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buzurovic, I; Cormack, R

2016-06-15

Purpose: We proposed a method for collision avoidance (CA) in external beam radiation therapy (EBRT). The method encompasses the analysis of all positions of the moving components of the beam delivery system such as the treatment table and gantry, including patient specific information obtained from the CT images. This method eliminates the need for time-consuming dry-runs prior to the actual treatments. Methods: The QA procedure for EBRT requires that the collision should be checked prior to treatment. We developed a system capable of a rigorous computer simulation of all moving components including positions of the couch and gantry during themore » delivery, position of the patients, and imaging equipment. By running this treatment simulation it is possible to quantify and graphically represent all positions and corresponding trajectories of all points of the moving parts during the treatment delivery. The development of the workflow for implementation of the CA includes several steps: a) derivation of combined dynamic equation of motion of the EBRT delivery systems, b) developing the simulation model capable of drawing the motion trajectories of the specific points, c) developing the interface between the model and the treatment plan parameters such as couch and gantry parameters for each field. Results: The patient CT images were registered to the treatment couch so the patient dimensions were included into the simulation. The treatment field parameters were structured in the xml-file which was used as the input into the dynamic equations. The trajectories of the moving components were plotted on the same graph using the dynamic equations. If the trajectories intersect that was the signal that collision exists. Conclusion: This CA method was proved to be effective in the simulation of treatment delivery. The proper implementation of this system can potentially improve the QA program and increase the efficacy in the clinical setup.« less

Pelvic floor dysfunction, and effects of pregnancy and mode of delivery on pelvic floor.

PubMed

Bozkurt, Murat; Yumru, Ayşe Ender; Şahin, Levent

2014-12-01

Pelvic floor dysfunction (PFD), although seems to be simple, is a complex process that develops secondary to multifactorial factors. The incidence of PFD is increasing with increasing life expectancy. PFD is a term that refers to a broad range of clinical scenarios, including lower urinary tract excretory and defecation disorders, such as urinary and anal incontinence, overactive bladder, and pelvic organ prolapse, as well as sexual disorders. It is a financial burden on the health care system and disrupts women's quality of life. Strategies applied to decrease PFD are focused on the course of pregnancy, mode and management of delivery, and pelvic exercise methods. Many studies in the literature define traumatic birth, usage of forceps, length of the second stage of delivery, and sphincter damage as modifiable risk factors for PFD. Maternal age, fetal position, and fetal head circumference are nonmodifiable risk factors. Although numerous studies show that vaginal delivery affects pelvic floor structures and their functions in a negative way, there is not enough scientific evidence to recommend elective cesarean delivery in order to prevent development of PFD. PFD is a heterogeneous pathological condition, and the effects of pregnancy, vaginal delivery, cesarean delivery, and possible risk factors of PFD may be different from each other. Observational studies have identified certain obstetrical exposures as risk factors for pelvic floor disorders. These factors often coexist; therefore, the isolated effects of these variables on the pelvic floor are difficult to study. The routine use of episiotomy for many years in order to prevent PFD is not recommended anymore; episiotomy should be used in selected cases, and the mediolateral procedures should be used if needed. Copyright © 2014. Published by Elsevier B.V.

Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

PubMed

Papiernik, E; Grangé, G; Zeitlin, J

1998-01-01

This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.

Multifunctional nanocarrier based on clay nanotubes for efficient intracellular siRNA delivery and gene silencing.

PubMed

Wu, Hui; Shi, Yinfeng; Huang, Chusen; Zhang, Yang; Wu, Jiahui; Shen, Hebai; Jia, Nengqin

2014-04-01

RNA interference-mediated gene silencing relating to disease has recently emerged as a powerful method in gene therapy. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. Halloysites are cheap and naturally available aluminosilicate clay nanotubes with high mechanical strength and biocompatibility. In this study, a novel multifunctional nanocarrier based on functionalized halloysite nanotubes (f-HNTs) has been developed via electrostatic layer-by-layer assembling approach for loading and intracellular delivery of therapeutic antisurvivin siRNA and simultaneously tracking their intracellular transport, in which PEI-modified HNTs are used as gene vector, antisurvivin siRNA as gene therapeutic agent, and mercaptoacetic acid-capped CdSe quantum dots as fluorescent labeling probes. The successful assembly of the f-HNTs-siRNA complexes was systematically characterized by transmission electron microscopy (TEM), UV-visible spectrophotometry, Zeta potential measurement, fluorescence spectrophotometry, and electrochemical impedance spectroscopy. Confocal microscopy, biological TEM, and flow cytometry studies revealed that the complexes enabled the efficient intracellular delivery of siRNA for cell-specific gene silencing. MTT assays exhibited that the complexes can enhance antitumor activity. Furthermore, Western blot analysis showed that f-HNTs-mediated siRNA delivery effectively knocked down gene expression of survivin and thereby decreased the levels of target proteins of PANC-1 cells. Therefore, this study suggested that the synthesized f-HNTs were a new effective drug delivery system for potential application in cancer gene therapy.

What are the Implications for Policy Makers? A Systematic Review of the Cost-Effectiveness of Screening and Brief Interventions for Alcohol Misuse in Primary Care

PubMed Central

Angus, Colin; Latimer, Nicholas; Preston, Louise; Li, Jessica; Purshouse, Robin

2014-01-01

Introduction: The efficacy of screening and brief interventions (SBIs) for excessive alcohol use in primary care is well established; however, evidence on their cost-effectiveness is limited. A small number of previous reviews have concluded that SBI programs are likely to be cost-effective but these results are equivocal and important questions around the cost-effectiveness implications of key policy decisions such as staffing choices for delivery of SBIs and the intervention duration remain unanswered. Methods: Studies reporting both the costs and a measure of health outcomes of programs combining SBIs in primary care were identified by searching MEDLINE, EMBASE, Econlit, the Cochrane Library Database (including NHS EED), CINAHL, PsycINFO, Assia and the Social Science Citation Index, and Science Citation Index via Web of Knowledge. Included studies have been stratified both by delivery staff and intervention duration and assessed for quality using the Drummond checklist for economic evaluations. Results: The search yielded a total of 23 papers reporting the results of 22 distinct studies. There was significant heterogeneity in methods and outcome measures between studies; however, almost all studies reported SBI programs to be cost-effective. There was no clear evidence that either the duration of the intervention or the delivery staff used had a substantial impact on this result. Conclusion: This review provides strong evidence that SBI programs in primary care are a cost-effective option for tackling alcohol misuse. PMID:25225487

Effects of women’s groups practising participatory learning and action on preventive and care-seeking behaviours to reduce neonatal mortality: A meta-analysis of cluster-randomised trials

PubMed Central

Neuman, Melissa; Azad, Kishwar; Costello, Anthony; Das, Sushmita; Nair, Nirmala; Shah More, Neena; Phiri, Tambosi; Tripathy, Prasanta; Prost, Audrey

2017-01-01

Background The World Health Organization recommends participatory learning and action (PLA) in women’s groups to improve maternal and newborn health, particularly in rural settings with low access to health services. There have been calls to understand the pathways through which this community intervention may affect neonatal mortality. We examined the effect of women’s groups on key antenatal, delivery, and postnatal behaviours in order to understand pathways to mortality reduction. Methods and findings We conducted a meta-analysis using data from 7 cluster-randomised controlled trials that took place between 2001 and 2012 in rural India (2 trials), urban India (1 trial), rural Bangladesh (2 trials), rural Nepal (1 trial), and rural Malawi (1 trial), with the number of participants ranging between 6,125 and 29,901 live births. Behavioural outcomes included appropriate antenatal care, facility delivery, use of a safe delivery kit, hand washing by the birth attendant prior to delivery, use of a sterilised instrument to cut the umbilical cord, immediate wrapping of the newborn after delivery, delayed bathing of the newborn, early initiation of breastfeeding, and exclusive breastfeeding. We used 2-stage meta-analysis techniques to estimate the effect of the women’s group intervention on behavioural outcomes. In the first stage, we used random effects models with individual patient data to assess the effect of groups on outcomes separately for the different trials. In the second stage of the meta-analysis, random effects models were applied using summary-level estimates calculated in the first stage of the analysis. To determine whether behaviour change was related to group attendance, we used random effects models to assess associations between outcomes and the following categories of group attendance and allocation: women attending a group and allocated to the intervention arm; women not attending a group but allocated to the intervention arm; and women allocated to the control arm. Overall, women’s groups practising PLA improved behaviours during and after home deliveries, including the use of safe delivery kits (odds ratio [OR] 2.92, 95% CI 2.02–4.22; I2 = 63.7%, 95% CI 4.4%–86.2%), use of a sterile blade to cut the umbilical cord (1.88, 1.25–2.82; 67.6%, 16.1%–87.5%), birth attendant washing hands prior to delivery (1.87, 1.19–2.95; 79%, 53.8%–90.4%), delayed bathing of the newborn for at least 24 hours (1.47, 1.09–1.99; 68.0%, 29.2%–85.6%), and wrapping the newborn within 10 minutes of delivery (1.27, 1.02–1.60; 0.0%, 0%–79.2%). Effects were partly dependent on the proportion of pregnant women attending groups. We did not find evidence of effects on uptake of antenatal care (OR 1.03, 95% CI 0.77–1.38; I2 = 86.3%, 95% CI 73.8%–92.8%), facility delivery (1.02, 0.93–1.12; 21.4%, 0%–65.8%), initiating breastfeeding within 1 hour (1.08, 0.85–1.39; 76.6%, 50.9%–88.8%), or exclusive breastfeeding for 6 weeks after delivery (1.18, 0.93–1.48; 72.9%, 37.8%–88.2%). The main limitation of our analysis is the high degree of heterogeneity for effects on most behaviours, possibly due to the limited number of trials involving women’s groups and context-specific effects. Conclusions This meta-analysis suggests that women’s groups practising PLA improve key behaviours on the pathway to neonatal mortality, with the strongest evidence for home care behaviours and practices during home deliveries. A lack of consistency in improved behaviours across all trials may reflect differences in local priorities, capabilities, and the responsiveness of health services. Future research could address the mechanisms behind how PLA improves survival, in order to adapt this method to improve maternal and newborn health in different contexts, as well as improve other outcomes across the continuum of care for women, children, and adolescents. PMID:29206833

Differences in primary health care delivery to Australia’s Indigenous population: a template for use in economic evaluations

PubMed Central

2012-01-01

Background Health economics is increasingly used to inform resource allocation decision-making, however, there is comparatively little evidence relevant to minority groups. In part, this is due to lack of cost and effectiveness data specific to these groups upon which economic evaluations can be based. Consequently, resource allocation decisions often rely on mainstream evidence which may not be representative, resulting in inequitable funding decisions. This paper describes a method to overcome this deficiency for Australia’s Indigenous population. A template has been developed which can adapt mainstream health intervention data to the Indigenous setting. Methods The ‘Indigenous Health Service Delivery Template’ has been constructed using mixed methods, which include literature review, stakeholder discussions and key informant interviews. The template quantifies the differences in intervention delivery between best practice primary health care for the Indigenous population via Aboriginal Community Controlled Health Services (ACCHSs), and mainstream general practitioner (GP) practices. Differences in costs and outcomes have been identified, measured and valued. This template can then be used to adapt mainstream health intervention data to allow its economic evaluation as if delivered from an ACCHS. Results The template indicates that more resources are required in the delivery of health interventions via ACCHSs, due to their comprehensive nature. As a result, the costs of such interventions are greater, however this is accompanied by greater benefits due to improved health service access. In the example case of the polypill intervention, 58% more costs were involved in delivery via ACCHSs, with 50% more benefits. Cost-effectiveness ratios were also altered accordingly. Conclusions The Indigenous Health Service Delivery Template reveals significant differences in the way health interventions are delivered from ACCHSs compared to mainstream GP practices. It is important that these differences are included in the conduct of economic evaluations to ensure results are relevant to Indigenous Australians. Similar techniques would be generalisable to other disadvantaged minority populations. This will allow resource allocation decision-makers access to economic evidence that more accurately represents the needs and context of disadvantaged groups, which is particularly important if addressing health inequities is a stated goal. PMID:22954136

Methods for engaging stakeholders in comparative effectiveness research: a patient-centered approach to improving diabetes care.

PubMed

Schmittdiel, Julie A; Desai, Jay; Schroeder, Emily B; Paolino, Andrea R; Nichols, Gregory A; Lawrence, Jean M; O'Connor, Patrick J; Ohnsorg, Kris A; Newton, Katherine M; Steiner, John F

2015-06-01

Engaging stakeholders in the research process has the potential to improve quality of care and the patient care experience. Online patient community surveys can elicit important topic areas for comparative effectiveness research. Stakeholder meetings with substantial patient representation, as well as representation from health care delivery systems and research funding agencies, are a valuable tool for selecting and refining pilot research and quality improvement projects. Giving patient stakeholders a deciding vote in selecting pilot research topics helps ensure their 'voice' is heard. Researchers and health care leaders should continue to develop best-practices and strategies for increasing patient involvement in comparative effectiveness and delivery science research.

Effect of Ketofol on Pain and Complication after Caesarean Delivery under Spinal Anaesthesia: A Randomized Double-blind Clinical Trial.

PubMed

Jaafarpour, Molouk; Vasigh, Aminolah; Khajavikhan, Javaher; Khani, Ali

2017-03-01

Pain is the key concern of women after caesarean delivery that may interfere with breastfeeding. The aim of this study was to assess effect of ketofol (ketamine/propofol combination) on pain and complication after caesarean delivery under spinal anaesthesia. In this randomized double-blind clinical trial, 92 parturient scheduled for elective caesarean delivery under spinal anaesthesia were included. The simple random sampling method was used to place subjects in four groups of ketamine (0.25 mg/kg), propofol (0.25 mg/kg), ketofol (25 mg ketamine plus 25 mg propofol) and placebo (saline). The drugs were administered intravenously immediately after clamping the umbilical cord. Visual Analog Scale (VAS) was used to determine the intensity of pain. Complications after surgery including shivering, nausea and vomiting as well as onset of breastfeeding were recorded. The mean score of pain, morphine consumption and time of breastfeeding in the ketofol group were significantly lower than other groups at various intervals (p<0.05, p<0.001). The frequencies of shivering, nausea, vomiting, retention and pruritus in the ketofol group were significantly lower than other groups (p<0.001, p<0.05). The effective role of ketofol on reducing pain and complication after caesarean delivery indicated that it can be considered as a safe and alternative drug in these patients.

Directed Differentiation of Embryonic Stem Cells Into Cardiomyocytes by Bacterial Injection of Defined Transcription Factors.

PubMed

Bai, Fang; Ho Lim, Chae; Jia, Jingyue; Santostefano, Katherine; Simmons, Chelsey; Kasahara, Hideko; Wu, Weihui; Terada, Naohiro; Jin, Shouguang

2015-10-09

Forced expression of defined transcriptional factors has been well documented as an effective method for cellular reprogramming or directed differentiation. However, transgene expression is not amenable for therapeutic application due to potential insertional mutagenesis. Here, we have developed a bacterial type III secretion system (T3SS)-based protein delivery tool and shown its application in directing pluripotent stem cell differentiation by a controlled delivery of transcription factors relevant to early heart development. By fusing to an N-terminal secretion sequence for T3SS-dependent injection, three transcriptional factors, namely Gata4, Mef2c, and Tbx5 (abbreviated as GMT), were translocated into murine embryonic stem cells (ESCs), where the proteins are effectively targeted to the nucleus with an average intracellular half-life of 5.5 hours. Exogenous GMT protein injection activated the cardiac program, and multiple rounds of GMT protein delivery significantly improved the efficiency of ESC differentiation into cardiomyocytes. Combination of T3SS-mediated GMT delivery and Activin A treatment showed an additive effect, resulting in on average 60% of the ESCs differentiated into cardiomyocytes. ESC derived cardiomyocytes displayed spontaneous rhythmic contractile movement as well as normal hormonal responses. This work serves as a foundation for the bacterial delivery of multiple transcription factors to direct cell fate without jeopardizing genomic integrity.

Directed Differentiation of Embryonic Stem Cells Into Cardiomyocytes by Bacterial Injection of Defined Transcription Factors

PubMed Central

Bai, Fang; Ho Lim, Chae; Jia, Jingyue; Santostefano, Katherine; Simmons, Chelsey; Kasahara, Hideko; Wu, Weihui; Terada, Naohiro; Jin, Shouguang

2015-01-01

Forced expression of defined transcriptional factors has been well documented as an effective method for cellular reprogramming or directed differentiation. However, transgene expression is not amenable for therapeutic application due to potential insertional mutagenesis. Here, we have developed a bacterial type III secretion system (T3SS)-based protein delivery tool and shown its application in directing pluripotent stem cell differentiation by a controlled delivery of transcription factors relevant to early heart development. By fusing to an N-terminal secretion sequence for T3SS-dependent injection, three transcriptional factors, namely Gata4, Mef2c, and Tbx5 (abbreviated as GMT), were translocated into murine embryonic stem cells (ESCs), where the proteins are effectively targeted to the nucleus with an average intracellular half-life of 5.5 hours. Exogenous GMT protein injection activated the cardiac program, and multiple rounds of GMT protein delivery significantly improved the efficiency of ESC differentiation into cardiomyocytes. Combination of T3SS-mediated GMT delivery and Activin A treatment showed an additive effect, resulting in on average 60% of the ESCs differentiated into cardiomyocytes. ESC derived cardiomyocytes displayed spontaneous rhythmic contractile movement as well as normal hormonal responses. This work serves as a foundation for the bacterial delivery of multiple transcription factors to direct cell fate without jeopardizing genomic integrity. PMID:26449528

The blood-brain barrier and nasal drug delivery to the central nervous system.

PubMed

Miyake, Marcel Menon; Bleier, Benjamin S

2015-01-01

The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. The objective of this study is to generally review these strategies of drug administration to the CNS. Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Examination of the Relationship of Community College Opticianry Student Outcomes with Instructional Delivery Methods and Student Age

ERIC Educational Resources Information Center

Underwood, William B.; Hernandez-Gantes, Victor M.

2017-01-01

The purpose of this study was to determine whether student outcomes are a function of participation in different modes of delivery and student age in an Opticianry program at the community college level. The three instructional delivery methods were traditional face-to-face instruction, online delivery, and a hybrid format where students take…

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

A panel analysis of the strategic association between information and communication technology and public health delivery.

PubMed

Wu, Sarah Jinhui; Raghupathi, Wullianallur

2012-10-22

In this exploratory research, we use panel data analysis to examine the correlation between Information and Communication Technology (ICTs) and public health delivery at the country level. The goal of this exploratory research is to examine the strategic association over time between ICTs and country-level public health. Using data from the World Development Indicators, we construct a panel data set of countries of five different income levels and look closely at the period from 2000 to 2008. The panel data analysis allows us to explore this dynamic relationship under the control for unobserved country-specific effects by using a fixed-effects estimation method. In particular,, we examine the association of five ICT factors with five public health indicators: adolescent fertility rate, child immunization coverage, tuberculosis case detected, life expectancy, and adult mortality rate. First, overall ICTs' factors substantially improve a country's public health delivery on the top of wealth effect. Second, among all the ICTs' factors, accessibility is the only one that is associated with improvements in all aspects of public health delivery, while the contributions from the usage, quality, and applications are negligible. ICTs' accessibility factor is associated with a considerable extension to life expectancy and reduced adult mortality rate. Third, all entity-specific factors are significant in each model, indicating that countries' economic development level does influence their public health delivery. Our results indicate that ICT accessibility has a strong association with effective delivery of public health. There are others, but the key strategic applications are eHealth and mHealth. The findings of this study will help government officials and public health policy makers to formulate strategic decisions regarding the best ICT investments and deployment. For example, the study shows that providing accessibility should be a critical focus.

Effective utility accommodation : final report.

DOT National Transportation Integrated Search

2009-12-08

The report presents research regarding methods to improve project delivery times and minimize construction delays due to utility coordination by conducting a study of the current best practices used by six (6) similar state transportation departments...

Closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery

NASA Astrophysics Data System (ADS)

Park, Eun-Joo; Werner, Jacob; Jaiswal, Devina; Smith, Nadine Barrie

2010-03-01

To prevent complications in diabetes, the proper management of blood glucose levels is essential. Previously, ultrasonic transdermal methods using a light-weight cymbal transducer array has been studied for noninvasive methods of insulin delivery for Type-1 diabetes and glucose level monitoring. In this study, the ultrasound systems of insulin delivery and glucose sensing have been combined by a feedback controller. This study was designed to show the feasibility of the feedback controlled ultrasound system for the noninvasive glucose control. For perspective human application, in vivo experiments were performed on large animals that have a similar size to humans. Four in vivo experiments were performed using about 200 lbs pigs. The cymbal array of 3×3 pattern has been used for insulin delivery at 30 kHz with the spatial-peak temporal-peak intensity (Isptp) of 100 mW/cm2. For glucose sensing, a 2×2 array was operated at 20 kHz with Isptp = 100 mW/cm2. Based on the glucose level determined by biosensors after the ultrasound exposure, the ultrasound system for the insulin delivery was automatically operated. The glucose level of 115 mg/dl was set as a reference value for operating the insulin delivery system. For comparison, the glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Using the ultrasound system operated by the close-loop, feed-back controller, the glucose levels of four pigs were determined every 20 minutes and continuously controlled for 120 minutes. In comparison to the commercial glucose meter, the glucose levels determined by the biosensor were slightly higher. The results of in vivo experiments indicate the feasibility of the feedback controlled ultrasound system using the cymbal array for noninvasive glucose sensing and insulin delivery. Further studies on the extension of the glucose control will be continued for the effective method of glucose control.

Economic Model Predictive Control of Bihormonal Artificial Pancreas System Based on Switching Control and Dynamic R-parameter.

PubMed

Tang, Fengna; Wang, Youqing

2017-11-01

Blood glucose (BG) regulation is a long-term task for people with diabetes. In recent years, more and more researchers have attempted to achieve automated regulation of BG using automatic control algorithms, called the artificial pancreas (AP) system. In clinical practice, it is equally important to guarantee the treatment effect and reduce the treatment costs. The main motivation of this study is to reduce the cure burden. The dynamic R-parameter economic model predictive control (R-EMPC) is chosen to regulate the delivery rates of exogenous hormones (insulin and glucagon). It uses particle swarm optimization (PSO) to optimize the economic cost function and the switching logic between insulin delivery and glucagon delivery is designed based on switching control theory. The proposed method is first tested on the standard subject; the result is compared with the switching PID and the switching MPC. The effect of the dynamic R-parameter on improving the control performance is illustrated by comparing the results of the EMPC and the R-EMPC. Finally, the robustness tests on meal change (size and timing), hormone sensitivity (insulin and glucagon), and subject variability are performed. All results show that the proposed method can improve the control performance and reduce the economic costs. The simulation results verify the effectiveness of the proposed algorithm on improving the tracking performance, enhancing robustness, and reducing economic costs. The method proposed in this study owns great worth in practical application.

Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

NASA Astrophysics Data System (ADS)

Cha, Kyoung Je; Kim, Taewan; Jea Park, Sung; Kim, Dong Sung

2014-11-01

Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications.

