Patient-centredness in integrated healthcare delivery systems - needs, expectations and priorities for organised healthcare systems

PubMed Central

Juhnke, Christin; Mühlbacher, Axel C.

2013-01-01

Introduction Patient-centred healthcare is becoming a more significant success factor in the design of integrated healthcare systems. The objective of this study is to structure a patient-relevant hierarchy of needs and expectations for the design of organised healthcare delivery systems. Methods A questionnaire with 84 items was conducted with N = 254 healthcare experts and N = 670 patients. Factor analyses were performed using SPSS©18. The number of factors retained was controlled by Kaiser's criterion, validation of screeplots and interpretability of the items. Cronbach's α was used to assess the internal consistency of the subscales. Results Exploratory factor analysis led to 24 factors in the expert sample and 20 in the patient sample. After analysing the screeplots, confirmatory factor analyses were computed for 7-factor solutions accounting for 42.963% of the total variance and Kaiser–Meyer–Olkin of 0.914 for the patients (experts: 38.427%, Kaiser–Meyer–Olkin = 0.797). Cronbach's α ranged between 0.899 and 0.756. Based on the analysis, coordinated care could be differentiated into seven dimensions: access, data and information, service and infrastructure, professional care, interpersonal care, individualised care, continuity and coordination. Conclusion and Discussion The study provides insight into patient and experts expectations towards the organisation of integrated healthcare delivery systems. If providers and payers can take into account patient needs and expectations while implementing innovative healthcare delivery systems, greater acceptance and satisfaction will be achieved. In the best case, this will lead to better adherence resulting in better clinical outcomes. PMID:24363639

Factors Influencing Solar Electric Propulsion Vehicle Payload Delivery for Outer Planet Missions

NASA Technical Reports Server (NTRS)

Cupples, Michael; Green, Shaun; Coverstone, Victoria

2003-01-01

Systems analyses were performed for missions utilizing solar electric propulsion systems to deliver payloads to outer-planet destinations. A range of mission and systems factors and their affect on the delivery capability of the solar electric propulsion system was examined. The effect of varying the destination, the trip time, the launch vehicle, and gravity-assist boundary conditions was investigated. In addition, the affects of selecting propulsion system and power systems characteristics (including primary array power variation, number of thrusters, thruster throttling mode, and thruster Isp) on delivered payload was examined.

Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy.

PubMed

Suzuki, Kazumichi; Gillin, Michael T; Sahoo, Narayan; Zhu, X Ronald; Lee, Andrew K; Lippy, Denise

2011-07-01

To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 +/- 35 patients. This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer's disease.

PubMed

Lauzon, Marc-Antoine; Daviau, Alex; Marcos, Bernard; Faucheux, Nathalie

2015-05-28

The number of people diagnosed with Alzheimer's disease (AD) is increasing steadily as the world population ages, thus creating a huge socio-economic burden. Current treatments have only transient effects and concentrate on a single aspect of AD. There is much evidence suggesting that growth factors (GFs) have a great therapeutic potential and can play on all AD hallmarks. Because GFs are prone to denaturation and clearance, a delivery system is required to ensure protection and a sustainable delivery. This review provides information about the latest advances in the development of GF delivery systems (GFDS) targeting the brain in terms of in vitro and in vivo effects in the context of AD and discusses new strategies designed to increase the availability and the specificity of GFs to the brain. This paper also discusses, on a mechanistic level, the different delivery hurdles encountered by the carrier or the GF itself from its injection site up to the brain tissue. The major mass transport phenomena influencing the delivery systems targeting the brain are addressed and insights are given about how mechanistic mathematical frameworks can be developed to use and optimize them. Copyright © 2015. Published by Elsevier B.V.

Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis

NASA Astrophysics Data System (ADS)

Rocker, Adam John

Cardiovascular disease remains as the leading cause of death worldwide and is frequently associated with partial or full occlusion of coronary arteries. Currently, angioplasty and bypass surgery are the standard approaches for treating patients with these ischemic heart conditions. However, a large number of patients cannot undergo these procedures. Therapeutic angiogenesis provides a minimally invasive tool for treating cardiovascular diseases by inducing new blood vessel growth from the existing vasculature. Angiogenic growth factors can be delivered locally through gene, cell, and protein therapy. Natural and synthetic polymer growth factor delivery systems are under extensive investigation due their widespread applications and promising therapeutic potential. Although biocompatible, natural polymers often suffer from batch-to-batch variability which can cause unpredictable growth factor release rates. Synthetic polymers offer advantages for growth factor delivery as they can be easily modified to control release kinetics. During the angiogenesis process, vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation while platelet-derived growth factor (PDGF) is needed later to help stabilize and mature new vessels. In the setting of myocardial infarction, additional anti-inflammatory cytokines like IL-10 are needed to help optimize cardiac repair and limit the damaging effects of inflammation following infarction. To meet these angiogenic and anti-inflammatory needs, an injectable polymer delivery system created from a sulfonated reverse thermal gel encapsulating micelle nanoparticles was designed and evaluated. The sulfonate groups on the thermal gel electrostatically bind to VEGF which controls its release rate, while the micelles are loaded with PDGF and are slowly released as the gel degrades. IL-10 was loaded into the system as well and diffused from the gel over time. An in vitro release study was performed which demonstrated the sequential release capabilities of the polymer system. The ability of the polymer system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response which showed that the polymer delivery system demonstrated a significant increase in functional and mature vessel formation while significantly reducing inflammation.

A Titan Explorer Mission Utilizing Solar Electric Propulsion and Chemical Propulsion Systems

NASA Technical Reports Server (NTRS)

Cupples, Michael; Coverstone, Vicki

2003-01-01

Mission and Systems analyses were performed for a Titan Explorer Mission scenario utilizing medium class launch vehicles, solar electric propulsion system (SEPS) for primary interplanetary propulsion, and chemical propulsion for capture at Titan. An examination of a range of system factors was performed to determine their affect on the payload delivery capability to Titan. The effect of varying the launch vehicle, solar array power, associated number of SEPS thrusters, chemical propellant combinations, tank liner thickness, and tank composite overwrap stress factor was investigated. This paper provides a parametric survey of the aforementioned set of system factors, delineating their affect on Titan payload delivery, as well as discussing aspects of planetary capture methodology.

Tumor Targeting and Drug Delivery by Anthrax Toxin.

PubMed

Bachran, Christopher; Leppla, Stephen H

2016-07-01

Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

PubMed

Izadifar, Mohammad; Haddadi, Azita; Chen, Xiongbiao; Kelly, Michael E

2015-01-09

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs. Identifying and understanding such factors as the desired release profiles, mechanisms of release, physicochemical characteristics of polymeric nanoparticles, and externally-triggering stimuli are essential for designing and optimizing such delivery systems. This review surveys the recent studies on the desired release profiles of GFs in various tissue engineering applications, elucidates the major release mechanisms and critical factors affecting release profiles, and overviews the role played by the mathematical models for optimizing nano-particulate delivery systems. Potentials of stimuli responsive nanoparticles for spatiotemporal control of GF release are also presented, along with the recent advances in strategies for spatiotemporal control of GF delivery within tissue engineered scaffolds. The recommendation for the future studies to overcome challenges for developing sophisticated particulate delivery systems in tissue engineering is discussed prior to the presentation of conclusions drawn from this paper.

Double emulsion electrospun nanofibers as a growth factor delivery vehicle for salivary gland regeneration

NASA Astrophysics Data System (ADS)

Foraida, Zahraa I.; Sharikova, Anna; Peerzada, Lubna N.; Khmaladze, Alexander; Larsen, Melinda; Castracane, James

2017-08-01

Sustained delivery of growth factors, proteins, drugs and other biologically active molecules is necessary for tissue engineering applications. Electrospun fibers are attractive tissue engineering scaffolds as they partially mimic the topography of the extracellular matrix (ECM). However, they do not provide continuous nourishment to the tissue. In search of a biomimetic scaffold for salivary gland tissue regeneration, we previously developed a blend nanofiber scaffold composed of the protein elastin and the synthetic polymer polylactic-co-glycolic acid (PLGA). The nanofiber scaffold promoted in vivo-like salivary epithelial cell tissue organization and apicobasal polarization. However, in order to enhance the salivary cell proliferation and biomimetic character of the scaffold, sustained growth factor delivery is needed. The composite nanofiber scaffold was optimized to act as a growth factor delivery system using epidermal growth factor (EGF) as a model protein. The nanofiber/EGF hybrid nanofibers were synthesized by double emulsion electrospinning where EGF is emulsified within a water/oil/water (w/o/w) double emulsion system. Successful incorporation of EGF was confirmed using Raman spectroscopy. EGF release profile was characterized using enzyme-linked immunosorbent assay (ELIZA) of the EGF content. Double emulsion electrospinning resulted in slower release of EGF. We demonstrated the potential of the proposed double emulsion electrospun nanofiber scaffold for the delivery of growth factors and/or drugs for tissue engineering and pharmaceutical applications.

Harnessing the potential of biomaterials for brain repair after stroke

NASA Astrophysics Data System (ADS)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Systemic delivery of factor IX messenger RNA for protein replacement therapy

PubMed Central

Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

2017-01-01

Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

Angiogenic therapy for cardiac repair based on protein delivery systems.

PubMed

Formiga, F R; Tamayo, E; Simón-Yarza, T; Pelacho, B; Prósper, F; Blanco-Prieto, M J

2012-05-01

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

PubMed

Gurram, A K; Deshpande, P B; Kar, S S; Nayak, Usha Y; Udupa, N; Reddy, M S

2015-01-01

Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

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.

Nanomedicine and its application in treatment of microglia-mediated neuroinflammation.

PubMed

Baby, N; Patnala, R; Ling, Eng-Ang; Dheen, S T

2014-01-01

Nanomedicine, an emerging therapeutic tool in current medical frontiers, offers targeted drug delivery for many neurodegenerative disorders. Neuroinflammation, a hallmark of many neurodegenerative disorders, is mediated by microglia, the resident immunocompetent cells of the central nervous system (CNS). Microglial cells respond to various stimuli in the CNS resulting in their activation which may have a beneficial or a detrimental effect. In general, the activated microglia remove damaged neurons and infectious agents by phagocytosis, therefore being neuroprotective. However, their chronic activation exacerbates neuronal damage through excessive release of proinflammatory cytokines, chemokines and other inflammatory mediators which contribute to neuroinflammation and subsequent neurodegeneration in the CNS. Hence, controlling microglial inflammatory response and their proliferation has been considered as an important aspect in treating neurodegenerative disorders. Regulatory factors that control microglial activation and proliferation also play an important role in microglia-mediated neuroinflammation and neurotoxicity. Various anti-inflammatory drugs and herbal compounds have been identified in treating microglia-mediated neuroinflammation in the CNS. However, hurdles in crossing blood brain barrier (BBB), expression of metabolic enzymes, presence of efflux pumps and several other factors prevent the entry of these drugs into the CNS. Use of non-degradable delivery systems and microglial activation in response to the drug delivery system further complicate drug delivery to the CNS. Nanomedicine, a nanoparticle-mediated drug delivery system, exhibits immense potential to overcome these hurdles in drug delivery to the CNS enabling new alternatives with significant promises in revolutionising the field of neurodegenerative disease therapy. This review attempts to summarise various regulatory factors in microglia, existing therapeutic strategies in controlling microglial activation, and how nanotechnology can serve to improve the delivery of therapeutic drugs across the BBB for treating microglia- mediated neuroinflammation and neurodegeneration.

Managerial process improvement: a lean approach to eliminating medication delivery.

PubMed

Hussain, Aftab; Stewart, LaShonda M; Rivers, Patrick A; Munchus, George

2015-01-01

Statistical evidence shows that medication errors are a major cause of injuries that concerns all health care oganizations. Despite all the efforts to improve the quality of care, the lack of understanding and inability of management to design a robust system that will strategically target those factors is a major cause of distress. The paper aims to discuss these issues. Achieving optimum organizational performance requires two key variables; work process factors and human performance factors. The approach is that healthcare administrators must take in account both variables in designing a strategy to reduce medication errors. However, strategies that will combat such phenomena require that managers and administrators understand the key factors that are causing medication delivery errors. The authors recommend that healthcare organizations implement the Toyota Production System (TPS) combined with human performance improvement (HPI) methodologies to eliminate medication delivery errors in hospitals. Despite all the efforts to improve the quality of care, there continues to be a lack of understanding and the ability of management to design a robust system that will strategically target those factors associated with medication errors. This paper proposes a solution to an ambiguous workflow process using the TPS combined with the HPI system.

Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation

PubMed Central

Kim, Sungwoo; Kang, Yunqing; Krueger, Chad A.; Sen, Milan; Holcomb, John B.; Chen, Di; Wenke, Joseph C.; Yang, Yunzhi

2012-01-01

The purpose of this study was to develop and characterize a chitosan gel/gelatin microspheres (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system than other treatments (p<0.05) after a week of culture. PMID:22293583

Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

PubMed

Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

2018-04-16

Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

Advancements in ocular drug delivery.

PubMed

Weiner, Alan L; Gilger, Brian C

2010-11-01

This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed. © 2010 American College of Veterinary Ophthalmologists.

Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

NASA Astrophysics Data System (ADS)

Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

2016-06-01

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

Introducing vouchers for malaria prevention in Ghana and Tanzania: context and adoption of innovation in health systems.

PubMed

de Savigny, Don; Webster, Jayne; Agyepong, Irene Akua; Mwita, Alex; Bart-Plange, Constance; Baffoe-Wilmot, Aba; Koenker, Hannah; Kramer, Karen; Brown, Nick; Lengeler, Christian

2012-10-01

There are striking similarities in health system and other contexts between Tanzania and Ghana that are relevant to the scaling up of continuous delivery of insecticide treated nets (ITNs) for malaria prevention. However, specific contextual factors of relevance to ITN delivery have led implementation down very different pathways in the two countries. Both countries have made major efforts and investments to address this intervention through integrating consumer discount vouchers into the health system. Discount vouchers require arrangements among the public, private and non-governmental sectors and constitute a complex intervention in both health systems and business systems. In Tanzania, vouchers have moved beyond the planning agenda, had policies and programmes formulated, been sustained in implementation at national scale for many years and have become as of 2012 the main and only publicly supported continuous delivery system for ITNs. In Ghana national-scale implementation of vouchers never progressed beyond consideration on the agenda and piloting towards formulation of policy; and the approach was replaced by mass distribution campaigns with less dependency on or integration with the health system. By 2011, Ghana entered a phase with no publicly supported continuous delivery system for ITNs. To understand the different outcomes, we compared the voucher programme timelines, phases, processes and contexts in both countries in reference to the main health system building blocks (governance, human resources, financing, informatics, technologies and service delivery). Contextual factors which provided an enabling environment for the voucher scheme in Tanzania did not do so in Ghana. The voucher scheme was never seen as an appropriate national strategy, other delivery systems were not complementary and the private sector was under-developed. The extensive time devoted to engagement and consensus building among all stakeholders in Tanzania was an important and clearly enabling difference, as was public sector support of the private sector. This contributed to the alignment of partner action behind a single co-ordinated strategy at service delivery level which in turn gave confidence to the business sector and avoided the 'interference' of competing delivery systems that occurred in Ghana. Principles of systems thinking for intervention design correctly emphasize the importance of enabling contexts and stakeholder management.

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

PubMed Central

Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

2012-01-01

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

Acceptability of potential rectal microbicide delivery systems for HIV prevention: a randomized crossover trial.

PubMed

Pines, Heather A; Gorbach, Pamina M; Weiss, Robert E; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A; Cranston, Ross D

2013-03-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.

Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

PubMed Central

Gorbach, Pamina M.; Weiss, Robert E.; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A.; Cranston, Ross D.

2012-01-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use. PMID:23114512

Growth factor delivery: How surface interactions modulate release in vitro and in vivo

PubMed Central

King, William J.; Krebsbach, Paul H.

2013-01-01

Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

Recent advances in oral pulsatile drug delivery.

PubMed

Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

2009-01-01

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Prioritization of Evidence-Based Preventive Health Services During Periodic Health Examinations

PubMed Central

Shires, Deirdre A.; Stange, Kurt C.; Divine, George; Ratliff, Scott; Vashi, Ronak; Tai-Seale, Ming; Lafata, Jennifer Elston

2011-01-01

Background Delivery of preventive services sometimes falls short of guideline recommendations. Purpose To evaluate the multilevel factors associated with evidence-based preventive service delivery during periodic health examinations (PHE). Methods Primary care physicians were recruited from an integrated delivery system in southeast Michigan. Office visit audio-recordings of PHE visits conducted from 2007–2009 were used to ascertain physician recommendation for or delivery of 19 guideline-recommended preventive services. Alternating logistic regression was used to evaluate factors associated with service delivery. Data analyses were completed in 2011. Results Among 484 PHE visits to 64 general internal medicine and family physicians by insured patients aged 50–80 years, there were 2662 services for which patients were due; 54% were recommended or delivered. Regression analyses indicated that the likelihood of service delivery decreased with patient age and with each concern the patient raised, and increased with increasing BMI and with each additional minute after scheduled appointment time the physician first presented. The likelihood was greater with patient/physician gender concordance and less if the physician used the electronic medical record in the exam room and had seen the patient in the past 12 months. Conclusions A combination of patient, physician, visit and contextual factors are associated with preventive service delivery. Additional studies are warranted to understand the complex interplay of factors that support and compromise preventive service delivery. PMID:22261213

Predictors of maternal health services utilization by poor, rural women: a comparative study in Indian States of Gujarat and Tamil Nadu.

PubMed

Vora, Kranti Suresh; Koblinsky, Sally A; Koblinsky, Marge A

2015-07-31

India leads all nations in numbers of maternal deaths, with poor, rural women contributing disproportionately to the high maternal mortality ratio. In 2005, India launched the world's largest conditional cash transfer scheme, Janani Suraksha Yojana (JSY), to increase poor women's access to institutional delivery, anticipating that facility-based birthing would decrease deaths. Indian states have taken different approaches to implementing JSY. Tamil Nadu adopted JSY with a reorganization of its public health system, and Gujarat augmented JSY with the state-funded Chiranjeevi Yojana (CY) scheme, contracting with private physicians for delivery services. Given scarce evidence of the outcomes of these approaches, especially in states with more optimal health indicators, this cross-sectional study examined the role of JSY/CY and other healthcare system and social factors in predicting poor, rural women's use of maternal health services in Gujarat and Tamil Nadu. Using the District Level Household Survey (DLHS)-3, the sample included 1584 Gujarati and 601 Tamil rural women in the lowest two wealth quintiles. Multivariate logistic regression analyses examined associations between JSY/CY and other salient health system, socio-demographic, and obstetric factors with three outcomes: adequate antenatal care, institutional delivery, and Cesarean-section. Tamil women reported greater use of maternal healthcare services than Gujarati women. JSY/CY participation predicted institutional delivery in Gujarat (AOR = 3.9), but JSY assistance failed to predict institutional delivery in Tamil Nadu, where mothers received some cash for home births under another scheme. JSY/CY assistance failed to predict adequate antenatal care, which was not incentivized. All-weather road access predicted institutional delivery in both Tamil Nadu (AOR = 3.4) and Gujarat (AOR = 1.4). Women's education predicted institutional delivery and Cesarean-section in Tamil Nadu, while husbands' education predicted institutional delivery in Gujarat. Overall, assistance from health financing schemes, good road access to health facilities, and socio-demographic and obstetric factors were associated with differential use of maternity health services by poor, rural women in the two states. Policymakers and practitioners should promote financing schemes to increase access, including consideration of incentives for antenatal care, and address health system and social factors in designing state-level interventions to promote safe motherhood.

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

PubMed

Zhang, Rui Xue; Li, Jason; Zhang, Tian; Amini, Mohammad A; He, Chunsheng; Lu, Brian; Ahmed, Taksim; Lip, HoYin; Rauth, Andrew M; Wu, Xiao Yu

2018-05-01

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

PubMed Central

Nguyen, Minh Khanh; Alsberg, Eben

2014-01-01

Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years. PMID:25242831

Bridging the Silos of Service Delivery for High-Need, High-Cost Individuals.

PubMed

Sherry, Melissa; Wolff, Jennifer L; Ballreich, Jeromie; DuGoff, Eva; Davis, Karen; Anderson, Gerard

2016-12-01

Health care reform efforts that emphasize value have increased awareness of the importance of nonmedical factors in achieving better care, better health, and lower costs in the care of high-need, high-cost individuals. Programs that care for socioeconomically disadvantaged, high-need, high-cost individuals have achieved promising results in part by bridging traditional service delivery silos. This study examined 5 innovative community-oriented programs that are successfully coordinating medical and nonmedical services to identify factors that stimulate and sustain community-level collaboration and coordinated care across silos of health care, public health, and social services delivery. The authors constructed a conceptual framework depicting community health systems that highlights 4 foundational factors that facilitate community-oriented collaboration: flexible financing, shared leadership, shared data, and a strong shared vision of commitment toward delivery of person-centered care.

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

Examining fiscal federalism, regionalization and community-based initiatives in Canada's health care delivery system.