Drug-targeting methodologies with applications: A review

PubMed Central

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

SU-F-T-273: Using a Diode Array to Explore the Weakness of TPS DoseCalculation Algorithm for VMAT and Sliding Window Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Lu, B; Yan, G

Purpose: To identify the weakness of dose calculation algorithm in a treatment planning system for volumetric modulated arc therapy (VMAT) and sliding window (SW) techniques using a two-dimensional diode array. Methods: The VMAT quality assurance(QA) was implemented with a diode array using multiple partial arcs that divided from a VMAT plan; each partial arc has the same segments and the original monitor units. Arc angles were less than ± 30°. Multiple arcs delivered through consecutive and repetitive gantry operating clockwise and counterclockwise. The source-toaxis distance setup with the effective depths of 10 and 20 cm were used for a diodemore » array. To figure out dose errors caused in delivery of VMAT fields, the numerous fields having the same segments with the VMAT field irradiated using different delivery techniques of static and step-and-shoot. The dose distributions of the SW technique were evaluated by creating split fields having fine moving steps of multi-leaf collimator leaves. Calculated doses using the adaptive convolution algorithm were analyzed with measured ones with distance-to-agreement and dose difference of 3 mm and 3%.. Results: While the beam delivery through static and step-and-shoot techniques showed the passing rate of 97 ± 2%, partial arc delivery of the VMAT fields brought out passing rate of 85%. However, when leaf motion was restricted less than 4.6 mm/°, passing rate was improved up to 95 ± 2%. Similar passing rate were obtained for both 10 and 20 cm effective depth setup. The calculated doses using the SW technique showed the dose difference over 7% at the final arrival point of moving leaves. Conclusion: Error components in dynamic delivery of modulated beams were distinguished by using the suggested QA method. This partial arc method can be used for routine VMAT QA. Improved SW calculation algorithm is required to provide accurate estimated doses.« less

Novel PLGA-based nanoparticles for the oral delivery of insulin

PubMed Central

Malathi, Sampath; Nandhakumar, Perumal; Pandiyan, Velayudham; Webster, Thomas J; Balasubramanian, Sengottuvelan

2015-01-01

Background Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). Objective To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. Methods A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. Results The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. Conclusion ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin. PMID:25848248

Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

PubMed

Sabra, Sally; Abdelmoneem, Mona; Abdelwakil, Mahmoud; Mabrouk, Moustafa Taha; Anwar, Doaa; Mohamed, Rania; Khattab, Sherine; Bekhit, Adnan; Elkhodairy, Kadria; Freag, May; Elzoghby, Ahmed

2017-01-01

Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ceramic nanocarriers: versatile nanosystem for protein and peptide delivery.

PubMed

Singh, Deependra; Dubey, Pooja; Pradhan, Madhulika; Singh, Manju Rawat

2013-02-01

Proteins and peptides have been established to be the potential drug candidate for various human diseases. But, delivery of these therapeutic protein and peptides is still a challenge due to their several unfavorable properties. Nanotechnology is expanding as a promising tool for the efficient delivery of proteins and peptides. Among numerous nano-based carriers, ceramic nanoparticles have proven themselves as a unique carrier for protein and peptide delivery as they provide a more stable, bioavailable, readily manufacturable, and acceptable proteins and polypeptide formulation. This article provides an overview of the various aspects of ceramic nanoparticles including their classification, methods of preparation, latest advances, and applications as protein and peptide delivery carriers. Ceramic nanocarriers seem to have potential for preserving structural integrity of proteins and peptides, thereby promoting a better therapeutic effect. This approach thus provides pharmaceutical scientists with a new hope for the delivery of proteins and peptides. Still, considerable study on ceramic nanocarrier is necessary with respect to pharmacokinetics, toxicology, and animal studies to confirm their efficiency as well as safety and to establish their clinical usefulness and scale-up to industrial level.

Immunization Route Dictates Cross-Priming Efficiency and Impacts the Optimal Timing of Adjuvant Delivery

PubMed Central

Bouvier, Isabelle; Jusforgues-Saklani, Hélène; Lim, Annick; Lemaître, Fabrice; Lemercier, Brigitte; Auriau, Charlotte; Nicola, Marie-Anne; Leroy, Sandrine; Law, Helen K.; Bandeira, Antonio; Moon, James J.; Bousso, Philippe; Albert, Matthew L.

2011-01-01

Delivery of cell-associated antigen represents an important strategy for vaccination. While many experimental models have been developed in order to define the critical parameters for efficient cross-priming, few have utilized quantitative methods that permit the study of the endogenous repertoire. Comparing different strategies of immunization, we report that local delivery of cell-associated antigen results in delayed T cell cross-priming due to the increased time required for antigen capture and presentation. In comparison, delivery of disseminated antigen resulted in rapid T cell priming. Surprisingly, local injection of cell-associated antigen, while slower, resulted in the differentiation of a more robust, polyfunctional, effector response. We also evaluated the combination of cell-associated antigen with poly I:C delivery and observed an immunization route-specific effect regarding the optimal timing of innate immune stimulation. These studies highlight the importance of considering the timing and persistence of antigen presentation, and suggest that intradermal injection with delayed adjuvant delivery is the optimal strategy for achieving CD8+ T cell cross-priming. PMID:22566860

Efficacy and Safety of Prophylactic Uterine Artery Embolization in Pregnancy Termination with Placenta Previa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Renguang, E-mail: mediprg@bjmu.edu.cn; Wang, Guoxiang; Wang, Heping

PurposeTo appraise the efficacy and safety of prophylactic uterine artery embolization in pregnancy termination with placenta previa.MethodsA cohort of 54 consecutive patients with placenta previa underwent prophylactic uterine artery embolization before vaginal delivery from February 2012 to March 2015. Vaginal delivery was attempted in all patients. Cesarean section or hysterectomy was introduced when vaginal delivery failed.ResultsVaginal delivery succeeded in 50 patients (93.6%) and failed in 4 patients (6.4%), thereupon converted to cesarean delivery. No patients resorted to hysterectomy. Six patients (11.1%) underwent blood transfusion. None of clinical characteristics, including maternal age, gestational age, history of abortion, history of cesarean delivery,more » and volume of vaginal bleeding, was significantly associated with complete placenta previa (P > 0.05). However, patients with complete placenta previa had a significantly lower successful rate of vaginal delivery than did patients without complete placenta previa (81 vs 100%, P = 0.038). The rate of complications was 3.7%. No major complications were observed.ConclusionUterine artery embolization is an effective and safe technique to assist pregnancy termination with placenta previa, which may lower the risk of cesarean section, hysterectomy, and blood transfusion.« less

Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

PubMed

Henshaw, Joshua W; Yuan, Fan

2008-02-01

Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

PubMed Central

Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

2013-01-01

Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

[Unwanted adolescent pregnancy and post-partum utilization of contraceptive methods].

PubMed

Núñez-Urquiza, Rosa María; Hernández-Prado, Bernardo; García-Barrios, Cecilia; González, Dolores; Walker, Dylis

2003-01-01

To describe the proportion of unwanted pregnancies among all pregnant adolescents, its association with sociodemographic characteristics, and the use of post-partum contraceptive methods. A cross-sectional study was conducted among 220 women between 13 and 19 years of age, in two semi-urban municipalities of the State of Morelos, Mexico, interviewed between 1992 and 1994. Women were interviewed at home, six to twelve weeks after their delivery date. Women were asked whether they had wanted their last pregnancy, and about knowledge and use of contraceptive methods after delivery. Adolescent pregnancies accounted for 17% of all births registered in these two municipalities. Among all adolescent mother 22.73% reported that their pregnancy had not been wanted. A positive association was found between the lack of access to health services provided by public medical insurance systems (Instituto Mexicano del Seguro Social IMSS and Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado ISSSTE) and unwanted pregnancy (adjusted OR = 3.03, 95% CI (1.31, 7.) An association was also found between living in an urban community (adjusted OR = 2.16, 95% CI (1.08, 4.33) and an unwanted pregnancy. Among all adolescent mothers, 91.3% were familiar with "the pill" as a contraceptive method; 84.72% knew about the IUD, and 63.68% knew about the condom. However, only 35% of them were actually using an effective contraceptive method six weeks after delivery. No difference in frequency of contraceptive use was found among the adolescent mothers, according to whether they wanted their last pregnancy. Only 43.39% of mothers who delivered at hospitals or health centers were using an effective contraceptive method. These findings suggest that there is a great potential for family planning programs to target adolescents, and that the use of contraceptive methods after delivery should be promoted among adolescent mothers, especially those lacking access to public medical insurance and those living in semi-urban settings. It is also recommended to conduct studies on family planning education programs that can be introduced earlier in the school system in Mexico.

Quantitative Measurement of Protease-Activity with Correction of Probe Delivery and Tissue Absorption Effects

PubMed Central

Salthouse, Christopher D.; Reynolds, Fred; Tam, Jenny M.; Josephson, Lee; Mahmood, Umar

2009-01-01

Proteases play important roles in a variety of pathologies from heart disease to cancer. Quantitative measurement of protease activity is possible using a novel spectrally matched dual fluorophore probe and a small animal lifetime imager. The recorded fluorescence from an activatable fluorophore, one that changes its fluorescent amplitude after biological target interaction, is also influenced by other factors including imaging probe delivery and optical tissue absorption of excitation and emission light. Fluorescence from a second spectrally matched constant (non-activatable) fluorophore on each nanoparticle platform can be used to correct for both probe delivery and tissue absorption. The fluorescence from each fluorophore is separated using fluorescence lifetime methods. PMID:20161242

Effects of infectious virus dose and bloodmeal delivery method on susceptibility of Aedes aegypti and Aedes albopictus to chikungunya virus.

PubMed

Pesko, Kendra; Westbrook, Catherine J; Mores, Christopher N; Lounibos, L Philip; Reiskind, Michael H

2009-03-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory.

Effects of Infectious Virus Dose and Bloodmeal Delivery Method on Susceptibility of Aedes aegypti and Aedes albopictus to Chikungunya Virus

PubMed Central

Pesko, Kendra; Westbrook, Catherine J.; Mores, Christopher N.; Lounibos, L. Philip; Reiskind, Michael H.

2009-01-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory. PMID:19351094

Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

PubMed

Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

2016-11-01

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy.

PubMed

Hosseini, Maryam; Haji-Fatahaliha, Mostafa; Jadidi-Niaragh, Farhad; Majidi, Jafar; Yousefi, Mehdi

2016-06-01

Cancer is one of the most important causes of death all over the world, which has not yet been treated efficiently. Although several therapeutic approaches have been used, some side effects such as toxicity and drug resistance have been observed in patients, particularly with chemotherapy. The nanoparticle-mediated drug delivery systems (DDS) have a great potential to improve cancer treatment by transferring therapeutic factors directly to the tumor site. Such a treatment significantly decreases the adverse effects associated with cancer therapy on healthy tissues. Two main strategies, including passive and active methods, have been considered to be effective techniques which can target the drugs to the tumor sites. The current review sheds some light on the place of nanotechnology in cancer drug delivery, and introduces nanomaterials and their specific characteristics that can be used in tumor therapy. Moreover, passive and active targeting approaches focus on antibodies, particularly single chain variable fragments (scFv), as a novel and important ligand in a drug delivery system.

The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma

NASA Astrophysics Data System (ADS)

Dhulekar, Jhilmil

Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the individual effect on cell toxicity of each drug and in combination. Finally, nanoparticles were loaded with the non-toxic drug and delivered with free temozolomide to determine the overall efficacy of the drugs in reducing neuroblastoma cell viability.

A comparative evaluation of coenzyme Q10-loaded liposomes and solid lipid nanoparticles as dermal antioxidant carriers

PubMed Central

Gokce, Evren H; Korkmaz, Emrah; Tuncay-Tanrıverdi, Sakine; Dellera, Eleonora; Sandri, Giuseppina; Bonferoni, M Cristina; Ozer, Ozgen

2012-01-01

Background The effective delivery of coenzyme Q10 (Q10) to the skin has several benefits in therapy for different skin pathologies. However, the delivery of Q10 to deeper layers of skin is challenging due to low aqueous solubility of Q10. Liposomes and solid lipid nanoparticles (SLN) have many advantages to accomplish the requirements in topical drug delivery. This study aims to evaluate the influence of these nanosystems on the effective delivery of Q10 into the skin. Methods Q10-loaded liposomes (LIPO-Q10) and SLNs (SLN-Q10) were prepared by thin film hydration and high shear homogenization methods, respectively. Particle size (PS), polydispersity index (PI), zeta potential (ZP), and drug entrapment efficiency were determined. Differential scanning calorimetry analysis and morphological transmission electron microscopy (TEM) examination were conducted. Biocompatibility/cytotoxicity studies of Q10-loaded nanosystems were performed by means of cell culture (human fibroblasts) under oxidative conditions. The protective effect of formulations against production of reactive oxygen species were comparatively evaluated by cytofluorometry studies. Results PS of uniform SLN-Q10 and LIPO-Q10 were determined as 152.4 ± 7.9 nm and 301.1 ± 8.2 nm, respectively. ZPs were −13.67 ± 1.32 mV and −36.6 ± 0.85 mV in the same order. The drug entrapment efficiency was 15% higher in SLN systems. TEM studies confirmed the colloidal size. SLN-Q10 and LIPO-Q10 showed biocompatibility towards fibroblasts up to 50 μM of Q10, which was determined as suitable for cell proliferation. The mean fluorescence intensity % depending on ROS production determined in cytofluorometric studies could be listed as Q10 ≥ SLN-Q10 > LIPO-Q10. Conclusion The LIPO-Q10 system was able to enhance cell proliferation. On the contrary, SLN-Q10 did not show protective effects against ROS accumulation. As a conclusion, liposomes seem to have advantages over SLN in terms of effective delivery of Q10 to skin for antioxidant purposes. PMID:23055723

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

ACTIVE DELIVERY CABLE TUNED TO DEVICE DEPLOYMENT STATE: ENHANCED VISIBILITY OF NITINOL OCCLUDERS DURING PRE-CLINICAL INTERVENTIONAL MRI

PubMed Central

Bell, Jamie A.; Saikus, Christina E.; Ratnayaka, Kanishka; Barbash, Israel M.; Faranesh, Anthony Z.; Franson, Dominique N.; Sonmez, Merdim; Slack, Michael C.; Lederman, Robert J.; Kocaturk, Ozgur

2012-01-01

Purpose To develop an active delivery system that enhances visualization of nitinol cardiac occluder devices during deployment under real-time MRI. Materials and Methods We constructed an active delivery cable incorporating a loopless antenna and a custom titanium microscrew to secure the occluder devices. The delivery cable was tuned and matched to 50Ω at 64 MHz with the occluder device attached. We used real-time balanced SSFP in a wide-bore 1.5T scanner. Device-related images were reconstructed separately and combined with surface-coil images. The delivery cable was tested in vitro in a phantom and in vivo in swine using a variety of nitinol cardiac occluder devices. Results In vitro, the active delivery cable provided little signal when the occluder device was detached and maximal signal with the device attached. In vivo, signal from the active delivery cable enabled clear visualization of occluder device during positioning and deployment. Device release resulted in decreased signal from the active cable. Post-mortem examination confirmed proper device placement. Conclusions The active delivery cable enhanced the MRI depiction of nitinol cardiac occluder devices during positioning and deployment, both in conventional and novel applications. We expect enhanced visibility to contribute to effectiveness and safety of new and emerging MRI-guided treatments. PMID:22707441

Double versus single cervical cerclage for patients with recurrent pregnancy loss: a randomized clinical trial.

PubMed

Zolghadri, Jaleh; Younesi, Masoumeh; Asadi, Nasrin; Khosravi, Dezire; Behdin, Shabnam; Tavana, Zohre; Ghaffarpasand, Fariborz

2014-02-01

To compare the effectiveness of the double cervical cerclage method versus the single method in women with recurrent second-trimester delivery. In this randomized clinical trial, we included 33 singleton pregnancies suffering from recurrent second-trimester pregnancy loss (≥2 consecutive fetal loss during second-trimester or with a history of unsuccessful procedures utilizing the McDonald method), due to cervical incompetence. Patients were randomly assigned to undergo either the classic McDonald method (n = 14) or the double cerclage method (n = 19). The successful pregnancy rate and gestational age at delivery was also compared between the two groups. The two study groups were comparable regarding their baseline characteristics. The successful pregnancy rate did not differ significantly between those who underwent the double cerclage method or the classic McDonald cerclage method (100% vs 85.7%; P = 0.172). In the same way, the preterm delivery rate (<34 weeks of gestation) was comparable between the two study groups (10.5% vs 35.7%; P = 0.106). Those undergoing the double cerclage method had longer gestational duration (37.2 ± 2.6 vs 34.3 ± 3.8 weeks; P = 0.016). The double cervical cerclage method seems to provide better cervical support, as compared with the classic McDonald cerclage method, in those suffering from recurrent pregnancy loss, due to cervical incompetence. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Analysis of the Effect a Student-Centred Mobile Learning Instructional Method Has on Language Acquisition

ERIC Educational Resources Information Center

Oberg, Andrew; Daniels, Paul

2013-01-01

In this study a self-paced instructional method based on the use of Apple's iPod Touch personal mobile devices to deliver content was compared with a group-oriented instructional method of content delivery in terms of learner acquisition of course material. One hundred and twenty-two first-year Japanese university students in four classes were…

An Exploratory Study of the Effects of Online Course Efficiency Perceptions on Student Evaluation of Teaching (SET) Measures

ERIC Educational Resources Information Center

Estelami, Hooman

2016-01-01

One of the fundamental drivers of the growing use of distance learning methods in modern business education has been the efficiency gains associated with this method of educational delivery. Distance methods benefit both students and educational institutions as they facilitate the processing of large volumes of learning material to overcome…

Comparison of Online Versus Classroom Delivery of an Immunization Elective Course

PubMed Central

Pitterle, Michael E.; Hayney, Mary S.

2014-01-01

Objective. To compare performance and preferences of students who were randomly allocated to classroom or online sections of an elective course on immunization. Methods. Students were randomly assigned to either the classroom or online section. All course activities (lectures, quizzes, case discussions, vaccine administration, and final examination) were the same for both sections, except for the delivery of lecture material. Assessment. Students were surveyed on their preferences at the beginning and end of the semester. At the end of the semester, the majority of students in the classroom group preferred classroom or blended delivery while the majority of students in the online group preferred blended or online delivery (p<0.01). Student performance was compared at the end of the semester. There was no significant difference for any of the grades in the course between the 2 sections. Conclusion. There was no difference in student performance between the classroom and online sections, suggesting that online delivery is an effective way to teach students about immunization. PMID:24954936

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

PubMed Central

Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

2012-01-01

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

Acute Air Pollution Exposure and Blood Pressure at Delivery Among Women With and Without Hypertension

PubMed Central

Männistö, Tuija; Liu, Danping; Leishear, Kira; Sherman, Seth; Laughon, S. Katherine

2015-01-01

BACKGROUND Chronic air pollution exposure increases risk for hypertensive disorders of pregnancy, but the effect of acute air pollution exposure on blood pressure during pregnancy is less well known. METHODS We studied 151,276 singleton term deliveries from the Consortium on Safe Labor (2002–2008) with clinical blood pressure measured at admission to labor/delivery and diagnoses of hypertensive disorders collected from electronic medical records and hospital discharge summaries. Air pollution exposures were estimated for the admission hour and the 4 hours preceding admission using a modified version of the Community Multiscale Air Quality models and observed air monitoring data. Blood pressure was categorized as normal; high normal; and mild, moderate, or severe hypertension based on pregnancy cut points. Adjusted ordinal logistic regression estimated the odds of women having a higher admission blood pressure category as a function of air pollutant, hypertensive disorders, and their interaction effect. RESULTS Odds of high blood pressure at admission to labor/delivery were increased in normotensive women after exposure to nitrogen oxides (by 0.2%/5 units), sulfur dioxide (by 0.3%/1 unit), carbon monoxide and several air toxics (by 3%–4%/high exposure). The effects were often similar or stronger among women with gestational hypertension and preeclampsia. Exposure to particulate matter <10 μm increased odds of high blood pressure in women with preeclampsia by 3%/5 units. CONCLUSIONS Air pollution can influence admission blood pressure in term deliveries and may increase likelihood of preeclampsia screening at delivery admission. PMID:24795401

PLGA Nanoparticles and Their Versatile Role in Anticancer Drug Delivery.

PubMed

Khan, Iliyas; Gothwal, Avinash; Sharma, Ashok Kumar; Kesharwani, Prashant; Gupta, Lokesh; Iyer, Arun K; Gupta, Umesh

2016-01-01

Nanotechnological advancement has become a key standard for the diagnosis and treatment of several complex disorders such as cancer by utilizing the enhanced permeability and retention effect and tumor-specific targeting. Synthesis and designing the formulation of active agents in terms of their efficient delivery is of prime importance for healthcare. The use of nanocarriers has resolved the undesirable characteristics of anticancer drugs such as low solubility and poor permeability in cells. Several types of nanoparticles (NPs) have been designed with the use of various polymers along or devoid of surface engineering for targeting tumor cells. All NPs include polymers in their framework and, of these, polylactide-co-glycolide (PLGA) is biodegradable and Food and Drug Administration approved for human use. PLGA has been used extensively in the development of NPs for anticancer drug delivery. The extensive use of PLGA NPs is promising for cancer therapy, with higher efficiency and less adverse effects. The present review focused on recent developments regarding PLGA NPs, the methods used for their preparation, their characterization, and their utility in the delivery of chemotherapeutic agents.

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

NASA Astrophysics Data System (ADS)

Kambalapally, Swetha Reddy

The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as fluorescent labels. They have been studied extensively due to their interesting optical and electrical properties. The study of their applications has led to their use as novel platforms for delivery into living systems for use in medical imaging. The second part of this thesis discusses the toxicity of the various semiconductor nanocrystals, CdSe and InP. The results show the toxicity of CdSe and InP QDs in in vitro cultures of whole skin biopsies exposed to similar concentrations. This forms the basis for further studies involving QDs and approaches to reduce the toxicity of these nanoparticles. Finally, ligand exchange mediated Solutol HS-15 modified CdSe QDs were prepared for the first time. The modified CdSe QDs demonstrated long term stability and reduced cytotoxicity. Such behavior is interpreted as arising from decreased aggregation of the QDs due to the incorporation of the surfactant.

The missing link in Aboriginal care: resource accounting.

PubMed

Ashton, C W; Duffie-Ashton, Denise

2008-01-01

Resource accounting principles provide more effective planning for Aboriginal healthcare delivery through driving best management practices, efficacious techniques for long-term resource allocation, transparency of information and performance measurement. Major improvements to Aboriginal health in New Zealand and Australia were facilitated in the context of this public finance paradigm, rather than cash accounting systems that remain the current method for public departments in Canada. Multiple funding sources and fragmented delivery of Aboriginal healthcare can be remedied through similar adoption of such principles.

MATHEMATICAL METHODS IN MEDICAL IMAGE PROCESSING

PubMed Central

ANGENENT, SIGURD; PICHON, ERIC; TANNENBAUM, ALLEN

2013-01-01

In this paper, we describe some central mathematical problems in medical imaging. The subject has been undergoing rapid changes driven by better hardware and software. Much of the software is based on novel methods utilizing geometric partial differential equations in conjunction with standard signal/image processing techniques as well as computer graphics facilitating man/machine interactions. As part of this enterprise, researchers have been trying to base biomedical engineering principles on rigorous mathematical foundations for the development of software methods to be integrated into complete therapy delivery systems. These systems support the more effective delivery of many image-guided procedures such as radiation therapy, biopsy, and minimally invasive surgery. We will show how mathematics may impact some of the main problems in this area, including image enhancement, registration, and segmentation. PMID:23645963

Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery.

PubMed

Demidova-Rice, Tatiana N; Hamblin, Michael R; Herman, Ira M

2012-08-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed.

Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

PubMed Central

Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

Cesarean delivery rates among family physicians versus obstetricians: a population-based cohort study using instrumental variable methods

PubMed Central

Dawe, Russell Eric; Bishop, Jessica; Pendergast, Amanda; Avery, Susan; Monaghan, Kelly; Duggan, Norah; Aubrey-Bassler, Kris

2017-01-01

Background: Previous research suggests that family physicians have rates of cesarean delivery that are lower than or equivalent to those for obstetricians, but adjustments for risk differences in these analyses may have been inadequate. We used an econometric method to adjust for observed and unobserved factors affecting the risk of cesarean delivery among women attended by family physicians versus obstetricians. Methods: This retrospective population-based cohort study included all Canadian (except Quebec) hospital deliveries by family physicians and obstetricians between Apr. 1, 2006, and Mar. 31, 2009. We excluded women with multiple gestations, and newborns with a birth weight less than 500 g or gestational age less than 20 weeks. We estimated the relative risk of cesarean delivery using instrumental-variable-adjusted and logistic regression. Results: The final cohort included 776 299 women who gave birth in 390 hospitals. The risk of cesarean delivery was 27.3%, and the mean proportion of deliveries by family physicians was 26.9% (standard deviation 23.8%). The relative risk of cesarean delivery for family physicians versus obstetricians was 0.48 (95% confidence interval [CI] 0.41-0.56) with logistic regression and 1.27 (95% CI 1.02-1.57) with instrumental-variable-adjusted regression. Interpretation: Our conventional analyses suggest that family physicians have a lower rate of cesarean delivery than obstetricians, but instrumental variable analyses suggest the opposite. Because instrumental variable methods adjust for unmeasured factors and traditional methods do not, the large discrepancy between these estimates of risk suggests that clinical and/or sociocultural factors affecting the decision to perform cesarean delivery may not be accounted for in our database. PMID:29233843

A New Low-frequency Sonophoresis System Combined with Ultrasonic Motor and Transducer

NASA Astrophysics Data System (ADS)

Zhu, Pancheng; Peng, Hanmin; Yang, Jianzhi; Mao, Ting; Sheng, Juan

2018-03-01

Low frequency sonophoresis (LFS) is currently being attempted as a transdermal drug delivery method in clinical areas. However, it lacks both an effective control method and the equipment to satisfy the varying drug dosage requirements of individual patients. Herein, a novel method aimed at controlling permeability is proposed and developed, using a pressure control strategy which is based on an accurate, adjustable and non-invasive ultrasound transdermal drug delivery system in in vitro LFS. The system mainly consists of a lead screw linear ultrasonic motor and an ultrasonic transducer, in which the former offers pressure and the latter provides ultrasound wave in the liquid. The ultrasound can enhance non-invasive permeation and the pressure from the motor can control the permeability. The calculated and experimental results demonstrate that the maximum pressure on artificial skin is under the area with the maximum vibration amplitude of the ultrasonic transducer, and the total pressure consists of acoustic pressure from the transducer and approximate static pressure from the motor. Changing the static pressure from the ultrasonic motor can effectively control the non-invasive permeability, by adjusting the duty ratio or the amplitude of the motor’s driving voltage. In addition, the permeability control of calcein by thrust control is realized in 15 min, indicating the suitability of this method for application in accurate medical technology. The obtained results reveal that the issue of difficult permeability control can be addressed, using this control method in in vitro LFS to open up a route to the design of accurate drug delivery technology for individual patients.

Prenatal health behaviors and psychosocial risk factors in pregnant women of Mexican origin: the role of acculturation.

PubMed Central

Zambrana, R E; Scrimshaw, S C; Collins, N; Dunkel-Schetter, C

1997-01-01

OBJECTIVES: This study examined the association between acculturation of Mexican-origin women and factors in low birthweight and preterm delivery. METHODS: Interviews were conducted with 911 Mexican-origin respondents in Los Angeles prenatal care clinics. Infant outcome data were retrieved from delivery records. RESULTS: Mexican-American women had generally more undesirable prenatal behaviors and risk factors than Mexican-immigrant women. Although higher acculturation was significantly associated with behavioral risk factors, there were no direct effects of acculturation on infant gestational age or birthweight. CONCLUSIONS: Future research needs to measure multiple factors to assess their effects on culture-specific protective factors. PMID:9224189

Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy.

PubMed

Galan, Alba; Barcelona, Pablo F; Nedev, Hinyu; Sarunic, Marinko V; Jian, Yifan; Saragovi, H Uri

2017-06-01

The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. We compared the pharmacokinetics of a single 40 μg subconjunctival (SCJ) depot to the reported effective 5 μg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.

Online Continuing Education for Health Professionals: Does Sticky Design Promote Practice-Relevance?

ERIC Educational Resources Information Center

Zaghab, Roxanne Ward; Maldonado, Carlos; Whitehead, Dongsook; Bartlett, Felicia; de Bittner, Magaly Rodriguez

2015-01-01

Online continuing education (CE) holds promise as an effective method for rapid dissemination of emerging evidence-based practices in health care. Yet, the field of CE continues to develop and delivery is predominately face-to-face programs. Practice-oriented online educational methods and e-learning platforms are not fully utilized. Educational…

Solving multi-customer FPR model with quality assurance and discontinuous deliveries using a two-phase algebraic approach.

PubMed

Chiu, Yuan-Shyi Peter; Chou, Chung-Li; Chang, Huei-Hsin; Chiu, Singa Wang

2016-01-01

A multi-customer finite production rate (FPR) model with quality assurance and discontinuous delivery policy was investigated in a recent paper (Chiu et al. in J Appl Res Technol 12(1):5-13, 2014) using differential calculus approach. This study employs mathematical modeling along with a two-phase algebraic method to resolve such a specific multi-customer FPR model. As a result, the optimal replenishment lot size and number of shipments can be derived without using the differential calculus. Such a straightforward method may assist practitioners who with insufficient knowledge of calculus in learning and managing the real multi-customer FPR systems more effectively.

Graduate Education through Telecommunications: The Computer and You.

ERIC Educational Resources Information Center

Mizell, Al P.

Providing a variety of instructional methods and materials, developing unique and effective communication systems, and evaluating the process are keys to the delivery and effectiveness of the field-based programs in graduate education offered by Nova Southeastern University (Florida). This 4-year nonprofit institution is a leader in distance…

42 CFR 51c.305 - Grant evaluation and award.

Code of Federal Regulations, 2010 CFR

2010-10-01

... potential of the center for the development of new and effective methods for health services delivery and management; (d) The soundness of the fiscal plan for assuring effective utilization of grant funds and maximizing non-grant revenue; (e) The administrative and management capability of the applicant; (f) The...

Using Observational Data to Estimate the Effect of Hand Washing and Clean Delivery Kit Use by Birth Attendants on Maternal Deaths after Home Deliveries in Rural Bangladesh, India and Nepal

PubMed Central

Seward, Nadine; Prost, Audrey; Copas, Andrew; Corbin, Marine; Li, Leah; Colbourn, Tim; Osrin, David; Neuman, Melissa; Azad, Kishwar; Kuddus, Abdul; Nair, Nirmala; Tripathy, Prasanta; Manandhar, Dharma; Costello, Anthony; Cortina-Borja, Mario

2015-01-01

Background Globally, puerperal sepsis accounts for an estimated 8–12% of maternal deaths, but evidence is lacking on the extent to which clean delivery practices could improve maternal survival. We used data from the control arms of four cluster-randomised controlled trials conducted in rural India, Bangladesh and Nepal, to examine associations between clean delivery kit use and hand washing by the birth attendant with maternal mortality among home deliveries. Methods We tested associations between clean delivery practices and maternal deaths, using a pooled dataset for 40,602 home births across sites in the three countries. Cross-sectional data were analysed by fitting logistic regression models with and without multiple imputation, and confounders were selected a priori using causal directed acyclic graphs. The robustness of estimates was investigated through sensitivity analyses. Results Hand washing was associated with a 49% reduction in the odds of maternal mortality after adjusting for confounding factors (adjusted odds ratio (AOR) 0.51, 95% CI 0.28–0.93). The sensitivity analysis testing the missing at random assumption for the multiple imputation, as well as the sensitivity analysis accounting for possible misclassification bias in the use of clean delivery practices, indicated that the association between hand washing and maternal death had been over estimated. Clean delivery kit use was not associated with a maternal death (AOR 1.26, 95% CI 0.62–2.56). Conclusions Our evidence suggests that hand washing in delivery is critical for maternal survival among home deliveries in rural South Asia, although the exact magnitude of this effect is uncertain due to inherent biases associated with observational data from low resource settings. Our findings indicating kit use does not improve maternal survival, suggests that the soap is not being used in all instances that kit use is being reported. PMID:26295838

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

PubMed

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent. © 2013 Elsevier B.V. All rights reserved.

Obstructed Labor and Caesarean Delivery: The Cost and Benefit of Surgical Intervention

PubMed Central

Burns, Christy Turlington; Metzler, Ian S.; Farmer, Paul E.; Meara, John G.

2012-01-01

Background Although advances in the reduction of maternal mortality have been made, up to 273,000 women will die this year from obstetric etiologies. Obstructed labor (OL), most commonly treated with Caesarean delivery, has been identified as a major contributor to global maternal morbidity and mortality. We used economic and epidemiological modeling to estimate the cost per disability-adjusted life-year (DALY) averted and benefit-cost ratio of treating OL with Caesarean delivery for 49 countries identified as providing an insufficient number of Caesarean deliveries to meet demand. Methods and Findings Using publicly available data and explicit economic assumptions, we estimated that the cost per DALY (3,0,0) averted for providing Caesarean delivery for OL ranged widely, from $251 per DALY averted in Madagascar to $3,462 in Oman. The median cost per DALY averted was $304. Benefit-cost ratios also varied, from 0.6 in Zimbabwe to 69.9 in Gabon. The median benefit-cost ratio calculated was 6.0. The main limitation of this study is an assumption that lack of surgical capacity is the main factor responsible for DALYs from OL. Conclusions Using the World Health Organization's cost-effectiveness standards, investing in Caesarean delivery can be considered “highly cost-effective” for 48 of the 49 countries included in this study. Furthermore, in 46 of the 49 included countries, the benefit-cost ratio was greater than 1.0, implying that investment in Caesarean delivery is a viable economic proposition. While Caesarean delivery alone is not sufficient for combating OL, it is necessary, cost-effective by WHO standards, and ultimately economically favorable in the vast majority of countries included in this study. PMID:22558089

The INCENTIVE protocol: an evaluation of the organisation and delivery of NHS dental healthcare to patients—innovation in the commissioning of primary dental care service delivery and organisation in the UK

PubMed Central

Pavitt, Sue H; Baxter, Paul D; Brunton, Paul A; Douglas, Gail; Edlin, Richard; Gibson, Barry J; Godson, Jenny; Hall, Melanie; Porritt, Jenny; Robinson, Peter G; Vinall, Karen; Hulme, Claire

2014-01-01

Introduction In England, in 2006, new dental contracts devolved commissioning of dental services locally to Primary Care Trusts to meet the needs of their local population. The new national General Dental Services contracts (nGDS) were based on payment for Units of Dental Activity (UDAs) awarded in three treatment bands based on complexity of care. Recently, contract currency in UK dentistry is evolving from UDAs based on volume and case complexity towards ‘blended contracts’ that include incentives linked with key performance indicators such as quality and improved health outcome. Overall, evidence of the effectiveness of incentive-driven contracting of health providers is still emerging. The INCENTIVE Study aims to evaluate a blended contract model (incentive-driven) compared to traditional nGDS contracts on dental service delivery in practices in West Yorkshire, England. Methods and analysis The INCENTIVE model uses a mixed methods approach to comprehensively evaluate a new incentive-driven model of NHS dental service delivery. The study includes 6 dental surgeries located across three newly commissioned dental practices (blended contract) and three existing traditional practices (nGDS contracts). The newly commissioned practices have been matched to traditional practices by deprivation index, age profile, ethnicity, size of practice and taking on new patients. The study consists of three interlinked work packages: a qualitative study to explore stakeholder perspectives of the new service delivery model; an effectiveness study to assess the INCENTIVE model in reducing the risk of and amount of dental disease and enhance oral health-related quality of life in patients; and an economic study to assess cost-effectiveness of the INCENTIVE model in relation to clinical status and oral health-related quality of life. Ethics and dissemination The study has been approved by NRES Committee London, Bromley. The results of this study will be disseminated at national and international conferences and in international journals. PMID:25231492

Analysis of phase conjugation in a turbid medium

NASA Astrophysics Data System (ADS)

Hollmann, Joseph L.; Cantero, Sergio; Tseng, Snow; DiMarzio, Charles A.

2014-03-01

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Recently, researchers have found they can concentrate light tightly despite these scattering effects by using a guidestar and optical phase conjugation to focus light to greater distances in tissue. An optical or probe signal is transmitted through a scattering medium and its resulting wavefront is detected. The wavefront is then conjugated and utilized as a new optical source or delivery wave that focuses back to the guidestar's location with minimal scattering. The power in the delivery wave may be greatly increased for enhanced energy delivery at the focus. Modulation by an ultrasound (US) beam may be utilized to generate the guidestar dynamically and allow for US-resolution at depths of several millimeters. The delivery wave is successful at focusing light back at the guidestar because it creates constructive interference at the desired focus. However, if the phases of the field contributions change, we expect the delivered power at the focus to be reduced. This paper will analyze the robustness of this method when the probe beam is at one wavelength and the delivery wave is at another. This will allow us to characterize the deleterious effects of varying the phase contributions at the focus.

Solid lipid nanoparticles for pulmonary delivery of insulin.

PubMed

Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

2008-05-22

Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.

PubMed

Menegatti, Stefano; Zakrewsky, Michael; Kumar, Sunny; De Oliveira, Joshua Sanchez; Muraski, John A; Mitragotri, Samir

2016-03-09

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

PubMed Central

Das, Sreemanti; Khuda-Bukhsh, Anisur Rahman

2016-01-01

Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review. PMID:27934796

Insulin pump use and glycemic control in adolescents with type 1 diabetes: Predictors of change in method of insulin delivery across two years.

PubMed

Wong, Jenise C; Dolan, Lawrence M; Yang, Tony T; Hood, Korey K

2015-12-01

Few studies have explored durability of insulin pump use, and none have explored the link between depression and pump discontinuation. To examine the relationship between depressive symptoms [measured by the Children's Depression Inventory (CDI)], method of insulin delivery, and hemoglobin A1c (A1c), mixed models were used with data from 150 adolescents with type 1 diabetes (T1D) and visits every 6 months for 2 years. Of the 63% who used a pump, compared with multiple daily injections (MDI) at baseline, there were higher proportions who were non-minorities, had caregivers with a college degree, private insurance, and two caregivers in the home (p ≤ 0.01). After adjusting for time, sex, age, T1D duration, frequency of blood glucose monitoring, ethnicity, insurance, and caregiver number and education, baseline pump use was associated with -0.79% lower mean A1c [95% confidence interval (CI): -1.48, -0.096; p = 0.03]. For those using a pump at baseline, but switching to MDI during the study (n = 9), mean A1c was 1.38% higher (95% CI: 0.68, 2.08; p < 0.001) than that for those who did not switch method of delivery. A 10-point increase in CDI was associated with a 0.39% increase in A1c (95% CI: 0.16, 0.61; p = 0.001), independent of pump use. Regarding the temporal relationship between CDI score and changing method of insulin delivery, prior higher CDI score was associated with switching from pump to MDI (odds ratio = 1.21; 95% CI: 1.05, 1.39; p = 0.007). Clinicians should be aware of the associations between depressive symptoms, change in insulin delivery method, and the effect on glycemic control. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

SU-F-P-30: Clinical Assessment of Auto Beam-Hold Triggered by Fiducial Localization During Prostate RapidArc Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atkinson, P; Chen, Q

2016-06-15

Purpose: To assess the clinical efficacy of auto beam hold during prostate RapidArc delivery, triggered by fiducial localization on kV imaging with a Varian True Beam. Methods: Prostate patients with four gold fiducials were candidates in this study. Daily setup was accomplished by aligning to fiducials using orthogonal kV imaging. During RapidArc delivery, a kV image was automatically acquired with a momentary beam hold every 60 degrees of gantry rotation. The position of each fiducial was identified by a search algorithm and compared to a predetermined 1.4 cm diameter target area. Treatment continued if all the fiducials were within themore » target area. If any fiducial was outside the target area the beam hold was not released, and the operators determined if the patient needed re-alignment using the daily setup method. Results: Four patients were initially selected. For three patients, the auto beam hold performed seamlessly. In one instance, the system correctly identified misaligned fiducials, stopped treatment, and the patient was re-positioned. The fourth patient had a prosthetic hip which sometimes blocked the fiducials and caused the fiducial search algorithm to fail. The auto beam hold was disabled for this patient and the therapists manually monitored the fiducial positions during treatment. Average delivery time for a 2-arc fraction was increased by 59 seconds. Phantom studies indicated the dose discrepancy related to multiple beam holds is <0.1%. For a plan with 43 fractions, the additional imaging increased dose by an estimated 68 cGy. Conclusion: Automated intrafraction kV imaging can effectively perform auto beam holds due to patient movement, with the exception of prosthetic hip patients. The additional imaging dose and delivery time are clinically acceptable. It may be a cost-effective alternative to Calypso in RapidArc prostate patient delivery. Further study is warranted to explore its feasibility under various clinical conditions.« less

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved.

PubMed

Inrig, Stephen J; Tiro, Jasmin A; Melhado, Trisha V; Argenbright, Keith E; Craddock Lee, Simon J

2014-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. To better understand how to implement a decentralized regional delivery "hub & spoke" model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow's RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow's RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting.

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

PubMed Central

Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

1998-01-01

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

Nanochanneled Device and Related Methods

NASA Technical Reports Server (NTRS)

Goodall, Randy (Inventor); Hosali, Sharath (Inventor); Grattoni, Alessandro (Inventor); Fine, Daniel (Inventor); Hudson, Lee (Inventor); Ferrari, Mauro (Inventor); Liu, Xuewu (Inventor); Medema, Ryan (Inventor)

2013-01-01

A nanochannel delivery device and method of manufacturing and use. The nanochannel delivery device comprises an inlet, an outlet, and a nanochannel. The nanochannel may be oriented parallel to the primary plane of the nanochannel delivery device. The inlet and outlet may be in direct fluid communication with the nanochannel.

Costs and effects of two public sector delivery channels for long-lasting insecticidal nets in Uganda

PubMed Central

2010-01-01

Background In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda. Methods Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used. Results After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani. Conclusions Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged. PMID:20406448

RNA Interference of the Muscle Actin Gene in Bed Bugs: Exploring Injection Versus Topical Application for dsRNA Delivery.

PubMed

Basnet, Sanjay; Kamble, Shripat T

2018-05-01

Bed bugs are one the most troublesome household pests that feed primarily on human blood. RNA interference (RNAi) is currently being pursued as a potential tool for insect population management and has shown efficacy against some phytophagous insects. We evaluated the different techniques to deliver dsRNA specific to bed bug muscle actin (dsactin) into bed bugs. Initially, stability of dsRNA in human blood was studied to evaluate the feasibility of feeding method. Adult bed bugs were injected with dsRNA between last thoracic segment and first abdominal segment on the ventral side, with a dose of 0.2 µg dsactin per insect. In addition to injection, dsactin was mixed in acetone and treated topically in the abdomens of fifth stage nymphs. We found the quick degradation of dsRNA in blood. Injection of dsactin caused significant depletion of actin transcripts and substantial reduction in oviposition and lethality in female adults. Topically treated dsRNA in fifth stage nymphs had no effect on actin mRNA expression and survival. Our results demonstrated that injection is a reliable method of dsRNA delivery into bed bugs while topical treatment was not successful. This research provides an understanding on effective delivery methods of dsRNA into bed bugs for functional genomics research and feasibility of the RNAi based molecules for pest management purposes.

Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Nishikawa, Makiya; Takakura, Yoshinobu

2016-01-01

Exosomes, which are expected to be delivery systems for biomolecules such as nucleic acids, are collected by several methods. However, the effect of exosome isolation methods on the characteristics of exosomes as drug carriers, such as recovery efficiency after sterile filtration and pharmacokinetics, has not been investigated despite the importance of these characteristics for the development of exosome-based delivery systems. In the present study, exosomes collected from murine melanoma B16-BL6 cells by several methods were compared with respect to dispersibility, recovery rate after filtering, and clearance from the blood circulation in mice. The exosomes were collected by three ultracentrifugation-based methods: simple ultracentrifugation/pelleting (pelleting method), ultracentrifugation with an iodixanol cushion (cushion method), and ultracentrifugation on an iodixanol density gradient (gradient method). The isolation methods had little effect on the particle number of exosomes. In contrast, transmission electron microscopy observation and size distribution measurement using tunable resistive pulse sensing indicated that the exosomes of the gradient method were more dispersed than the others. The exosomes were labeled with Gaussia luciferase and intravenously injected into mice. Clearance of injected exosomes from the blood circulation did not significantly change with isolation methods. When the exosomes were filtered using a 0.2-μm filter, the recovery rate was 82% for the exosomes of the gradient method, whereas it was less than 50% for the others. These results indicate that the exosome isolation method markedly affects the dispersibility and filtration efficiency of the exosomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of Enhancing Visual Effects Education Delivery to Encounter Career Challenges in Malaysia

ERIC Educational Resources Information Center

Ng, Lynn-Sze

2017-01-01

Problem-based Learning (PBL) is one of the most effective methods of instruction that helps Visual Effects (VFX) students to be more adaptable at encountering career challenges in Malaysia. These challenges are; lack of several important requirements such as, the basic and fundamental knowledge of VFX concepts, the ability to understand real-world…

The efficacy of self-management programmes for increasing physical activity in community-dwelling adults with acquired brain injury (ABI): a systematic review

PubMed Central

2014-01-01

Background Acquired brain injury (ABI), often arising from stroke or trauma, is a common cause of long-term disability, physical inactivity and poor health outcomes globally. Individuals with ABI face many barriers to increasing physical activity, such as impaired mobility, access to services and knowledge regarding management of physical activity. Self-management programmes aim to build skills to enable an individual to manage their condition, including their physical activity levels, over a long period of time. Programme delivery modes can include traditional face-to-face methods, or remote delivery, such as via the Internet. However, it is unknown how effective these programmes are at specifically improving physical activity in community-dwelling adults with ABI, or how effective and acceptable remote delivery of self-management programmes is for this population. Methods/Design We will conduct a comprehensive search for articles indexed on MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, Cochrane Central Register of Controlled Trials (CENTRAL), PEDro and Science Citation Index Expanded (SCI-EXPANDED) databases that assess the efficacy of a self-management intervention, which aims to enhance levels of physical activity in adults living in the community with ABI. Two independent reviewers will screen studies for eligibility, assess risk of bias, and extract relevant data. Where possible, a meta-analysis will be performed to calculate the overall effect size of self-management interventions on physical activity levels and on outcomes associated with physical activity. A comparison will also be made between face-to-face and remote delivery modes of self-management programmes, in order to examine efficacy and acceptability. A content analysis of self-management programmes will also be conducted to compare aspects of the intervention that are associated with more favourable outcomes. Discussion This systematic review aims to review the efficacy of self-management programmes aimed at increasing physical activity levels in adults living in the community with ABI, and the efficacy and acceptability of remote delivery of these programmes. If effective, remote delivery of self-management programmes may offer an alternative way to overcome barriers and empower individuals with ABI to increase their levels of physical activity, improving health and general wellbeing. Trial registration Our protocol has been registered on PROSPERO 2013: CRD42013006748. PMID:24745356

Non-invasive MRI detection of individual pellets in the human stomach.

PubMed

Knörgen, Manfred; Spielmann, Rolf Peter; Abdalla, Ahmed; Metz, Hendrik; Mäder, Karsten

2010-01-01

MRI is a powerful and non-invasive method to follow the fate of oral drug delivery systems in humans. Until now, most MRI studies focused on monolithic dosage forms (tablets and capsules). Small-sized multi-particulate drug delivery systems are very difficult to detect due to the poor differentiation between the delivery system and the food. A new approach was developed to overcome the described difficulties and permit the selective imaging of small multi-particulate dosage forms within the stomach. We took advantage of the different sensitivities to susceptibility artefacts of T(2)-weighted spin-echo sequences and T(2)-weighted gradient echo pulse sequences. Using a combination of both methods within a breath hold followed by a specific mathematical image analysis involving co-registration, motion correction, voxel-by-voxel comparison of the maps from different pulse sequences and graphic 2D-/3D-presentation, we were able to obtain pictures with a high sensitivity due to susceptibility effects caused by a 1% magnetite load. By means of the new imaging sequence, single pellets as small as 1mm can be detected with high selectivity within surrounding heterogeneous food in the human stomach. The developed method greatly expands the use of MRI to study the fate of oral multi-particulate drug delivery systems and their food dependency in men. Copyright 2009 Elsevier B.V. All rights reserved.

[In vitro transdermal delivery of the active fraction of xiangfusiwu decoction based on principal component analysis].