PubMed

Forest, Pierre-Gerlier; Palley, Howard A

2008-01-01

This study focuses on the ability of Canadian provinces to shape in different ways the development of various provincial health delivery systems within the constraints of the mandates of the federal Canada Health Act of 1984 and the fiscal revenues that the provinces receive if they comply with these mandates. In so doing, it will examine the operation of Canadian federalism with respect to various provincial health systems. This study applies a comparative analysis framework developed by Heisler and Peters to facilitate an understanding of the dimensionality of provincial health delivery systems as applied to the case of provincial regionalization and community-based initiatives. The three sets of relationships touched upon are: first, the levels of government and the nature of their involvement in public policy concerning the provincial health care delivery systems; and secondly, understanding of the factors influencing provincial governments' political dispositions to act in various directions. A third dimension that is taken are the factors influencing the "timing" of particular decisions. A fourth area noted by Heisler and Peters and other comparative analysts is the nature and characteristics of public and private sector activities in health care and other social policy areas. While the evolving nature of public and private sector health care delivery activities within Canada's provincial and territorial systems is a significant policy matter in the Canadian context, due to the space limitations of this article, they are not discussed herein.

Calcium phosphate ceramics in drug delivery

NASA Astrophysics Data System (ADS)

Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

2011-04-01

Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

[Integrated delivery systems in California--success and failure determining factors for the first 10 years and impetus for Germany].

PubMed

Janus, K; Amelung, V E

2004-10-01

Since the coming into effect of the Health Care Modernization Act (Gesundheitsmodernisierungsgesetz) the conditions for integrated health care delivery are favourable in Germany. However, comprehensive approaches are a long time in coming. In contrast, integrated health care delivery as an integral part of the spreading of managed care entered a further stage of development, which enables health care decision makers to draw conclusions regarding the further development of integrated health care delivery in Germany. Based on case studies integrated delivery systems in the San Francisco Bay Area have been analyzed with the objective to evaluate pitfalls and successful strategies for integrated health care delivery. The major pitfalls refer to an insufficient local focus, a lack of actual integration and the application of per capita reimbursement (which is a key subject on the political agenda in Germany as well) within integrated delivery systems. On the contrary, successful strategies include achieving a dynamic tension between centralized and decentralized coordination, internal and external relationship management, well organised human resource management including a well-defined corporate policy and a comprehensive implementation of information technology. Based on US experiences with integrated delivery systems implications for the design of integrated health care delivery in Germany are discussed.

[Incidence of and related risk factors on preterm delivery among HIV-infected pregnant women in China].

PubMed

Wang, Ailing; Wang, Xiaoyan; Dou, Lixia; Wang, Fang; Wang, Qian; Qiao, Yaping; Su, Min; Jin, Xi

2015-04-01

To measure the incidence rates of preterm delivery in HIV-infected pregnant women and to explore related potential risk factors. Data from 'Information System of Prevention of Mother-to-child Transmission of HIV Management in China, 2013' was used in the study. Information regarding demographic characteristics, pregnancy, HIV relevant situations and pregnancy outcomes related to these HIV-infected pregnant women, were extracted and analyzed. Incidence of preterm delivery was calculated with related potential risk factors explored. 3 913 HIV-infected pregnant women were involved in this study, including 336 of them having undergone preterm deliveries (8.6%). Results from univariate and multivariate analyses showed that preterm delivery was associated with factors as: maternal age, ethnicity, education, being migrant, pregnancy hypertension, multiple pregnancy and times of antenatal care visits (P < 0.05) of the pregnant women. Compared with those who contracted the HIV infection through drug injection, the ones who were infected through other routes suffered fewer preterm deliveries (adjusted OR = 0.562, 95% CI: 0.360-0.879). Pregnant women who received antiretroviral therapy either between 14 to 27 gestational weeks or during the period of less than 14, were more likely to experience preterm delivery, comparison to those who did not receive the therapy during pregnancy. The adjusted ORs were 1.712 (95% CI: 1.196-2.451) and 1.862 (95% CI: 1.261-2.749), respectively. Preterm delivery was a common adverse outcome during pregnancy among HIV-infected women in China. Other than traditionally known risk factors, routes of transmission and the use of antiretroviral therapy might also be associated with the increased risks for preterm delivery.

Waste Feed Delivery System Phase 1 Preliminary Reliability and Availability and Maintainability Analysis [SEC 1 and 2

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

CARLSON, A.B.

The document presents updated results of the preliminary reliability, availability, maintainability analysis performed for delivery of waste feed from tanks 241-AZ-101 and 241-AN-105 to British Nuclear Fuels Limited, inc. under the Tank Waste Remediation System Privatization Contract. The operational schedule delay risk is estimated and contributing factors are discussed.

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

Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus.

PubMed

Hamady, Zaed Z R; Scott, Nigel; Farrar, Mark D; Lodge, J Peter A; Holland, Keith T; Whitehead, Terence; Carding, Simon R

2010-04-01

Human growth factors are potential therapeutic agents for various inflammatory disorders affecting the gastrointestinal tract. However, they are unstable when administered orally and systemic administration requires high doses increasing the risk of unwanted side effects. Live microorganism-based delivery systems can overcome these problems although they suffer from the inability to control heterologous protein production and there are concerns regarding biosafety and environmental contamination. To overcome these limitations we have developed a new live bacteria drug-delivery system using the human commensal gut bacterium Bacteroides ovatus engineered to secrete human growth factors in response to dietary xylan. The anaerobic nature of B ovatus provides an inherent biosafety feature. B ovatus strains expressing human keratinocyte growth factor-2, which plays a central role in intestinal epithelial homeostasis and repair (BO-KGF), were generated by homologous recombination and evaluated using the dextran sodium sulfate (DSS)-induced model of intestinal epithelial injury and colitis. In response to xylan BO-KGF produced biologically active KGF both in vitro and in vivo. In DSS treated mice administration of xylan and BO-KGF had a significant therapeutic effect in reducing weight loss, improving stool consistency, reducing rectal bleeding, accelerating healing of damaged epithelium, reducing inflammation and neutrophil infiltration, reducing expression of pro-inflammatory cytokines, and accelerating production of goblet cells. BO-KGF and xylan treatment also had a marked prophylactic effect limiting the development of inflammation and disruption of the epithelial barrier. This novel, diet-regulated, live bacterial drug delivery system may be applicable to treating various bowel disorders.

Factors Influencing Health Facility Delivery in Predominantly Rural Communities across the Three Ecological Zones in Ghana: A Cross-Sectional Study

PubMed Central

Enuameh, Yeetey Akpe Kwesi; Okawa, Sumiyo; Asante, Kwaku Poku; Kikuchi, Kimiyo; Mahama, Emmanuel; Ansah, Evelyn; Tawiah, Charlotte; Adjei, Kwame; Shibanuma, Akira; Nanishi, Keiko; Yeji, Francis; Agyekum, Enoch Oti; Yasuoka, Junko; Gyapong, Margaret; Oduro, Abraham Rexford; Quansah Asare, Gloria; Hodgson, Abraham; Jimba, Masamine; Owusu-Agyei, Seth

2016-01-01

Background Maternal and neonatal mortality indicators remain high in Ghana and other sub-Saharan African countries. Both maternal and neonatal health outcomes improve when skilled personnel provide delivery services within health facilities. Determinants of delivery location are crucial to promoting health facility deliveries, but little research has been done on this issue in Ghana. This study explored factors influencing delivery location in predominantly rural communities in Ghana. Methods Data were collected from 1,500 women aged 15–49 years with live or stillbirths that occurred between January 2011 and April 2013. This was done within the three sites operating Health and Demographic Surveillance Systems, i.e., the Dodowa (Greater Accra Region), Kintampo (Brong Ahafo Region), and Navrongo (Upper-East Region) Health Research Centers in Ghana. Multivariable logistic regression was used to identify the determinants of delivery location, controlling for covariates that were statistically significant in univariable regression models. Results Of 1,497 women included in the analysis, 75.6% of them selected health facilities as their delivery location. After adjusting for confounders, the following factors were associated with health facility delivery across all three sites: healthcare provider’s influence on deciding health facility delivery, (AOR = 13.47; 95% CI 5.96–30.48), place of residence (AOR = 4.49; 95% CI 1.14–17.68), possession of a valid health insurance card (AOR = 1.90; 95% CI 1.29–2.81), and socio-economic status measured by wealth quintiles (AOR = 2.83; 95% CI 1.43–5.60). Conclusion In addition to known factors such as place of residence, socio-economic status, and possession of valid health insurance, this study identified one more factor associated with health facility delivery: healthcare provider’s influence. Ensuring care provider’s counseling of clients could improve the uptake of health facility delivery in rural communities in Ghana. PMID:27031301

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.

Mesoporous silicate nanoparticles/3D nanofibrous scaffold-mediated dual-drug delivery for bone tissue engineering.

PubMed

Yao, Qingqing; Liu, Yangxi; Selvaratnam, Balaranjan; Koodali, Ranjit T; Sun, Hongli

2018-04-09

Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF). Therefore, we developed a novel mesoporous silicate nanoparticles (MSNs) incorporated-3D nanofibrous gelatin (GF) scaffold for dual-delivery of BMP2 and deferoxamine (DFO). DFO is a hypoxia-mimetic drug that can activate hypoxia-inducible factor-1 alpha (HIF-1α), and trigger subsequent angiogenesis. Sustained BMP2 release system was achieved through encapsulation into large-pored MSNs, while the relative short-term release of DFO was engineered through covalent conjugation with chitosan to reduce its cytotoxicity and elongate its half-life. Both MSNs and DFO were incorporated onto a porous 3D GF scaffold to serve as a biomimetic osteogenic microenvironment. Our data indicated that DFO and BMP2 were released from a scaffold at different release rates (10 vs 28 days) yet maintained their angiogenic and osteogenic ability, respectively. Importantly, our data indicated that the released DFO significantly improved BMP2-induced osteogenic differentiation where the dose/duration was important for its effects in both mouse and human stem cell models. Thus, we developed a novel and tunable MSNs/GF 3D scaffold-mediated dual-drug delivery system and studied the potential application of the both FDA-approved DFO and BMP2 for bone tissue engineering. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Modena, Tiziana; Conti, Bice; Benazzo, Francesco; Gastaldi, Giulia; Genta, Ida

2017-01-01

A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue regeneration. This mini-review is focused on the combination of the local delivery of antibiotic agents with bone regenerative therapy for the treatment of a severe bone infection such as osteomyelitis. The review includes a brief explanation of scaffolds for bone regeneration including scaffolds characteristics and types, a focus on severe bone infections (especially osteomyelitis and its treatment), and a literature review of local antibiotic delivery by the combination of scaffolds and drug-delivery systems. Some examples related to published studies on gentamicin sulfate-loaded drug-delivery systems combined with scaffolds are discussed, and future perspectives are highlighted. PMID:29231857

The Role of Telecommunications in the Regional Delivery of Education Services: A Study of the Potential Use of Instructional Television for Vocational Education in the Appalachian States.

ERIC Educational Resources Information Center

INTASA, Inc., Menlo Park, CA.

This report documents a research project focusing on the role of telecommunications technology in the regional delivery of educational services, including assessment of needs, factors in choosing the technology for implementation, alternative delivery systems, cost analysis, and a study of possible demonstration projects in South Carolina,…

A Native American Community with a 7% Cesarean Delivery Rate: Does Case Mix, Ethnicity, or Labor Management Explain the Low Rate?

PubMed Central

Leeman, Lawrence; Leeman, Rebecca

2003-01-01

PURPOSE Cesarean delivery rates vary widely across populations. Studying communities with low rates of cesarean delivery may identify practices that can lower the cesarean rate. METHODS A population-based historical cohort study included all pregnant women (N = 1132) from 1992 through 1996 in a predominantly Native American region of northwestern New Mexico known to have a high prevalence of gestational diabetes and preeclampsia. The outcomes studied included delivery type (eg, cesarean, operative vaginal, spontaneous vaginal), indication for cesarean delivery, presence of obstetrical risk factors, and use of labor induction or augmentation. RESULTS The cesarean delivery rate of the study group (7.3%) was only 35% of the 1996 US rate of 20.7%. Among study participants, the relative risk of a primary cesarean delivery for dystocia was 0.22 (95% CI, 0.14, 0.35). Trial of labor after cesarean delivery was attempted by 93% of study participants compared with 42% of women nationwide in 1994. The cesarean delivery rates for women with diabetes in pregnancy (11.5% versus 35.4%) and preeclampsia (14.8% versus 37.4%) were significantly lower than nationwide rates. Case-mix analysis comparison with a standardized population and comparison of standard (ie, term, singleton, vertex) primiparous women demonstrate that the low rate of cesarean delivery was not because of a lower prevalence of risk factors. CONCLUSIONS The community’s low rate of cesarean delivery is primarily the result of a decreased use of cesarean delivery for labor dystocia and an almost universal acceptance of trial of labor after cesarean delivery. Cultural attitudes toward childbirth, design of the perinatal system, and genetic factors also may explain the low rate of cesarean delivery. PMID:15043178

A Native American community with a 7% cesarean delivery rate: does case mix, ethnicity, or labor management explain the low rate?

PubMed

Leeman, Lawrence; Leeman, Rebecca

2003-01-01

Cesarean delivery rates vary widely across populations. Studying communities with low rates of cesarean delivery may identify practices that can lower the cesarean rate. A population-based historical cohort study included all pregnant women (N = 1132) from 1992 through 1996 in a predominantly Native American region of northwestern New Mexico known to have a high prevalence of gestational diabetes and preeclampsia. The outcomes studied included delivery type (eg, cesarean, operative vaginal, spontaneous vaginal), indication for cesarean delivery, presence of obstetrical risk factors, and use of labor induction or augmentation. The cesarean delivery rate of the study group (7.3%) was only 35% of the 1996 US rate of 20.7%. Among study participants, the relative risk of a primary cesarean delivery for dystocia was 0.22 (95% CI, 0.14, 0.35). Trial of labor after cesarean delivery was attempted by 93% of study participants compared with 42% of women nationwide in 1994. The cesarean delivery rates for women with diabetes in pregnancy (11.5% versus 35.4%) and preeclampsia (14.8% versus 37.4%) were significantly lower than nationwide rates. Case-mix analysis comparison with a standardized population and comparison of standard (ie, term, singleton, vertex) primiparous women demonstrate that the low rate of cesarean delivery was not because of a lower prevalence of risk factors. The community's low rate of cesarean delivery is primarily the result of a decreased use of cesarean delivery for labor dystocia and an almost universal acceptance of trial of labor after cesarean delivery. Cultural attitudes toward childbirth, design of the perinatal system, and genetic factors also may explain the low rate of cesarean delivery.

Laboratory formulated magnetic nanoparticles for enhancement of viral gene expression in suspension cell line.

PubMed

Bhattarai, Shanta Raj; Kim, Sun Young; Jang, Kyu Yun; Lee, Ki Chang; Yi, Ho Keun; Lee, Dae Yeol; Kim, Hak Yong; Hwang, Pyoung Han

2008-02-01

One factor critical to successful gene therapy is the development of efficient delivery systems. Although advances in gene transfer technology including viral and non-viral vectors have been made, an ideal vector system has not yet been constructed. Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via improve viral routes has become more desirable and advantageous. The ideal improve viral DNA delivery system should be a synthetic materials plus viral vectors. The materials should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The successful steps towards this improve viral DNA delivery system is demonstrated: a magnetofection system mediated by modified cationic chitosan-coated iron oxide nanoparticles. Dense colloidal cationic iron oxide nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface in presence of external magnetic fields; enhanced viral gene expression (3-100-fold) due to the particles is seen as compared to virus vector alone with little virus dose.

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

PubMed Central

Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

2014-01-01

Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

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

Archaeosomes: an excellent carrier for drug and cell delivery.

PubMed

Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-09-01

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

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.

Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

PubMed

Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

2016-02-01

The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

PubMed

Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

2010-08-15

Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

Efficiency performance of China's health care delivery system.

PubMed

Zhang, Luyu; Cheng, Gang; Song, Suhang; Yuan, Beibei; Zhu, Weiming; He, Li; Ma, Xiaochen; Meng, Qingyue

2017-07-01

Improving efficiency performance of the health care delivery system has been on the agenda for the health system reform that China initiated in 2009. This study examines the changes in efficiency performance and determinants of efficiency after the reform to provide evidence to assess the progress of the reform from the perspective of efficiency. Descriptive analysis, Data Envelopment Analysis, the Malmquist Index, and multilevel regressions are used with data from multiple sources, including the World Bank, the China Health Statistical Yearbook, and routine reports. The results indicate that over the last decade, health outcomes compared with health investment were relatively higher in China than in most other countries worldwide, and the trend was stable. The overall efficiency and total factor productivity increased after the reform, indicating that the reform was likely to have had a positive impact on the efficiency performance of the health care delivery system. However, the health care delivery structure showed low system efficiency, mainly attributed to the weakened primary health care system. Strengthening the primary health care system is central to enhancing the future performance of China's health care delivery system. Copyright © 2017 John Wiley & Sons, Ltd.

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.

PubMed

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred; Micera, Silvestro

2009-04-01

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.

Drug Delivery of the Future: Chasing the Invisible Gorilla

PubMed Central

Park, Kinam

2015-01-01

For more than 60 years drug delivery systems have produced numerous controlled release formulations helping patients improve compliance and maximize the drug efficacy. Development of new controlled drug delivery systems was very productive during the period 1950-1980. The productivity, as measured by the number of clinically used formulations, dropped significantly during 1980-2010. This reduced productivity needs to be understood so that the future development of drug delivery systems can be accelerated and prolific again. This requires critical evaluation of the current drug delivery field, so that the factors inhibiting rapid progress can be identified and resolved. The current drug delivery field is faced with an invisible gorilla syndrome, i.e., seeing a gorilla when it is not present and missing a gorilla when it actually exists. Overcoming this syndrome requires a new way of thinking, questioning the status quo. Advances in drug delivery technologies occur by an evolutionary process, and thus, the more trials and errors lead to faster advances. The drug delivery area needs to nurture the environment where vastly different ideas can be tested, and all data, positive or negative, need to be exchanged freely as they have equal importance. PMID:26519857

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.

Innovations in gene and growth factor delivery systems for diabetic wound healing

PubMed Central

Laiva, Ashang Luwang; O'Brien, Fergal J.

2017-01-01

Abstract The rise in lower extremity amputations due to nonhealing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off‐the‐shelf treatment; however, the dose‐ and time‐dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GF delivery. As an alternative, the delivery of therapeutic genes using viral and nonviral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise. The development of implantable biomaterial dressings capable of modulating the release of either single or combinatorial GFs/genes may offer solutions to this overgrowing problem. This article reviews the state of the art on gene and protein delivery and the strategic optimization of clinically adopted delivery strategies for the healing of diabetic wounds. PMID:28482114

The new organization of the health care delivery system.

PubMed

Shortell, S M; Hull, K E

1996-01-01

The U.S. health care system is restructuring at a dizzying pace. In many parts of the country, managed care has moved into third-generation models emphasizing capitated payment for enrolled lives and, in the process, turning most providers and institutions into cost centers to be managed rather than generators of revenue. While the full impact of the new managed care models remains to be seen, most evidence to date suggests that it tends to reduce inpatient use, may be associated with greater use of physician services and preventive care, and appears to result in no net differences either positive or negative with regard to quality or outcomes of care in comparison with fee-for-service plans. Some patients, however, tend to be somewhat less satisfied with scheduling of appointments and the amount of time spent with providers. There is no persuasive evidence that managed care lowers the rate of growth in overall health care costs within a given market. Further, managed care performance varies considerably across the country, and the factors influencing managed care performance are not well understood. Organized delivery systems are a somewhat more recent phenomenon representing various forms of ownership and strategic alliances among hospitals, physicians, and insurers designed to provide more cost-effective care to defined populations by achieving desired levels of functional, physician-system, and clinical integration. Early evidence suggests that organized delivery systems that are more integrated have the potential to provide more accessible coordinated care across the continuum, and appear to be associated with higher levels of inpatient productivity, greater total system revenue, greater total system cash flow, and greater total system operating margin than less integrated delivery forms. Some key success factors for developing organized delivery systems have been identified. Important roles are played by organizational culture, information systems, internal incentives, total quality management, physician leadership, and the growth of group practices. This chapter describes the growth and evolution of managed care and organized delivery systems, the research evidence regarding managed care and organized delivery systems, and the likely future organization of the health system in light of recent trends and evidence. It also highlights some of the more important public policy implications of the new health care infrastructure.