PubMed

Li, Zhen-Hao; Liu, Pei; Qian, Da-Wei; Li, Wei; Shang, Er-Xin; Duan, Jin-Ao

2013-06-01

The objective of the present study was to establish a method based on principal component analysis (PCA) for the study of transdermal delivery of multiple components in Chinese medicine, and to choose the best penetration enhancers for the active fraction of Xiangfusiwu decoction (BW) with this method. Improved Franz diffusion cells with isolated rat abdomen skins were carried out to experiment on the transdermal delivery of six active components, including ferulic acid, paeoniflorin, albiflorin, protopine, tetrahydropalmatine and tetrahydrocolumbamine. The concentrations of these components were determined by LC-MS/MS, then the total factor scores of the concentrations at different times were calculated using PCA and were employed instead of the concentrations to compute the cumulative amounts and steady fluxes, the latter of which were considered as the indexes for optimizing penetration enhancers. The results showed that compared to the control group, the steady fluxes of the other groups increased significantly and furthermore, 4% azone with 1% propylene glycol manifested the best effect. The six components could penetrate through skin well under the action of penetration enhancers. The method established in this study has been proved to be suitable for the study of transdermal delivery of multiple components, and it provided a scientific basis for preparation research of Xiangfusiwu decoction and moreover, it could be a reference for Chinese medicine research.

Protective Immunity in Mice Achieved with Dry Powder Formulation and Alternative Delivery of Plague F1-V Vaccine▿

PubMed Central

Huang, Joanne; D'Souza, Ajit J.; Alarcon, Jason B.; Mikszta, John A.; Ford, Brandi M.; Ferriter, Matthew S.; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G.; Sullivan, Vincent J.

2009-01-01

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits. PMID:19261773

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

PubMed

Huang, Joanne; D'Souza, Ajit J; Alarcon, Jason B; Mikszta, John A; Ford, Brandi M; Ferriter, Matthew S; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G; Sullivan, Vincent J

2009-05-01

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.

Robust and High Order Computational Method for Parachute and Air Delivery and MAV System

DTIC Science & Technology

2017-11-01

Report: Robust and High Order Computational Method for Parachute and Air Delivery and MAV System The views, opinions and/or findings contained in this...University Title: Robust and High Order Computational Method for Parachute and Air Delivery and MAV System Report Term: 0-Other Email: xiaolin.li...model coupled with an incompressible fluid solver through the impulse method . Our approach to simulating the parachute system is based on the front

Highly water-soluble, porous, and biocompatible boron nitrides for anticancer drug delivery.

PubMed

Weng, Qunhong; Wang, Binju; Wang, Xuebin; Hanagata, Nobutaka; Li, Xia; Liu, Dequan; Wang, Xi; Jiang, Xiangfen; Bando, Yoshio; Golberg, Dmitri

2014-06-24

Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.

A community of practice approach to bioanalysis delivery: the role of the Preclinical Bioanalysis and Toxicokinetics department at AstraZeneca.

PubMed

Wilson, Amanda; Silvester, Stephen; Woods, Karen

2014-05-01

Retaining regulated bioanalysis within AstraZeneca (AZ) is important for the effective delivery of nonclinical and clinical bioanalysis. The focus for the in-house team is the delivery of high-throughput bioanalysis and toxicokinetics support for investigational toxicology; however, by retaining GLP compliance, AZ will have an in-house understanding of every candidate drug that is progressed into development by supporting the first rodent GLP study for each project. The majority of nonclinical bioanalysis and all of the clinical bioanalysis are delivered by two external partnership models. This article describes the key benefits of retaining GLP compliance, the partnership interactions, discusses the management of non-GLP support in a GLP environment and how, having practical experience of regulatory facing method development, validation and study execution adds value to the AZ portfolio delivery.

Oral delivery of dsRNA by microbes: Beyond pest control.

PubMed

Abrieux, Antoine; Chiu, Joanna C

2016-01-01

RNA interference (RNAi) by oral delivery of dsRNA in insects has great potential as a tool for integrated pest management (IPM), especially with respect to addressing the need to reduce off-target effect and slow down resistance development to chemical insecticides. Employing the natural association existing between insect and yeast, we developed a novel method to enable the knock down of vital genes in the pest insect Drosophila suzukii through oral delivery of species-specific dsRNA using genetically modified Saccharomyces cerevisae. D. suzukii that were fed with our "yeast biopesticide" showed a significant decrease in fitness. In this perspective article, we postulate that this approach could be adapted to a large number of species, given the great diversity of symbiotic interactions involving microorganisms and host species. Furthermore, we speculate that beyond its application as biopesticide, dsRNA delivery by genetically modified microbes can also serve to facilitate reverse genetic applications, specifically in non-model organisms.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection.

PubMed

O'Donnell, Hope; Pham, Oanh H; Benoun, Joseph M; Ravesloot-Chávez, Marietta M; McSorley, Stephen J

2015-01-01

In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 h allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Together, these data question the need for gavage delivery for infection with oral pathogens.

Nano-Chitosan Particles in Anticancer Drug Delivery: An Up-to-Date Review.

PubMed

Kamath, Pooja R; Sunil, Dhanya

2017-01-01

Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery. • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Meta-heuristic Approach for Variants of VRP in Terms of Generalized Saving Method

NASA Astrophysics Data System (ADS)

Shimizu, Yoshiaki

Global logistic design is becoming a keen interest to provide an essential infrastructure associated with modern societal provision. For examples, we can designate green and/or robust logistics in transportation systems, smart grids in electricity utilization systems, and qualified service in delivery systems, and so on. As a key technology for such deployments, we engaged in practical vehicle routing problem on a basis of the conventional saving method. This paper extends such idea and gives a general framework available for various real-world applications. It can cover not only delivery problems but also two kind of pick-up problems, i.e., straight and drop-by routings. Moreover, multi-depot problem is considered by a hybrid approach with graph algorithm and its solution method is realized in a hierarchical manner. Numerical experiments have been taken place to validate effectiveness of the proposed method.

Methods for Engaging Stakeholders in Comparative Effectiveness Research: A Patient-Centered Approach to Improving Diabetes Care

PubMed Central

Schmittdiel, Julie A.; Desai, Jay; Schroeder, Emily B.; Paolino, Andrea R.; Nichols, Gregory A.; Lawrence, Jean M.; O’Connor, Patrick J.; Ohnsorg, Kris A.; Newton, Katherine M.; Steiner, John F.

2016-01-01

ABSTRACT/Implementation Lessons Engaging stakeholders in the research process has the potential to improve quality of care and the patient care experience.Online patient community surveys can elicit important topic areas for comparative effectiveness research.Stakeholder meetings with substantial patient representation, as well as representation from health care delivery systems and research funding agencies, are a valuable tool for selecting and refining pilot research and quality improvement projects.Giving patient stakeholders a deciding vote in selecting pilot research topics helps ensure their ‘voice’ is heard.Researchers and health care leaders should continue to develop best-practices and strategies for increasing patient involvement in comparative effectiveness and delivery science research. PMID:26179728

Benchmarking to improve the quality of cystic fibrosis care.

PubMed

Schechter, Michael S

2012-11-01

Benchmarking involves the ascertainment of healthcare programs with most favorable outcomes as a means to identify and spread effective strategies for delivery of care. The recent interest in the development of patient registries for patients with cystic fibrosis (CF) has been fueled in part by an interest in using them to facilitate benchmarking. This review summarizes reports of how benchmarking has been operationalized in attempts to improve CF care. Although certain goals of benchmarking can be accomplished with an exclusive focus on registry data analysis, benchmarking programs in Germany and the United States have supplemented these data analyses with exploratory interactions and discussions to better understand successful approaches to care and encourage their spread throughout the care network. Benchmarking allows the discovery and facilitates the spread of effective approaches to care. It provides a pragmatic alternative to traditional research methods such as randomized controlled trials, providing insights into methods that optimize delivery of care and allowing judgments about the relative effectiveness of different therapeutic approaches.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Placenta-specific drug delivery by trophoblast-targeted nanoparticles in mice

PubMed Central

Zhang, Baozhen; Tan, Lunbo; Yu, Yan; Wang, Baobei; Chen, Zhilong; Han, Jinyu; Li, Mengxia; Chen, Jie; Xiao, Tianxia; Ambati, Balamurali K; Cai, Lintao; Yang, Qing; Nayak, Nihar R; Zhang, Jian; Fan, Xiujun

2018-01-01

Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to other cell types in the placenta or to CSA-expressing cells in other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option. PMID:29774074

Rural and urban transit district benchmarking : effectiveness and efficiency guidance document.

DOT National Transportation Integrated Search

2011-05-01

Rural and urban transit systems have sought ways to compare performance across agencies, : identifying successful service delivery strategies and applying these concepts to achieve : successful results within their agency. Benchmarking is a method us...

Making Decisions about Service Delivery in Early Childhood Programs

ERIC Educational Resources Information Center

Case-Smith, Jane; Holland, Terri

2009-01-01

Purpose: This article presents a rationale for specialized services personnel to use fluid models of service delivery and explains how specialized services personnel make decisions about the blend of service delivery methods that will best serve a child. Method: The literature on occupational therapy, physical therapy, and speech-language…

Blueberry (Vaccinium corymbosum L.).

PubMed

Song, Guo-Qing

2015-01-01

Vaccinium consists of approximately 450 species, of which highbush blueberry (Vaccinium corymbosum) is one of the three major Vaccinium fruit crops (i.e., blueberry, cranberry, and lingonberry) domesticated in the twentieth century. In blueberry the adventitious shoot regeneration using leaf explants has been the most desirable regeneration system to date; Agrobacterium tumefaciens-mediated transformation is the major gene delivery method and effective selection has been reported using either the neomycin phosphotransferase II gene (nptII) or the bialaphos resistance (bar) gene as selectable markers. The A. tumefaciens-mediated transformation protocol described in this chapter is based on combining the optimal conditions for efficient plant regeneration, reliable gene delivery, and effective selection. The protocol has led to successful regeneration of transgenic plants from leaf explants of four commercially important highbush blueberry cultivars for multiple purposes, providing a powerful approach to supplement conventional breeding methods for blueberry by introducing genes of interest.

Technologic advances in aural rehabilitation: applications and innovative methods of service delivery.

PubMed

Sweetow, Robert W; Sabes, Jennifer Henderson

2007-06-01

The level of interest in aural rehabilitation has increased recently, both in clinical use and in research presentations and publications. Advances in aural rehabilitation have seen previous techniques such as speech tracking and analytic auditory training reappear in computerized forms. These new delivery methods allow for a consistent, cost-effective, and convenient training program. Several computerized aural rehabilitation programs for hearing aid wearers and cochlear implant recipients have recently been developed and were reported on at the 2006 State of the Science Conference of the Rehabilitation Engineering Research Center on Hearing Enhancement at Gallaudet University. This article reviews these programs and outlines the similarities and differences in their design. Another promising area of aural rehabilitation research is the use of pharmaceuticals in the rehabilitation process. The results from a study of the effect of d-amphetamine in conjunction with intensive aural rehabilitation with cochlear implant patients are also described.

Technologic Advances in Aural Rehabilitation: Applications and Innovative Methods of Service Delivery

PubMed Central

Sweetow, Robert W.; Sabes, Jennifer Henderson

2007-01-01

The level of interest in aural rehabilitation has increased recently, both in clinical use and in research presentations and publications. Advances in aural rehabilitation have seen previous techniques such as speech tracking and analytic auditory training reappear in computerized forms. These new delivery methods allow for a consistent, cost-effective, and convenient training program. Several computerized aural rehabilitation programs for hearing aid wearers and cochlear implant recipients have recently been developed and were reported on at the 2006 State of the Science Conference of the Rehabilitation Engineering Research Center on Hearing Enhancement at Gallaudet University. This article reviews these programs and outlines the similarities and differences in their design. Another promising area of aural rehabilitation research is the use of pharmaceuticals in the rehabilitation process. The results from a study of the effect of d-amphetamine in conjunction with intensive aural rehabilitation with cochlear implant patients are also described. PMID:17494876

Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization.

PubMed

Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L; Labbé, Alain; Prakash, Satya

2012-02-16

Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

Novel drug delivery systems in pain therapy.

PubMed

Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N

2007-03-01

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

PubMed Central

Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L.; Labbé, Alain; Prakash, Satya

2012-01-01

Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain. PMID:24288090

Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma

PubMed Central

Badawi, Ashraf M; Osman, Mai Abdelraouf

2018-01-01

Background Melasma is a difficult-to-treat hyperpigmentary disorder. Ablative fractional laser (AFL)-assisted delivery of topically applied drugs to varied targets in the skin has been an area of ongoing study and research. Objective The objective of this study was to evaluate the efficacy and safety of fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser as an assisted drug delivery for enhancing topical hydroquinone (HQ) permeation into the skin of melasma patients. Patients and methods Thirty female patients with bilateral melasma were randomly treated in a split-face controlled manner with a fractional Er:YAG laser followed by 4% HQ cream on one side and 4% HQ cream alone on the other side. All patients received six laser sessions with a 2-week interval. The efficacy of treatments was determined through photographs, dermoscopic photomicrographs and Melasma Area Severity Index (MASI) score, all performed at baseline and at 12 weeks of starting therapy. The patient’s level of satisfaction was also recorded. Results Er:YAG laser + HQ showed significantly better results (p<0.005) with regard to decrease in the degree of pigmentation as assessed on the 4-point scale than HQ alone. There was a significant decrease in MASI scores on Er:YAG laser + HQ side vs HQ side. Minor reversible side effects were observed on both sides. Conclusion AFL-assisted delivery of HQ is a safe and effective method for the treatment of melasma. PMID:29379308

The impact of mode of delivery on outcomes in patients with perianal Crohn's disease

PubMed Central

Cheng, Alice G; Oxford, Emily C; Sauk, Jenny; Nguyen, Deanna D; Yajnik, Vijay; Friedman, Sonia; Ananthakrishnan, Ashwin N

2014-01-01

Introduction Crohn's disease (CD) often affects women during the reproductive years. While several studies have examined the impact of pregnancy on luminal disease, limited literature exists in those with perianal CD. Decision regarding mode of delivery is a unique challenge in such patients due to concerns regarding the effect of pelvic floor trauma during delivery on pre-existing perianal involvement. Methods We performed a retrospective chart review of CD patients with established perianal disease undergoing either vaginal delivery or Caesarean section (C-section) at our institutions. We examined the occurrence of symptomatic perianal disease flares within 5 years after delivery in such women compared to non-pregnant CD controls. We also compared the occurrence of such flares between the two modes of delivery in women with established perianal CD. Results We identified 61 pregnant CD patients with established perianal disease (11 vaginal delivery, 50 via C-section) and 61 non-pregnant CD controls with perianal disease. One-third of the C-sections were primarily for obstetric indications. Six of the vaginal deliveries were complicated. Approximately 36% of cases had a symptomatic perianal flare within 1 year after delivery. This was similar across both modes of delivery (p=0.53), and similar to non-pregnant CD patients. There was no difference in the rates of perianal surgical intervention or luminal disease flares in our population based on mode of delivery, or between pregnant CD patients and non-pregnant CD controls. Conclusion We observed no difference in risk of symptomatic perianal flares in patients with established perianal CD delivering vaginally or via C-section. PMID:24918322

The Hotel Study—Clinical and Health Service Effectiveness in a Cohort of Homeless or Marginally Housed Persons

PubMed Central

Cervantes-Larios, Alejandro; Jones, Andrea A.; Vila-Rodriguez, Fidel; Montaner, Julio S.; Tran, Howard; Nham, Jimmy; Panenka, William J.; Lang, Donna J.; Thornton, Allen E.; Vertinsky, Talia; Barr, Alasdair M.; Procyshyn, Ric M.; Smith, Geoffrey N.; Buchanan, Tari; Krajden, Mel; Krausz, Michael; MacEwan, G. William; Gicas, Kristina M.; Leonova, Olga; Langheimer, Verena; Rauscher, Alexander; Schultz, Krista

2017-01-01

Objective: The Hotel Study was initiated in Vancouver’s Downtown East Side (DTES) neighborhood to investigate multimorbidity in homeless or marginally housed people. We evaluated the clinical effectiveness of existing, illness-specific treatment strategies and assessed the effectiveness of health care delivery for multimorbid illnesses. Method: For context, we mapped the housing locations of patients presenting for 552,062 visits to the catchment hospital emergency department (2005-2013). Aggregate data on 22,519 apprehensions of mentally ill people were provided by the Vancouver Police Department (2009-2015). The primary strategy was a longitudinal cohort study of 375 people living in the DTES (2008-2015). We analysed mortality and evaluated the clinical and health service delivery effectiveness for infection with human immunodeficiency virus or hepatitis C virus, opioid dependence, and psychosis. Results: Mapping confirmed the association between poverty and greater number of emergency visits related to substance use and mental illness. The annual change in police apprehensions did not differ between the DTES and other policing districts. During 1581 person-years of cohort observation, the standardized mortality ratio was 8.43 (95% confidence interval, 6.19 to 11.50). Physician visits were common (84.3% of participants over 6 months). Clinical treatment effectiveness was highest for HIV/AIDS, intermediate for opioid dependence, and lowest for psychosis. Health service delivery mechanisms provided examples of poor access, poor treatment adherence, and little effect on multimorbid illnesses. Conclusions: Clinical effectiveness was variable, and illness-specific service delivery appeared to have little effect on multimorbidity. New models of care may need to be implemented. PMID:28199798

Maternal and cord plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin at delivery; effect of analgesia.

PubMed

Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A; Crawford, J S

1983-12-01

Maternal venous plasma concentrations of beta-LPH, beta-EP and gamma-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein beta-LPH, beta-EP and gamma-LPH concentrations and umbilical artery pH and positive correlations between beta-LPH and beta-EP but not gamma-LPH and cord PCO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.

Cultural competence in mental health care: a review of model evaluations

PubMed Central

Bhui, Kamaldeep; Warfa, Nasir; Edonya, Patricia; McKenzie, Kwame; Bhugra, Dinesh

2007-01-01

Background Cultural competency is now a core requirement for mental health professionals working with culturally diverse patient groups. Cultural competency training may improve the quality of mental health care for ethnic groups. Methods A systematic review that included evaluated models of professional education or service delivery. Results Of 109 potential papers, only 9 included an evaluation of the model to improve the cultural competency practice and service delivery. All 9 studies were located in North America. Cultural competency included modification of clinical practice and organizational performance. Few studies published their teaching and learning methods. Only three studies used quantitative outcomes. One of these showed a change in attitudes and skills of staff following training. The cultural consultation model showed evidence of significant satisfaction by clinicians using the service. No studies investigated service user experiences and outcomes. Conclusion There is limited evidence on the effectiveness of cultural competency training and service delivery. Further work is required to evaluate improvement in service users' experiences and outcomes. PMID:17266765

A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems.

PubMed

Bassi da Silva, Jéssica; Ferreira, Sabrina Barbosa de Souza; de Freitas, Osvaldo; Bruschi, Marcos Luciano

2017-07-01

Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. Moreover, it has contributed to many benefits like increased residence time at application sites, drug protection, increased drug permeation and improved drug availability. In this context, investigation into the mucoadhesive properties of pharmaceutical dosage forms is fundamental, in order to characterize, understand and simulate the in vivo interaction between the formulation and the biological substrate, contributing to the development of new mucoadhesive systems with effectiveness, safety and quality. There are a lot of in vivo, in vitro and ex vivo methods for the evaluation of the mucoadhesive properties of drug delivery systems. However, there also is a lack of standardization of these techniques, which makes comparison between the results difficult. Therefore, this work aims to show an overview of the most commonly employed methods for mucoadhesion evaluation, relating them to different proposed systems and using artificial or natural mucosa from humans and animals.

Estimating the Hospital Delivery Costs Associated With Severe Maternal Morbidity in New York City, 2008-2012.

PubMed

Howland, Renata E; Angley, Meghan; Won, Sang Hee; Wilcox, Wendy; Searing, Hannah; Tsao, Tsu-Yu

2018-02-01

To quantify the average and total hospital delivery costs associated with severe maternal morbidity in excess of nonsevere maternal morbidity deliveries over a 5-year period in New York City adjusting for other sociodemographic and clinical factors. We conducted a population-based cross-sectional study using linked birth certificates and hospital discharge data for New York City deliveries from 2008 to 2012. Severe maternal morbidity was defined using a published algorithm of International Classification of Diseases, 9 Revision, Clinical Modification disease and procedure codes. Hospital costs were estimated by converting hospital charges using factors specific to each year and hospital and to each diagnosis. These estimates approximate what it costs the hospital to provide services (excluding professional fees) and were used in all subsequent analyses. To estimate adjusted mean costs associated with severe maternal morbidity, we used multivariable regression models with a log link, gamma distribution, robust standard errors, and hospital fixed effects, controlling for age, race and ethnicity, neighborhood poverty, primary payer, number of deliveries, method of delivery, comorbidities, and year. We used the adjusted mean cost to determine the average and total hospital delivery costs associated with severe maternal morbidity in excess of nonsevere maternal morbidity deliveries from 2008 to 2012. Approximately 2.3% (n=13,502) of all New York City delivery hospitalizations were complicated by severe maternal morbidity. Compared with nonsevere maternal morbidity deliveries, these hospitalizations were clinically complicated, required more and intensive clinical services, and had a longer stay in the hospital. The average cost of delivery with severe maternal morbidity was $14,442 (95% CI $14,128-14,756), compared with $7,289 (95% CI $7,276-7,302) among deliveries without severe maternal morbidity. After adjusting for other factors, the difference between deliveries with and without severe maternal morbidity remained high ($6,126). Over 5 years, this difference resulted in approximately $83 million in total excess costs (13,502×$6,126). Severe maternal morbidity nearly doubled the cost of delivery above and beyond other drivers of cost, resulting in tens of millions of excess dollars spent in the health care system in New York City. These findings can be used to demonstrate the burden of severe maternal morbidity and evaluate the cost-effectiveness of interventions to improve maternal health.

Nanocarriers Made from Non-Ionic Surfactants or Natural Polymers for Pulmonary Drug Delivery.

PubMed

Carter, K C; Puig-Sellart, M

2016-01-01

Treatment by the pulmonary route can be used for drugs that act locally in the lungs (e.g. lung cancer) or non-invasive administration of drugs that act systemically (e.g. diabetes). The potential of using drug delivery systems (DDS) formed from non-ionic surfactants or natural products for pulmonary drug delivery are reviewed. The effectiveness of each DDS depends on it ability to not only entrap the relevant drug and alter its bio distribution, but also its ability to withstand the physical stresses during nebulization and for the nebuliser to produce aerosol particles with the size for deposition in the appropriate part of the lungs. Different methods must be used to prepare nanoparticles (NP) using non-ionic surfactants, or biocompatible polymers from natural proteins or sugars, and the aqueous solubility of the drug also influences the manufacture method. NP produced using non-ionic surfactants, proteins such as collagen, albumin or gluten, and polysaccharides such as chitosan, hyaluronate, cellulose, carrageenans, alginate or starch has successfully delivered different types of drugs given by the pulmonary route. Drug entrapment efficiency depends on the DDS constituents and the manufacture method used. Large scale manufacture of DDS from natural products is technically challenging but changing from batch manufacture to continuous manufacturing processes has addressed some of these issues, and inclusion of a spray drying step has been beneficial in some cases. DDS for lung delivery can be produced using natural products but identifying a cost effective manufacture method may be challenging and the impact of using different type of nebulisers on the physiochemical characteristics of the aerosolised formulation should be an essential part of formulation development. This would ensure that some of the development work e.g. stability studies do not have to be repeated as they will identify if a carrier to protect the DDS from the physical trauma caused by nebulisation.

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

PubMed

Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

2017-02-28

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effect of Meperidine on Peripartum Breastfeeding and Neonatal Weight

PubMed Central

Asadi, Mahboobeh; Rahimi, Fateme; Hoseinzade, Mohammad Javad; Tanha, Fatemeh Davari; Barkhordari, Khosro; Yasseri, Ali Mohammad Fakhre

2013-01-01

Objective To evaluate the effect of Meperidine, commonly administered for labor analgesia, on newborn weight and peripartum breastfeeding during two months after delivery. Materials and methods This pilot cohort study was conducted between October 2010 and October 2011 at the Women Hospital of the Tehran University of Medical Sciences. In this study, we examined the effects of meperidine on breastfeeding and neonatal weight. A total number of 184 full term pregnant women, planned to deliver at this center (normal vaginally delivery or cesarean), participated in this study. The study group included the women who received meperidine in peripartum time to be compared with a control group who did not receive any opioid. Meperidine was administrated to them based on their peripartum breastfeeding behaviour and baby weight, two month after delivery. Results Of the 184 woman recruited to the trial, 38 women had normal vaginal delivery and 146 had ccesarean. Within the first two-month, 4% of mothers in control group and 11% of meperidine group used formula. However, this differences were not statistically significant (p value= 0.07). Furthermore, baby weight distribution was not statistically different between two groups. Conclusion The inhibitory effect of using Meperidine on peripartum breastfeeding and weight of newborn in the first two months was not statistically significant in this study. More research is needed to clarify the association between meperidine and peripartum breastfeeding. PMID:24971099

Dynamic characterization of hydrophobic and hydrophilic solutes in oleic-acid enhanced transdermal delivery using two-photon fluorescence microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tseng, Te-Yu; Yang, Chiu-Sheng; Chen, Yang-Fang

In this letter, we propose an efficient methodology of investigating dynamic properties of sulforhodamine B and rhodamine B hexyl ester molecules transporting across ex-vivo human stratum corneum with and without oleic acid enhancement. Three-dimensional, time-lapse fluorescence images of the stratum corneum can be obtained using two-photon fluorescence microscopy. Furthermore, temporal quantifications of transport enhancements in diffusion parameters can be achieved with the use of Fick's second law. Dynamic characterization of solutes transporting across the stratum corneum is an effective method for understanding transient phenomena in transdermal delivery of probe molecules, leading to improved delivery strategies of molecular species for therapeuticmore » purposes.« less

The prospect of gene therapy for prostate cancer: update on theory and status.

PubMed

Koeneman, K S; Hsieh, J T

2001-09-01

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.

The Dose-response of Intrathecal Ropivacaine Co-administered with Sufentanil for Cesarean Delivery under Combined Spinal-epidural Anesthesia in Patients with Scarred Uterus

PubMed Central

Xiao, Fei; Xu, Wen-Ping; Zhang, Yin-Fa; Liu, Lin; Liu, Xia; Wang, Li-Zhong

2015-01-01

Background: Spinal anesthesia is considered as a reasonable anesthetic option in lower abdominal and lower limb surgery. This study was to determine the dose-response of intrathecal ropivacaine in patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia. Methods: Seventy-five patients with scarred uterus undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal hyperbaric ropivacaine with 5 μg sufentanil. Successful spinal anesthesia was defined as a T4 sensory level achieved with no need for epidural supplementation. The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with a logistic regression model. Results: ED50 and ED95 of intrathecal hyperbaric ropivacaine for patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval [CI]: 2.28–9.83 mg) and 12.24 mg (95% CI: 10.53–21.88 mg), respectively. Conclusion: When a CSEA technique is to use in patients with scarred uterus for an elective cesarean delivery, the ED50 and ED95 of intrathecal hyperbaric ropivacaine along with 5 μg sufentanil were 8.28 mg and 12.24 mg, respectively. In addition, this local anesthetic is unsuitable for emergent cesarean delivery, but it has advantages for ambulatory patients. PMID:26415793

Effects of Periodontal Therapy on Rate of Preterm Delivery A Randomized Controlled Trial

PubMed Central

Offenbacher, Steven; Beck, James D.; Jared, Heather L.; Mauriello, Sally M.; Mendoza, Luisto C.; Couper, David J.; Stewart, Dawn D.; Murtha, Amy P.; Cochran, David L.; Dudley, Donald J.; Reddy, Michael S.; Geurs, Nicolaas C.; Hauth, John C.

2010-01-01

OBJECTIVE To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed to delivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a χ2 test of equality of two proportions. RESULTS The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. CONCLUSION Periodontal therapy did not reduce the incidence of preterm delivery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT00097656. LEVEL OF EVIDENCE I PMID:19701034

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

PubMed

Thakkar, Miloni; Brijesh, S

2016-01-01

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

Calculating length of gestation from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database versus vital records may alter reported rates of prematurity.

PubMed

Stern, Judy E; Kotelchuck, Milton; Luke, Barbara; Declercq, Eugene; Cabral, Howard; Diop, Hafsatou

2014-05-01

To compare length of gestation after assisted reproductive technology (ART) as calculated by three methods from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and vital records (birth and fetal death) in the Massachusetts Pregnancy to Early Life Longitudinal Data System (PELL). Historical cohort study. Database linkage analysis. Live or stillborn deliveries. None. ART deliveries were linked to live birth or fetal death certificates. Length of gestation in 7,171 deliveries from fresh autologous ART cycles (2004-2008) was calculated and compared with that of SART CORS with the use of methods: M1 = outcome date - cycle start date; M2 = outcome date - transfer date + 17 days; and M3 = outcome date - transfer date + 14 days + day of transfer. Generalized estimating equation models were used to compare methods. Singleton and multiple deliveries were included. Overall prematurity (delivery <37 weeks) varied by method of calculation: M1 29.1%; M2 25.6%; M3 25.2%; and PELL 27.2%. The SART methods, M1-M3, varied from those of PELL by ≥ 3 days in >45% of deliveries and by more than 1 week in >22% of deliveries. Each method differed from each other. Estimates of preterm birth in ART vary depending on source of data and method of calculation. Some estimates may overestimate preterm birth rates for ART conceptions. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Training Requirements and Curriculum Content for Primary Care Providers Delivering Preventive Oral Health Services to Children Enrolled in Medicaid.

PubMed

Sams, Lattice D; Rozier, R Gary; Quinonez, Rocio B

2016-07-01

Despite the emphasis on delivery of preventive oral health services in non-dental settings, limited information exists about state Medicaid policies and strategies to educate practicing physicians in the delivery of these services. This study aims to determine: (1) training requirements and policies for reimbursement of oral health services, (2) teaching delivery methods used to train physicians, and (3) curricula content available to providers among states that reimburse non-dental providers for oral health services. Using Web-based Internet searches as the primary data source, and a supplemental e-mail survey of all states offering in-person training, we assessed training requirements, methods of delivery for training, and curriculum content for states with Medicaid reimbursement to primary care providers delivering preventive oral health services. RESULTS of descriptive analyses are presented for information collected and updated in 2014. Forty-two states provide training sessions or resources to providers, 34 requiring provider training before reimbursement for oral health services. Web-based training is the most common CME delivery method. Only small differences in curricular content were reported by the 11 states that use in-person didactic sessions as the delivery method. Although we found that most states require training and curricular content is similar, training was most often delivered using Web-based courses without any additional delivery methods. Research is needed to evaluate the impact of a mixture of training methods and other quality improvement methods on increased adoption and implementation of preventive oral health services in medical practices.

Multi-beam laser-induced hydrodynamic shock waves used for delivery of microparticles and liquids in skin.

PubMed

Belikov, Andrey V; Skrypnik, Alexei V; Shatilova, Ksenia V; Tuchin, Valery V

2015-11-01

Laser radiation is often used to provide micro and nanoparticle delivery into the skin for medical and cosmetic purposes. This technique inherently has limited speed and effective penetration. We proposed and investigated a new method of rapid delivery of solid microparticles, nanoparticles and liquids into tissue through multiple microchannels created by a fractional laser microablation (FLMA) using Er:YAG-laser. The dependence of microchannel depth on laser pulse temporal structure and number of pulses and dermal coloration changes are studied in this paper. Microchannels created in the porcine skin in vitro by a fractional Er:YAG-laser were used to deliver Zirconium oxide (ZrO2) microparticles or hydrocortisone solution. Each laser pulse consisted of subpulses. Number of laser pulses (Np) and subpulses (Nsp) can be adjusted. The enhancement of delivery is expected due to hydrodynamic impact of laser pulse on the layer of the aqueous suspension of the particles or hydrocortisone solution placed on the skin surface. For color investigation, we used standard CIE Lab parameter analysis. The relationship between microchannel depth in the skin and number of laser pulses and subpulses was established. We found that free filling of microchannels with ZrO2-particle suspension has a low speed of ∼4 × 10(-5)  mm/s. Particle delivery into microchannels induced by the hydrodynamic shock waves generated by Er:YAG-laser pulses is carried out with a high speed of 28.5 mm/s. We also found that skin color at ZrO2 -particle delivery differs from color of the intact skin, namely: the parameter L, which characterizes the "lightness" increased by 9 ± 1%; parameter a, which characterizes the "redness" decreased by 38 ± 4%; and parameter b, which characterizes the "yellowness" decreased by 21 ± 2%. The effective delivery of hydrocortisone was demonstrated using fluorescence method technique. Multi-beam laser-induced hydrodynamic shock waves generated by Er:YAG-laser pulses on the layer of the aqueous suspension of the particles or solution of a high molecular weight drug placed on the skin can be used for their rapid delivery into the skin. © 2015 Wiley Periodicals, Inc.

pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery

PubMed Central

Feng, Shini; Zhi, Chunyi; Gao, Xiao-Dong

2018-01-01

Background Anticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)−citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells. Methods BNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@ PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay. Results The PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency. Conclusion Our findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy. PMID:29440891

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Aptamer-loaded Gold Nanoconstructs for Targeted Cancer Therapy

NASA Astrophysics Data System (ADS)

Dam, Duncan Hieu Minh

Traditional cancer treatments, including chemotherapy, often cause severe side effects in patients. Targeted therapy where tumor cells are targeted via biomarkers overexpressed on the cell surface has been shown to reduce such adverse effects. Monoclonal antibodies (mAbs) are currently the most common chemotherapeutic agents that bind with high affinity to these cancer markers. However, poor intratumoral uptake of mAb and release of drugs from mAb carriers have been the biggest challenge for this delivery method. As a result, recent work has focused on other strategies to improve the efficacy of drug delivery in targeted therapy. Among potential carriers for drug delivery, gold nanoparticles (AuNPs) have emerged as one of the most promising vehicles. This thesis describes the development of a drug delivery nanoconstruct that can both target cancer cells and induce therapeutic effects. The nanoconstructs are composed of gold nanostars (AuNS) as delivery vehicles loaded with the DNA aptamer AS1411 that can target the ubiquitous shuttle protein nucleolin (NCL) in various cancer cell types. The gold nanocarrier stabilizes the oligonucleotides for intracellular delivery and promotes high loading densities of the oligonucleotide drugs. We have investigated the interactions of the nanoconstruct with different subcellular compartments of the cancer cells. This physical phenomenon has shown to correlate with the biological activities such as apoptosis and cell death that happen in the cancer cells after incubation with the nanoconstructs. A thorough screening of the nanoconstructs in 13 different cancer cell lines is conducted to narrow down the potential targets for in vivo study. Before testing the in vivo efficacy, we evaluate the toxicity of the nanoconstructs in non-tumor animals, which confirms its safety for further in vivo applications. The accumulation of the nanoconstructs in two different cancerous tumors, however, suggests that further optimization of the design is required. Thus, we introduced an improved nanoconstruct with higher loading of AS1411 on the surface of AuNS. The significant enhancement in the loading of the Apt increases the cellular uptake as well as the in vitro efficacy of the nanoconstruct in both fibrosarcoma and pancreatic cancer cells. To further optimize the design of the nanoconstruct, we create a conjugation method in which the loading of AS1411 can be effectively controlled at various pH conditions. This method can potentially be applied for any DNA or RNA; however, the stability of oligonucleotides is unknown as a function of pH. Therefore, we also evaluate how pH conditions can affect the loading densities and structural integrity of a range of different oligonucleotides (single stranded DNA, hairpin DNA, duplexes, quadruplexes) on AuNS. The ultimate goal of this process is to identify a set of design principles to optimize oligonucleotide loading based on the local chemical environment around the nanoparticle.

Examining the Effectiveness of Student Authentication and Authenticity in Online Learning at Community Colleges

ERIC Educational Resources Information Center

Hoshiar, Mitra; Dunlap, Jody; Li, Jinyi; Friedel, Janice Nahra

2014-01-01

Online learning is rapidly becoming one of the most prevalent delivery methods of learning in institutions of higher education. It provides college students, especially adult students, an alternative, convenient, and cost-efficient method to earn their credentials, upgrade their skills and knowledge, and keep or upgrade their employment. But at…

Real-time implementation of model predictive control on Maricopa-Stanfield irrigation and drainage district's WM canal

USDA-ARS?s Scientific Manuscript database

Water resources are limited in many agricultural areas. One method to improve the effective use of water is to improve delivery service from irrigation canals. This can be done by applying automatic control methods that control the gates in an irrigation canal. The model predictive control MPC is ...

Heparin Microparticle Effects on Presentation and Bioactivity of Bone Morphogenetic Protein-2

PubMed Central

Hettiaratchi, Marian H.; Miller, Tobias; Temenoff, Johnna S.; Guldberg, Robert E.; McDevitt, Todd C.

2014-01-01

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration. PMID:24881028

Effect of LI4 and BL32 acupressure on labor pain and delivery outcome in the first stage of labor in primiparous women: A randomized controlled trial.

PubMed

Ozgoli, Giti; Sedigh Mobarakabadi, Sedigheh; Heshmat, Reza; Alavi Majd, Hamid; Sheikhan, Zohreh

2016-12-01

This study examines and compares the effect of LI4 and BL32 acupressure with each other and control group on labor pain and delivery outcomes. In this randomized controlled trial, 105 primiparous women in active phase of first-stage of labor were equally assigned to two experimental groups [acupressure on LI4 (n=35) or BL32 (n=35)] and a control group (n=35). The experimental groups received routine labor care and acupressure in LI4 or BL32 points in three cervical dilatations (4-5, 6-7, and 8-10cm). The control group only received routine labor care. Pain was assessed by numerical rating scale in three cervical dilatations, before and after intervention. Type of delivery (cesarean, vaginal or operative delivery) and neonatal Apgar score were considered as delivery outcomes, these data collected by a check list. Data were analyzed using Repeated Measurement, ANOVA, Chi-Square, Kruskal-Wallis, and Mann-Whitney tests. Pain reduction was significantly greater in LI4 and BL32 groups compared with control in all periods of study. Also, acupressure on BL32 point was superior to LI4 point in pain relief in the first and second but not third intervention. No statistically significant difference was observed in terms of delivery outcomes. Acupressure on BL32 and LI4 points are effective in reducing labor pain compared to control group with a slight superiority for BL32 points. Acupressure on these points could apply for relief pain in labor as an inexpensive and easy to administered method. Copyright © 2016 Elsevier Ltd. All rights reserved.

pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery.

PubMed

Koetting, Michael Clinton; Guido, Joseph Frank; Gupta, Malvika; Zhang, Annie; Peppas, Nicholas A

2016-01-10

Two potential platform technologies for the oral delivery of protein therapeutics were synthesized and tested. pH-responsive poly(itaconic acid-co-N-vinyl-2-pyrrolidone) (P(IA-co-NVP)) hydrogel microparticles were tested in vitro with model proteins salmon calcitonin, urokinase, and rituximab to determine the effects of particle size, protein size, and crosslinking density on oral delivery capability. Particle size showed no significant effect on overall delivery potential but did improve percent release of encapsulated protein over the micro-scale particle size range studied. Protein size was shown to have a significant impact on the delivery capability of the P(IA-co-NVP) hydrogel. We show that when using P(IA-co-NVP) hydrogel microparticles with 3 mol% tetra(ethylene glycol) dimethacrylate crosslinker, a small polypeptide (salmon calcitonin) loads and releases up to 45 μg/mg hydrogel while the mid-sized protein urokinase and large monoclonal antibody rituximab load and release only 19 and 24 μg/mg hydrogel, respectively. We further demonstrate that crosslinking density offers a simple method for tuning hydrogel properties to variously sized proteins. Using 5 mol% TEGDMA crosslinker offers optimal performance for the small peptide, salmon calcitonin, whereas lower crosslinking density of 1 mol% offers optimal performance for the much larger protein rituximab. Finally, an enzymatically-degradable hydrogels of P(MAA-co-NVP) crosslinked with the peptide sequence MMRRRKK were synthesized and tested in simulated gastric and intestinal conditions. These hydrogels offer ideal loading and release behavior, showing no degradative release of encapsulated salmon calcitonin in gastric conditions while yielding rapid and complete release of encapsulated protein within 1h in intestinal conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

How does delivery method influence factors that contribute to women's childbirth experiences?

PubMed

Carquillat, Pierre; Boulvain, Michel; Guittier, Marie-Julia

2016-12-01

whether delivery method influences factors contributing to women's childbirth experience remains debated. we compared subjective childbirth experience according to different delivery methods. this study used a cross-sectional design. the setting comprised two university hospitals: one in Geneva, Switzerland and one in Clermont-Ferrand, France. a total of 291 primiparous women were recruited from July 2014 to January 2015 during their stay in the maternity wards. The mean age of the participants was 30.8 (SD=4.7) years, and most were Swiss or European (86%). the 'Questionnaire for Assessing Childbirth Experience' was sent between four and six weeks after delivery. Clinimetric and psychometric approaches were used to assess childbirth experience according to delivery method. the mean scores of the four questionnaire dimensions varied significantly by delivery method. 'First moments with the newborn' was more negatively experienced by women from the caesarean section group compared to those who delivered vaginally (p<0.001). Similar results regarding the dimension of 'emotional status' were also observed, as women who delivered by caesarean section felt more worried, less secure, and less confident (p=0.001). 'Relationship with staff' significantly differed between groups (p=0.047) as more negative results were shown in the 'unexpected medical intervention groups' (i.e. emergency caesarean section and instrumental delivered vaginally). Women's 'feelings at one-month post partum' in the emergency caesarean section group were less satisfactory than the other groups. Delivery method and other obstetric variables explained only a low proportion of the total variance in the global scores (R 2 adjusted=0.18), which emphasized the importance of subjective factors in women's childbirth experience. a comparison of best expected positive responses to each item (clinimetric approach) showed useful results for clinicians. This research indicated that delivery method influenced key factors (psychometric approach) of the childbirth experience. delivery method should not be considered alone and health professionals should focus on what is important for women to foster a more positive experience. In addition, women who have had an emergency caesarean section require special attention during post partum. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Amperometric Glucose Sensor Integrated into an Insulin Delivery Cannula: In Vitro and In Vivo Evaluation

PubMed Central

Heinrich, Gabriel; Breen, Matthew; Benware, Sheila; Vollum, Nicole; Morris, Kristin; Knutsen, Chad; Kowalski, Joseph D.; Campbell, Scott; Biehler, Jerry; Vreeke, Mark S.; Vanderwerf, Scott M.; Castle, Jessica R.; Cargill, Robert S.

2017-01-01

Abstract Background: Labeling prohibits delivery of insulin at the site of subcutaneous continuous glucose monitoring (CGM). Integration of the sensing and insulin delivery functions into a single device would likely increase the usage of CGM in persons with type 1 diabetes. Methods: To understand the nature of such interference, we measured glucose at the site of bolus insulin delivery in swine using a flexible electrode strip that was laminated to the outer wall of an insulin delivery cannula. In terms of sensing design, we compared H2O2-measuring sensors biased at 600 mV with redox mediator-type sensors biased at 175 mV. Results: In H2O2-measuring sensors, but not in sensors with redox-mediated chemistry, a spurious rise in current was seen after insulin lis-pro boluses. This prolonged artifact was accompanied by electrode poisoning. In redox-mediated sensors, the patterns of sensor signals acquired during delivery of saline and without any liquid delivery were similar to those acquired during insulin delivery. Conclusion: Considering in vitro and in vivo findings together, it became clear that the mechanism of interference is the oxidation, at high bias potentials, of phenolic preservatives present in insulin formulations. This effect can be avoided by the use of redox mediator chemistry using a low bias potential. PMID:28221814

Simulation-based education for building clinical teams

PubMed Central

Marshall, Stuart D; Flanagan, Brendan

2010-01-01

Failure to work as an effective team is commonly cited as a cause of adverse events and errors in emergency medicine. Until recently, individual knowledge and skills in managing emergencies were taught, without reference to the additional skills required to work as part of a team. Team training courses are now becoming commonplace, however their strategies and modes of delivery are varied. Just as different delivery methods of traditional education can result in different levels of retention and transfer to the real world, the same is true in team training of the material in different ways in traditional forms of education may lead to different levels of retention and transfer to the real world, the same is true in team training. As team training becomes more widespread, the effectiveness of different modes of delivery including the role of simulation-based education needs to be clearly understood. This review examines the basis of team working in emergency medicine, and the components of an effective emergency medical team. Lessons from other domains with more experience in team training are discussed, as well as the variations from these settings that can be observed in medical contexts. Methods and strategies for team training are listed, and experiences in other health care settings as well as emergency medicine are assessed. Finally, best practice guidelines for the development of team training programs in emergency medicine are presented. PMID:21063559

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

PubMed Central

Varshosaz, J.; Minaiyan, M.; Forghanian, M.

2014-01-01

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

Electro-osmotically driven liquid delivery method and apparatus

DOEpatents

Rakestraw, David J.; Anex, Deon S.; Yan, Chao; Dadoo, Rajeev; Zare, Richard N.

1999-01-01

Method and apparatus for controlling precisely the composition and delivery of liquid at sub-.mu.L/min flow rate. One embodiment of such a delivery system is an electro-osmotically driven gradient flow delivery system that generates dynamic gradient flows with sub-.mu.L/min flow rates by merging a plurality of electro-osmotic flows. These flows are delivered by a plurality of delivery arms attached to a mixing connector, where they mix and then flow into a receiving means, preferably a column. Each inlet of the plurality of delivery arms is placed in a corresponding solution reservoir. A plurality of independent programmable high-voltage power supplies is used to apply a voltage program to each of the plurality of solution reservoirs to regulate the electro-osmotic flow in each delivery arm. The electro-osmotic flow rates in the delivery arms are changed with time according to each voltage program to deliver the required gradient profile to the column.

Nano-enabled drug delivery systems for brain cancer and Alzheimer's disease: research patterns and opportunities.

PubMed

Ma, Jing; Porter, Alan L; Aminabhavi, Tejraj M; Zhu, Donghua

2015-10-01

"Tech mining" applies bibliometric and text analytic methods to scientific literature of a target field. In this study, we compare the evolution of nano-enabled drug delivery (NEDD) systems for two different applications - viz., brain cancer (BC) and Alzheimer's disease (AD) - using this approach. In this process, we derive research intelligence from papers indexed in MEDLINE. Review by domain specialists helps understand the macro-level disease problems and pathologies to identify commonalities and differences between BC and AD. Results provide a fresh perspective on the developmental pathways for NEDD approaches that have been used in the treatment of BC and AD. Results also point toward finding future solutions to drug delivery issues that are critical to medical practitioners and pharmaceutical scientists addressing the brain. Drug delivery to brain cells has been very challenging due to the presence of the blood-brain barrier (BBB). Suitable and effective nano-enabled drug delivery (NEDD) system is urgently needed. In this study, the authors utilized "tech-mining" tools to describe and compare various choices of delivery system available for the diagnosis, as well as treatment, of brain cancer and Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Microneedles for intradermal and transdermal delivery

PubMed Central

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2014-01-01

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery.

PubMed

Patel, Viral; Sharma, Om Prakash; Mehta, Tejal

2018-04-01

Skin is an important route of drug delivery for the treatment of various dermatological conditions. The advent of nanotechnology is paving the roadmaps for topical drug delivery by providing sustained release as well as maintaining a localized effect, outweighing the toxicity concern. Area covered: This review highlighted the morphology of skin, its barrier nature as well as drug penetration pathways after topical application of formulations. The existing methods to improve topical drug delivery, by infringing or permeating the skin barriers, are discussed. This context concretes the foundation to accentuate the need for the development of nanocrystal-based topical formulation. The mechanism of drug release, immediate as well as sustained release, after topical administration of drug nanocrystals is also elaborated. The special emphasis is given on the breakthrough achieved, in topical drug delivery using drug nanocrystals, so far in the plethora of literature, patents, and products, under clinical trial as well as in the market. Expert opinion: The current research on nanocrystals for topical drug delivery is highlighting the breakthroughs achieved so far. The output of these research envisages that topical nanocrystals based formulations can be a novel strategy for the drugs which are facing solubility, bioavailability and toxicity concerns.

Nano drug delivery systems and gamma radiation sterilization.