Managing Patient Factors in the Assessment of Swallowing via Telerehabilitation

PubMed Central

Ward, Elizabeth C.; Sharma, Shobha; Burns, Clare; Theodoros, Deborah; Russell, Trevor

2012-01-01

Undoubtedly, the identification of patient suitability for a telerehabilitation assessment should be carried out on a case-by-case basis. However, at present there is minimal discussion of how telerehabilitation systems can accommodate and adapt to various patient factors, which may pose challenges to successful service delivery. The current study examines a subgroup of 10 patients who underwent an online assessment of their swallowing difficulties. Although all assessments were completed successfully; there were certain patient factors, which complicated the delivery of the online assessment session. The paper presents a discussion of the main patient factors observed in this cohort including the presence of speech and/or voice disorders, hearing impairment, dyskinesia, and behavioural and/or emotional issues and examines how the assessment session, the telerehabilitation system, and the staff involved were manipulated to accommodate these patient factors. In order for telerehabilitation systems to be more widely incorporated into routine clinical care, systems need to have the flexibility and design capabilities to adjust and accommodate for patients with varying levels of function and physical and psychological comorbidities. PMID:23008704

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Vectorology and Factor Delivery in Induced Pluripotent Stem Cell Reprogramming

PubMed Central

2014-01-01

Induced pluripotent stem cell (iPSC) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10–30 days). Conventional iPSC reprogramming was achieved using lentiviral or simple retroviral vectors. Retroviral reprogramming has flaws of insertional mutagenesis, uncontrolled silencing, residual expression and re-activation of transgenes, and immunogenicity. To overcome these issues, various technologies were explored, including adenoviral vectors, protein transduction, RNA transfection, minicircle DNA, excisable PiggyBac (PB) transposon, Cre-lox excision system, negative-sense RNA replicon, positive-sense RNA replicon, Epstein-Barr virus-based episomal plasmids, and repeated transfections of plasmids. This review provides summaries of the main vectorologies and factor delivery systems used in current reprogramming protocols. PMID:24625220

Zero-order drug delivery system: theory and preliminary testing.

PubMed

Brooke, D; Washkuhn, R J

1977-02-01

A new approach to zero-order drug delivery that includes geometric factors is described. An experimental device based on the theory was tested by following the release of stearic acid into ethanol. Three separate trials indicated that the solid was released via a zero-order process in a reproducible manner.

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

PubMed Central

Lev, Rachel

2018-01-01

Muscular diseases such as muscular dystrophies and muscle injuries constitute a large group of ailments that manifest as muscle weakness, atrophy or fibrosis. Although cell therapy is a promising treatment option, the delivery and retention of cells in the muscle is difficult and prevents sustained regeneration needed for adequate functional improvements. Various types of biomaterials with different physical and chemical properties have been developed to improve the delivery of cells and/or growth factors for treating muscle injuries. Hydrogels are a family of materials with distinct advantages for use as cell delivery systems in muscle injuries and ailments, including their mild processing conditions, their similarities to natural tissue extracellular matrix, and their ability to be delivered with less invasive approaches. Moreover, hydrogels can be made to completely degrade in the body, leaving behind their biological payload in a process that can enhance the therapeutic process. For these reasons, hydrogels have shown great potential as cell delivery matrices. This paper reviews a few of the hydrogel systems currently being applied together with cell therapy and/or growth factor delivery to promote the therapeutic repair of muscle injuries and muscle wasting diseases such as muscular dystrophies. PMID:29343633

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.

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Novel drug delivery systems for releasing growth factors to the CNS: focus on Alzheimer's and Parkinson's diseases.

PubMed

Herran, E; Igartua, M; Pedraz, J L; Hernandez, R M

2014-01-01

Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most common neurodegenerative disorders and affect more than 35 million people. Due to the limited effectiveness of available treatments in halting the neurodegenerative process, new therapies, such therapies based on growth factors (GFs), have been investigated. Nevertheless, the efficacies of these new treatments depend not only on the application of neurotrophins but also on the approaches used to deliver these proteins such that they can reach the brain. This review summarises the most widely used drug delivery systems (DDSs) for releasing GFs as possible treatments for AD and PD.

Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders.

PubMed

Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

2017-06-01

The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.

Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

PubMed

du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

2014-01-01

In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles.

PubMed

Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu; Liu, Guohua

2017-04-01

Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. Copyright © 2016 Elsevier B.V. All rights reserved.

Mucoadhesive drug delivery systems

PubMed Central

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

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

A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration.

PubMed

Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

2013-01-01

Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.

The role of public insurance and the public delivery system in improving birth outcomes for low-income pregnant women.

PubMed

Susan Marquis, M; Long, Stephen H

2002-11-01

Insurance expansions and service delivery system expansions are alternative policy instruments used to try to improve birth outcomes for low-income women. The objective of this research is to investigate the effect of expansions of public insurance on access and birth outcomes for pregnant women and the role of different delivery systems in these outcomes. The experience in Florida during the years 1989-1994 is studied. Data are from linked birth certificates, hospital discharge data, Medicaid eligibility and claims files, and county health department records. Use of prenatal care and birthweight for low-income women is compared under different financing for prenatal care and for those using different delivery systems. Several approaches to control for self-selection are adopted, and similar results are obtained with each. Women enrolled in Medicaid have more prenatal care visits than the uninsured. Outcomes for those on Medicaid and the uninsured are significantly better if they receive care in the public health system than if they receive care in the private system-including private offices, clinics, and HMOs. Over time, the gap in outcomes between those in the public system and those receiving prenatal care from private physicians has diminished. Public insurance improves access to services, but the delivery system is a key factor in improving outcomes.

Integration of Drug, Protein, and Gene Delivery Systems with Regenerative Medicine

PubMed Central

Lorden, Elizabeth R.; Levinson, Howard M.; Leong, Kam W.

2013-01-01

Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g. hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and micro-particle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein and gene delivery in the context of regenerative medicine. Next we will present case examples of how delivery technologies are being applied to promote angiogenesis in non-healing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench-to-bedside for the clinical translation of these novel therapeutics. PMID:25787742

Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

PubMed Central

Kozhevnikova, Mariya; König, Niclas; Zhou, Chunfang; Leao, Richardson; Knöpfel, Thomas; Pankratova, Stanislava; Trolle, Carl; Berezin, Vladimir; Bock, Elisabeth; Aldskogius, Håkan

2013-01-01

Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation. PMID:24089415

Engineered BDNF producing cells as a potential treatment for neurologic disease

PubMed Central

Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.

2018-01-01

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050

Future trends in health and health care: implications for social work practice in an aging society.

PubMed

Spitzer, William J; Davidson, Kay W

2013-01-01

Major economic, political, demographic, social, and operational system factors are prompting evolutionary changes in health care delivery. Of particular significance, the "graying of America" promises new challenges and opportunities for health care social work. At the same time, the Patient Protection and Affordable Care Act of 2010, evolution of Accountable Care Organizations, and an emphasis on integrated, transdisciplinary, person-centered care represent fundamental shifts in service delivery with implications for social work practice and education. This article identifies the aging shift in American demography, its impact on health policy legislation, factors influencing fundamentally new service delivery paradigms, and opportunities of the profession to address the health disparities and care needs of an aging population. It underscores the importance of social work inclusion in integrated health care delivery and offers recommendations for practice education.

Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation.

PubMed

Wu, Yanqing; Wang, Zhouguang; Cai, Pingtao; Jiang, Ting; Li, Yiyang; Yuan, Yuan; Li, Rui; Khor, Sinan; Lu, Yingfeng; Wang, Jian; Chen, Daqing; Zeng, Qiqiang; Zhong, Ruisheng; Zhang, Hongyu; Lin, Yuan; Li, Xiaokun; Xiao, Jian

2018-06-12

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are essential for proper development, survival, growth, and maintenance of neurons in the central and peripheral nervous systems. However, because bFGF and NGF have short half-life and rapid diffusion rate, they have limited clinical efficacy. Thus, there is an urgent need to develop an effective delivery system to protect bFGF and NGF from proteolysis while maintaining their normal bioactivities. To more efficiently deliver bFGF and NGF, we used a coacervate (synthesized with heparin and a biodegradable polycation at mass ratio of 500: 100). The maximal package loads of GFs in coacervate were determined by Western Blotting; release efficiency of bFGF and NGF was measured by ELISA. Additionally, we evaluated the effect of bFGF and NGF on the viability, survival, and proliferation of neurons by MTT assay, BrdU cell proliferation, and calcein staining. Our coacervate incorporated bFGF and NGF and continuously released them for at least three weeks. This enhanced the growth and proliferation of PC12 cells and SH-SY5Y cells. Moreover, co-delivery of bFGF and NGF using coacervate was more neuroprotective than free application of both factors or coacervate delivery of each GF separately. Dual delivery of bFGF and NGF binding coacervate was neuroprotective via stimulating the growth and proliferation of neurons. © 2018 The Author(s). Published by S. Karger AG, Basel.

Gelatin device for the delivery of growth factors involved in endochondral ossification.

PubMed

Ahrens, Lucas A J; Vonwil, Daniel; Christensen, Jon; Shastri, V Prasad

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

Gelatin device for the delivery of growth factors involved in endochondral ossification

PubMed Central

Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

Activation of signaling pathways following localized delivery of systemically administered neurotrophic factors across the blood-brain barrier using focused ultrasound and microbubbles

NASA Astrophysics Data System (ADS)

Baseri, Babak; Choi, James J.; Deffieux, Thomas; Samiotaki, Gesthimani; Tung, Yao-Sheng; Olumolade, Oluyemi; Small, Scott A.; Morrison, Barclay, III; Konofagou, Elisa E.

2012-04-01

The brain-derived neurotrophic factor (BDNF) has been shown to have broad neuroprotective effects in addition to its therapeutic role in neurodegenerative disease. In this study, the efficacy of delivering exogenous BDNF to the left hippocampus is demonstrated in wild-type mice (n = 7) through the noninvasively disrupted blood-brain barrier (BBB) using focused ultrasound (FUS). The BDNF bioactivity was found to be preserved following delivery as assessed quantitatively by immunohistochemical detection of the pTrkB receptor and activated pAkt, pMAPK, and pCREB in the hippocampal neurons. It was therefore shown for the first time that systemically administered neurotrophic factors can cross the noninvasively disrupted BBB and trigger neuronal downstream signaling effects in a highly localized region in the brain. This is the first time that the administered molecule is tracked through the BBB and localized in the neuron triggering molecular effects. Additional preliminary findings are shown in wild-type mice with two additional neurotrophic factors such as the glia-derived neurotrophic factor (n = 12) and neurturin (n = 2). This further demonstrates the impact of FUS for the early treatment of CNS diseases at the cellular and molecular level and strengthens its premise for FUS-assisted drug delivery and efficacy.

Factors associated with home delivery in Bahirdar, Ethiopia: a case control study.

PubMed

Abebe, Fantu; Berhane, Yemane; Girma, Belaineh

2012-11-24

In Ethiopia although pregnant mothers increasingly attend antenatal clinics, utilization of skilled delivery service remains very low. The individual or health system factors that affect women's preferences for delivery places are not well known. A case control study was conducted in July 2010 to assess factors associated with utilization of institutional delivery service. A total of 324 mothers who recently delivered and visited either postnatal care or sought immunization services were included. Cases (n = 108) were mothers who gave birth at home and controls (n = 216) were those who delivered at health facility. Pre-tested and standardized questionnaires were used to collect relevant data by trained data collectors. Logistic regression model was used to control for confounding. The likelihood of delivering at home was greater among mothers with inadequate knowledge of pregnancy related services (AOR = 62, 95% CI: 3, 128.4), those who started attending ANC after 24 weeks of gestation (AOR 8.7, 95% CI: 2.2, 33.3), mothers having no formal education (Adjusted OR 4.2, 95% CI 1.63, 11.27) and rural residents (AOR = 3.6, 95%CI: 1.4, 9.0). The predominant factors associated with home delivery services were lack of knowledge about obstetrics care, delay in starting Antenatal Care (ANC) follow up, having, Illiteracy and rural residence. Audience specific behavioral change communication should be designed to improve the demand for delivery services. Health professionals should take the opportunity to encourage mothers attend delivery services during ANC follow up. Improvements should be made in social conditions including literacy and major social mobilization endeavors.

Factors influencing deliveries at health facilities in a rural Maasai Community in Magadi sub-County, Kenya.

PubMed

Karanja, Sarah; Gichuki, Richard; Igunza, Patrick; Muhula, Samuel; Ofware, Peter; Lesiamon, Josephine; Leshore, Lepantas; Kyomuhangi-Igbodipe, Lenny Bazira; Nyagero, Josephat; Binkin, Nancy; Ojakaa, David

2018-01-03

In response to poor maternal, newborn, and child health indicators in Magadi sub-county, the "Boma" model was launched to promote health facility delivery by establishing community health units and training community health volunteers (CHVs) and traditional birth attendants (TBAs) as safe motherhood promoters. As a result, health facility delivery increased from 14% to 24%, still considerably below the national average (61%). We therefore conducted this study to determine factors influencing health facility delivery and describe barriers and motivators to the same. A mixed methods cross-sectional study involving a survey with 200 women who had delivered in the last 24 months, 3 focus group discussions with health providers, chiefs and CHVs and 26 in-depth interviews with mothers, key decision influencers and TBAs. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) using logistic regression were calculated to identify predictive factors for health facility delivery. Thematic analysis was done to describe barriers and motivators to the same. Of the women interviewed, 39% delivered at the health facility. Factors positively associated with health facility deliveries included belonging to the highest wealth quintiles [aOR 4.9 (95%CI 1.5-16.5)], currently not married [aOR 2.4 (95%CI 1.1-5.4)] and living near the health facility [aOR 2.2 (95%CI 1.1 = 4.4)]. High parity [aOR 0.7 (95%CI 0.5-0.9)] was negatively associated with health facility delivery. Barriers to health facility delivery included women not being final decision makers on place of birth, lack of a birth plan, gender of health provider, unfamiliar birthing position, disrespect and/or abuse, distance, attitude of health providers and lack of essential drugs and supplies. Motivators included proximity to health facility, mother's health condition, integration of TBAs into the health system, and health education/advice received. Belonging to the highest wealth quintile, currently not married and living near a health facility were positively associated with health facility delivery. Gender inequity and cultural practices such as lack of birth preparedness should be addressed. Transport mechanisms need to be established to avoid delay in reaching a health facility. The health systems also need to be functional with adequate supplies and motivated staff.

Assessing delivery practices of mothers over time and over space in Uganda, 2003-2012.

PubMed

Sprague, Daniel A; Jeffery, Caroline; Crossland, Nadine; House, Thomas; Roberts, Gareth O; Vargas, William; Ouma, Joseph; Lwanga, Stephen K; Valadez, Joseph J

2016-01-01

It is well known that safe delivery in a health facility reduces the risks of maternal and infant mortality resulting from perinatal complications. What is less understood are the factors associated with safe delivery practices. We investigate factors influencing health facility delivery practices while adjusting for multiple other factors simultaneously, spatial heterogeneity, and trends over time. We fitted a logistic regression model to Lot Quality Assurance Sampling (LQAS) data from Uganda in a framework that considered individual-level covariates, geographical features, and variations over five time points. We accounted for all two-covariate interactions and all three-covariate interactions for which two of the covariates already had a significant interaction, were able to quantify uncertainty in outputs using computationally intensive cluster bootstrap methods, and displayed outputs using a geographical information system. Finally, we investigated what information could be predicted about districts at future time-points, before the next LQAS survey is carried out. To do this, we applied the model to project a confidence interval for the district level coverage of health facility delivery at future time points, by using the lower and upper end values of known demographics to construct a confidence range for the prediction and define priority groups. We show that ease of access, maternal age and education are strongly associated with delivery in a health facility; after accounting for this, there remains a significant trend towards greater uptake over time. We use this model together with known demographics to formulate a nascent early warning system that identifies candidate districts expected to have low prevalence of facility-based delivery in the immediate future. Our results support the hypothesis that increased development, particularly related to education and access to health facilities, will act to increase facility-based deliveries, a factor associated with reducing perinatal associated mortality. We provide a statistical method for using inexpensive and routinely collected monitoring and evaluation data to answer complex epidemiology and public health questions in a resource-poor setting. We produced a model based on this data that explained the spatial distribution of facility-based delivery in Uganda. Finally, we used this model to make a prediction about the future priority of districts that was validated by monitoring and evaluation data collected in the next year.

Current Status of Messenger RNA Delivery Systems.

PubMed

Stanton, Matthew G

2018-06-01

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

PubMed

Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

2017-01-01

Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

PubMed

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

PubMed Central

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. PMID:26251592

Application of Various Types of Liposomes in Drug Delivery Systems

PubMed Central

Alavi, Mehran; Karimi, Naser; Safaei, Mohsen

2017-01-01

Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes. PMID:28507932

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing.

PubMed

Tellechea, Ana; Silva, Eduardo A; Min, Jianghong; Leal, Ermelindo C; Auster, Michael E; Pradhan-Nabzdyk, Leena; Shih, William; Mooney, David J; Veves, Aristidis

2015-06-01

Diabetic foot ulcers (DFU) represent a severe health problem and an unmet clinical challenge. In this study, we tested the efficacy of novel biomaterials in improving wound healing in mouse models of diabetes mellitus (DM). The biomaterials are composed of alginate- and deoxyribonucleic acid (DNA)-based gels that allow incorporation of effector cells, such as outgrowth endothelial cells (OEC), and provide sustained release of bioactive factors, such as neuropeptides and growth factors, which have been previously validated in experimental models of DM wound healing or hind limb ischemia. We tested these biomaterials in mice and demonstrate that they are biocompatible and can be injected into the wound margins without major adverse effects. In addition, we show that the combination of OEC and the neuropeptide Substance P has a better healing outcome than the delivery of OEC alone, while subtherapeutic doses of vascular endothelial growth factor (VEGF) are required for the transplanted cells to exert their beneficial effects in wound healing. In summary, alginate and DNA scaffolds could serve as potential delivery systems for the next-generation DFU therapies. © The Author(s) 2015.

Overcoming the Cutaneous Barrier with Microemulsions

PubMed Central

Lopes, Luciana B.

2014-01-01

Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

Liver cell-targeted delivery of therapeutic molecules.

PubMed

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Geographic and socioeconomic factors affecting delivery of bariatric surgery across high- and low-utilization healthcare systems.

PubMed

Doumouras, A G; Saleh, F; Sharma, A M; Anvari, S; Gmora, S; Anvari, M; Hong, D

2017-06-01

In countries with universal health coverage, the delivery of care should be driven by need. However, other factors, such as proximity to local facilities or neighbourhood socioeconomic status, may be more important. The objective of this study was to evaluate which geographic and socioeconomic factors affect the delivery of bariatric care in Canada. This was a national retrospective cohort study of all adult patients undergoing bariatric surgery between April 2008 and March 2015 in Canada (excluding Quebec). The main outcome was neighbourhood rate of bariatric surgery per 1000 obese individuals (BMI over 30 kg/m 2 ). Geographic cluster analysis and multilevel ordinal logistic regression were used to identify high-use clusters, and to evaluate the effect of geographic and socioeconomic factors on care delivery. Having a bariatric facility within the same public health unit as the neighbourhood was associated with a 6·6 times higher odds of being in a bariatric high-use cluster (odds ratio (OR) 6·60, 95 per cent c.i. 1·90 to 22·88; P = 0·003). This finding was consistent across provinces after adjusting for utilization rates. Neighbourhoods with higher obesity rates were also more likely to be within high-use clusters (OR per 5 per cent increase: 2·95, 1·54 to 5·66; P = 0·001), whereas neighbourhoods closer to bariatric centres were less likely to be (OR per 50 km: 0·91, 0·82 to 1·00; P = 0·048). In this study, across provincial healthcare systems with high and low utilization, the delivery of care was driven by the presence of local facilities and neighbourhood obesity rates. Increasing distance to bariatric centres substantially influenced care delivery. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

National Initiatives to Improve Healthcare Outcomes: A Comparative Study of Health Delivery Systems in Slovakia and the United States.

PubMed

Curtis, Robert; Caplanova, Anetta; Novak, Marcel

2015-01-01

While the United States and Slovakia offer different healthcare delivery systems, each country faces the same challenges of improving the health status of their populations. The authors explore the impact of their respective systems on the health of their populations and compare the health outcomes of both nations. They point out that socioeconomic factors play a far more important role in determining population health outcomes than do the structures of the systems surrounding the care delivery. The authors illustrate this finding through a comparison of the poverty and education levels of a selected minority group from each country in relation to the health outcomes for each population group. The comparison reveals that education is a more influential determinant in a population's health outcomes, than the improved access to care offered by a universal system.

Characterization and In Vitro Permeation Study of Cubic Liquid Crystal Containing Sinomenine Hydrochloride.

PubMed

Chu, Xiaoqin; Li, Qian; Gui, Shuangying; Li, Zhengguang; Cao, Jiaojiao; Jiang, Jianqin

2018-05-08

This study developed a new transdermal delivery system for the improved delivery of sinomenine hydrochloride (SH). The delivery system utilized the advantages of lyotropic liquid crystals (LLC) creating an adaptable system that offers a variety of options for the field of transdermal delivery. The formulation was prepared, characterized, and evaluated for its skin penetration in vitro. In the study, the appearance of samples was characterized by visual observation, and these LLC gels were colorless and transparent. Polarizing light microscopy (PLM) and small-angle X-ray diffraction (SAXS) were used to analyze the internal structures of gels, and the gels displayed a cubic double-diamond (P n 3 m ) internal structure with a dark field of vision. The Franze diffusion cell was used to evaluate its skin penetration. There were several factors which might influence the skin penetration of drugs, such as drug loading, water content, and the layer spacing of the LLC. In our case, drug concentration gradient played a more powerful role. The result of in vitro permeation studies demonstrated that the drug concentration was higher; the cumulative osmotic quantity of SH (Q) was greater. Therefore, the system was a promising formulation for successful percutaneous delivery of SH through the skin.

Transdermal deferoxamine prevents pressure-induced diabetic ulcers

PubMed Central

Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

2015-01-01

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

Integration of Biosensors and Drug Delivery Technologies for Early Detection and Chronic Management of Illness

PubMed Central

Ngoepe, Mpho; Choonara, Yahya E.; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C.; Kumar, Pradeep; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157

Optimisation of a two-liquid component pre-filled acrylic bone cement system: a design of experiments approach to optimise cement final properties.

PubMed

Clements, James; Walker, Gavin; Pentlavalli, Sreekanth; Dunne, Nicholas

2014-10-01

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery-acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

A model for predicting field-directed particle transport in the magnetofection process.

PubMed

Furlani, Edward P; Xue, Xiaozheng

2012-05-01

To analyze the magnetofection process in which magnetic carrier particles with surface-bound gene vectors are attracted to target cells for transfection using an external magnetic field and to obtain a fundamental understanding of the impact of key factors such as particle size and field strength on the gene delivery process. A numerical model is used to study the field-directed transport of the carrier particle-gene vector complex to target cells in a conventional multiwell culture plate system. The model predicts the transport dynamics and the distribution of particle accumulation at the target cells. The impact of several factors that strongly influence gene vector delivery is assessed including the properties of the carrier particles, the strength of the field source, and its extent and proximity relative to the target cells. The study demonstrates that modeling can be used to predict and optimize gene vector delivery in the magnetofection process for novel and conventional in vitro systems.

Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

NASA Astrophysics Data System (ADS)

Sharma, Anup Dutt

Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

PubMed Central

Xie, Yuran; Merkel, Olivia M

2015-01-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues has limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases and costimulatory factors that have been reported as targets of siRNA mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages and dendritic cells, which could potentially be applied in asthma therapy. PMID:26148454

Factors affecting the implementation of childhood vaccination communication strategies in Nigeria: a qualitative study.

PubMed

Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Eteng, Glory; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon

2017-02-15

The role of health communication in vaccination programmes cannot be overemphasized: it has contributed significantly to creating and sustaining demand for vaccination services and improving vaccination coverage. In Nigeria, numerous communication approaches have been deployed but these interventions are not without challenges. We therefore aimed to explore factors affecting the delivery of vaccination communication in Nigeria. We used a qualitative approach and conducted the study in two states: Bauchi and Cross River States in northern and southern Nigeria respectively. We identified factors affecting the implementation of communication interventions through interviews with relevant stakeholders involved in vaccination communication in the health services. We also reviewed relevant documents. Data generated were transcribed verbatim and analysed using thematic analysis. We used the SURE framework to organise the identified factors (barriers and facilitators) affecting vaccination communication delivery. We then grouped these into health systems and community level factors. Some of the commonly reported health system barriers amongst stakeholders interviewed included: funding constraints, human resource factors (health worker shortages, training deficiencies, poor attitude of health workers and vaccination teams), inadequate infrastructure and equipment and weak political will. Community level factors included the attitudes of community stakeholders and of parents and caregivers. We also identified factors that appeared to facilitate communication activities. These included political support, engagement of traditional and religious institutions and the use of organised communication committees. Communication activities are a crucial element of immunization programmes. It is therefore important for policy makers and programme managers to understand the barriers and facilitators affecting the delivery of vaccination communication so as to be able to implement communication interventions more effectively.

Mechanistic Studies of an Autonomously Pulsing Hydrogel/Enzyme System for Rhythmic Hormone Delivery

PubMed Central

Bhalla, Amardeep S.; Siegel, Ronald A.

2014-01-01

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion. A bench prototype system based on this scheme was previously shown to produce near rhythmic oscillations in internal pH and in GnRH delivery over a period of one week. In the present work, a systematic study of conditions permitting such oscillations is presented, along with a study of factors causing period of oscillations to increase with time and ultimately cease. Membrane composition, glucose concentration, and surface area of marble (CaCO3), which is incorporated as a reactant, were found to affect the capacity of the system to oscillate, and the pH range over which oscillations occur. Accumulation of gluconate- and Ca2+ in the system over time correlated with lengthening of oscillation period, and possibly with cessation of oscillations. Enzyme degradation may also be a factor. These studies provide the groundwork for future improvements in device design. PMID:25450402

Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method.

PubMed

Kawakubo, Kazumichi; Kawakami, Hiroshi; Toyokawa, Yoshihide; Otani, Koichi; Kuwatani, Masaki; Abe, Yoko; Kawahata, Shuhei; Kubo, Kimitoshi; Kubota, Yoshimasa; Sakamoto, Naoya

2015-01-01

Endoscopic double self-expandable metallic stent (SEMS) placement by the partial stent-in-stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO). Between December 2009 and May 2013, 50 consecutive patients with MHBO underwent endoscopic double SEMS placement by the PSIS method. We retrospectively evaluated the rate of successful double SEMS placement and identified the risk factors for technical failure. The technical success rate for double SEMS placement was 82.0% (95% confidence interval [CI]: 69.2-90.2). On univariate analysis, the rate of technical failure was high in patients with metastatic disease and unilateral placement. Multivariate analysis revealed that metastatic disease was a significant risk factor for technical failure (odds ratio: 9.63, 95% CI: 1.11-105.5). The subgroup analysis after double guidewire insertion showed that the rate of technical success was higher in the laser-cut type SEMS with a large mesh and thick delivery system than in the braided type SEMS with a small mesh and thick delivery system. Metastatic disease was a significant risk factor for technical failure of double SEMS placement for unresectable MHBO. The laser-cut type SEMS with a large mesh and thin delivery system might be preferable for the PSIS procedure. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric Nanoparticles

PubMed Central

Chernenko, Tatyana; Buyukozturk, Fulden; Miljkovic, Milos; Carrier, Rebecca; Diem, Max; Amiji, Mansoor

2013-01-01

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we have used label-free Raman micro-spectral analysis and kinetic modeling to study cellular interactions and intracellular delivery of C6-ceramide using a non-targeted and an epidermal growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The results show that EGFR peptide-modified nanoparticles were rapidly internalized in SKOV3 cells leading to significant intracellular accumulation as compared to non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral analysis enables visualization and quantification of the carrier system, drug-load, and responses of the biological systems interrogated, without exogenous staining and labeling procedures. PMID:24298430

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

PubMed

de Bock, Martin; Dart, Julie; Roy, Anirban; Davey, Raymond; Soon, Wayne; Berthold, Carolyn; Retterath, Adam; Grosman, Benyamin; Kurtz, Natalie; Davis, Elizabeth; Jones, Timothy

2017-01-01

Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

Leveraging Health Care Simulation Technology for Human Factors Research: Closing the Gap Between Lab and Bedside.

PubMed

Deutsch, Ellen S; Dong, Yue; Halamek, Louis P; Rosen, Michael A; Taekman, Jeffrey M; Rice, John

2016-11-01

We describe health care simulation, designed primarily for training, and provide examples of how human factors experts can collaborate with health care professionals and simulationists-experts in the design and implementation of simulation-to use contemporary simulation to improve health care delivery. The need-and the opportunity-to apply human factors expertise in efforts to achieve improved health outcomes has never been greater. Health care is a complex adaptive system, and simulation is an effective and flexible tool that can be used by human factors experts to better understand and improve individual, team, and system performance within health care. Expert opinion is presented, based on a panel delivered during the 2014 Human Factors and Ergonomics Society Health Care Symposium. Diverse simulators, physically or virtually representing humans or human organs, and simulation applications in education, research, and systems analysis that may be of use to human factors experts are presented. Examples of simulation designed to improve individual, team, and system performance are provided, as are applications in computational modeling, research, and lifelong learning. The adoption or adaptation of current and future training and assessment simulation technologies and facilities provides opportunities for human factors research and engineering, with benefits for health care safety, quality, resilience, and efficiency. Human factors experts, health care providers, and simulationists can use contemporary simulation equipment and techniques to study and improve health care delivery. © 2016, Human Factors and Ergonomics Society.

Peptide/protein vaccine delivery system based on PLGA particles.

PubMed

Allahyari, Mojgan; Mohit, Elham

2016-03-03

Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

Peptide/protein vaccine delivery system based on PLGA particles

PubMed Central

Allahyari, Mojgan; Mohit, Elham

2016-01-01

abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

PubMed Central

Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

2016-01-01

Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

Factors Associated with Failure to Achieve SVR in Hepatitis C Genotype 3 Patients Within an Integrated Care Delivery System.

PubMed

Cheetham, T Craig; Niu, Fang; Chiang, Kevin; Yuan, Yong; Kalsekar, Anu; Hechter, Rulin; Hay, Joel W; Nyberg, Lisa

2015-08-01

Achievement of sustained virologic response (SVR) and factors associated with treatment failure in hepatitis C virus (HCV) genotype 3 have been described in tertiary and referral care settings, with rates of SVR reported to range between 72% and 89%. Fewer data exist on SVR outside of these settings. To describe rates of SVR and characterize factors associated with achievement of SVR within an integrated health care delivery system. A retrospective cohort study of genotype 3 HCV patients treated with dual therapy (pegylated interferon-alpha plus ribavirin) was conducted at Kaiser Permanente Southern California. Adult patients diagnosed with HCV and testing positive for HCV-RNA genotype 3 were identified from electronic medical records. Data were collected on patient demographics, baseline health status, and comorbid conditions. A multivariate logistic regression model was used to determine the association between baseline patient factors and SVR. A total of 484 HCV genotype 3 patients met the eligibility criteria. The median age was 49 years, and 65.7% were male. Overall, 252 (52.1%) achieved SVR. Aged ≥ 45 years and male gender were associated with lower rates of SVR; cirrhosis and chronic diseases (diabetes and chronic obstructive pulmonary disease) were also associated with lower rates of SVR. SVR was lower in patients within an integrated care delivery system than in those in tertiary and referral centers. Males and older patients had lower rates of SVR, as well as patients with cirrhosis, diabetes, and chronic obstructive pulmonary disease.

Generation of infectious recombinant Adeno-associated virus in Saccharomyces cerevisiae.

PubMed

Barajas, Daniel; Aponte-Ubillus, Juan Jose; Akeefe, Hassibullah; Cinek, Tomas; Peltier, Joseph; Gold, Daniel

2017-01-01

The yeast Saccharomyces cerevisiae has been successfully employed to establish model systems for a number of viruses. Such model systems are powerful tools to study the virus biology and in particular for the identification and characterization of host factors playing a role in the viral infection cycle. Adeno-associated viruses (AAV) are heavily studied due to their use as gene delivery vectors. AAV relies on other helper viruses for successful replication and on host factors for several aspects of the viral life cycle. However the role of host and helper viral factors is only partially known. Production of recombinant AAV (rAAV) vectors for gene delivery applications depends on knowledge of AAV biology and the limited understanding of host and helper viral factors may be precluding efficient production, particularly in heterologous systems. Model systems in simpler eukaryotes like the yeast S. cerevisiae would be useful tools to identify and study the role of host factors in AAV biology. Here we show that expression of AAV2 viral proteins VP1, VP2, VP3, AAP, Rep78, Rep52 and an ITR-flanked DNA in yeast leads to capsid formation, DNA replication and encapsidation, resulting in formation of infectious particles. Many of the AAV characteristics observed in yeast resemble those in other systems, making it a suitable model system. Future findings in the yeast system could be translatable to other AAV host systems and aid in more efficient production of rAAV vectors.

Investigation of the mediating effects of IT governance-value delivery on service quality and ERP performance

NASA Astrophysics Data System (ADS)

Tsai, Wen-Hsien; Chou, Yu-Wei; Leu, Jun-Der; Chao Chen, Der; Tsaur, Tsen-Shu

2015-02-01

This study aimed to explore the mediating effects of IT governance (ITG)-value delivery in the relationships among the quality of vendor service, the quality of consultant services, ITG-value delivery and enterprise resource planning (ERP) performance. The sampling of this research was acquired from a questionnaire survey concerning ERP implementations in Taiwan. In this survey, 4366 questionnaires were sent to manufacturing and service companies listed in the TOP 5000: The Largest Corporations in Taiwan 2009. The results showed that an ERP system will exhibit a decreased error rate and improved performance if ERP system vendors and consultants provide good service quality. The results also demonstrated that significant relationships exist among the quality of vendor service, the quality of consultant services and value delivery. The contribution of this article is twofold. First, it found that value delivery provides an effective measure of ERP performance under an ITG framework. Second, it provides evidence of the partial mediating effects of value delivery between service quality and ERP performance. In other words, if enterprises want to improve ERP performance, they need to consider factors such as value delivery and the quality of a vendor/consultant's service.

Extending access to essential services against constraints: the three-tier health service delivery system in rural China (1949-1980).

PubMed

Feng, Xing Lin; Martinez-Alvarez, Melisa; Zhong, Jun; Xu, Jin; Yuan, Beibei; Meng, Qingyue; Balabanova, Dina

2017-05-23

China has made remarkable progress in scaling up essential services during the last six decades, making health care increasingly available in rural areas. This was partly achieved through the building of a three-tier health system in the 1950s, established as a linked network with health service facilities at county, township and village level, to extend services to the whole population. We developed a Theory of Change to chart the policy context, contents and mechanisms that may have facilitated the establishment of the three-tier health service delivery system in rural China. We systematically synthesized the best available evidence on how China achieved universal access to essential services in resource-scarce rural settings, with a particular emphasis on the experiences learned before the 1980s, when the country suffered a particularly acute lack of resources. The search identified only three peered-reviewed articles that fit our criteria for scientific rigor. We therefore drew extensively on government policy documents, and triangulated them with other publications and key informant interviews. We found that China's three-tier health service delivery system was established in response to acute health challenges, including high fertility and mortality rates. Health system resources were extremely low in view of the needs and insufficient to extend access to even basic care. With strong political commitment to rural health and a "health-for-all" policy vision underlying implementation, a three-tier health service delivery model connecting villages, townships and counties was quickly established. We identified several factors that contributed to the success of the three-tier system in China: a realistic health human resource development strategy, use of mass campaigns as a vehicle to increase demand, an innovative financing mechanisms, public-private partnership models in the early stages of scale up, and an integrated approach to service delivery. An implementation process involving gradual adaptation and incorporation of the lessons learnt was also essential. China's 60 year experience in establishing a de-professionalized, community-based, health service delivery model that is economically feasible, institutionally and culturally appropriate mechanism can be useful to other low- and middle-income countries (LMICs) seeking to extend essential services. Lessons can be drawn from both reform content and from its implementation pathway, identifying the political, institutional and contextual factors shaping the three-tier delivery model over time.

System Dynamics Modeling for Public Health: Background and Opportunities

PubMed Central

Homer, Jack B.; Hirsch, Gary B.

2006-01-01

The systems modeling methodology of system dynamics is well suited to address the dynamic complexity that characterizes many public health issues. The system dynamics approach involves the development of computer simulation models that portray processes of accumulation and feedback and that may be tested systematically to find effective policies for overcoming policy resistance. System dynamics modeling of chronic disease prevention should seek to incorporate all the basic elements of a modern ecological approach, including disease outcomes, health and risk behaviors, environmental factors, and health-related resources and delivery systems. System dynamics shows promise as a means of modeling multiple interacting diseases and risks, the interaction of delivery systems and diseased populations, and matters of national and state policy. PMID:16449591

Mixed Picture of Readiness for Adoption of Evidence-Based Prevention Programs in Communities: Exploratory Surveys of State Program Delivery Systems

PubMed Central

Schainker, Lisa M.; Redmond, Cleve; Ralston, Ekaterina; Yeh, Hsiu-Chen; Perkins, Daniel F.

2015-01-01

An emerging literature highlights the potential for broader dissemination of evidence-based prevention programs in communities through existing state systems, such as the land grant university Extension outreach system and departments of public education and health (DOE– DPH). This exploratory study entailed surveying representatives of the national Extension system and DOE– DPH, to evaluate dissemination readiness factors, as part of a larger project on an evidence-based program delivery model called PROSPER. In addition to assessing systems’ readiness factors, differences among US regions and comparative levels of readiness between state systems were evaluated. The Extension web-based survey sample N was 958 and the DOE–DPH telephone survey N was 338, with response rates of 23 and 79 %, respectively. Extension survey results suggested only a moderate level of overall readiness nationally, with relatively higher perceived need for collaborative efforts and relatively lower perceived resource availability. There were significant regional differences on all factors, generally favoring the Northeast. Results from DOE–DPH surveys showed significantly higher levels for all readiness factors, compared with Extension systems. Overall, the findings present a mixed picture. Although there were clear challenges related to measuring readiness in complex systems, addressing currently limited dissemination resources, and devising strategies for optimizing readiness, all systems showed some readiness-related strengths. PMID:25791916

Birth wind and fire: raising awareness to operating room fires during delivery.

PubMed

Wolf, Omer; Weissman, Oren; Harats, Moti; Farber, Nimrod; Stavrou, Demetris; Tessone, Ariel; Zilinsky, Isaac; Winkler, Eyal; Haik, Josef

2013-09-01

We researched whether the obstetric operating room (OR) qualified as a fire-risk environment so as to take preventive measures accordingly. We analyzed a series of iatrogenic burns inflicted during birth by collecting clinical data and comparing it with known OR fire risk factors and with other factors that repeated in all cases in search of unique characteristics of the obstetric OR. All three cases shared in common the same type of oxygen-rich open ventilation system, alcohol-based prepping solution, and the hastiness of cesarean delivery while spontaneous vaginal delivery was already in progress. The obstetric OR is, as suspected, a fire-prone zone in more ways than the regular OR. Therefore, preventive measures should be undertaken and awareness for the possibility for such occurrences should be raised.

CEO summit. The new delivery & financing realities. Part III of III.

PubMed

Becker, B F; Cramer, H; Easley, D; Nathanson, P; Neeson, R; Raney, J; Samuelson, C; Ummel, S

1994-08-20

In cooperation with McManis Associates Inc., Washington, Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This installment is the third of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues summit participants discussed in the second segment: What level of understanding do purchasers have of the factors that differentiate quality in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when a large integrated delivery system merges with a dominant insurer, as happened in the Philadelphia market? Can that model be successfully replicated in other markets? In this final segment, participants talk about whether providers' deep connections to their communities will add value in a reformed delivery system; how incentives might be aligned among all the players in integrated networks and organizations; how the concept of community focus might be redefined under systems integration; and the process involved in preparing for constant, accelerated change. The second segment concluded with comments about the assets providers and insurers bring to integrated health systems, and whether the merger experience of Graduate Health System and QCC/Independence Blue Cross could be replicated in other markets or not.

Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model.

PubMed

Bahadoran, Azadeh; Ebrahimi, Mehdi; Yeap, Swee Keong; Safi, Nikoo; Moeini, Hassan; Hair-Bejo, Mohd; Hussein, Mohd Zobir; Omar, Abdul Rahman

2017-01-01

This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3 + /CD4 + T cells and CD3 + /CD8 + T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3 + /CD4 + and CD3 + /CD8 + T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.

The influence of distance and level of care on delivery place in rural Zambia: a study of linked national data in a geographic information system.

PubMed

Gabrysch, Sabine; Cousens, Simon; Cox, Jonathan; Campbell, Oona M R

2011-01-25

Maternal and perinatal mortality could be reduced if all women delivered in settings where skilled attendants could provide emergency obstetric care (EmOC) if complications arise. Research on determinants of skilled attendance at delivery has focussed on household and individual factors, neglecting the influence of the health service environment, in part due to a lack of suitable data. The aim of this study was to quantify the effects of distance to care and level of care on women's use of health facilities for delivery in rural Zambia, and to compare their population impact to that of other important determinants. Using a geographic information system (GIS), we linked national household data from the Zambian Demographic and Health Survey 2007 with national facility data from the Zambian Health Facility Census 2005 and calculated straight-line distances. Health facilities were classified by whether they provided comprehensive EmOC (CEmOC), basic EmOC (BEmOC), or limited or substandard services. Multivariable multilevel logistic regression analyses were performed to investigate the influence of distance to care and level of care on place of delivery (facility or home) for 3,682 rural births, controlling for a wide range of confounders. Only a third of rural Zambian births occurred at a health facility, and half of all births were to mothers living more than 25 km from a facility of BEmOC standard or better. As distance to the closest health facility doubled, the odds of facility delivery decreased by 29% (95% CI, 14%-40%). Independently, each step increase in level of care led to 26% higher odds of facility delivery (95% CI, 7%-48%). The population impact of poor geographic access to EmOC was at least of similar magnitude as that of low maternal education, household poverty, or lack of female autonomy. Lack of geographic access to emergency obstetric care is a key factor explaining why most rural deliveries in Zambia still occur at home without skilled care. Addressing geographic and quality barriers is crucial to increase service use and to lower maternal and perinatal mortality. Linking datasets using GIS has great potential for future research and can help overcome the neglect of health system factors in research and policy. Please see later in the article for the Editors' Summary.

An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemia.