PubMed

Sakar, F; Özer, A Y; Erdogan, S; Ekizoglu, M; Kart, D; Özalp, M; Colak, S; Zencir, Y

2017-09-01

In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point of view, a parenterally applied drug and drug delivery systems must be sterile and pyrogen free. Radiation sterilization is a method recognized by pharmacopoeias to achieve sterility criteria of parenterals. It has the ability to kill microorganisms in therapeutic products. The ability of, however, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the irradiation, especially with the traditionally applied dose of 25 kGy. Its ionizing property may cause fragmentation of covalent bond. The care must be paid to the applied dose. In this research, the effects of gamma irradiation on different drug delivery systems such as chitosan microparticles, liposomes, niosomes and sphingosomes were investigated. According to the experimental data, it can be concluded that gamma irradiation can be a suitable sterilization technique for liposome, niosome and sphingosome dispersions. When all irradiated drug carrier systems were taken into consideration, chitosan glutamate microparticles were found as the most radioresistant drug delivery system among the others.

Assay of 6-gingerol in CO2 supercritical fluid extracts of ginger and evaluation of its sustained release from a transdermal delivery system across rat skin.

PubMed

Chen, Yan; Zhang, Cuiping; Zhang, Mei; Fu, Xiaobing

2014-07-01

Ginger has been widely used as healthy food condiment as well as traditional Chinese medicine since antiquity. Multiple potentials of ginger for treatment of various ailments have been revealed. However, the biological half-life of 6-gingerol (a principal pungent ingredient of ginger) is only 7.23 minutes while taken orally. Delivery of ginger compositions by routes other than oral have scarcely been reported. Therefore, we studied a noninvasive transdermal drug delivery system (TDDS) of ginger to bypass hepatic first pass metabolism, avoid gastrointestinal degradation and achieve long persistent release of effective compositions. After establishment of a HPLC analysis method of 6-gingerol, assays of 6-gingerol were performed to compare two kinds of ginger extracts. Then, the characteristics of transdermal delivery of 6-gingerol in TDDS were exhibited. The results showed that the contents of 6-gingerol in two kinds of ginger extracts were significantly different. The maximal delivery percentage of 6-gingerol across rat skin at 20 h was more than 40% in different TDDS formulations. TDDS may provide long-lasting delivery of ginger compounds.

It's All in the Delivery! An Analysis of Instructional Strategies from Effective Health Education Curricula

ERIC Educational Resources Information Center

Herbert, Patrick C.; Lohrmann, David K.

2011-01-01

Background: This study explores the relationship between instructional strategies and effective health education curricula. Methods: A content analysis of 10 health education curricula was conducted to determine if they include common instructional strategies for actively engaging students in acquisition of health skills. To be included, the…

Comparing Distance vs. Campus-Based Delivery of Research Methods Courses

ERIC Educational Resources Information Center

Girod, Mark; Wojcikiewicz, Steve

2009-01-01

A causal-comparative pre-test, post-test design was used to investigate differences in learning in a research methods course for face-to-face and web-based delivery models. Analyses of participant achievement (N = 205) revealed almost no differences but post-hoc analyses revealed important differences in pedagogy between delivery models despite…

Statistics Student Performance and Anxiety: Comparisons in Course Delivery and Student Characteristics

ERIC Educational Resources Information Center

Hedges, Sarai

2017-01-01

The statistics education community continues to explore the differences in performance outcomes and in student attitudes between online and face-to-face delivery methods of statistics courses. In this quasi-experimental study student persistence, exam, quiz, and homework scores were compared between delivery methods, class status, and programs of…

Design-Build Highway Projects : A Review of Practices and Experiences, Final Report.

DOT National Transportation Integrated Search

2016-11-01

Texas has employed different project delivery methods in recent years in an effort to add capacity, reduce congestion, and improve the effectiveness and efficiency of the states transportation system. These transportation improvement projects are ...

Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue

PubMed Central

Joshi, Shailendra; Singh-Moon, Rajinder P.; Wang, Mei; Chaudhuri, Durba B.; Holcomb, Mark; Straubinger, Ninfa L.; Bruce, Jeffrey N.; Bigio, Irving J.; Straubinger, Robert M.

2014-01-01

Object Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (< 3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Methods Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery vs. intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain four hours after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. Results IA injections of cationic liposomes during TCH increased their delivery approximately four-fold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue four hours after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Conclusions Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 hours after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH. PMID:24664370

Potentiation of an anthrax DNA vaccine with electroporation.

PubMed

Luxembourg, A; Hannaman, D; Nolan, E; Ellefsen, B; Nakamura, G; Chau, L; Tellez, O; Little, S; Bernard, R

2008-09-19

DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.

Comparison of three different methods for effective introduction of platelet-rich plasma on PLGA woven mesh.

PubMed

Lee, Ji-Hye; Nam, Jinwoo; Kim, Hee Joong; Yoo, Jeong Joon

2015-03-11

For successful tissue regeneration, effective cell delivery to defect site is very important. Various types of polymer biomaterials have been developed and applied for effective cell delivery. PLGA (poly lactic-co-glycolic acid), a synthetic polymer, is a commercially available and FDA approved material. Platelet-rich plasma (PRP) is an autologous growth factor cocktail containing various growth factors including PDGF, TGFβ-1 and BMPs, and has shown positive effects on cell behaviors. We hypothesized that PRP pretreatment on PLGA mesh using different methods would cause different patterns of platelet adhesion and stages which would modulate cell adhesion and proliferation on the PLGA mesh. In this study, we pretreated PRP on PLGA using three different methods including simple dripping (SD), dynamic oscillation (DO) and centrifugation (CE), then observed the amount of adhered platelets and their activation stage distribution. The highest amount of platelets was observed on CE mesh and calcium treated CE mesh. Moreover, calcium addition after PRP coating triggered dramatic activation of platelets which showed large and flat morphologies of platelets with rich fibrin networks. Human chondrocytes (hCs) and human bone marrow stromal cells (hBMSCs) were next cultured on PRP-pretreated PLGA meshes using different preparation methods. CE mesh showed a significant increase in the initial cell adhesion of hCs and proliferation of hBMSCs compared with SD and DO meshes. The results demonstrated that the centrifugation method can be considered as a promising coating method to introduce PRP on PLGA polymeric material which could improve cell-material interaction using a simple method.

FeNi nanotubes: perspective tool for targeted delivery

NASA Astrophysics Data System (ADS)

Kaniukov, Egor; Shumskaya, Alena; Yakimchuk, Dzmitry; Kozlovskiy, Artem; Korolkov, Ilya; Ibragimova, Milana; Zdorovets, Maxim; Kadyrzhanov, Kairat; Rusakov, Vyacheslav; Fadeev, Maxim; Lobko, Eugenia; Saunina, Kristina; Nikolaevich, Larisa

2018-05-01

Targeted delivery of drugs and proteins by magnetic field is a promising method to treat cancer that reduces undesired systemic toxicity of drugs. In this method, the therapeutic agent is attached through links to functional groups with magnetic nanostructure and injected into the blood to be transported to the problem area. To provide a local effect of drug treatment, nanostructures are concentrated and fixed in the selected area by the external magnetic field (magnet). After the exposure, carriers are removed from the circulatory system by magnetic field. In this study, Fe20Ni80 nanotubes are considered as carriers for targeted delivery of drugs and proteins. A simple synthesis method is proposed to form these structures by electrodeposition in PET template pores, and structural and magnetic properties are studied in detail. Nanotubes have polycrystalline walls providing mechanical strength of carriers and magnetic anisotropy that allow controlling the nanostructure movement under the exposure of by magnetic field. Moreover, potential advantages of magnetic nanotubes are discussed in comparison with other carrier types. Most sufficient of them is predictable behavior in magnetic field due to the absence of magnetic core, low specific density that allows floating in biological media, and large specific surface area providing the attachment of a larger number of payloads for the targeted delivery. A method of coating nanotube surfaces with PMMA is proposed to exclude possible negative impact of the carrier material and to form functional bonds for the payload connection. Cytotoxicity studies of coated and uncoated nanotubes are carried out to understand their influence on the biological media.

Comparing the Effects of Teen Mentors to Adult Teachers on Child Lifestyle Behaviors and Health Outcomes in Appalachia

ERIC Educational Resources Information Center

Smith, Laureen H.; Holloman, Christopher

2013-01-01

Childhood obesity prevalence rates in the United States are the highest in the rural Appalachian areas. Teens mentoring younger children to reverse obesity health risks are an understudied approach. This randomized-controlled trial compared the effects of two curriculum delivery methods and assessed the mediating effects of the number of sessions…

Disruptive Technology: Saving Money and Inspiring Engagement in Professional Staff.

PubMed

McPherson, Penne; Talbot, Elizabeth

Competent, efficient, and cost-effective delivery of professional development is a challenge in health care. Collaboration of teaching methodologies with academia and acute care offers fresh perspectives and delivery methods that can facilitate optimal outcomes. One multihospital system introduced the academic "flipped classroom" model to its acute care setting and integrated it into professional development requirements. The concept of the flipped classroom requires independent student engagement prior to classroom activities versus the traditional classroom lecture model. Results realized a cost savings in 2 years of $28,737 in addition to positive employee engagement.

Hurricane Charley Exposure and Hazard of Preterm Delivery, Florida 2004.

PubMed

Grabich, Shannon C; Robinson, Whitney R; Engel, Stephanie M; Konrad, Charles E; Richardson, David B; Horney, Jennifer A

2016-12-01

Objective Hurricanes are powerful tropical storm systems with high winds which influence many health effects. Few studies have examined whether hurricane exposure is associated with preterm delivery. We aimed to estimate associations between maternal hurricane exposure and hazard of preterm delivery. Methods We used data on 342,942 singleton births from Florida Vital Statistics Records 2004-2005 to capture pregnancies at risk of delivery during the 2004 hurricane season. Maternal exposure to Hurricane Charley was assigned based on maximum wind speed in maternal county of residence. We estimated hazards of overall preterm delivery (<37 gestational weeks) and extremely preterm delivery (<32 gestational weeks) in Cox regression models, adjusting for maternal/pregnancy characteristics. To evaluate heterogeneity among racial/ethnic subgroups, we performed analyses stratified by race/ethnicity. Additional models investigated whether exposure to multiples hurricanes increased hazard relative to exposure to one hurricane. Results Exposure to wind speeds ≥39 mph from Hurricane Charley was associated with a 9 % (95 % CI 3, 16 %) increase in hazard of extremely preterm delivery, while exposure to wind speed ≥74 mph was associated with a 21 % (95 % CI 6, 38 %) increase. Associations appeared greater for Hispanic mothers compared to non-Hispanic white mothers. Hurricane exposure did not appear to be associated with hazard of overall preterm delivery. Exposure to multiple hurricanes did not appear more harmful than exposure to a single hurricane. Conclusions Hurricane exposure may increase hazard of extremely preterm delivery. As US coastal populations and hurricane severity increase, the associations between hurricane and preterm delivery should be further studied.

Cost-effectiveness of health care service delivery interventions in low and middle income countries: a systematic review.

PubMed

Watson, Samuel I; Sahota, Harvir; Taylor, Celia A; Chen, Yen-Fu; Lilford, Richard J

2018-01-01

Low and middle income countries (LMICs) face severe resource limitations but the highest burden of disease. There is a growing evidence base on effective and cost-effective interventions for these diseases. However, questions remain about the most cost-effective method of delivery for these interventions. We aimed to review the scope, quality, and findings of economic evaluations of service delivery interventions in LMICs. We searched PUBMED, MEDLINE, EconLit, and NHS EED for studies published between 1st January 2000 and 30th October 2016 with no language restrictions. We included all economic evaluations that reported incremental costs and benefits or summary measures of the two such as an incremental cost effectiveness ratio. Studies were grouped by both disease area and outcome measure and permutation plots were completed for similar interventions. Quality was judged by the Drummond checklist. Overall, 3818 potentially relevant abstracts were identified of which 101 studies were selected for full text review. Thirty-seven studies were included in the final review. Twenty-three studies reported on interventions we classed as "changing by whom and where care was provided", specifically interventions that entailed task-shifting from doctors to nurses or community health workers or from facilities into the community. Evidence suggests this type of intervention is likely to be cost-effective or cost-saving. Nine studies reported on quality improvement initiatives, which were generally found to be cost-effective. Quality and methods differed widely limiting comparability of the studies and findings. There is significant heterogeneity in the literature, both methodologically and in quality. This renders further comparisons difficult and limits the utility of the available evidence to decision makers.

Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System

PubMed Central

2010-01-01

Purpose: An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. Methods: The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37°C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Results: Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Conclusions: Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye. PMID:20148655

Barriers and enablers to delivery of the Healthy Kids Check: an analysis informed by the Theoretical Domains Framework and COM-B model

PubMed Central

2014-01-01

Background More than a fifth of Australian children arrive at school developmentally vulnerable. To counteract this, the Healthy Kids Check (HKC), a one-off health assessment aimed at preschool children, was introduced in 2008 into Australian general practice. Delivery of services has, however, remained low. The Theoretical Domains Framework, which provides a method to understand behaviours theoretically, can be condensed into three core components: capability, opportunity and motivation, and the COM-B model. Utilising this system, this study aimed to determine the barriers and enablers to delivery of the HKC, to inform the design of an intervention to promote provision of HKC services in Australian general practice. Methods Data from 6 focus group discussions with 40 practitioners from general practices in socio-culturally diverse areas of Melbourne, Victoria, were analysed using thematic analysis. Results Many practitioners expressed uncertainty regarding their capabilities and the practicalities of delivering HKCs, but in some cases HKCs had acted as a catalyst for professional development. Key connections between immunisation services and delivery of HKCs prompted practices to have systems of recall and reminder in place. Standardisation of methods for developmental assessment and streamlined referral pathways affected practitioners’ confidence and motivation to perform HKCs. Conclusion Application of a systematic framework effectively demonstrated how a number of behaviours could be targeted to increase delivery of HKCs. Interventions need to target practice systems, the support of office staff and referral options, as well as practitioners’ training. Many behavioural changes could be applied through a single intervention programme delivered by the primary healthcare organisations charged with local healthcare needs (Medicare Locals) providing vital links between general practice, community and the health of young children. PMID:24886520

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

PubMed

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

Improving health outcomes of children through effective parenting: model and methods.

PubMed

Okafor, Martha; Sarpong, Daniel F; Ferguson, Aneeqah; Satcher, David

2013-12-23

This article reports on the design, development, testing and presentation of preliminary evidence of a translational, culturally relevant parenting education model, titled Smart and Secured Children (SSC). SSC, a quality parenting curriculum, prepares disparate African American parents as leaders for transforming their parenting behaviors and leading their peers and community in changing existing parenting culture. The article recommends expanded utility of identified promising processes, approaches and practices to engage African American parents to lead in addressing health inequity conditions in their families and communities. It adds to the growing scientific literature on the association between parent-child relationship quality and a wide variety of children physical, emotional and social outcomes. SSC applied principles of developmental theories; community based participatory research (CBPR), and iterative Delphi method between the community stakeholders, parents and researchers. The delivery approach of SSC was revamped from professional-led to parent-led content presentation and delivery methods using a conversational learning approach, referred to as 'conversepedia'. Parents' leadership development training and delivery of this curriculum in social supportive groups improved their mental wellbeing, parenting capacity and leadership skills. Parents do matter and can choose positive influence in their lives and are capable of reversing negative peer influence.

Improving Health Outcomes of Children through Effective Parenting: Model and Methods

PubMed Central

Okafor, Martha; Sarpong, Daniel F.; Ferguson, Aneeqah; Satcher, David

2013-01-01

This article reports on the design, development, testing and presentation of preliminary evidence of a translational, culturally relevant parenting education model, titled Smart and Secured Children (SSC). SSC, a quality parenting curriculum, prepares disparate African American parents as leaders for transforming their parenting behaviors and leading their peers and community in changing existing parenting culture. The article recommends expanded utility of identified promising processes, approaches and practices to engage African American parents to lead in addressing health inequity conditions in their families and communities. It adds to the growing scientific literature on the association between parent–child relationship quality and a wide variety of children physical, emotional and social outcomes. SSC applied principles of developmental theories; community based participatory research (CBPR), and iterative Delphi method between the community stakeholders, parents and researchers. The delivery approach of SSC was revamped from professional-led to parent-led content presentation and delivery methods using a conversational learning approach, referred to as ‘conversepedia’. Parents’ leadership development training and delivery of this curriculum in social supportive groups improved their mental wellbeing, parenting capacity and leadership skills. Parents do matter and can choose positive influence in their lives and are capable of reversing negative peer influence. PMID:24366048

Cord blood collection for banking and the risk of maternal hemorrhage.

PubMed

Amat, Lluís; Sabrià, Joan; Martínez, Eva; Rodríguez, Núria L; Querol, Sergio; Lailla, Josep M

2011-09-01

We determined the effect of cord blood collection before placental expulsion on postpartum maternal blood loss in a retrospective study between a group of cord blood donors and a group of non-donors. The study was conducted in a university hospital blood bank and obstetric services and included Spanish women entered in a European study project (EUPHRATES) and who had consented to donate cord blood for public banking purposes. We measured blood volume lost during delivery by a bag collection method, as well as the need for transfusion and postpartum anemia symptoms. Deliveries at which cord blood was collected presented a significant increase in blood loss (321 ± 273 vs. 255 ± 237 ml, p=0.02). Instrumental deliveries were associated with higher postpartum blood loss than spontaneous deliveries. Cord blood collection can increase intrapartum blood loss, especially at instrumental deliveries. Additional staff who handle the collection are required to allow the leading clinician to focus on maternal care. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Electro-gene transfer to skin using a noninvasive multielectrode array

PubMed Central

Guo, Siqi; Donate, Amy; Basu, Gaurav; Lundberg, Cathryn; Heller, Loree; Heller, Richard

2011-01-01

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest EP with the MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications. PMID:21262290

Novel catalytic micromotor of porous zeolitic imidazolate framework-67 for precise drug delivery.

PubMed

Wang, Linlin; Zhu, Hongli; Shi, Ying; Ge, You; Feng, Xiaomiao; Liu, Ruiqing; Li, Yi; Ma, Yanwen; Wang, Lianhui

2018-06-07

Micromotors hold promise as drug carriers for targeted drug delivery owing to the characteristics of self-propulsion and directional navigation. However, several defects still exist, including high cost, short movement life, low drug loading and slow release rate. Herein, a novel catalytic micromotor based on porous zeolitic imidazolate framework-67 (ZIF-67) synthesized by a greatly simplified wet chemical method assisted with ultrasonication is described as an efficient anticancer drug carrier. These porous micromotors display effective autonomous motion in hydrogen peroxide and long durable movement life of up to 90 min. Moreover, the multifunctional micromotor ZIF-67/Fe3O4/DOX exhibits excellent performance in precise drug delivery under external magnetic field with high drug loading capacity of fluorescent anticancer drug DOX up to 682 μg mg-1 owing to its porous nature, high surface area and rapid drug release based on dual stimulus of catalytic reaction and solvent effects. Therefore, these porous ZIF-67-based catalytic micromotors combine the domains of metal-organic frameworks (MOFs) and micomotors, thus developing potential resources for micromotors and holding great potential as label-free and precisely controlled high-quality candidates of drug delivery systems for biomedical applications.

Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

PubMed

Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

2017-07-01

The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

Effective Practices in the Delivery of Research Ethics Education: A Qualitative Review of Instructional Methods.

PubMed

Todd, E Michelle; Torrence, Brett S; Watts, Logan L; Mulhearn, Tyler J; Connelly, Shane; Mumford, Michael D

2017-01-01

In order to delineate best practices for courses on research ethics, the goal of the present effort was to identify themes related to instructional methods reflected in effective research ethics and responsible conduct of research (RCR) courses. By utilizing a qualitative review, four themes relevant to instructional methods were identified in effective research ethics courses: active participation, case-based activities, a combination of individual and group approaches, and a small number of instructional methods. Three instructional method themes associated with less effective courses were also identified: passive learning, a group-based approach, and a large number of instructional methods. Key characteristics of each theme, along with example courses relative to each theme, are described. Additionally, implications regarding these instructional method themes and recommendations for best practices in research ethics courses are discussed.

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

PubMed Central

Wilkie, Joel R.; Matuszak, Martha M.; Feng, Mary; Moran, Jean M.; Fraass, Benedick A.

2013-01-01

Purpose: Plan degradation resulting from compromises made to enhance delivery efficiency is an important consideration for intensity modulated radiation therapy (IMRT) treatment plans. IMRT optimization and/or multileaf collimator (MLC) sequencing schemes can be modified to generate more efficient treatment delivery, but the effect those modifications have on plan quality is often difficult to quantify. In this work, the authors present a method for quantitative assessment of overall plan quality degradation due to tradeoffs between delivery efficiency and treatment plan quality, illustrated using comparisons between plans developed allowing different numbers of intensity levels in IMRT optimization and/or MLC sequencing for static segmental MLC IMRT plans. Methods: A plan quality degradation method to evaluate delivery efficiency and plan quality tradeoffs was developed and used to assess planning for 14 prostate and 12 head and neck patients treated with static IMRT. Plan quality was evaluated using a physician's predetermined “quality degradation” factors for relevant clinical plan metrics associated with the plan optimization strategy. Delivery efficiency and plan quality were assessed for a range of optimization and sequencing limitations. The “optimal” (baseline) plan for each case was derived using a clinical cost function with an unlimited number of intensity levels. These plans were sequenced with a clinical MLC leaf sequencer which uses >100 segments, assuring delivered intensities to be within 1% of the optimized intensity pattern. Each patient's optimal plan was also sequenced limiting the number of intensity levels (20, 10, and 5), and then separately optimized with these same numbers of intensity levels. Delivery time was measured for all plans, and direct evaluation of the tradeoffs between delivery time and plan degradation was performed. Results: When considering tradeoffs, the optimal number of intensity levels depends on the treatment site and on the stage in the process at which the levels are limited. The cost of improved delivery efficiency, in terms of plan quality degradation, increased as the number of intensity levels in the sequencer or optimizer decreased. The degradation was more substantial for the head and neck cases relative to the prostate cases, particularly when fewer than 20 intensity levels were used. Plan quality degradation was less severe when the number of intensity levels was limited in the optimizer rather than the sequencer. Conclusions: Analysis of plan quality degradation allows for a quantitative assessment of the compromises in clinical plan quality as delivery efficiency is improved, in order to determine the optimal delivery settings. The technique is based on physician-determined quality degradation factors and can be extended to other clinical situations where investigation of various tradeoffs is warranted. PMID:23822412

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews

PubMed Central

2014-01-01

Background Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals. Methods We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review. Results Six reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion. Conclusions While most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings. PMID:24886159

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

PubMed

Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2017-04-01

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

PubMed

Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

2018-05-17

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing. Copyright © 2018 Elsevier B.V. All rights reserved.

TIL system with nonlinear phase conjugation

NASA Astrophysics Data System (ADS)

Khizhnyak, Anatoliy; Markov, Vladimir

2007-09-01

Efficient laser beam delivery on a distant target remains a key problem for practical implementation of tactical laser systems. Since the conventional target-in-the-loop (TIL) concept is generally not effective in such operational environments, new solutions are needed. In this report we discuss an innovative approach for effective compensation of laser beam aberrations in TIL systems. It is based on a recently devised technique that combines optical phase conjugation (OPC) with a TIL system for effective hot-spot formation. The proposed method should enable delivery of enhanced density laser energy to a target within a finite number of iteration cycles. Using the model based on an analogy between the TIL system and laser resonator, pointing of the laser beam on the target is performed at the image plane, resulting in reduced hot-spot formation time.

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.

PubMed

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-08-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a "smart needle" to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure.

Biodegradable polymer nanocarriers for therapeutic antisense microRNA delivery in living animals

NASA Astrophysics Data System (ADS)

Paulmurugan, Ramasamy; Sekar, Narayana M.; Sekar, Thillai V.