PubMed

Dash, Biraja C; Thomas, Dilip; Monaghan, Michael; Carroll, Oliver; Chen, Xizhe; Woodhouse, Kimberly; O'Brien, Timothy; Pandit, Abhay

2015-10-01

Critical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL-10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 μg) and IL-10 (10 μg)/eNOS (20 μg) and reduced inflammation with IL-10 (10 μg) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELP injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recent Perspectives in Ocular Drug Delivery

PubMed Central

Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

2015-01-01

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

Clinical review: The hospital of the future - building intelligent environments to facilitate safe and effective acute care delivery

PubMed Central

2012-01-01

The translation of knowledge into rational care is as essential and pressing a task as the development of new diagnostic or therapeutic devices, and is arguably more important. The emerging science of health care delivery has identified the central role of human factor ergonomics in the prevention of medical error, omission, and waste. Novel informatics and systems engineering strategies provide an excellent opportunity to improve the design of acute care delivery. In this article, future hospitals are envisioned as organizations built around smart environments that facilitate consistent delivery of effective, equitable, and error-free care focused on patient-centered rather than provider-centered outcomes. PMID:22546172

Sonographic large fetal head circumference and risk of cesarean delivery.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Israel, Ariel; Baron, Joel; Porat, Shay; Valsky, Dan V; Yagel, Oren; Amsalem, Hagai; Kabiri, Doron; Gilboa, Yinon; Sivan, Eyal; Unger, Ron; Schiff, Eyal; Hershkovitz, Reli; Yagel, Simcha

2018-03-01

Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management. Copyright © 2018 Elsevier Inc. All rights reserved.

Length of Stay After Childbirth in 92 Countries and Associated Factors in 30 Low- and Middle-Income Countries: Compilation of Reported Data and a Cross-sectional Analysis from Nationally Representative Surveys

PubMed Central

Campbell, Oona M. R.; Cegolon, Luca; Macleod, David; Benova, Lenka

2016-01-01

Background Following childbirth, women need to stay sufficiently long in health facilities to receive adequate care. Little is known about length of stay following childbirth in low- and middle-income countries or its determinants. Methods and Findings We described length of stay after facility delivery in 92 countries. We then created a conceptual framework of the main drivers of length of stay, and explored factors associated with length of stay in 30 countries using multivariable linear regression. Finally, we used multivariable logistic regression to examine the factors associated with stays that were “too short” (<24 h for vaginal deliveries and <72 h for cesarean-section deliveries). Across countries, the mean length of stay ranged from 1.3 to 6.6 d: 0.5 to 6.2 d for singleton vaginal deliveries and 2.5 to 9.3 d for cesarean-section deliveries. The percentage of women staying too short ranged from 0.2% to 83% for vaginal deliveries and from 1% to 75% for cesarean-section deliveries. Our conceptual framework identified three broad categories of factors that influenced length of stay: need-related determinants that required an indicated extension of stay, and health-system and woman/family dimensions that were drivers of inappropriately short or long stays. The factors identified as independently important in our regression analyses included cesarean-section delivery, birthweight, multiple birth, and infant survival status. Older women and women whose infants were delivered by doctors had extended lengths of stay, as did poorer women. Reliance on factors captured in secondary data that were self-reported by women up to 5 y after a live birth was the main limitation. Conclusions Length of stay after childbirth is very variable between countries. Substantial proportions of women stay too short to receive adequate postnatal care. We need to ensure that facilities have skilled birth attendants and effective elements of care, but also that women stay long enough to benefit from these. The challenge is to commit to achieving adequate lengths of stay in low- and middle-income countries, while ensuring any additional time is used to provide high-quality and respectful care. PMID:26954561

Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

PubMed

Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

2018-04-03

Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF systems. Furthermore, we intend to provide insight into harnessing CF-synthesized proteoliposomes for efficient therapeutic delivery. Copyright © 2018. Published by Elsevier Ltd.

Factors Associated with Teacher Delivery of a Classroom-Based Tier 2 Prevention Program.

PubMed

Sutherland, Kevin S; Conroy, Maureen A; McLeod, Bryce D; Algina, James; Kunemund, Rachel L

2018-02-01

Teachers sometimes struggle to deliver evidence-based programs designed to prevent and ameliorate chronic problem behaviors of young children with integrity. Identifying factors associated with variations in the quantity and quality of delivery is thus an important goal for the field. This study investigated factors associated with teacher treatment integrity of BEST in CLASS, a tier-2 prevention program designed for young children at risk for developing emotional/behavioral disorders. Ninety-two early childhood teachers and 231 young children at-risk for emotional/behavioral disorders participated in the study. Latent growth curve analyses indicated that both adherence and competence of delivery increased across six observed time points. Results suggest that teacher education and initial levels of classroom quality may be important factors to consider when teachers deliver tier-2 (i.e., targeted to children who are not responsive to universal or tier-1 programming) prevention programs in early childhood settings. Teachers with higher levels of education delivered the program with more adherence and competence initially. Teachers with higher initial scores on the Emotional Support subscale of the Classroom Assessment Scoring System (CLASS) delivered the program with more competence initially and exhibited higher growth in both adherence and competence of delivery across time. Teachers with higher initial scores on the Classroom Organization subscale of the CLASS exhibited lower growth in adherence across time. Contrary to hypotheses, teacher self-efficacy did not predict adherence, and teachers who reported higher initial levels of Student Engagement self-efficacy exhibited lower growth in competence of delivery. Results are discussed in relation to teacher delivery of evidence-based programs in early childhood classrooms.

Large-scale educational telecommunications systems for the US: An analysis of educational needs and technological opportunities

NASA Technical Reports Server (NTRS)

Morgan, R. P.; Singh, J. P.; Rothenberg, D.; Robinson, B. E.

1975-01-01

The needs to be served, the subsectors in which the system might be used, the technology employed, and the prospects for future utilization of an educational telecommunications delivery system are described and analyzed. Educational subsectors are analyzed with emphasis on the current status and trends within each subsector. Issues which affect future development, and prospects for future use of media, technology, and large-scale electronic delivery within each subsector are included. Information on technology utilization is presented. Educational telecommunications services are identified and grouped into categories: public television and radio, instructional television, computer aided instruction, computer resource sharing, and information resource sharing. Technology based services, their current utilization, and factors which affect future development are stressed. The role of communications satellites in providing these services is discussed. Efforts to analyze and estimate future utilization of large-scale educational telecommunications are summarized. Factors which affect future utilization are identified. Conclusions are presented.

33 CFR 155.1020 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... vessel or aircraft outfitted with the dispersant-application equipment acting as the delivery system for...: Adverse weather means the weather conditions that will be considered when identifying response systems and equipment in a response plan for the applicable operating environment. Factors to consider include, but are...

33 CFR 155.1020 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... vessel or aircraft outfitted with the dispersant-application equipment acting as the delivery system for...: Adverse weather means the weather conditions that will be considered when identifying response systems and equipment in a response plan for the applicable operating environment. Factors to consider include, but are...

Neonatal clavicle fracture in cesarean delivery: incidence and risk factors.

PubMed

Choi, Hyun Ah; Lee, Yeon Kyung; Ko, Sun Young; Shin, Son Moon

2017-07-01

Neonatal clavicle fracture in cesarean delivery is rare and has not been extensively studied. We performed a retrospective review of cesarean deliveries with neonatal clavicle fracture during a 12-year period. Maternal and neonatal factors as well as surgical factors related to cesarean delivery for the fracture were determined and compared to the control group to analyze their significance. Among a total 89 367 deliveries during the study period, 36 286 babies were born via cesarean section. Nineteen cases of clavicle fractures in cesarean section were identified (0.05% of total live births via cesarean section). In the analysis of maternal and neonatal risk factors, birthweight, birthweight ≥ 4000  g and maternal age were significantly associated with clavicle fracture in cesarean section. However, clavicle fractures were not correlated with the selected surgical factors such as indication for cesarean section, skin incision to delivery time and incision type of skin and uterus. Logistic regression analysis showed that birthweight was the major risk factor for clavicle fracture. Clavicle fractures complicated 0.05% of cesarean deliveries. The main risk factor related to a clavicle fracture in cesarean section was the birthweight of an infant. As reported in previous studies associated with vaginal delivery, clavicle fracture is considered to be an unavoidable event and may not be eliminated, even in cesarean delivery.

From Molecular to Nanotechnology Strategies for Delivery of Neurotrophins: Emphasis on Brain-Derived Neurotrophic Factor (BDNF)

PubMed Central

Géral, Claire; Angelova, Angelina; Lesieur, Sylviane

2013-01-01

Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has been proposed for the administration of these leading therapeutic candidates, which are essential for the development, survival and function of human neurons. In this review, we describe the existing approaches for delivery of brain-derived neurotrophic factor (BDNF), which is the most abundant neurotrophin in the mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged as a promising therapy against neurodegenerative disorders. Polymer-based carriers have provided sustained neurotrophin delivery, whereas lipid-based particles have contributed also to potentiation of the BDNF action. Nanotechnology offers new possibilities for the design of vehicles for neuroprotection and neuroregeneration. Recent developments in nanoscale carriers for encapsulation and transport of BDNF are highlighted. PMID:24300402

Topical Gene Electrotransfer to the Epidermis of Hairless Guinea Pig by Non-Invasive Multielectrode Array

PubMed Central

Guo, Siqi; Israel, Annelise L.; Basu, Gaurav; Donate, Amy; Heller, Richard

2013-01-01

Topical gene delivery to the epidermis has the potential to be an effective therapy for skin disorders, cutaneous cancers, vaccinations and systemic metabolic diseases. Previously, we reported on a non-invasive multielectrode array (MEA) that efficiently delivered plasmid DNA and enhanced expression to the skin of several animal models by in vivo gene electrotransfer. Here, we characterized plasmid DNA delivery with the MEA in a hairless guinea pig model, which has a similar histology and structure to human skin. Significant elevation of gene expression up to 4 logs was achieved with intradermal DNA administration followed by topical non-invasive skin gene electrotransfer. This delivery produced gene expression in the skin of hairless guinea pig up to 12 to 15 days. Gene expression was observed exclusively in the epidermis. Skin gene electrotransfer with the MEA resulted in only minimal and mild skin changes. A low level of human Factor IX was detected in the plasma of hairless guinea pig after gene electrotransfer with the MEA, although a significant increase of Factor IX was obtained in the skin of animals. These results suggest gene electrotransfer with the MEA can be a safe, efficient, non-invasive skin delivery method for skin disorders, vaccinations and potential systemic diseases where low levels of gene products are sufficient. PMID:24015305

Semiconductor laser insert with uniform illumination for use in photodynamic therapy

NASA Astrophysics Data System (ADS)

Charamisinau, Ivan; Happawana, Gemunu; Evans, Gary; Rosen, Arye; Hsi, Richard A.; Bour, David

2005-08-01

A low-cost semiconductor red laser light delivery system for esophagus cancer treatment is presented. The system is small enough for insertion into the patient's body. Scattering elements with nanoscale particles are used to achieve uniform illumination. The scattering element optimization calculations, with Mie theory, provide scattering and absorption efficiency factors for scattering particles composed of various materials. The possibility of using randomly deformed spheres and composite particles instead of perfect spheres is analyzed using an extension to Mie theory. The measured radiation pattern from a prototype light delivery system fabricated using these design criteria shows reasonable agreement with the theoretically predicted pattern.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

PubMed

Xie, Yuran; Merkel, Olivia M

2015-10-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Health Professionals Special Pays Study: Report to Congress on Armed Forces Health Professionals Special Pays -- Other Health Care Providers

DTIC Science & Technology

1988-12-01

of its force in those years, while others were able to maintain their size fairly well. Various factors have contributed to the relative health of each...specialized health care providers. These factors have particular significance for health care in the Military Health Services System (MHSS). The Military...system. Many factors interrelate to cause major changes in health care delivery since the early 1970s. And health care is continuing to evolve as a result

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.

Mechanistic studies of an autonomously pulsing hydrogel/enzyme system for rhythmic hormone delivery.

PubMed

Bhalla, Amardeep S; Siegel, Ronald A

2014-12-28

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion. A bench prototype system based on this scheme was previously shown to produce near rhythmic oscillations in internal pH and in GnRH delivery over a period of one week. In the present work, a systematic study of conditions permitting such oscillations is presented, along with a study of factors causing period of oscillations to increase with time and ultimately cease. Membrane composition, glucose concentration, and surface area of marble (CaCO3), which is incorporated as a reactant, were found to affect the capacity of the system to oscillate, and the pH range over which oscillations occur. Accumulation of gluconate- and Ca2+ in the system over time correlated with lengthening of oscillation period, and possibly with cessation of oscillations. Enzyme degradation may also be a factor. These studies provide the groundwork for future improvements in device design. Copyright © 2014 Elsevier B.V. All rights reserved.

A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery.

PubMed

Skardal, Aleksander; Murphy, Sean V; Crowell, Kathryn; Mack, David; Atala, Anthony; Soker, Shay

2017-10-01

For many cellular therapies being evaluated in preclinical and clinical trials, the mechanisms behind their therapeutic effects appear to be the secretion of growth factors and cytokines, also known as paracrine activity. Often, delivered cells are transient, and half-lives of the growth factors that they secrete are short, limiting their long-term effectiveness. The goal of this study was to optimize a hydrogel system capable of in situ cell delivery that could sequester and release growth factors secreted from those cells after the cells were no longer present. Here, we demonstrate the use of a fast photocross-linkable heparin-conjugated hyaluronic acid (HA-HP) hydrogel as a cell delivery vehicle for sustained growth factor release, which extends paracrine activity. The hydrogel could be modulated through cross-linking geometries and heparinization to support sustained release proteins and heparin-binding growth factors. To test the hydrogel in vivo, we used it to deliver amniotic fluid-derived stem (AFS) cells, which are known to secrete cytokines and growth factors, in full thickness skin wounds in a nu/nu murine model. Despite transience of the AFS cells in vivo, the HA-HP hydrogel with AFS cells improved wound closure and reepithelialization and increased vascularization and production of extracellular matrix in vivo. These results suggest that HA-HP hydrogel has the potential to prolong the paracrine activity of cells, thereby increasing their therapeutic effectiveness in wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1986-2000, 2017. © 2016 Wiley Periodicals, Inc.

Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.

PubMed

Yu, Xiaohua; Biedrzycki, Adam H; Khalil, Andrew S; Hess, Dalton; Umhoefer, Jennifer M; Markel, Mark D; Murphy, William L

2017-09-01

Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrate enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect is attributed to the maintenance of protein conformational structure, which is closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintains its biological activity for weeks during release, while it maintains activity for less than 7 d during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor using a mineral coated surgical suture significantly improves functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a two fold improvement in mechanical properties. The findings of this study demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies for Controlled Delivery of Biologics for Cartilage Repair

PubMed Central

Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

2014-01-01

The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

Non-viral gene therapy for bone tissue engineering.

PubMed

Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

2013-01-01

The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

Clinical Opinion: "Doing Something" About the Cesarean Delivery Rate.

PubMed

Clark, S L; Garite, T J; Hamilton, E J; Belfort, M A; Hankins, G D

2018-05-04

There is a general consensus that the cesarean delivery rate in the U.S. is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the U.S. cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives which are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent ACOG/SMFM Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second stage arrest without incorporating other clinical factors into the decision making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current U.S. cesarean delivery rate is the expected result of the unique demographic, geographic and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces. Copyright © 2018 Elsevier Inc. All rights reserved.

Does vacuum delivery carry a higher risk of shoulder dystocia? Review and meta-analysis of the literature.

PubMed

Dall'Asta, Andrea; Ghi, Tullio; Pedrazzi, Giuseppe; Frusca, Tiziana

2016-09-01

Vacuum extractor has been increasingly used over the last decades and is acknowledged as a risk factor for shoulder dystocia (SD). In this meta-analysis we assess the actual risk of SD following a vacuum delivery compared to spontaneous vaginal delivery (SVD) and forceps. Systematic literature search (English literature only) on MEDLINE, EMBASE, ScienceDirect, the Cochrane library and ClinicalTrials.gov conducted up to May 2015. Key search terms included: Operative/Vacuum/Forceps delivery [Mesh] and shoulder dystocia and subheadings. 2 stage-process study selection. We included only studies where data concerning the occurrence of SD following operative vaginal delivery were reported as adjusted odds ratio (AOR) and no significant difference in confounding factors for SD was recorded. Included trials clustered according to the delivery mode (1) vacuum vs. SVD, (2) forceps vs. vacuum. Methodological quality of each study evaluated with the Newcastle-Ottawa System (NOS). 87 potentially relevant papers. After applying inclusion and exclusion criteria only 7 were selected for the meta-analysis. Vacuum delivery appeared associated with a higher risk of SD than SVD in both fixed and random model (OR 2.87 and 2.98 respectively). No difference in the rate of SD was found between vacuum and forceps (p>0.05). Vacuum extractor carries an increased risk of SD compared with spontaneous vaginal delivery whereas the occurrence of SD does not seem to vary following vacuum or forceps. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives.

PubMed

Chen, Fa-Ming; Shelton, Richard M; Jin, Yan; Chapple, Iain L C

2009-05-01

Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus.

Approaches for Enhancing Oral Bioavailability of Peptides and Proteins

PubMed Central

Renukuntla, Jwala; Vadlapudi, Aswani Dutt; Patel, Ashaben; Boddu, Sai HS.; Mitra, Ashim K

2013-01-01

Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. PMID:23428883

Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

PubMed

Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

2016-01-01

Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

The analytical solution for drug delivery system with nonhomogeneous moving boundary condition

NASA Astrophysics Data System (ADS)

Saudi, Muhamad Hakimi; Mahali, Shalela Mohd; Harun, Fatimah Noor

2017-08-01

This paper discusses the development and the analytical solution of a mathematical model based on drug release system from a swelling delivery device. The mathematical model is represented by a one-dimensional advection-diffusion equation with nonhomogeneous moving boundary condition. The solution procedures consist of three major steps. Firstly, the application of steady state solution method, which is used to transform the nonhomogeneous moving boundary condition to homogeneous boundary condition. Secondly, the application of the Landau transformation technique that gives a significant impact in removing the advection term in the system of equation and transforming the moving boundary condition to a fixed boundary condition. Thirdly, the used of separation of variables method to find the analytical solution for the resulted initial boundary value problem. The results show that the swelling rate of delivery device and drug release rate is influenced by value of growth factor r.

Inhaled gene therapy in lung cancer: proof-of-concept for nano-oncology and nanobiotechnology in the management of lung cancer.

PubMed

Zarogoulidis, Paul; Darwiche, Kaid; Hohenforst-Schmidt, Wolfgang; Huang, Haidong; Li, Qiang; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-08-01

Lung cancer still remains one of the leading causes of death among cancer patients. Although novel targeted therapies have been established in everyday treatment practice, and conventional platinum-based doublets have demonstrated effective results regarding overall and progression-free survival, we have still failed to achieve long-term survival. Therefore, several strategies of applying locoregional therapy are under investigation. Aerosol chemotherapy is already under investigation and, taking this a step further, aerosol gene therapies with multiple delivery systems are being developed. Several efforts have demonstrated its efficiency and effectiveness, but there are still multiple factors that have to be considered and combined to achieve an overall more effective multifunctional treatment. In the current review, we present data regarding aerosol delivery systems, transporters, carriers, vectors, genes, toxicity, efficiency, specificity, lung microenvironment and delivery gene therapy systems. Finally, we present current studies and future perspectives.

Expanding Alternative Delivery Systems.

ERIC Educational Resources Information Center

Baltzer, Jan A.

Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

What Health Service Provider Factors Are Associated with Low Delivery of HIV Testing to Children with Acute Malnutrition in Dowa District of Malawi?

PubMed

Chitete, Lusungu; Puoane, Thandi

2015-01-01

The Community-based Management of Acute Malnutrition is the national program for treating acute malnutrition in Malawi. Under this program's guidelines all children enrolled should undergo an HIV test, so that those infected can receive appropriate treatment and care. However, the national data of 2012 shows a low delivery of testing. Prior studies have investigated client-related factors affecting uptake of HIV testing in Community-based Management of Acute Malnutrition program. Lacking is the information on the service provider factors that are associated with the delivery of testing. This study investigated service provider factors that affect delivery of HIV testing among children enrolled in the program and explored ways in which this could be improved. A descriptive study that used qualitative methods of data collection. Client registers were reviewed to obtain the number of children enrolled in Community-based Management of Acute Malnutrition and the number of children who were tested for HIV over a 12-month period. In-depth interviews were conducted with Community-based Management of Acute Malnutrition and HIV Testing and Counselling focal persons to investigate factors affecting HIV test delivery. Descriptive statistics were used to analyze data from client registers. Information from interviews was analyzed using a thematic approach. Quantitative data revealed that 1738 (58%) of 2981 children enrolled in Community-based Management of Acute Malnutrition were tested for HIV. From in-depth interviews four themes emerged, that is, lack of resources for HIV tests; shortage of staff skilled in HIV testing and counseling; lack of commitment among staff in referring children for HIV testing; and inadequately trained staff. There is a need for a functioning health system to help reduce child mortality resulting from HIV related conditions.

Review paper: critical issues in tissue engineering: biomaterials, cell sources, angiogenesis, and drug delivery systems.

PubMed

Naderi, Hojjat; Matin, Maryam M; Bahrami, Ahmad Reza

2011-11-01

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

Biomedical Properties Study of Modified Chitosan Nanoparticles for Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Saboktakin, Mohammad Reza

2013-09-01

The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.

Novel Approaches in Formulation and Drug Delivery using Contact Lenses

PubMed Central

Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

2011-01-01

The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

Numbers, systems, people: how interactions influence integration. Insights from case studies of HIV and reproductive health services delivery in Kenya

PubMed Central

Mayhew, Susannah H; Warren, Charlotte E; Collumbien, Martine; Ndwiga, Charity; Mutemwa, Richard; Lut, Irina; Colombini, Manuela; Vassall, Anna

2017-01-01

Abstract Drawing on rich data from the Integra evaluation of integrated HIV and reproductive-health services, we explored the interaction of systems hardware and software factors to explain why some facilities were able to implement and sustain integrated service delivery while others were not. This article draws on detailed mixed-methods data for four case-study facilities offering reproductive-health and HIV services between 2009 and 2013 in Kenya: (i) time-series client flow, tracking service uptake for 8841 clients; (ii) structured questionnaires with 24 providers; (iii) in-depth interviews with 17 providers; (iv) workload and facility data using a periodic activity review and cost-instruments; and (v) contextual data on external activities related to integration in study sites. Overall, our findings suggested that although structural factors like stock-outs, distribution of staffing and workload, rotation of staff can affect how integrated care is provided, all these factors can be influenced by staff themselves: both frontline and management. Facilities where staff displayed agency of decision making, worked as a team to share workload and had management that supported this, showed better integration delivery and staff were able to overcome some structural deficiencies to enable integrated care. Poor-performing facilities had good structural integration, but staff were unable to utilize this because they were poorly organized, unsupported or teams were dysfunctional. Conscientious objection and moralistic attitudes were also barriers. Integra has demonstrated that structural integration is not sufficient for integrated service delivery. Rather, our case studies show that in some cases excellent leadership and peer-teamwork enabled facilities to perform well despite resource shortages. The ability to provide support for staff to work flexibly to deliver integrated services and build resilient health systems to meet changing needs is particularly relevant as health systems face challenges of changing burdens of disease, climate change, epidemic outbreaks and more. PMID:29194544

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

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

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Difference and alteration in pharmacokinetic and metabolic characteristics of low-solubility natural medicines.

PubMed

Yan, Shenglei; Liu, Yuying; Feng, Jianfang; Zhao, Hua; Yu, Zhongshu; Zhao, Jing; Li, Yao; Zhang, Jingqing

2018-05-01

Drug metabolism plays vital roles in the absorption and pharmacological activity of poorly soluble natural medicines. It is important to choose suitable delivery systems to increase the bioavailability and bioactivity of natural medicines with low solubility by regulating their metabolism and pharmacokinetics. This review investigates recent developments about the metabolic and pharmacokinetic behavior of poorly soluble natural medicines and their delivery systems. Delivery systems, dosage, administration route and drug-drug interactions alter the metabolic pathway, and bioavailability of low-solubility natural medicines to different degrees. Influencing factors such as formulation, dosage, and administration route are discussed. The metabolic reactions, metabolic enzymes, metabolites and pharmacokinetic behaviors of low-solubility natural medicines, and their delivery systems are systematically reviewed. There are various metabolic situations in the case of low-solubility natural medicines. CYP3A4 and CYP2C are the most common metabolic enzymes, and hydroxylation is the most common metabolic reaction of low solubility natural medicines. The stereo isomeric configuration can have a large influence on metabolism. This review will be useful for physicians and pharmacists to guide more accurate treatment with low-solubility natural medicines by increasing drug efficacies and protecting patients from toxic side effects.

A qualitative study of nulliparous women's decision making on mode of delivery under China's two-child policy.

PubMed

Gu, Chunyi; Zhu, Xinli; Ding, Yan; Setterberg Simone; Wang, Xiaojiao; Tao, Hua; Zhang, Yu

2018-07-01

To explore nulliparous women's perceptions of decision making regarding mode of delivery under China's two-child policy. Qualitative descriptive design with in-depth semi-structured interviews. Postnatal wards at a tertiary specialized women's hospital in Shanghai, China. 21 nulliparous women 2-3 days postpartum were purposively sampled until data saturation. In-depth semi-structured interviews were conducted between October 8th, 2015 and January 31st, 2016. Two overarching descriptive categories were identified: (1) women's decision-making process: stability versus variability, and (2) factors affecting decision making: variety versus interactivity. Four key themes emerged from each category: (1) initial decision making with certainty: anticipated trial of labour, failed trial of labour, 'shy away' and compromise, anticipated caesarean delivery; (2) initial decision making with uncertainty: anticipated trial of labour, failed trial of labour, 'shy away' and compromise; (3) internal factors affecting decision making: knowledge and attitude, and childbirth self-efficacy; and (4) external factors affecting decision making: social support, and the situational environment. At the initial period of China's two-child policy, nulliparous women have perceived their decision-making process regarding mode of delivery as one with complexity and uncertainty, influenced by both internal and external factors. This may have implications for the obstetric setting to develop a well-designed decision support system for pregnant women during the entire pregnancy periods. And it is recommended that care providers should assess women's preferences for mode of delivery from early pregnancy and provide adequate perinatal support and continuity of care for them. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Surgical methods for delivery in modern obstetrics and their influence on maternal and infant health].

PubMed

Kokhanevych, Ie V; Mitsoda, R M; Konoplianko, T V; Konoplianko, V V

2000-03-01

The article addresses issues of comparative characterization of deliveries involving surgery and impact thereof on the health of the mother and her child. Risk factors are identified that the mother and her child run in sectio cesarea, in application of obstetrical forceps, and in vacuum-extraction of the fetus. Cesarean section was found out to be the most acceptable mode of delivery in origination of organic and functional nervous system involvement in children but the most ill-chosen and unpropitious one in the mother, especially so in those groups at risk for bleeding, septic complications, and genital endometriosis. Among those surgical methods of delivery being the least traumatic to the mother are obstetrical forceps and vacuum-extraction of the fetus.

Key factors of successful JIT integration with IBS - An overview

NASA Astrophysics Data System (ADS)

Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

2016-08-01

The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

PubMed

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Gelatin Methacrylate Microspheres for Growth Factor Controlled Release

PubMed Central

Nguyen, Anh H.; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C.

2014-01-01

Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles formulated with a wide range of different cross-linking densities (15–90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor over conventional GA cross-linked MPs, despite an order of magnitude greater gelatin content of GA MPs. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery. PMID:25463489

Weather in the cockpit : priorities, sources, delivery, and needs in the next generation air transportation system.

DOT National Transportation Integrated Search

2012-07-01

A study was conducted to identify/verify weather factors important to the conduct of aviation activities and : that would be important to consider in systems intended to operate within the NextGen environment. The : study reviewed weather-information...

Impact of free delivery policy on utilization of maternal health services in county referral hospitals in Kenya.

PubMed

Njuguna, John; Kamau, Njoroge; Muruka, Charles

2017-06-21

Kenya has a high maternal mortality rate. Provision of skilled delivery plays a major role in reducing maternal mortality. Cost is a hindrance to the utilization of skilled delivery. The Government of Kenya introduced a policy of free delivery services in government facilities beginning June 2013. We sought to determine the impact of this intervention on facility based deliveries in Kenya. We compared deliveries and antenatal attendance in 47 county referral hospitals and 30 low cost private hospitals not participating in the free delivery policy for 2013 and 2014 respectively. The data was extracted from the Kenya Health Information System. Multiple regression was done to assess factors influencing increase in number of deliveries among the county referral hospitals. The number of deliveries and antenatal attendance increased by 26.8% and 16.2% in county referral hospitals and decreased by 11.9% and 5.4% respectively in low cost private hospitals. Increase in deliveries among county referral hospitals was influenced by population size of county and type of county referral hospital. Counties with level 5 hospitals recorded more deliveries compared to those with level 4 hospitals. This intervention increased the number of facility based deliveries. Policy makers may consider incorporating low cost private hospitals so as to increase the coverage of this intervention.

Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

PubMed

Krishnaiah, Yellela S R; Khan, Mansoor A

2012-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC.

The development of a novel cricket bowling system: recreating spin and swing bowling deliveries at the elite level

NASA Astrophysics Data System (ADS)

West, A. A.; Justham, L.

2008-03-01

During the game of cricket, bowlers create different deliveries by altering the manner in which they release the ball from their hand. The orientation of the seam, the speed at which the ball is released and the magnitude and direction of the spin combine to determine the motion of the ball through the air and its movement after impact with the wicket. These factors have to be considered if automatic training machines are to be capable of replicating elite bowling deliveries. The need for automotive systems for batting and fielding training at the elite level has arisen due to: (i) the capabilities of human bowlers are limited by the onset of fatigue and the risk of injury and (ii) a large number of accurate and repeatable deliveries to be ''programmable'' by coaches to ensure batsmen and fielders are tested to the limits of their abilities and a training benefit is achieved.

A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

PubMed

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2013-08-01

Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Epidemiology of anesthesia-related complications in labor and delivery, New York State, 2002-2005.

PubMed

Cheesman, Khadeen; Brady, Joanne E; Flood, Pamela; Li, Guohua

2009-10-01

Epidemiologic data on anesthesia-related complications occurring during labor and delivery are essential for measuring and evaluating the safety and quality of obstetric anesthesia care but are lacking. We aimed to fill this research gap by exploring the epidemiologic patterns and risk factors of anesthesia-related complications in a large sample of women giving birth in New York hospitals. Using the Healthcare Cost and Utilization Project State Inpatient Databases files, we identified all discharge records for labor and delivery from New York hospitals between 2002 and 2005. We then identified women who experienced any recorded anesthesia-related complication during labor and delivery as determined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. The incidence of anesthesia-related complications was calculated by demographic and clinical characteristics. Multivariate logistic regression was performed to assess risk factors of anesthesia-related complications. Of the 957,471 deliveries studied, 4438 (0.46%) had at least one anesthesia-related complication. The majority (55%) of anesthesia-related events occurring during labor and delivery were spinal complications, followed by systemic complications (43%) and overdose or adverse effects (2%). Multivariate logistic regression revealed five risk factors of anesthesia-related complications: cesarean delivery (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.36-2.68), rural area (OR 1.33, 95% CI 1.21-1.46), Charlson-Deyo Comorbidity Index >or=1 (OR 1.47, 95% CI 1.28-1.69), Caucasian race (OR 1.37, 95% CI 1.24-1.52), and scheduled admission (OR 1.10, 95% CI 1.03-1.18). Anesthesia-related complications were associated with about a one-day increase in the average length of stay (3.89 +/- 3.69 [mean +/- SD] days vs 2.92 +/- 2.38 days for deliveries without anesthesia-related complications, P < 0.0001) and a 22-fold increased risk of maternal mortality (OR 22.26, 95% CI 11.20-44.24). The incidence of anesthesia-related complications during labor and delivery seems to be low but remains a cause of concern, particularly in women undergoing cesarean delivery, living in rural areas, or having preexisting medical conditions.

Tubal Factor Infertility and Perinatal Risk After Assisted Reproductive Technology

PubMed Central

Kawwass, Jennifer F.; Crawford, Sara; Kissin, Dmitry M.; Session, Donna R.; Boulet, Sheree; Jamieson, Denise J.

2014-01-01

OBJECTIVE To assess trends of tubal factor infertility and to evaluate risk of miscarriage and delivery of preterm or low birth weight (LBW) neonates among women with tubal factor infertility using assisted reproductive technology (ART). METHODS We assessed trends of tubal factor infertility among all fresh and frozen, donor, and nondonor ART cycles performed annually in the United States between 2000 and 2010 (N=1,418,774) using the National ART Surveillance System. The data set was then limited to fresh, nondonor in vitro fertilization cycles resulting in pregnancy to compare perinatal outcomes for cycles associated with tubal compared with male factor infertility. We performed bivariate and multivariable analyses controlling for maternal characteristics and calculated adjusted risk ratios (RRs) and 95% confidence intervals (CI). RESULTS The percentage of ART cycles associated with tubal factor infertility diagnoses decreased from 2000 to 2010 (26.02–14.81%). Compared with male factor infertility, tubal factor portended an increased risk of miscarriage (14.0% compared with 12.7%, adjusted RR 1.08, 95% CI 1.04–1.12); risk was increased for both early and late miscarriage. Singleton neonates born to women with tubal factor infertility had an increased risk of pre-term birth (15.8% compared with 11.6%, adjusted RR 1.27, 95% CI 1.20–1.34) and LBW (10.9% compared with 8.5%, adjusted RR 1.28, 95% CI 1.20–1.36). Significant increases in risk persisted for early and late preterm delivery and very low and moderately LBW delivery. A significantly elevated risk was also detected for twin, but not triplet, pregnancies. CONCLUSION Tubal factor infertility, which is decreasing in prevalence in the United States, is associated with an increased risk of miscarriage, preterm birth, and LBW delivery as compared with couples with male factor infertility using ART. PMID:23812461

Factors associated with recovery from 1 minute Apgar score <4 in live, singleton, term births: an analysis of Malaysian National Obstetrics Registry data 2010-2012.

PubMed

Jeganathan, Ravichandran; Karalasingam, Shamala D; Hussein, Julia; Allotey, Pascale; Reidpath, Daniel D

2017-04-08

The neonatal Apgar score at 5 min has been found to be a better predictor of outcomes than the Apgar score at 1 min. A baby, however, must pass through the first minute of life to reach the fifth. There has been no research looking at predictors of recovery (Apgar scores ≥7) by 5 min in neonates with 1 min Apgar scores <4. An analysis of observational data was conducted using live, singleton, term births recorded in the Malaysian National Obstetrics Registry between 2010 and 2012. A total of 272,472 live, singleton, term births without congential anomalies were recorded, of which 1,580 (0.59%) had 1 min Apgar scores <4. Descriptive methods and bi- and multi-variable logistic regression were used to identify risk factors associated with recovery (5 min Apgar score ≥7) from 1 min Apgar scores <4. Less than 1% of births have a 1 min Apgar scores <4. Only 29.4% of neonates with 1 min Apgar scores <4 recover to a 5 min Apgar score ≥7. Among uncomplicated vaginal deliveries, after controlling for other factors, deliveries by a doctor of neonates with a 1 min Apgar score <4 had odds of recovery 2.4 times greater than deliveries of neonates with a 1 min Apgar score <4 by a nurse-midwife. Among deliveries of neonates with a 1 min Apgar score <4 by doctors, after controlling for other factors, planned and unplanned CS was associated with better odds of recovery than uncomplicated vaginal deliveries. Recovery was also associated with maternal obesity, and there was some ethnic variation - in the adjusted analysis indigenous (Orang Asal) Malaysians had lower odds of recovery. A 1 min Apgar score <4 is relatively rare, and less than a third recover by five minutes. In those newborns the qualification of the person performing the delivery and the type of delivery are independent predictors of recovery as is maternal BMI and ethnicity. These are associations only, not necessarily causes, and they point to potential areas of research into health systems factors in the labour room, as well as possible biological and cultural factors.

Special problems in aerosol delivery: neonatal and pediatric considerations.

PubMed

Cole, C H

2000-06-01

Identification of the determinants of efficient aerosol delivery and the specific challenges of aerosol delivery to infants and children can facilitate a systematic approach to optimize aerosol delivery to this population. There are inherent anatomical, physiologic, pathophysiologic, and technical limitations of aerosol efficiency in infants and young children. Nevertheless, one can enhance aerosol efficiency through application of sound principles of aerosol delivery and by exerting control over factors that are amenable to intervention. Improvements in aerosol formulations and delivery systems are being made that will enhance efficiency, decrease risk, and reduce waste and cost. Attention to aerosol particle size (1-3 microm mass median aerodynamic diameter and geometric standard deviation < 2 microm), and the concentration of this respirable particle fraction produced by an aerosol system may enhance delivery through endotracheal tubes and to the lower respiratory tract in infants and children with low V(T) and low inspiratory rates. Attention to the choice of delivery system and to details of proper MDI technique (shaking, priming, immediate actuation, and avoiding multiple actuations prior to inhalation), choice of the aerosol spacer and patient interface (type of face mask, endotracheal tube, mouthpiece), spacer cleaning, and consideration of the medicine to be aerosolized (solution or suspension, viscosity) permit adjustment of the aerosol regimen to optimize delivery. All the patient-related, system-related, and operator-dependent considerations combined can greatly impact aerosol delivery efficacy and improve therapeutic response. Therefore, education and motivation of medical personnel, parents and caregivers, and patients regarding factors that influence aerosol efficiency and teaching of proper technique must be prioritized in order to improve aerosol delivery. Aerosol therapy to all patients, especially infants and young children, would be well served if we had a clear understanding of the efficiency and functional differences among the various drugs and devices. These are substantive issues with daily therapeutic impact that have received increasingly outspoken concern over the past decade by aerosol scientists and clinicians. These issues must be given due attention by drug and device manufacturers as well as by regulatory agencies. The medication, the device, and the conditions under which they are tested must be considered together and studied as thoroughly as the medications themselves with respect to total output and particle size distribution. As noted by Bisgaard, medication dose recommendations are useless unless the device and technique used are specified. Medication dose recommendation could be facilitated by setting equivalent standards for generic and brand-name medications and devices. In addition, standardization of in vitro models with better replicas of infants' and children's anatomy (oropharynx, upper airways), and better in vitro lung models, plus utilization of realistic breathing patterns of infants and children will improve in vitro prediction of the in vivo dose delivered to lower airways. This would greatly facilitate selection of delivery systems under specific circumstances for infants and children of various ages). Safety profile, therapeutic efficacy, and efficiency of aerosolized medications delivered to infants and children need to be rigorously studied. This is particularly true for medications with potentially great benefit but possible adverse effects, such as inhaled glucocorticoid therapy in extremely premature infants. Common sense, ethics, and due respect for the same high standard of approval requirements of adults and older children should motivate further research in understanding and improving aerosol delivery in infants and young children.

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive.

PubMed

Xie, Xiangyang; Yang, Yang; Yang, Yanfang; Li, Zhiping; Zhang, Hui; Chi, Qiang; Cai, Xingshi; Mei, Xingguo

2016-09-01

A novel, self-administration drug delivery system for subcutaneous infusion was developed and evaluated. The device includes two main components: an osmotic tablet controlled gas actuator and a syringe catheter system. The sodium carbonate in the osmotic pump tablet will release into the surround citric acid solution and produce CO 2 gas, which will drive the drug solution into subcutaneous tissue. The key formulation factors of the osmotic tablet that would influence the infusion profiles of the device were investigated by single factor exploration. The formulation was optimized via a response surface methodology. With an 18 ± 4 min of lag time, the delivery system was able to infuse at an approximate zero-order up to 5.90 ± 0.37 h with a precision of 9.0% RSD (n = 6). A linear correlation was found for the infusion profile and the fitting equation was Y = 0.014X - 0.004 (r = 0.998). A temperature change of 4 °C was found to modify the flow rate by about 12.0%. In vivo results demonstrated that the present subcutaneous infusion device was similar to the commercial infusion pump, and it could bring a long and constant ampicillin plasma level with minimized fluctuations.

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

PubMed

Gonzalez, Ana Maria; Leadbeater, Wendy; Podvin, Sonia; Borboa, Alexandra; Burg, Michael; Sawada, Ritsuko; Rayner, James; Sims, Karen; Terasaki, Tetsuya; Johanson, Conrad; Stopa, Edward; Eliceiri, Brian; Baird, Andrew

2010-11-04

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Updates on smart polymeric carrier systems for protein delivery.

PubMed

El-Sherbiny, Ibrahim; Khalil, Islam; Ali, Isra; Yacoub, Magdi

2017-10-01

Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

Factors Affecting Selection of Learning Management Systems in Higher Education Institutions

ERIC Educational Resources Information Center

Spelke, Kenneth A.

2011-01-01

Learning Management Systems, or LMSs, are widely used throughout higher education to deliver a range of instructional services including content delivery, discussion boards and collaborative work space, testing tools, and gradebook functions. LMSs can be used asynchronously or synchronously in support of online learning, classroom-based learning,…

The Influence of Distance and Level of Care on Delivery Place in Rural Zambia: A Study of Linked National Data in a Geographic Information System

PubMed Central

Gabrysch, Sabine; Cousens, Simon; Cox, Jonathan; Campbell, Oona M. R.