2012-03-01

MicroRNAs are endogenous regulators of gene expression, deregulated in several cellular diseases including cancer. Altering the cellular microenvironment by modulating the microRNAs functions can regulate different genes involved in major cellular processes, and this approach is now being investigated as a promising new generation of molecularly targeted anti-cancer therapies. AntagomiRs (Antisense-miRNAs) are a novel class of chemically modified stable oligonucleotides used for blocking the functions of endogenous microRNAs, which are overexpressed. A key challenge in achieving effective microRNAbased therapeutics lies in the development of an efficient delivery system capable of specifically delivering antisense oligonucleotides and target cancer cells in living animals. We are now developing an effective delivery system designed to selectively deliver antagomiR- 21 and antagomiR-10b to triple negative breast cancer cells, and to revert tumor cell metastasis and invasiveness. The FDA-approved biodegradable PLGA-nanoparticles were selected as a carrier for antagomiRs delivery. Chemically modified antagomiRs (antagomiR-21 and antagomiR-10b) were co-encapsulated in PEGylated-PLGA-nanoparticles by using the double-emulsification (W/O/W) solvent evaporation method, and the resulting average particle size of 150-200nm was used for different in vitro and in vivo experiments. The antagomiR encapsulated PLGA-nanoparticles were evaluated for their in vitro antagomiRs delivery, intracellular release profile, and antagomiRs functional effects, by measuring the endogenous cellular targets, and the cell growth and metastasis. The xenografts of tumor cells in living mice were used for evaluating the anti-metastatic and anti-invasive properties of cells. The results showed that the use of PLGA for antagomiR delivery is not only efficient in crossing cell membrane, but can also maintain functional intracellular antagomiRs level for a extended period of time and achieve therapeutic effect in living animals.

[Role of ST-analysis of fetal ECG in intrapartal fetus monitoring with presumed growth retardation].

PubMed

Hruban, L; Janků, P; Zahradnícková, J; Kurecová, B; Roztocil, A; Kachlík, P; Kucera, M; Jelenek, G

2006-07-01

Evaluation of the role of ST analysis of fetus ECG for early detection of developing acute hypoxia in the course of delivery of fetuses with presumed growth retardation. A comparison with present way of intrapartal fetus monitoring. Impact on the number of surgical births for indications of threatening fetus hypoxia. Influence of the method on perinatal results and postnatal adaptation of the newborns. A prospective study. Gynecology-Obstetrics Clinic, Masaryk University and Teaching Hospital Brno. Forty seven women with a growth retardation of the fetus diagnosed before delivery who gave birth in the Teaching Hospital in Brno during 2003-2005 and intrapartal ST analysis of fetus ECG was subsequently used, were enrolled into this prospective study (group A). The control group consisted of 87 deliveries taking place in the same period of time and concerning women with fetuses suffering from growth retardation and monitored by standard methods (group B). The standard methods included cardiotocography (CTG), supplemented with pulse oximetry (IFPO) if needed. The diagnosis of intrauterine fetus growth retardation was established on the basis of the results of repeated prepartal ultrasound fetus biometry with estimation of the mass, which corresponded to a group below 10 percentile for the given gestational age. The numbers of vaginal deliveries and surgically treated delivery due to threatening fetus hypoxia (Cesarean section, forceps delivery) were recorded. The authors evaluated postpartal pH from umbilical artery, independently for the group of values of pH < 7.00, the group of pH 7.00-0.10 and pH 7.10 or more. The values of Apgar score were evaluated for the first, fifth and tenth minute, respectively. The neonatologist followed the duration of stay of the newborn at the Newborn Intensive Care Unit, the Intermediate Care Unit, total duration of hospitalization, the occurrence of sepsis in the early newbotn period, the occurrence of hyperbilirubinemia, and the conclusion of neurological examination. All the results were evaluated statistically by the chi2 test, Kruskal-Wallis test or the Anova method. There was no statistically significantly difference in the number of delivery ended by surgery for threatening fetus hypoxia (p = 0.856) or the detection rate of intrapartal hypoxia according to pH values of umbilical blood divided into the three groups (p = 0.657, p = 0.958, p = 0.730, respectively). The values of Apgar score differed in favor of the group A significantly only in the first minute at the level of 5% opf significance (p = 0.018). The values of Apgar score in the fifth and tenth minute did not show any significant difference (P = 0301 and p = 0313, respectively). There was no statistically significant difference in neonatological results between the group A and B. The use of ST analysis of fetal ECG in the course of delivery of fetuses with presumed intrauterine growth retardation did not show any significant difference from the presently used methods (CTG supplemented with IFPO if needed). In using the method there was not any effect on the number of surgically treated deliveries for indications of threatening acute fetus hypoxia or perinatal results and postnatal adaptation of the newborns.

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

Research of Ultrasound-Mediated Transdermal Drug Delivery System Using Cymbal-Type Piezoelectric Composite Transducer

NASA Astrophysics Data System (ADS)

Huan, Huiting; Gao, Chunming; Liu, Lixian; Sun, Qiming; Zhao, Binxing; Yan, Laijun

2015-06-01

Transdermal drug delivery (TDD) implemented by especially low-frequency ultrasound is generally known as sonophoresis or phonophoresis which has drawn considerable wide attention. However, TDD has not yet achieved its full potential as an alternative to conventional drug delivery methods due to its bulky instruments. In this paper, a cymbal-type piezoelectric composite transducer (CPCT) which has advantages over a traditional ultrasound generator in weight, flexibility, and power consumption, is used as a substitute ultrasonicator to realize TDD. First, theoretical research on a CPCT based on the finite element analysis was carried out according to which a series of applicable CPCTs with bandwidths of 20 kHz to 100 kHz were elaborated. Second, a TDD experimental setup was built with previously fabricated CPCTs aimed at the administration of glucose. Finally, the TDD performance of glucose molecule transport in porcine skin was measured in vitro by quantifying the concentration of glucose, and the time variation curves were subsequently obtained. During the experiment, the driving wave form, frequency, and power consumption of the transducers were selected as the main elements which determined the efficacy of glucose delivery. The results indicate that the effectiveness of the CPCT-based delivery is constrained more by the frequency and intensity of ultrasound rather than the driving waveform. The light-weight, flexibility, and low-power consumption of a CPCT can potentially achieve effective TDD.

A novel self-assembled nanoparticle platform based on pectin-eight-arm polyethylene glycol-drug conjugates for co-delivery of anticancer drugs.

PubMed

Liu, Yanxue; Liu, Kefeng; Li, Xiaomin; Xiao, Shangzhen; Zheng, Dan; Zhu, Pengbo; Li, Chunxiao; Liu, Jing; He, Jing; Lei, Jiandu; Wang, Luying

2018-05-01

The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release. The obtained Pec-8PUH NPs possessed appropriate size (~91nm), drug-loaded efficiency and encapsulation efficiency through the regulation of eight-arm polyethylene glycol. In addition, Pec-8PUH NPs could enhance cell cytotoxicity, shorten blood retention time (7.3-fold UA, 7.2-fold HCPT) and more effective cellular uptake than free drugs, which exhibited an obvious synergistic effect of UA and HCPT by the co-delivery. 4T1 tumor-bearing mice also showed a higher survival rate than free UA and free HCPT. The result further shows that this novel drug delivery system has a promising potential for anti-cancer combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.

PubMed

Zeniya, Satoshi; Kuwahara, Hiroya; Daizo, Kaiichi; Watari, Akihiro; Kondoh, Masuo; Yoshida-Tanaka, Kie; Kaburagi, Hidetoshi; Asada, Ken; Nagata, Tetsuya; Nagahama, Masahiro; Yagi, Kiyohito; Yokota, Takanori

2018-05-17

Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. Our delivery strategy of modulating the tricellular tight junction in the blood-brain barrier via angubindin-1 provides a novel avenue of research for the development of antisense oligonucleotide-based therapeutics for the treatment of neurological disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Selective Gene Transfection of Individual Cells In Vitro with Plasmonic Nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina; Samaniego, Adam P.; Wen, Jianguo; Metelitsa, Leonid; Chang, Chung-Che; Lapotko, Dmitri

2011-01-01

Gene delivery and transfection of eukaryotic cells is widely used for research and for developing gene cell therapy. However, the existing methods lack selectivity, efficacy and safety when heterogeneous cell systems must be treated. We report a new method that employs plasmonic nanobubbles (PNBs) for delivery and transfection. A PNB is a novel, tunable cellular agent with a dual mechanical and optical action due to the formation of the vapor nanobubble around a transiently heated gold nanoparticle upon its exposure to a laser pulse. PNBs enabled the mechanical injection of the extracellular cDNA plasmid into the cytoplasm of individual target living cells, cultured leukemia cells and human CD34+CD117+ stem cells and expression of a green fluorescent protein (GFP) in those cells. PNB generation and lifetime correlated with the expression of green fluorescent protein in PNB-treated cells. Optical scattering by PNBs additionally provided the detection of the target cells and the guidance of cDNA injection at single cell level. In both cell models PNBs demonstrated a gene transfection effect in a single pulse treatment with high selectivity, efficacy and safety. Thus, PNBs provided targeted gene delivery at the single cell level in a single pulse procedure that can be used for safe and effective gene therapy. PMID:21315120

Selective gene transfection of individual cells in vitro with plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Samaniego, Adam P; Wen, Jianguo; Metelitsa, Leonid S; Chang, Chung-Che; Lapotko, Dmitri O

2011-06-10

Gene delivery and transfection of eukaryotic cells are widely used for research and for developing gene cell therapy. However, the existing methods lack selectivity, efficacy and safety when heterogeneous cell systems must be treated. We report a new method that employs plasmonic nanobubbles (PNBs) for delivery and transfection. A PNB is a novel, tunable cellular agent with a dual mechanical and optical action due to the formation of the vapor nanobubble around a transiently heated gold nanoparticle upon its exposure to a laser pulse. PNBs enabled the mechanical injection of the extracellular cDNA plasmid into the cytoplasm of individual target living cells, cultured leukemia cells and human CD34+ CD117+ stem cells and expression of a green fluorescent protein (GFP) in those cells. PNB generation and lifetime correlated with the expression of green fluorescent protein in PNB-treated cells. Optical scattering by PNBs additionally provided the detection of the target cells and the guidance of cDNA injection at single cell level. In both cell models PNBs demonstrated a gene transfection effect in a single pulse treatment with high selectivity, efficacy and safety. Thus, PNBs provided targeted gene delivery at the single cell level in a single pulse procedure that can be used for safe and effective gene therapy. Copyright © 2011 Elsevier B.V. All rights reserved.

Efficient femtosecond driven SOX 17 delivery into mouse embryonic stem cells: differentiation studies

NASA Astrophysics Data System (ADS)

Thobakgale, Lebogang; Manoto, Sello Lebohang; Lemboumba, Satuurnin Ombinda; Maaza, Malik; Mthunzi-Kufa, Patience

2017-02-01

Embryonic stem cells have great promise in regenerative medicine because of their ability to self-renew and differentiate into various cell types. Delivery of therapeutic genes into cells has already been achieved using of chemical agents and viral vectors with high transfection efficiencies. However, these methods have also been documented as toxic and in the latter case they can cause latent cell infections. In this study we use femtosecond laser pulses to optically deliver genetic material in mouse embryonic stem cells. Femtosecond laser pulses in contrast to the conventional approach, minimises the risk of unwanted side effects because photons are used to create transient pores on the membrane which allow free entry of molecules with no need for delivery agents. Using an Olympus microscope, fluorescence imaging of the samples post irradiation was performed and decreased expression of stage specific embryonic antigen one (SSEA-1) consistent with on-going cellular differentiation was observed. Our results also show that femtosecond laser pulses were effective in delivering SOX 17 plasmid DNA (pSOX17) which resulted in the differentiation of mouse embryonic stem cells into endoderm cells. We thus concluded that laser transfection of stem cells for the purpose of differentiation, holds potential for applications in tissue engineering as a method of generating new cell lines.

Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models

PubMed Central

Shoji, Takuhiro; Saito, Ryuta; Chonan, Masashi; Shibahara, Ichiyo; Sato, Aya; Kanamori, Masayuki; Sonoda, Yukihiko; Kondo, Toru; Ishii, Naoto; Tominaga, Teiji

2016-01-01

Background Glioblastoma is one of the most malignant brain tumors in adults and has a dismal prognosis. In a previous report, we reported that CD40, a TNF-R-related cell surface receptor, and its ligand CD40L were associated with glioma outcomes. Here we attempted to activate CD40 signaling in the tumor and determine if it exerted therapeutic efficacy. Methods CD40 expression was examined in 3 mouse glioma cell lines (GL261, NSCL61, and bRiTs-G3) and 5 human glioma cell lines (U87, U251, U373, T98, and A172). NSCL61 and bRiTs-G3, as glioma stem cells, also expressed the glioma stem cell markers MELK and CD44. In vitro, we demonstrated direct antitumor effects of an anti-CD40 agonistic monoclonal antibody (FGK45) against the cell lines. The efficacy of FGK45 was examined by local convection-enhanced delivery of the monoclonal antibody against each glioma model. Results CD40 was expressed in all mouse and human cell lines tested and was found at the cell membrane of each of the 3 mouse cell lines. FGK45 administration induced significant, direct antitumor effects in vitro. The local delivery of FGK45 significantly prolonged survival compared with controls in the NSCL61 and bRiTs-G3 models, but the effect was not significant in the GL261 model. Increases in apoptosis and CD4+ and CD8+ T cell infiltration were observed in the bRiTs-G3 model after FGK45 treatment. Conclusions Local delivery of FGK45 significantly prolonged survival in glioma stem cell models. Thus, local delivery of this monoclonal antibody is promising for immunotherapy against gliomas. PMID:26917236

Project Delivery Methods.

ERIC Educational Resources Information Center

Dolan, Thomas G.

2003-01-01

Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

Skin Permeabilization for Transdermal Drug Delivery: Recent Advances and Future Prospects

PubMed Central

Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert

2014-01-01

Introduction Transdermal delivery has potential advantages over other routes of administration. It could reduce first-pass metabolism associated with oral delivery and is less painful than injections. However, the outermost layer of the skin, the stratum corneum (SC), limits passive diffusion to small lipophilic molecules. Therefore, methods are needed to safely permeabilize the SC so that ionic and larger molecules may be delivered transdermally. Areas Covered This review focuses on low-frequency sonophoresis, microneedles, electroporation and iontophoresis, and combinations of these methods to permeabilize the SC. The mechanisms of enhancement and developments in the last five years are discussed. Potentially high-impact applications, including protein delivery, vaccination, and sensing, are presented. Finally, commercial interest and clinical trials are discussed. Expert Opinion Not all permeabilization methods are appropriate for all applications. Focused studies into applications utilizing the advantages of each method are needed. The total dose and kinetics of delivery must be considered. Vaccination is one application where permeabilization methods could make an impact. Protein delivery and analyte sensing are also areas of potential impact, although the amount of material that can be delivered (or extracted) is of critical importance. Additional work on the miniaturization of these technologies will help to increase commercial interest. PMID:24392787

Does the Method of Instruction Matter? An Experimental Examination of Information Literacy Instruction in the Online, Blended, and Face-to-Face Classrooms

ERIC Educational Resources Information Center

Anderson, Karen; May, Frances A.

2010-01-01

The researchers, a librarian and a faculty member, collaborated to investigate the effectiveness of delivery methods in information literacy instruction. The authors conducted a field experiment to explore how face-to-face, online, and blended learning instructional formats influenced students' retention of information literacy skills. Results are…

Local drug delivery agents as adjuncts to endodontic and periodontal therapy

PubMed Central

Puri, K; Puri, N

2013-01-01

Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes

NASA Astrophysics Data System (ADS)

Tang, Shengnan; Gao, Dawei; Zhao, Tingting; Zhou, Jing; Zhao, Xiaoning

2013-06-01

The effective delivery of oleanolic acid (OA) to the target site has several benefits in therapy for different pathologies. However, the delivery of OA is challenging due to its poor aqueous solubility. The study aims to evaluate the tumor inhibition effect of the PEGylated OA nanoliposome on the U14 cervical carcinoma cell line. In our previous study, OA was successfully encapsulated into PEGylated liposome with the modified ethanol injection method. Oral administration of PEGylated OA liposome was demonstrated to be more efficient in inhibiting xenograft tumors. The results of organ index indicated that PEG liposome exhibited higher anti-tumor activity and lower cytotoxicity. It was also found that OA and OA liposomes induced tumor cell apoptosis detected by flow cytometry. Furthermore, effects of OA on the morphology of tumor and other tissues were observed by hematoxylin and eosin staining. The histopathology sections did not show pathological changes in kidney or liver in tested mice. In contrast, there was a significant difference in tumor tissues between treatment groups and the negative control group. These observations imply that PEGylated liposomes seem to have advantages for cancer therapy in terms of effective delivery of OA.

Presetting ECG electrodes for earlier heart rate detection in the delivery room.

PubMed

Gulati, Rashmi; Zayek, Michael; Eyal, Fabien

2018-07-01

To determine whether heart rate (HR) could be detected earlier than by pulse oximeter (POX), using a novel method of application of electrocardiogram (ECG) electrodes during neonatal resuscitation in the delivery room. ECG electrodes were set before delivery to be applied to the back of infants' thorax. Time to detect HR was recorded as soon as a numerical HR along with a recognizable and persistent QRS complex was observed on ECG monitor (HRECG) and a plethysmographic waveform was seen on POX monitor (HRPOX). Out of 334 infants, 49 were <31 weeks of gestational age. Overall, the median (interquartile range, IQR) time to detect HRECG was significantly shorter [29 (5, 60) seconds] than time by POX [60 (45,120) seconds], (p < 0.001). Similarly, in <31-week infants, the median (IQR) time to detect HRECG was 10 (2, 40) seconds compared to 60 (30,120) seconds by POX, (p < 0.001). Failure to have HR detected by 1 minute occurred in 30%, 54% and 20% of infants by ECG, POX and either of the devices, respectively. In the delivery room, electrodes applied by the study method are more effective than pulse oximetry in providing the neonatal team with timely HR information that is necessary for proper resuscitative actions. Published by Elsevier B.V.

[Methods and Applications to estimate the conversion factor of Resource-Based Relative Value Scale for nurse-midwife's delivery service in the national health insurance].

PubMed

Kim, Jinhyun; Jung, Yoomi

2009-08-01

This paper analyzed alternative methods of calculating the conversion factor for nurse-midwife's delivery services in the national health insurance and estimated the optimal reimbursement level for the services. A cost accounting model and Sustainable Growth Rate (SGR) model were developed to estimate the conversion factor of Resource-Based Relative Value Scale (RBRVS) for nurse-midwife's services, depending on the scope of revenue considered in financial analysis. The data and sources from the government and the financial statements from nurse-midwife clinics were used in analysis. The cost accounting model and SGR model showed a 17.6-37.9% increase and 19.0-23.6% increase, respectively, in nurse-midwife fee for delivery services in the national health insurance. The SGR model measured an overall trend of medical expenditures rather than an individual financial status of nurse-midwife clinics, and the cost analysis properly estimated the level of reimbursement for nurse-midwife's services. Normal vaginal delivery in nurse-midwife clinics is considered cost-effective in terms of insurance financing. Upon a declining share of health expenditures on midwife clinics, designing a reimbursement strategy for midwife's services could be an opportunity as well as a challenge when it comes to efficient resource allocation.

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

NASA Technical Reports Server (NTRS)

Meyer, Peter F.; Oddsson, Lars I E.

2003-01-01

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes-Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. ( approximately 10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. ( approximately 246 mN) and averaged 4.97 a.u. ( approximately 92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.

A comparison of online versus face-to-face teaching delivery in statistics instruction for undergraduate health science students.

PubMed

Lu, Fletcher; Lemonde, Manon

2013-12-01

The objective of this study was to assess if online teaching delivery produces comparable student test performance as the traditional face-to-face approach irrespective of academic aptitude. This study involves a quasi-experimental comparison of student performance in an undergraduate health science statistics course partitioned in two ways. The first partition involves one group of students taught with a traditional face-to-face classroom approach and the other through a completely online instructional approach. The second partition of the subjects categorized the academic aptitude of the students into groups of higher and lower academically performing based on their assignment grades during the course. Controls that were placed on the study to reduce the possibility of confounding variables were: the same instructor taught both groups covering the same subject information, using the same assessment methods and delivered over the same period of time. The results of this study indicate that online teaching delivery is as effective as a traditional face-to-face approach in terms of producing comparable student test performance but only if the student is academically higher performing. For academically lower performing students, the online delivery method produced significantly poorer student test results compared to those lower performing students taught in a traditional face-to-face environment.

Five years of lesson modification to implement non-traditional learning sessions in a traditional-delivery curriculum: A retrospective assessment using applied implementation variables.

PubMed

Gleason, Shaun E; McNair, Bryan; Kiser, Tyree H; Franson, Kari L

Non-traditional learning (NTL), including aspects of self-directed learning (SDL), may address self-awareness development needs. Many factors can impact successful implementation of NTL. To share our multi-year experience with modifications that aim to improve NTL sessions in a traditional curriculum. To improve understanding of applied implementation variables (some of which were based on successful SDL implementation components) that impact NTL. We delivered a single lesson in a traditional-delivery curriculum once annually for five years, varying delivery annually in response to student learning and reaction-to-learning results. At year 5, we compared student learning and reaction-to-learning to applied implementation factors using logistic regression. Higher instructor involvement and overall NTL levels predicted correct exam responses (p=0.0007 and p<0.0001, respectively). Exam responses were statistically equivalent between the most traditional and highest overall NTL deliveries. Students rated instructor presentation skills and teaching methods higher when greater instructor involvement (p<0.0001, both) and lower overall NTL levels (P<0.0001, both) were used. Students perceived that teaching methods were most effective when lower student involvement and higher technology levels (p<0.0001, both) were used. When implementing NTL sessions as a single lesson in a traditional-delivery curriculum, instructor involvement appears essential, while the impact of student involvement and educational technology levels varies. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-D-201-04: Study On the Impact of Tumor Shape and Size On Drug Delivery to Pancreatic Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soltani, M; Bazmara, H; Sefidgar, M

Purpose: Drug delivery to solid tumors can be expressed physically using transport phenomena such as convection and diffusion for the drug of interest within extracellular matrices. We aimed to carefully model these phenomena, and to investigate the effect of tumor shape and size on drug delivery to solid tumors in the pancreas. Methods: In this study, multiple tumor geometries as obtained from clinical PET/CT images were considered. An advanced numerical method was used to simultaneously solve fluid flow and solute transport equations. Data from n=45 pancreatic cancer patients with non-resectable locoregional disease were analyzed, and geometrical information from the tumorsmore » including size, shape, and aspect ratios were classified. To investigate effect of tumor shape, tumors with similar size but different shapes were selected and analyzed. Moreover, to investigate effect of tumor size, tumors with similar shapes but different sizes, ranging from 1 to 77 cm{sup 3}, were selected and analyzed. A hypothetical tumor similar to one of the analyzed tumors, but scaled to reduce its size below 0.2 cm{sup 3}, was also analyzed. Results: The results showed relatively similar average drug concentration profiles in tumors with different sizes. Generally, smaller tumors had higher absolute drug concentration. In the hypothetical tumor, with volume less than 0.2 cm{sup 3}, the average drug concentration was 20% higher in comparison to its counterparts. For the various real tumor geometries, however, the maximum difference between average drug concentrations was 10% for the smallest and largest tumors. Moreover, the results demonstrated that for pancreatic tumors the shape is not significant. The negligible difference of drug concentration in different tumor shapes was due to the minimum effect of convection in pancreatic tumors. Conclusion: In tumors with different sizes, smaller tumors have higher drug delivery; however, the impact of tumor shape in the case of pancreatic tumors is not significant.« less

Non-pharmacological self-management for people living with migraine or tension-type headache: a systematic review including analysis of intervention components.