2011-01-01

Background Maternal and perinatal mortality could be reduced if all women delivered in settings where skilled attendants could provide emergency obstetric care (EmOC) if complications arise. Research on determinants of skilled attendance at delivery has focussed on household and individual factors, neglecting the influence of the health service environment, in part due to a lack of suitable data. The aim of this study was to quantify the effects of distance to care and level of care on women's use of health facilities for delivery in rural Zambia, and to compare their population impact to that of other important determinants. Methods and Findings Using a geographic information system (GIS), we linked national household data from the Zambian Demographic and Health Survey 2007 with national facility data from the Zambian Health Facility Census 2005 and calculated straight-line distances. Health facilities were classified by whether they provided comprehensive EmOC (CEmOC), basic EmOC (BEmOC), or limited or substandard services. Multivariable multilevel logistic regression analyses were performed to investigate the influence of distance to care and level of care on place of delivery (facility or home) for 3,682 rural births, controlling for a wide range of confounders. Only a third of rural Zambian births occurred at a health facility, and half of all births were to mothers living more than 25 km from a facility of BEmOC standard or better. As distance to the closest health facility doubled, the odds of facility delivery decreased by 29% (95% CI, 14%–40%). Independently, each step increase in level of care led to 26% higher odds of facility delivery (95% CI, 7%–48%). The population impact of poor geographic access to EmOC was at least of similar magnitude as that of low maternal education, household poverty, or lack of female autonomy. Conclusions Lack of geographic access to emergency obstetric care is a key factor explaining why most rural deliveries in Zambia still occur at home without skilled care. Addressing geographic and quality barriers is crucial to increase service use and to lower maternal and perinatal mortality. Linking datasets using GIS has great potential for future research and can help overcome the neglect of health system factors in research and policy. Please see later in the article for the Editors' Summary PMID:21283606

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

PubMed

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Mesoporous silica nanorods toward efficient loading and intracellular delivery of siRNA

NASA Astrophysics Data System (ADS)

Chen, Lijue; She, Xiaodong; Wang, Tao; Shigdar, Sarah; Duan, Wei; Kong, Lingxue

2018-02-01

The technology of RNA interference (RNAi) that uses small interfering RNA (siRNA) to silence the gene expression with complementary messenger RNA (mRNA) sequence has great potential for the treatment of cancer in which certain genes were usually found overexpressed. However, the carry and delivery of siRNA to the target site in the human body can be challenging for this technology to be used clinically to silence the cancer-related gene expression. In this work, rod shaped mesoporous silica nanoparticles (MSNs) were developed as siRNA delivery system for specific intracellular delivery. The rod MSNs with an aspect ratio of 1.5 had a high surface area of 934.28 m2/g and achieved a siRNA loading of more than 80 mg/g. With the epidermal growth factor (EGF) grafted on the surface of the MSNs, siRNA can be delivered to the epidermal growth factor receptor (EGFR) overexpressed colorectal cancer cells with high intracellular concentration compared to MSNs without EGF and lead to survivin gene knocking down to less than 30%.

Utilisation of maternal health care in western rural China under a new rural health insurance system (New Co-operative Medical System).

PubMed

Long, Qian; Zhang, Tuohong; Xu, Ling; Tang, Shenglan; Hemminki, Elina

2010-10-01

To investigate factors influencing maternal health care utilisation in western rural China and its relation to income before (2002) and after (2007) introducing a new rural health insurance system (NCMS). Data from cross-sectional household-based health surveys carried out in ten western rural provinces of China in 2003 and 2008 were used in the study. The study population comprised women giving birth in 2002 or 2007, with 917 and 809 births, respectively. Correlations between outcomes and explanatory variables were studied by logistic regression models and a log-linear model. Between 2002 and 2007, having no any pre-natal visit decreased from 25% to 12% (difference 13%, 95% CI 10-17%); facility-based delivery increased from 45% to 80% (difference 35%, 95% CI 29-37%); and differences in using pre-natal and delivery care between the income groups narrowed. In a logistic regression analysis, women with lower education, from minority groups, or high parity were less likely to use pre-natal and delivery care in 2007. The expenditure for facility-based delivery increased over the period, but the out-of-pocket expenditure for delivery as a percentage of the annual household income decreased. In 2007, it was 14% in the low-income group. NCMS participation was found positively correlated with lower out-of-pocket expenditure for facility-based delivery (coefficient -1.14 P < 0.05) in 2007. Facility-based delivery greatly increased between 2002 and 2007, coinciding with the introduction of the NCMS. The rural poor were still facing substantial payment for facility-based delivery, although NCMS participation reduced the out-of-pocket expenditure on average. © 2010 Blackwell Publishing Ltd.

Evaluating use and outcomes of mobility technology: a multiple stakeholder analysis.

PubMed

Hammel, Joy; Southall, Kenneth; Jutai, Jeffrey; Finlayson, Marcia; Kashindi, Gabriel; Fok, Daniel

2013-07-01

This qualitative, multi-site study compared and contrasted the outcomes of mobility technology (MT) and the factors influencing these outcomes from the perspective of MT users, caregivers, and professionals involved in MT service delivery. Qualitative focus groups were held in the USA and Canada with multiple stakeholder groups (consumer: n = 45, caregiver: n = 10, service provider: n = 10). Data were analyzed thematically. MT outcomes were conceptualized by participants as a match between expectations for MT and the actual outcomes experienced. Several factors influenced the match including a) MT features, b) environmental factors (e.g. built/physical environment, societal context of acceptance, MT delivery systems/policies), and c) the ability to self-manage the interaction across person, technology and environment, which involved constant negotiation and strategizing. Stakeholders identified MT outcomes that corresponded to ICF levels including body structure and function, activity, and participation across environments; however, varied on their importance and influence on MT impact. The conceptual fit model and factors related to self-management of MT represent new knowledge and provide a framework for stakeholder-based evaluation of MT outcomes. Implications for MT assessment, service delivery, outcomes research, and interventions are discussed.

It takes a village: Exploring the impact of social determinants on delivery system outcomes for heart failure patients.

PubMed

Knighton, Andrew J; Savitz, Lucy A; Benuzillo, Jose; VanDerslice, James A

2017-06-24

Local social determinants may act as effect modifiers for the impact of neighborhood material deprivation on patient-level healthcare outcomes. The objective of this study was to understand the mediating effect of local social determinants on neighborhood material deprivation and delivery outcomes in heart failure (HF) patients. A retrospective cohort study was conducted using 4737 HF patients receiving inpatient care (n=6065 encounters) from an integrated healthcare delivery system from 2010 to 2014. Outcomes included post-discharge mortality, readmission risk and length of stay. Deprivation was measured using an area deprivation index by address of residence. Effect modifications measured included urban-rural residency and faith identification using generalized linear regression models. Patient-level data was drawn from the delivery system data warehouse. Faith identification had a significant protective effect on HF patients from deprived areas, lowering 30-day mortality odds by one-third over patients who did not identify with a faith (OR 0.35 95%CI:0.12-0.98;p=0.05). Significant effects persisted at the 90 and 180-day timeframes. In rural areas, lack of faith identification had a multiplicative effect on 30-day mortality for deprived patients (OR 14.0 95%CI:1.47-132.7;p=0.02). No significant effects were noted for other healthcare outcomes. The lack of expected association between area deprivation and healthcare outcomes in some communities may be explained by the presence of effect modifiers. Understanding existing effect modifiers for area deprivation in local communities that delivery systems serve can inform targeted quality improvement. These factors should also be considered when comparing delivery system performance for reimbursement and in population health management. Copyright © 2017 Elsevier Inc. All rights reserved.

PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration

PubMed Central

Chang, Po-Chun; Seol, Yang-Jo; Cirelli, Joni A; Pellegrini, Gaia R.; Jin, Qiming; Franco, Lea M.; Goldstein, Steven A.; Chandler, Lois A.; Sosnowski, Barbara; Giannobile, William V.

2009-01-01

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo. PMID:19741730

Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing, China.

PubMed

Song, Geng; Wei, Yu-Mei; Zhu, Wei-Wei; Yang, Hui-Xia

2017-10-20

The cesarean section rate (CSR) has been a main concern worldwide. The present study aimed to investigate the CSR in Beijing, China, and to analyze the related factors of CS delivery. An observational study was conducted in 15 medical centers in Beijing using a systemic cluster sampling method. In total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to examine differences between two groups, and related factors of the CSR were examined by multivariable logistic regression. The CSR was 41.9% (4471/10,671) in singleton primiparae. Women who were more than 35 years old had a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561-9.816, P < 0.001). Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640-2.584, P < 0.001). The excessive weight gain group had a 1.4-fold increased risk of CS delivery compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289-1.568, P < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood glucose women. Women who were born in rural areas had a lower risk of CS delivery than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625-0.775, P < 0.001). The risk of CS delivery gradually increased with a decreasing education level. Neonates weighing 3000-3499 g had the lowest CSR (36.2%). Neonates weighing <2500 g had a 2-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 2.020, 95% CI = 1.537-2.656, P < 0.001). Neonates weighing ≥4500 g had an 8.3-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 8.313, 95% CI = 4.436-15.579, P < 0.001). Maternal age, prepregnancy body mass index, gestational weight gain, blood glucose levels, residence, education level, and singleton fetal birth weight are all factors that might significantly affect the CSR.

Impact of Place of Delivery on Neonatal Mortality in Rural Tanzania

PubMed Central

Ajaari, Justice; Masanja, Honorati; Weiner, Renay; Abokyi, Shalom Akonvi; Owusu-Agyei, Seth

2012-01-01

Objectives Studies on factors affecting neonatal mortality have rarely considered the impact of place of delivery on neonatal mortality. This study provides epidemiological information regarding the impact of place of delivery on neonatal deaths. Methods We analyzed data from the Rufiji Health and Demographic Surveillance System (RHDSS) in Tanzania. A total of 5,124 live births and 166 neonatal deaths were recorded from January 2005 to December 2006. The place of delivery was categorized as either in a health facility or outside, and the neonatal mortality rate (NMR) was calculated as the number of neonatal deaths per 1,000 live births. Univariate and multivariate logistic regression models were used to assess the association between neonatal mortality and place of delivery and other maternal risk factors while adjusting for potential confounders. Results Approximately 67% (111) of neonatal deaths occurred during the first week of life. There were more neonatal deaths among deliveries outside health facilities (NMR = 43.4 per 1,000 live births) than among deliveries within health facilities (NMR = 27.0 per 1,000 live births). The overall NMR was 32.4 per 1,000 live births. Mothers who delivered outside a health facility experienced 1.85 times higher odds of experiencing neonatal deaths (adjusted odds ratio = 1.85; 95% confidence interval = 1.33−2.58) than those who delivered in a health facility. Conclusions and Public Health Implications Place of delivery is a significant predictor of neonatal mortality. Pregnant women need to be encouraged to deliver at health facilities and this should be done by intensifying education on where to deliver. Infrastructure, such as emergency transport, to facilitate health facility deliveries also requires urgent attention. PMID:27621958

Drug delivery interfaces in the 21st century: from science fiction ideas to viable technologies.

PubMed

Chertok, Beata; Webber, Matthew J; Succi, Marc D; Langer, Robert

2013-10-07

Early science fiction envisioned the future of drug delivery as targeted micrometer-scale submarines and "cyborg" body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery: the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the predefined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics.

Drug Delivery Interfaces in the 21st Century: From Science Fiction Ideas to Viable Technologies

PubMed Central

Chertok, Beata; Webber, Matthew J.; Succi, Marc D.; Langer, Robert S.

2013-01-01

Early science fiction envisioned the future of drug delivery as targeted micron-scale submarines and ‘Cyborg’ body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery – the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the pre-defined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics. PMID:23915375

Genome editing via delivery of Cas9 ribonucleoprotein.

PubMed

DeWitt, Mark A; Corn, Jacob E; Carroll, Dana

2017-05-15

The CRISPR-Cas genome editing system is very powerful. The format of the CRISPR reagents and the means of delivery are often important factors in targeting efficiency. Delivery of recombinant Cas9 protein and guide RNA (gRNA) as a preformed ribonucleoprotein (RNP) complex has recently emerged as a powerful and general approach to genome editing. Here we outline methods to produce and deliver Cas9 RNPs. A donor DNA carrying desired sequence changes can also be included to program precise sequence introduction or replacement. RNP delivery limits exposure to genome editing reagents, reduces off-target events, drives high rates of homology-dependent repair, and can be applied to embryos to rapidly generate animal models. RNP delivery thus minimizes some of the pitfalls of alternative editing modalities and is rapidly being adopted by the genome editing community. Copyright © 2017 Elsevier Inc. All rights reserved.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

PubMed

Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

[Risk factors associated with dystocic delivery].

PubMed

Romero Gutiérrez, Gustavo; Ríos López, Juan Carlos; Cortés Salim, Patricia; Ponce Ponce de León, Ana Lilia

2007-09-01

the dystocic delivery is a frequent complication and its perinatal repercussions vary from minor lesions to severe brain damage. It has been reported diverse factors associated with this medical complication. to identify the risk factors with significant association with dystocic delivery. a case-control study was carried out. There were included 750 patients, divided into 250 women with dystocic deliveries (cases) and 500 women with eutocic deliveries (controls). Demographic and clinical variables were registered. The statistical analysis was performed with percentages, arithmetic media, standard deviation, Student t test, chi2 and logistic regression analysis. An alpha value was set at 0.05. the factors with statistical significance were: advanced age (p < 0.001), major patient's height (p < 0.001), major new born's weight (p = 0.009), lower parity (p < 0.001), and prolonged duration of labor (p = 0.04). Other variables such as number of pregnancies, previous cesarean sections, spontaneous abortions, weight of the patient, weight earned during pregnancy, number of medical appointments during antenatal care, previous dystocic delivery, and premature rupture of the membranes, were not significant. there are clinical and demographic risk factors associated with dystocic delivery. To identify this risk factors during the antenatal care could diminish the frequency of dystocic deliveries and therefore to avoid the associated maternal-fetal complications.

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

PubMed

Liu, Quan; Fassihi, Reza

2008-02-04

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

Health care quality, access, cost, workforce, and surgical education: the ultimate perfect storm.

PubMed

Schwartz, Marshall Z

2012-01-01

The discussions on health care reform over the past two years have focused on cost containment while trying to maintain quality of care. Focusing on just cost and quality unfortunately does not address other very important factors that impact on our health care delivery system. Availability of a well-trained workforce, maintaining the sophisticated medical/surgical education system, and ultimately access to quality care by the public are critical to maintaining and enhancing our health care delivery system. Unfortunately, all five of these components are under at risk. Thus, we have evolving the ultimate perfect storm affecting our health care delivery system. Although not ideal and given the uniqueness of our population and their expectations, our current delivery system is excellent compared to other countries. However, the cost of our current system is rising at an alarming rate. Currently, health care consumes 17% of our gross domestic product. If our system is not revised this will continue to rise and by 2025 it will consume 48%. The dilemma, given the current state of our overall economy and rising debt, is how to address this major problem. Unfortunately, the Affordable Care Act, which is now law, does not address most of the issues and the cost was initially grossly under estimated. Furthermore, the law does not address the issues of workforce, maintaining our medical education system or ultimately, access. A major revision of our system will be necessary to truly create a system that protects and enhances all five of the components of our health care delivery system. To effectively accomplish this will require addressing those issues that lead to wasteful spending and diversion of our health care dollars to profit instead of care. Improved and efficient delivery systems that reduce complications, reduction of duplication of tertiary and quaternary programs or services within the same markets (i.e. regionalization of care), health insurance reform, and tort reform collectively could save hundreds of billion dollars per year! These changes may not be easy to accomplish politically but will be essential to save what is likely the best health care system in the world. Copyright © 2012. Published by Elsevier Inc.

Formulation and delivery of vaccines: Ongoing challenges for animal management

PubMed Central

Sharma, Sameer; Hinds, Lyn A.

2012-01-01

Development of a commercially successful animal vaccine is not only influenced by various immunological factors, such as type of antigen but also by formulation and delivery aspects. The latter includes the need for a vector or specific delivery system, the choice of route of administration and the nature of the target animal population and their habitat. This review describes the formulation and delivery aspects of various types of antigens such as killed microorganisms, proteins and nucleic acids for the development of efficacious and safe animal vaccines. It also focuses on the challenges associated with the different approaches that might be required for formulating and delivering species specific vaccines, particularly if their intended use is for improved animal management with respect to disease and/or reproductive control. PMID:23248557

Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment.

PubMed

Jiang, Ying; Hardie, Joseph; Liu, Yuanchang; Ray, Moumita; Luo, Xiang; Das, Riddha; Landis, Ryan F; Farkas, Michelle E; Rotello, Vincent M

2018-06-05

The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.28 mg/kg. Significantly, the delivery of siRNA targeting tumor necrosis factor-α efficiently silenced TNF-α expression in LPS-challenged mice, demonstrating efficacy in modulating immune response in an organ-selective manner. This research highlights the potential of the NPSC platform for targeted immunotherapy and further manipulation of the immune system. Copyright © 2018 Elsevier B.V. All rights reserved.

Factors influencing the purity of electronic grade phosphine delivered to MOCVD tools

NASA Astrophysics Data System (ADS)

Feng, Jun; Owens, Mitch; Raynor, Mark W.

2010-04-01

Increasing mobility of InP films with usage time of one PH 3 cylinder prompted an investigation into factors influencing the purity of delivered PH 3. The presence of hygroscopic H xPO y residues in a delivery system greatly increases the dry-down time compared to that of a clean system. Static delivery system tests show increasing H 2O concentration with time and twice the increase in PH 3 versus N 2 over 48 h indicating reaction of metal oxides in components with PH 3 to generate H 2O. Gas purity may also vary during cylinder usage. Depletion of a high-purity PH 3 cylinder shows consistently low gas phase H 2O levels before phase-break but increasing levels after phase-break, as the cylinder depressurizes. The results highlight the importance of using pure PH 3, employing rigorous cycle-purging procedures to prevent H xPO y contamination, switching out cylinders in good time and using purification technology to control H 2O.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

Can we predict shoulder dystocia?

PubMed

Revicky, Vladimir; Mukhopadhyay, Sambit; Morris, Edward P; Nieto, Jose J

2012-02-01

To analyse the significance of risk factors and the possibility of prediction of shoulder dystocia. This was a retrospective cohort study. There were 9,767 vaginal deliveries at 37 and more weeks of gestation analysed during 2005-2007. Studied population included 234 deliveries complicated by shoulder dystocia. Shoulder dystocia was defined as a delivery that required additional obstetric manoeuvres to release the shoulders after gentle downward traction has failed. First, a univariate analysis was done to identify the factors that had a significant association with shoulder dystocia. Parity, age, gestation, induction of labour, epidural analgesia, birth weight, duration of second stage of labour and mode of delivery were studied factors. All factors were then combined in a multivariate logistic regression analysis. Adjusted odds ratios (Adj. OR) with 95% confidence intervals (CI) were calculated. The incidence of shoulder dystocia was 2.4% (234/9,767). Only mode of delivery and birth weight were independent risk factors for shoulder dystocia. Parity, age, gestation, induction of labour, epidural analgesia and duration of second stage of labour were not independent risk factors. Ventouse delivery increases the risk of shoulder dystocia almost 3 times, forceps delivery comparing to the ventouse delivery increases risk almost 3.4 times. Risk of shoulder dystocia is minimal with the birth weight of 3,000 g or less. It is difficult to foretell the exact birth weight and the mode of delivery, therefore occurrence of shoulder dystocia is highly unpredictable. Regular drills for shoulder dystocia and awareness of increased incidence with instrumental deliveries are important to reduce fetal and maternal morbidity and mortality.

Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

PubMed

Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

2009-01-01

We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

Non-Covalent Assembly of Targeted Carbon Nanovectors Enables Synergistic Drug and Radiation Cancer Therapy In Vivo

PubMed Central

Sano, Daisuke; Berlin, Jacob M.; Pham, Tam T.; Marcano, Daniela C.; Valdecanas, David R.; Zhou, Ge; Milas, Luka; Myers, Jeffrey N.; Tour, James M.

2012-01-01

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, Cetuximab. This construct is unusual in that all three components are assembled through non-covalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development. PMID:22316245

Induction of cytotoxic T lymphocyte response against Mycobacterial antigen using domain I of anthrax edema factor as antigen delivery system

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

Chandra, Subhash; Kaur, Manpreet; Midha, Shuchi

2007-05-25

We have investigated the efficiency of N-terminal 1-260 residues of Edema factor (EFn) as a delivery system for ESAT-6, an antigenic protein of Mycobacterium tuberculosis H{sub 37}R{sub v}, into the cytosol of mammalian cells. The EFn.ESAT-6 recombinant protein was obtained by genetic fusion of EFn and ESAT-6 DNA. Our data shows that in the presence of PA, EFn.ESAT-6 fusion protein is internalized into the cytosol of antigen presenting cells, and the splenocytes produced both Th1 and Th2 cytokines in vitro. Further, EFn.ESAT-6 elicited effective cytotoxicT lymphocyte (CTL) response in an in vitro CTL assay. This study for the first timemore » demonstrates that EFn can be used as a vehicle to deliver heterologous proteins of therapeutic importance.« less

Worksite health and wellness programs: Canadian achievements & prospects.

PubMed

Després, Jean-Pierre; Alméras, Natalie; Gauvin, Lise

2014-01-01

Canada has experienced a substantial reduction in mortality related to cardiovascular disease (CVD). There is a general consensus that more effective and widespread health promotion interventions may lead to further reductions in CVD risk factors and actual disease states. In this paper, we briefly outline the prevalence of selected risk factors for CVD in Canada, describe characteristics of the Canadian labor market and workforce, and depict what is known about health and wellness program delivery systems in Canadian workplaces. Our review indicates that there have been numerous and diverse relevant legislative and policy initiatives to create a context conducive to improve the healthfulness of Canadian workplaces. However, there is still a dearth of evidence on the effectiveness of the delivery system and the actual impact of workplace health and wellness programs in reducing CVD risk in Canada. Thus, while a promising model, more research is needed in this area. Copyright © 2014 Elsevier Inc. All rights reserved.

Insight to drug delivery aspects for colorectal cancer.

PubMed

Gulbake, Arvind; Jain, Aviral; Jain, Ashish; Jain, Ankit; Jain, Sanjay K

2016-01-14

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma.

PubMed

Chang, Le; Wang, Guojing; Jia, Tingting; Zhang, Lei; Li, Yulong; Han, Yanxi; Zhang, Kuo; Lin, Guigao; Zhang, Rui; Li, Jinming; Wang, Lunan

2016-04-26

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy.

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.

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

PubMed

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc.