PubMed

Probyn, Katrin; Bowers, Hannah; Mistry, Dipesh; Caldwell, Fiona; Underwood, Martin; Patel, Shilpa; Sandhu, Harbinder Kaur; Matharu, Manjit; Pincus, Tamar

2017-08-11

To assess the effect of non-pharmacological self-management interventions against usual care, and to explore different components and delivery methods within those interventions PARTICIPANTS: People living with migraine and/or tension-type headache INTERVENTIONS: Non-pharmacological educational or psychological self-management interventions; excluding biofeedback and physical therapy.We assessed the overall effectiveness against usual care on headache frequency, pain intensity, mood, headache-related disability, quality of life and medication consumption in meta-analysis.We also provide preliminary evidence on the effectiveness of intervention components and delivery methods. We found a small overall effect for the superiority of self-management interventions over usual care, with a standardised mean difference (SMD) of -0.36 (-0.45 to -0.26) for pain intensity; -0.32 (-0.42 to -0.22) for headache-related disability, 0.32 (0.20 to 0.45) for quality of life and a moderate effect on mood (SMD=0.53 (-0.66 to -0.40)). We did not find an effect on headache frequency (SMD=-0.07 (-0.22 to 0.08)).Assessment of components and characteristics suggests a larger effect on pain intensity in interventions that included explicit educational components (-0.51 (-0.68 to -0.34) vs -0.28 (-0.40 to -0.16)); mindfulness components (-0.50 (-0.82 to -0.18) vs 0.34 (-0.44 to -0.24)) and in interventions delivered in groups vs one-to-one delivery (0.56 (-0.72 to -0.40) vs -0.39 (-0.52 to -0.27)) and larger effects on mood in interventions including a cognitive-behavioural therapy (CBT) component with an SMD of -0.72 (-0.93 to -0.51) compared with those without CBT -0.41 (-0.58 to -0.24). Overall we found that self-management interventions for migraine and tension-type headache are more effective than usual care in reducing pain intensity, mood and headache-related disability, but have no effect on headache frequency. Preliminary findings also suggest that including CBT, mindfulness and educational components in interventions, and delivery in groups may increase effectiveness. PROSPERO 2016:CRD42016041291. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Course Evaluation: Reconfigurations for Learning with Learning Management Systems

ERIC Educational Resources Information Center

Park, Ji Yong

2014-01-01

The introduction of online delivery platforms such as learning management systems (LMS) in tertiary education has changed the methods and modes of curriculum delivery and communication. While course evaluation methods have also changed from paper-based in-class-administered methods to largely online-administered methods, the data collection…

Localized Hyperthermia for Enhanced Targeted Delivery of Polymer Therapeutics

NASA Astrophysics Data System (ADS)

Frazier, Nicholas

It is estimated that in 2016, more than 848,000 new cases of cancer will be diagnosed in men with more than a quarter being prostate cancer and more than 26,000 deaths attributed to this disease. Prostate cancer poses a limited risk when detected at an early stage and treatment of stages II-III has a 5-year survival rate of almost 100%. However, these early-stage cancers can eventually progress and develop into stage IV, dramatically dropping the 5-year survival rate to 28%. Thus, development of a new therapy is needed to fully eliminate these tumors. Combination of heat and chemotherapy improves therapeutic efficacy while allowing for reduced dosing of drugs and limiting side effects. Localized hyperthermia has been used to enhance the delivery of polymer therapeutics to prostate tumors through increased blood flow, vascular permeability, and incorporation of heat shock targeting. This strategy has been shown to increase the delivery and retention of polymer-drug conjugates leading to enhanced efficacy. Although much work has been done using this strategy, the effects of different thermal dosing on polymer accumulation are unknown. The first aim of this research is to examine how altering heating parameters influences polymer tumor accumulation. The hypothesis for this aim is that there is an optimal thermal treatment that leads to the maximal amount of polymer accumulation in the tumors. Additionally, the previously used heating method of plasmonic photothermal therapy (PPTT) can result in long-term accumulation of gold nanoparticles in healthy organs, potentially limiting clinical applicability. The second aim of this proposal will be focused on investigating the alternative method of high intensity focused ultrasound (HIFU) for selective heating of tumors and enhancing macromolecular delivery. HIFU has shown the capability for precise, noninvasive heating of specific regions within the prostate through magnetic resonance imaging (MRI) guidance. The hypothesis to be tested in this aim is that mild hyperthermia produced with HIFU will have the same effect as that produced by PPTT in improving the delivery of macromolecular systems to solid tumors. Finally, in the third aim, the enhanced delivery of targeted polymer therapeutics to prostate tumors in mice models will be investigated using mild hyperthermia produced with HIFU. In the long term, it is anticipated that HIFU can be used in conjunction with delivery of polymer-drug conjugates for enhanced efficacy and reduced toxicity of chemotherapy to produce a clinically relevant treatment of advanced prostate cancer.

Overcoming ocular drug delivery barriers through the use of physical forces.

PubMed

Huang, Di; Chen, Ying-Shan; Rupenthal, Ilva D

2018-02-15

Overcoming the physiological barriers in the eye remains a key obstacle in the field of ocular drug delivery. While ocular barriers naturally have a protective function, they also limit drug entry into the eye. Various pharmaceutical strategies, such as novel formulations and physical force-based techniques, have been investigated to weaken these barriers and transport therapeutic agents effectively to both the anterior and the posterior segments of the eye. This review summarizes and discusses the recent research progress in the field of ocular drug delivery with a focus on the application of physical methods, including electrical fields, sonophoresis, and microneedles, which can enhance penetration efficiency by transiently disrupting the ocular barriers in a minimally or non-invasive manner. Copyright © 2017 Elsevier B.V. All rights reserved.

In-flight food delivery and waste collection service: the passengers’ perspective and potential improvement

NASA Astrophysics Data System (ADS)

Romli, F. I.; Rahman, K. Abdul; Ishak, F. D.

2016-10-01

Increased competition in the commercial air transportation industry has made service quality of the airlines as one of the key competitive measures to attract passengers against their rivals. In-flight services, particularly food delivery and waste collection, have a notable impact on perception of the overall airline's service quality because they are directly and interactively provided to passengers during flight. An online public survey is conducted to explore general passengers' perception of current in-flight food delivery and waste collection services, and to identify potential rooms for improvement. The obtained survey results indicate that in-flight service does have an effect on passengers' choice of airlines. Several weaknesses of the current service method and possible improvements have been established from the collected responses.

Biomimetic proteolipid vesicles for targeting inflamed tissues

NASA Astrophysics Data System (ADS)

Molinaro, R.; Corbo, C.; Martinez, J. O.; Taraballi, F.; Evangelopoulos, M.; Minardi, S.; Yazdi, I. K.; Zhao, P.; De Rosa, E.; Sherman, M. B.; de Vita, A.; Toledano Furman, N. E.; Wang, X.; Parodi, A.; Tasciotti, E.

2016-09-01

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles--which we refer to as leukosomes--retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Effective in vitro and in vivo gene delivery by the combination of liposomal bubbles (bubble liposomes) and ultrasound exposure.

PubMed

Suzuki, Ryo; Maruyama, Kazuo

2010-01-01

Gene delivery with a physical mechanism using ultrasound (US) and nano/microbubbles is expected as an ideal system in terms of delivering plasmid DNA noninvasively into a specific target site. We developed novel liposomal bubbles (Bubble liposomes (BLs)) containing the lipid nanobubbles of perfluoropropane which were utilized for contrast enhancement in ultrasonography. BLs were smaller in diameter than conventional microbubbles and induced cavitation upon exposure ultrasound. In addition, when coupled with US exposure, BLs could deliver plasmid DNA into various types of cells in vitro and in vivo. The transfection efficiency with BLs and US was higher than that with conventional lipofection method. Therefore, the combination of BLs and US might be an efficient and novel nonviral gene delivery system.

Research and Development Project Summaries, October 1991

DTIC Science & Technology

1991-10-01

delivery methods, training cost reduction, demonstration of technology’ effectiveness, and the reduction of acquisition risk . The majority of the work...demonstrations, risk reduction developments, and cost-effectiveness investigations in simulator and training technologzv. This advanced development program is a...systems. The program is organized around specific demonstration tasks that target critical technical risks that confront future weapons system

Videoconferencing a Stroke Assessment Training Workshop: Effectiveness, Acceptability, and Cost

ERIC Educational Resources Information Center

Miller, Patricia A.; Huijbregts, Maria; French, Esme; Taylor, Denise; Reinikka, Kirsti; Berezny, Laura; Fry, Sherri; Grunin, Anna; Harvey, Melissa

2008-01-01

Introduction: Videoconferencing (VC) is becoming a common method for the delivery of continuing education (CE) to clinicians in remote locations. The purpose of this study was to compare the effectiveness, acceptability, and costs of a full-day training workshop (TW) delivered through two different formats: face-to-face (FTF) and VC. The TW was…

Leukocytes as carriers for targeted cancer drug delivery.

PubMed

Mitchell, Michael J; King, Michael R

2015-03-01

Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues.

Leukocytes as carriers for targeted cancer drug delivery

PubMed Central

Mitchell, Michael J

2017-01-01

Introduction Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. Areas covered This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Expert opinion Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues. PMID:25270379

Obstetric outcomes of pre-induction of labor with a 200 μg misoprostol vaginal insert.

PubMed

Jagielska, Iwona; Kazdepka-Ziemińska, Anita; Tyloch, Małgorzata; Sopońska-Brzoszczyk, Paulina; Nowak, Karina; Dziedzic, Dawid; Dzikowska, Ewa; Grabiec, Marek

2017-01-01

Labor induction is indicated in 20% to 40% of pregnancies. Over half of pregnancies qualified for the induction of labor require stimulation of the cervix to ripen. The drug used increasingly more often in pre-induction is the PGE-1 pros-taglandin analog - misoprostol 200 μg. The study includes a total of 100 patients qualified for labor pre-induction with Misodel® (miso-prostol 200 μg vaginal insert). The study group comprises two subgroups: primigravidas and multiparas. Assessments included: indications for labor pre-induction, time from Misodel application to delivery, caesarean section rate and indica-tions, duration of first and second stage of labor, rate of vaginal deliveries, need for oxytocin or fenoterol administration side effects and newborn condition. The most common indication for labor induction was gestational diabetes and pregnancy past term. The average time to vaginal delivery was 14 h 45 min, time to the onset of active phase of labor - 11 h 45 min, time to membranes' rupture - 15 h, time to vaginal delivery - 14 h 18 min. The times of multiparas were significantly shorter. The rate of vaginal deliveries within 12 hours amounted to 42.42%, while within 24 hours it reached 83.33%. The overall caesarean section rate was 33%. The most common indication for caesarean section was the risk of intrauterine hypoxia. Tachysystole and hyperstimulation was observed in 4% of cases, while abnormalities in the cardiotocographic tracing in 43%. Misodel is an effective method for labor pre-induction, without affecting the caesarean section rate and has no adverse effect on the newborn condition.

Fiber coupled optical spark delivery system

DOEpatents

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

Physically facilitating drug-delivery systems

PubMed Central

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

PROPEL: implementation of an evidence based pelvic floor muscle training intervention for women with pelvic organ prolapse: a realist evaluation and outcomes study protocol.

PubMed

Maxwell, Margaret; Semple, Karen; Wane, Sarah; Elders, Andrew; Duncan, Edward; Abhyankar, Purva; Wilkinson, Joyce; Tincello, Douglas; Calveley, Eileen; MacFarlane, Mary; McClurg, Doreen; Guerrero, Karen; Mason, Helen; Hagen, Suzanne

2017-12-22

Pelvic Organ Prolapse (POP) is estimated to affect 41%-50% of women aged over 40. Findings from the multi-centre randomised controlled "Pelvic Organ Prolapse PhysiotherapY" (POPPY) trial showed that individualised pelvic floor muscle training (PFMT) was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. However, provision of PFMT for prolapse continues to vary across the UK, with limited numbers of women's health physiotherapists specialising in its delivery. Implementation of this robust evidence from the POPPY trial will require attention to different models of delivery (e.g. staff skill mix) to fit with differing care environments. A Realist Evaluation (RE) of implementation and outcomes of PFMT delivery in contrasting NHS settings will be conducted using multiple case study sites. Involving substantial local stakeholder engagement will permit a detailed exploration of how local sites make decisions on how to deliver PFMT and how these lead to service change. The RE will track how implementation is working; identify what influences outcomes; and, guided by the RE-AIM framework, will collect robust outcomes data. This will require mixed methods data collection and analysis. Qualitative data will be collected at four time-points across each site to understand local contexts and decisions regarding options for intervention delivery and to monitor implementation, uptake, adherence and outcomes. Patient outcome data will be collected at baseline, six months and one year follow-up for 120 women. Primary outcome will be the Pelvic Organ Prolapse Symptom Score (POP-SS). An economic evaluation will assess the costs and benefits associated with different delivery models taking account of further health care resource use by the women. Cost data will be combined with the primary outcome in a cost effectiveness analysis, and the EQ-5D-5L data in a cost utility analysis for each of the different models of delivery. Study of the implementation of varying models of service delivery of PFMT across contrasting sites combined with outcomes data and a cost effectiveness analysis will provide insight into the implementation and value of different models of PFMT service delivery and the cost benefits to the NHS in the longer term.

How does tele-learning compare with other forms of education delivery? A systematic review of tele-learning educational outcomes for health professionals.

PubMed

Tomlinson, Jo; Shaw, Tim; Munro, Ana; Johnson, Ros; Madden, D Lynne; Phillips, Rosemary; McGregor, Deborah

2013-11-01

Telecommuniciation technologies, including audio and videoconferencing facilities, afford geographically dispersed health professionals the opportunity to connect and collaborate with others. Recognised for enabling tele-consultations and tele-collaborations between teams of health care professionals and their patients, these technologies are also well suited to the delivery of distance learning programs, known as tele-learning. To determine whether tele-learning delivery methods achieve equivalent learning outcomes when compared with traditional face-to-face education delivery methods. A systematic literature review was commissioned by the NSW Ministry of Health to identify results relevant to programs applying tele-learning delivery methods in the provision of education to health professionals. The review found few studies that rigorously compared tele-learning with traditional formats. There was some evidence, however, to support the premise that tele-learning models achieve comparable learning outcomes and that participants are generally satisfied with and accepting of this delivery method. The review illustrated that tele-learning technologies not only enable distance learning opportunities, but achieve comparable learning outcomes to traditional face-to-face models. More rigorous evidence is required to strengthen these findings and should be the focus of future tele-learning research.

Gene Delivery to Postnatal Rat Brain by Non-ventricular Plasmid Injection and Electroporation

PubMed Central

Molotkov, Dmitry A.; Yukin, Alexey Y.; Afzalov, Ramil A.; Khiroug, Leonard S.

2010-01-01

Creation of transgenic animals is a standard approach in studying functions of a gene of interest in vivo. However, many knockout or transgenic animals are not viable in those cases where the modified gene is expressed or deleted in the whole organism. Moreover, a variety of compensatory mechanisms often make it difficult to interpret the results. The compensatory effects can be alleviated by either timing the gene expression or limiting the amount of transfected cells. The method of postnatal non-ventricular microinjection and in vivo electroporation allows targeted delivery of genes, siRNA or dye molecules directly to a small region of interest in the newborn rodent brain. In contrast to conventional ventricular injection technique, this method allows transfection of non-migratory cell types. Animals transfected by means of the method described here can be used, for example, for two-photon in vivo imaging or in electrophysiological experiments on acute brain slices. PMID:20972387

Mother's milk and the muffin man: grassroots innovations in medical marijuana delivery systems.

PubMed

Chapkis, Wendy; Webb, Richard J

2005-01-01

In the ongoing debates over medical marijuana, opponents often conflate the alleged risks of cannabis therapeutics with the acknowledged harms associated with smoking. Although smoking is the most widely used method of administering marijuana, it is not the only available means. This paper provides an account of the production, distribution, and administration of non-smokable cannabis products by members of a California health care collective, the Wo/Men's Alliance for Medical Marijuana. WAMM has developed a variety of alternative methods of administering cannabis orally and externally that challenge the rhetorical equivalence between smoking as a delivery method and botanical marijuana as a medicine. Their experience with low-cost and low-tech production techniques has enabled even the poor and uninsured among them to manage the debilitating symptoms of their illnesses and the side-effects of their often onerous courses of treatment, without smoking. The organization provides an informative example of.

Integrating technology into radiologic science education.

PubMed

Wertz, Christopher Ira; Hobbs, Dan L; Mickelsen, Wendy

2014-01-01

To review the existing literature pertaining to the current learning technologies available in radiologic science education and how to implement those technologies. Only articles from peer-reviewed journals and scholarly reports were used in the research for this review. The material was further restricted to those articles that emphasized using new learning technologies in education, with a focus on radiologic science education. Teaching in higher education is shifting from a traditional classroom-based lecture format to one that incorporates new technologies that allow for more varied and diverse educational models. Radiologic technology educators must adapt traditional education delivery methods to incorporate current technologies. Doing so will help engage the modern student in education in ways in which they are already familiar. As students' learning methods change, so must the methods of educational delivery. The use of new technologies has profound implications for education. If implemented properly, these technologies can be effective tools to help educators.

Electro-osmotically driven liquid delivery method and apparatus

DOEpatents

Rakestraw, D.J.; Anex, D.S.; Yan, C.; Dadoo, R.; Zare, R.N.

1999-08-24

Method and apparatus are disclosed for controlling precisely the composition and delivery of liquid at sub-{micro}L/min flow rate. One embodiment of such a delivery system is an electro-osmotically driven gradient flow delivery system that generates dynamic gradient flows with sub-{micro}L/min flow rates by merging a plurality of electro-osmotic flows. These flows are delivered by a plurality of delivery arms attached to a mixing connector, where they mix and then flow into a receiving means, preferably a column. Each inlet of the plurality of delivery arms is placed in a corresponding solution reservoir. A plurality of independent programmable high-voltage power supplies is used to apply a voltage program to each of the plurality of solution reservoirs to regulate the electro-osmotic flow in each delivery arm. The electro-osmotic flow rates in the delivery arms are changed with time according to each voltage program to deliver the required gradient profile to the column. 4 figs.

The Effect of the Air-Delivery Method on Parameters of the Precessing Vortex Core in a Hydrodynamic Vortex Chamber

NASA Astrophysics Data System (ADS)

Alekseenko, S. V.; Shtork, S. I.; Yusupov, R. R.

2018-03-01

The effect of the method of gas-phase injection into a swirled fluid flow on parameters of a precessing vortex core is studied experimentally. Conditions of the appearance of the vortex-core precession effect were modeled in a hydrodynamic sudden expansion vortex chamber. The dependences of the vortexcore precession frequency, flow-pulsation level, and full pressure differential in the vortex chamber on the consumption gas content in the flow have been obtained. The results of measurements permit one to determine optimum conditions for the most effective control of vortex-core precession.

45 CFR 605.22 - Existing facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., assignment of aides to beneficiaries, home visits, delivery of health, welfare, or other social services at... changes in existing facilities where other methods are effective in achieving compliance with paragraph (a... in the most integrated setting appropriate. (c) Small health, welfare, or other social service...

45 CFR 605.22 - Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., assignment of aides to beneficiaries, home visits, delivery of health, welfare, or other social services at... changes in existing facilities where other methods are effective in achieving compliance with paragraph (a... in the most integrated setting appropriate. (c) Small health, welfare, or other social service...

34 CFR 104.22 - Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., delivery of health, welfare, or other social services at alternate accessible sites, alteration of existing... not required to make structural changes in existing facilities where other methods are effective in... handicapped persons in the most integrated setting appropriate. (c) Small health, welfare, or other social...

Laser beam uniformity and stability using homogenizer-based fiber optic launch method: square core fiber delivery

NASA Astrophysics Data System (ADS)

Lizotte, Todd E.

2011-03-01

Over the years, technological achievements within the laser medical diagnostic, treatment, and therapy markets have led to ever increasing requirements for greater control of critical laser beam parameters. Increased laser power/energy stabilization, temporal and spatial beam shaping and flexible laser beam delivery systems with ergonomic focusing or imaging lens systems are sought by leading medical laser system producers. With medical procedures that utilize laser energy, there is a constant emphasis on reducing adverse effects that come about by the laser itself or its optical system, but even when these variables are well controlled the medical professional will still need to deal with the multivariate nature of the human body. Focusing on the variables that can be controlled, such as accurate placement of the laser beam where it will expose a surface being treated as well as laser beam shape and uniformity is critical to minimizing adverse conditions. This paper covers the use of fiber optic beam delivery as a means of defining the beam shape (intensity/power distribution uniformity) at the target plane as well as the use of fiber delivery as a means to allow more flexible articulation of the laser beam over the surface being treated. The paper will present a new concept of using a square core fiber beam delivery design utilizing a unique micro lens array (MLA) launch method that improves the overall stability of the system, by minimizing the impact of the laser instability. The resulting performance of the prototype is presented to demonstrate its stability in comparison to simple lens launch techniques, with an emphasis on homogenization and articulated fiber delivery.

Selective gene silencing by viral delivery of short hairpin RNA

PubMed Central

2010-01-01

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells. PMID:20858246

Educating the delivery of bad news in medicine: Preceptorship versus simulation

PubMed Central

Jacques, Andrew P; Adkins, Eric J; Knepel, Sheri; Boulger, Creagh; Miller, Jessica; Bahner, David P

2011-01-01

Simulation experiences have begun to replace traditional education models of teaching the skill of bad news delivery in medical education. The tiered apprenticeship model of medical education emphasizes experiential learning. Studies have described a lack of support in bad news delivery and inadequacy of training in this important clinical skill as well as poor familial comprehension and dissatisfaction on the part of physicians in training regarding the resident delivery of bad news. Many residency training programs lacked a formalized training curriculum in the delivery of bad news. Simulation teaching experiences may address these noted clinical deficits in the delivery of bad news to patients and their families. Unique experiences can be role-played with this educational technique to simulate perceived learner deficits. A variety of scenarios can be constructed within the framework of the simulation training method to address specific cultural and religious responses to bad news in the medical setting. Even potentially explosive and violent scenarios can be role-played in order to prepare physicians for these rare and difficult situations. While simulation experiences cannot supplant the model of positive, real-life clinical teaching in the delivery of bad news, simulation of clinical scenarios with scripting, self-reflection, and peer-to-peer feedback can be powerful educational tools. Simulation training can help to develop the skills needed to effectively and empathetically deliver bad news to patients and families in medical practice. PMID:22229135

Educating the delivery of bad news in medicine: Preceptorship versus simulation.

PubMed

Jacques, Andrew P; Adkins, Eric J; Knepel, Sheri; Boulger, Creagh; Miller, Jessica; Bahner, David P

2011-07-01

Simulation experiences have begun to replace traditional education models of teaching the skill of bad news delivery in medical education. The tiered apprenticeship model of medical education emphasizes experiential learning. Studies have described a lack of support in bad news delivery and inadequacy of training in this important clinical skill as well as poor familial comprehension and dissatisfaction on the part of physicians in training regarding the resident delivery of bad news. Many residency training programs lacked a formalized training curriculum in the delivery of bad news. Simulation teaching experiences may address these noted clinical deficits in the delivery of bad news to patients and their families. Unique experiences can be role-played with this educational technique to simulate perceived learner deficits. A variety of scenarios can be constructed within the framework of the simulation training method to address specific cultural and religious responses to bad news in the medical setting. Even potentially explosive and violent scenarios can be role-played in order to prepare physicians for these rare and difficult situations. While simulation experiences cannot supplant the model of positive, real-life clinical teaching in the delivery of bad news, simulation of clinical scenarios with scripting, self-reflection, and peer-to-peer feedback can be powerful educational tools. Simulation training can help to develop the skills needed to effectively and empathetically deliver bad news to patients and families in medical practice.

Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats.

PubMed

Yokoo, T; Kamimura, K; Suda, T; Kanefuji, T; Oda, M; Zhang, G; Liu, D; Aoyagi, Y

2013-08-01

The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml(-1)) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone.

Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

PubMed Central

Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

2012-01-01

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern

NASA Astrophysics Data System (ADS)

Ding, Weifeng; Wang, Feng; Zhang, Jianfeng; Guo, Yibing; Ju, Shaoqing; Wang, Huimin

2013-09-01

The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery costitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings.

Comparative effectiveness of faecal microbiota transplant by route of administration.

PubMed

Gundacker, N D; Tamhane, A; Walker, J B; Morrow, C D; Rodriguez, J M

2017-08-01

The optimal route of delivery for faecal microbiota transplant (FMT) is unknown. This observational single-centre study analysed the two-week cure rates for all patients who received FMT from 2013 to 2016 according to route of delivery. Overall, nasogastric delivery of FMT was less effective than lower endoscopic delivery. When patients were stratified by illness severity, nasogastric delivery achieved similar cure rates in healthier individuals, whereas lower endoscopic delivery was preferred for relatively ill individuals. Nasogastric delivery may be less effective than lower endoscopic delivery; however, when taking the cost, preparation and potential risk into account, this difference may not be clinically significant for patients with mild disease. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.