Physical Factors Affecting Plasmid DNA Compaction in Stearylamine-Containing Nanoemulsions Intended for Gene Delivery

PubMed Central

Silva, André Leandro; Júnior, Francisco Alexandrino; Verissimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Socrates Tabosa

2012-01-01

Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery. PMID:24281666

Size, Loading Efficiency, and Cytotoxicity of Albumin-Loaded Chitosan Nanoparticles: An Artificial Neural Networks Study.

PubMed

Baharifar, Hadi; Amani, Amir

2017-01-01

When designing nanoparticles for drug delivery, many variables such as size, loading efficiency, and cytotoxicity should be considered. Usually, smaller particles are preferred in drug delivery because of longer blood circulation time and their ability to escape from immune system, whereas smaller nanoparticles often show increased toxicity. Determination of parameters which affect size of particles and factors such as loading efficiency and cytotoxicity could be very helpful in designing drug delivery systems. In this work, albumin (as a protein drug model)-loaded chitosan nanoparticles were prepared by polyelectrolyte complexation method. Simultaneously, effects of 4 independent variables including chitosan and albumin concentrations, pH, and reaction time were determined on 3 dependent variables (i.e., size, loading efficiency, and cytotoxicity) by artificial neural networks. Results showed that concentrations of initial materials are the most important factors which may affect the dependent variables. A drop in the concentrations decreases the size directly, but they simultaneously decrease loading efficiency and increase cytotoxicity. Therefore, an optimization of the independent variables is required to obtain the most useful preparation. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Improving drug delivery technology for treating neurodegenerative diseases.

PubMed

Choonara, Yahya E; Kumar, Pradeep; Modi, Girish; Pillay, Viness

2016-07-01

Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer's disease and Parkinson's disease. However, much work is still required in this field beyond the preclinical testing phase.

Economic impact of switching from an open to a closed enteral nutrition feeding system in an acute care setting.

PubMed

Phillips, Wendy; Roman, Brandis; Glassman, Kendra

2013-08-01

This study compared an open-system (OS) enteral nutrition (EN) delivery system with a closed system (CS). Factors evaluated included nursing time for administration, patient safety factors, and cost of formula and supplies. This study analyzed the cost of formula and supplies in 1 major academic medical center. Data were collected on patients requiring EN in acute care settings. Information collected included formula type and amount of formula ordered and delivered. The average daily cost to feed each adult patient using delivered volume with the OS was $3.84 compared with $4.31 if the patient had been receiving EN from a CS. Considering waste costs, the average cost to feed increased to $4.21 compared with $4.80, respectively. After factoring in increased nursing time with the OS, the cost increased to $9.83. For pediatric patients, formula delivery reached 1 L in only 2% of patient days. The average cost to feed each patient each day using actual delivered volume was $1.89 in the OS and $1.94 in the CS. When factoring in the cost of waste, those costs increased to $2.12 and $3.30, respectively. After factoring in increased nursing time with the OS, the cost increased to $8.92. Due to the higher contract price and increased waste of the CS formulas compared with the OS formulas, a higher daily average cost for formula delivered may be incurred by switching to a CS. However, the CS is more cost-effective when factoring in nursing time.

Bone Regeneration from PLGA Micro-Nanoparticles

PubMed Central

Ortega-Oller, Inmaculada; Galindo-Moreno, Pablo; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

2015-01-01

Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. PMID:26509156

Quantitative measurement of delivery and gene silencing activities of siRNA polyplexes containing pyridylthiourea-grafted polyethylenimines.

PubMed

Pinel, Sophie; Aman, Emmanuel; Erblang, Felix; Dietrich, Jonathan; Frisch, Benoit; Sirman, Julien; Kichler, Antoine; Sibler, Annie-Paule; Dontenwill, Monique; Schaffner, Florence; Zuber, Guy

2014-05-28

The activity of synthetic interfering nucleic acids (siRNAs) relies on the capacity of delivery systems to efficiently transport nucleic acids into the cytosol of target cells. The pyridylthiourea-grafted 25KDa polyethylenimine (πPEI) is an excellent carrier for siRNA delivery into cells and it was extensively investigated in this report. Quantification of the siRNA-mediated gene silencing efficiency indicated that the πPEI specific delivery activity at the cell level may be measured and appears relatively constant in various cell lines. Delivery experiments assaying inhibitors of various entry pathways or concanamycin A, an inhibitor of the H(+)/ATPase vacuolar pump showed that the πPEI/siRNA polyplexes did not require any specific entry mode but strongly relied on vacuolar acidification for functional siRNA delivery. Next, πPEI polyplexes containing a siRNA targeting the transcription factor HIF-1α, known to be involved in tumor progression, were locally injected into mice xenografted with a human glioblastoma. A 55% reduction of the level of the target mRNA was observed at doses comparable to those used in vitro when the πPEI delivery activity was calculated per cell. Altogether, our study underscores the usefulness of "simple"/rough cationic polymers for siRNA delivery despite their intrinsic limitations. The study underscores as well as that bottom-up strategies make sense. The in vitro experiments can precede in vivo administration and be of high value for selection of the carrier with enhanced specific delivery activity and parallel other research aiming at improving synthetic delivery systems for resilience in the blood and for enhanced tissue-targeting capacity. Copyright © 2014 Elsevier B.V. All rights reserved.

What Affect Student Cognitive Style in the Development of Hypermedia Learning System?

ERIC Educational Resources Information Center

Lee, Catherine Hui Min; Cheng, Yuk Wing; Rai, Shri; Depickere, Arnold

2005-01-01

Recent developments in learning technology such as hypermedia is becoming widespread and offer significant contribution to improve the delivery of learning and teaching materials. A key factor in the development of hypermedia learning system is cognitive style (CS) as it relates to users' information processing habits, representing individual…

Coupling of FM Systems to Individuals with Unilateral Hearing Loss.

ERIC Educational Resources Information Center

Kopun, Judy G.; And Others

1992-01-01

This study examined the attenuation characteristics of 5 Frequency Modulation system sound delivery options for 25 adults and children (ages 5-13). Degree of ear canal occlusion was a major factor in degree of attenuation. For children with unilateral hearing impairments, the most acoustically appropriate option was the tube-fitting. (Author/JDD)

Application of Advanced Laser Diagnostics to High Impact Technologies. Delivery Order 0001: Laser Diagnostics Applications

DTIC Science & Technology

2011-02-01

identified the hysteresis property of this flame system; this was later confirmed by experiments. For the given flow conditions, the flame system can......transport properties . This concept increased the computational speed by a factor of five for a 208-species mechanism and is expected to have even higher

Ruggedness of 2D code printed on grain tracers for implementing a prospective grain traceability system to the bulk grain delivery system

USDA-ARS?s Scientific Manuscript database

Food-grade tracers were printed with two-dimensional Data Matrix (DM) barcode so that they could carry simulated identifying information about grain as part of a prospective traceability system. The key factor in evaluating the tracers was their ability to be read with a code scanner after being rem...

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PubMed

Chen, Chuanyu; You, Peijun

2017-01-01

Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.

Factor structure of the geriatric care environment scale.

PubMed

Kim, Hongsoo; Capezuti, Elizabeth; Boltz, Marie; Fairchild, Susan; Fulmer, Terry; Mezey, Mathy

2007-01-01

Older adults comprise approximately 60% of all adult, nonobstetric hospital admissions. Nurses Improving Care for Health System Elders (NICHE) is a national program aimed at system improvement to achieve patient-centered care for older adults. The NICHE hospitals use the Geriatric Institutional Assessment Profile (GIAP) to assess their institutional readiness to provide quality care to older adults and to document improvement in geriatric care delivery. To explore the factorial structure of the 28-item Geriatric Care Environment Scale (GCES) of the GIAP, test its validity with a sample of staff registered nurses (RNs), and evaluate its invariance across 4 groups of RNs who worked at 4 different types of hospitals. Staff RNs (N = 9,400) at 71 acute hospitals, who responded to the GIAP from 1999 to 2004, were split randomly into 2 groups for cross-validation. A 3-step data analysis was completed. The a priori factor structure was developed using exploratory factor analysis. The obtained factor model was validated, and its invariance by types of hospitals was examined by confirmatory factor analyses. The GCES is internally consistent (Cronbach's alpha = .93) and accounts for approximately 55% of the total variance. The 4 factors extracted from the exploratory factor analysis are Aging-Sensitive Care Delivery, Resource Availability, Institutional Values Regarding Older Adults and Staff, and Capacity for Collaboration. The 4-factor structured model is validated in a half-randomly selected sample (normed fit index [NFI] = .931, nonnormed fit index [NNFI] = .933, comparative fit index [CFI] = .939, root-mean-square error of approximation [RMSEA] = .058) and does not vary significantly across the 4 groups of RNs who worked at the 4 different types of hospitals (NFI = .969, NNFI = .975, CFI = .976, RMSEA = .027). The GCES is a reliable measure of RN perception of how care provided to older adults reflects age-sensitive principles and the organizational practice environment that supports or hinders care delivery.

Histone-Targeted Nucleic Acid Delivery for Tissue Regenerative Applications

NASA Astrophysics Data System (ADS)

Munsell, Erik V.

Nucleic acid delivery has garnered significant attention as an innovative therapeutic approach for treating a wide variety of diseases. However, the design of non-viral delivery systems that negotiate efficient intracellular trafficking and nuclear entry represents a significant challenge. Overcoming these hurdles requires a combination of well-controlled materials approaches with techniques to understand and direct cellular delivery. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and retention, as well as activating DNA transcription. We established the ability to recapitulate these natural histone tail activities within non-viral gene nanocarriers, driving gene transfer/expression by enabling effective navigation to the nucleus via retrograde vesicular trafficking. A unique finding of this histone-targeted approach was that nanocarriers gained enhanced access to the nucleus during mitosis. The work described in this dissertation builds off of these fundamental insights to facilitate the translation of this histone-targeted delivery approach toward regenerative medicine applications. During native tissue repair, actively proliferating mesenchymal stem cells (MSCs) respond to a complex series of growth factor signals that direct their differentiation. Accordingly, the investigations in this work focused on utilizing the histone-targeted nanocarriers to enhance osteogenic growth factor gene transfer in dividing MSCs leading to augmented MSC chondrogenic differentiation, an essential first step in skeletal tissue repair. Concurrently, additional studies focused on optimizing the histone-targeted nanocarrier design strategy to enable improved plasmid DNA (pDNA) binding stability and tunable harnessing of native cellular processing pathways for enhanced gene transfer. Overall, the work presented herein demonstrated substantial increases in growth factor expression following histone-targeted gene transfer. This enhanced expression enabled more robust levels of chondrogenesis in MSCs than treatments with equivalent amounts of recombinant growth factor protein. Additionally, nanocarrier design optimization provided effective pDNA condensation and controllable interactions with native histone effectors. Importantly, these optimized nanocarriers conferred stable nanoplex formation and maintained transfection efficiency under physiologically relevant conditions. Taken together, these advances may help drive the clinical translation of histone-targeted nucleic acid delivery strategies for the regeneration of damaged tissue following traumatic injury.

Factors influencing the delivery of the fundamentals of care: Perceptions of nurses, nursing leaders and healthcare consumers.

PubMed

Conroy, Tiffany

2017-11-17

To explore the factors described by nurses and consumer representatives influencing the delivery of the fundamentals of care. An ongoing challenge facing nursing is ensuring the "basics" or fundamentals of care are delivered optimally. The way nurses and patients perceive the delivery of the fundamentals of care had not been explored. Once identified, the factors that promote the delivery of the fundamentals of care may be facilitated. Inductive content analysis of scenario based focus groups. A qualitative approach was taken using three stages, including direct observation, focus groups and interviews. This paper reports the second stage. Focus groups discussed four patient care scenarios derived from the observational data. Focus groups were conducted separately for registered nurses, nurses in leadership roles and consumer representatives. Content analysis was used. The analysis of the focus group data resulted in three themes: Organisational factors; Individual nurse or patient factors; and Interpersonal factors. Organisational factors include nursing leadership, the context of care delivery and the availability of time. Individual nurse and patient factors include the specific care needs of the patient and the individual nurse and patient characteristics. Interpersonal factors include the nurse-patient relationship; involving the patient in their care, ensuring understanding and respecting choices; communication; and setting care priorities. Seeking the perspective of the people involved in delivering and receiving the fundamentals of care showed a shared understanding of the factors influencing the delivery of the fundamentals of care. The influence of nursing leadership and the quality of the nurse-patient relationship were perceived as important factors. Nurses and consumers share a common perspective of the factors influencing the delivery of the fundamentals of care and both value a therapeutic nurse-patient relationship. Clinical nursing leaders must understand the impact of their role in shaping the delivery of the fundamentals of care. © 2017 John Wiley & Sons Ltd.

Improving care by understanding the way we work: human factors and behavioural science in the context of intensive care

PubMed Central

Sevdalis, Nick; Brett, Stephen J

2009-01-01

Effectiveness and efficiency of care of the critically ill patient are subject to a number of systemic influences, including skills of individual physicians/nurses (technical and non-technical), team-working in the intensive care unit (ICU), and the ICU environment. We first discuss the paper of Fackler and colleagues as a contribution to the systems approach to clinical performance in the context of intensive care. We then highlight features of care delivery that are unique to intensive care and discuss the need for better understanding of human and non-human elements of the system of care of the critically ill patient as a driver for improvement of care delivery. PMID:19439048

Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking

PubMed Central

Ahern, J; Pickett, K; Selvin, S; Abrams, B

2003-01-01

Study objective: Research shows that neighbourhood socioeconomic factors are associated with preterm delivery. This study examined whether cigarette smoking and individual socioeconomic factors modify the effects of neighbourhood factors on preterm delivery. Design: Case-control study. Setting: Moffit Hospital in San Francisco, California. Participants: 417 African American and 1244 white women, including all preterm and a random selection of term deliveries 1980–1990, excluding non-singleton pregnancies, congenital anomolies, induced deliveries, and women transported for special care. US census data from 1980 and 1990 were used to characterise the women's neighbourhoods, defined as census tracts. Results: Cigarette smoking increased the risk of preterm delivery among both African American (OR=1.77, 95% confidence intervals (CI) (1.12 to 2.79)) and white women (OR=1.25, 95% CI (1.01 to 1.55)). However, cigarette smoking did not attenuate or modify the association of neighbourhood factors with preterm delivery. Among African American women, having public insurance modified the relation between neighbourhood unemployment and preterm delivery; among women without public insurance, the risk of preterm delivery was low in areas with low unemployment and high in areas with high unemployment, while among women with public insurance the risk of preterm delivery was highest at low levels of neighbourhood unemployment. Conclusions: Cigarette smoking was associated with preterm delivery, especially among African Americans. Adverse neighbourhood conditions had an influence on preterm delivery beyond that of cigarette smoking. The effects of some neighbourhood characteristics were different depending on individual socioeconomic status. Examining socioeconomic and behavioural/biological risk factors together may increase understanding of the complex causes of preterm delivery. PMID:12883067

Facilitating process changes in meal delivery and radiological testing to improve inpatient insulin timing using six sigma method.

PubMed

Yamamoto, J Jay; Malatestinic, Bill; Lehman, Angela; Juneja, Rattan

2010-01-01

The objective of this project was to improve the timing of inpatient insulin administration related to meal delivery and the scheduling of radiology tests by Lean Six Sigma method. A multidisciplinary hospital team and a Six Sigma team from a pharmaceutical manufacturer collaborated to evaluate food delivery and radiology scheduling processes related to the timing of insulin administration. Key factors leading to problems within each system were addressed to improve the efficiency of each process while improving the timeliness of glucose testing and insulin administration. Standardizing the food delivery schedule and utilizing scorecards to track on-time meal deliveries to the floor enabled nursing to more accurately administer insulin in coordination with the delivery of meals. Increasing communication and restricting the scheduling of inpatient procedures during mealtimes reduced disruptions to insulin administration. Data at 6 months postimplementation demonstrated that the institution met goals for most primary outcome metrics including increasing on-time meal delivery and the proportion of patients taking insulin scheduled for radiology tests during appropriate times. By implementing the recommendations identified via Lean Six Sigma, this collaborative effort improved the timing of inpatient insulin administration related to meal delivery and radiology testing.

The economic, institutional, and political determinants of public health delivery system structures.

PubMed

Ingram, Richard C; Scutchfield, F Douglas; Mays, Glen P; Bhandari, Michelyn W

2012-01-01

A typology of local public health systems was recently introduced, and a large degree of structural transformation over time was discovered in the systems analyzed. We present a qualitative exploration of the factors that determine variation and change in the seven structural configurations that comprise the local public health delivery system typology. We applied a 10-item semistructured telephone interview protocol to representatives from the local health agency in two randomly selected systems from each configuration--one that had maintained configuration over time and one that had changed configuration over time. We assessed the interviews for patterns of variation between the configurations. Four key determinants of structural change emerged: availability of financial resources, interorganizational relationships, public health agency organization, and political relationships. Systems that had changed were more likely to experience strengthened partnerships between public health agencies and other community organizations and enjoy support from policy makers, while stable systems were more likely to be characterized by strong partnerships between public health agencies and other governmental bodies and less supportive relationships with policy makers. This research provides information regarding the determinants of system change, and may help public health leaders to better prepare for the impacts of change in the areas discussed. It may also help those who are seeking to implement change to determine the contextual factors that need to be in place before change can happen, or how best to implement change in the face of contextual factors that are beyond their control.

Controlled release of GAG-binding enhanced transduction (GET) peptides for sustained and highly efficient intracellular delivery.

PubMed

Abu-Awwad, Hosam Al-Deen M; Thiagarajan, Lalitha; Dixon, James E

2017-07-15

Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored protein release profiles could be achieved, however intracellular transduction was significantly inhibited post-release. To retain GET peptide activity we optimized a strategy of co-encapsulation of l-Histidine, which may form a complex with the PLGA degradation products under acidic conditions. Simulations of the polymer microclimate showed that hydrolytic acidic PLGA degradation products directly inhibited GET peptide transduction activity, and use of l-Histidine significantly enhanced released protein delivery. The ability to control the intracellular transduction of functional proteins into cells will facilitate new localized delivery methods and allow approaches to direct cellular behaviour for many regenerative medicine applications. The goal for regenerative medicine is to restore functional biological tissue by controlling and augmenting cellular behaviour. Either Transcription (TFs) or growth factors (GFs) can be presented to cells in spatio-temporal gradients for programming cell fate and gene expression. Here, we have created a sustained and controlled release system for GET (Glycosaminoglycan-enhanced transducing)-tagged proteins using S/O/W PLGA microparticle fabrication. We demonstrated that PLGA and its acidic degradants inhibit GET-mediated transduction, which can be overcome by using pH-activated l-Histidine. l-Histidine inhibits the electrostatic interaction of GET/PLGA and allows enhanced intracellular transduction. GET could provide a powerful tool to program cell behaviour either in gradients or with sustained delivery. We believe that our controlled release systems will allow application of GET for tissue regeneration directly by TF cellular programming. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

NASA Astrophysics Data System (ADS)

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

Impact of Medicare's prospective payment system on hospitals, skilled nursing facilities, and home health agencies: how the Balanced Budget Act of 1997 may have altered service patterns for Medicare providers.

PubMed

Kulesher, Robert R

2006-01-01

The prospective payment system is one of many changes in reimbursement that has affected the delivery of health care. Originally developed for the payment of inpatient hospital services, it has become a major factor in how all health insurance is reimbursed. The policy implications extend beyond the Medicare program and affect the entire health care delivery system. Initially implemented in 1982 for payments to hospitals, prospective payment system was extended to payments for skilled nursing facility and home health agency services by the Balanced Budget Act of 1997. The intent of the Balanced Budget Act was to bring into balance the federal budget through reductions in spending. The decisions that providers have made to mitigate the impact are a function of ownership type, organizational mission, and current level of Medicare participation. This article summarizes the findings of several initial studies on the Balanced Budget Act's impact and discusses how changes in Medicare reimbursement policy have influenced the delivery of health care for the general public and for Medicare beneficiaries.

Biomimetic Delivery with Micro- and Nanoparticles

PubMed Central

Balmert, Stephen C.; Little, Steven R.

2013-01-01

The nascent field of biomimetic delivery with micro- and nanoparticles (MNP) has advanced considerably in recent years. Drawing inspiration from the ways that cells communicate in the body, several different modes of “delivery” (i.e. temporospatial presentation of biological signals) have been investigated in a number of therapeutic contexts. In particular, this review focuses on (1) controlled release formulations that deliver natural soluble factors with physiologically relevant temporal context, (2) presentation of surface-bound ligands to cells, with spatial organization of ligands ranging from isotropic to dynamically anisotropic, and (3) physical properties of particles, including size, shape and mechanical stiffness, which mimic those of natural cells. Importantly, the context provided by multimodal, or multifactor delivery represents a key element of most biomimetic MNP systems, a concept illustrated by an analogy to human interpersonal communication. Regulatory implications of increasingly sophisticated and “cell-like” biomimetic MNP systems are also discussed. PMID:22528985

Designing food delivery systems: challenges related to the in vitro methods employed to determine the fate of bioactives in the gut.

PubMed

Arranz, Elena; Corredig, Milena; Guri, Anilda

2016-08-10

An in depth understanding of the underpinning mechanisms that relate to food disruption and processing in the gastrointestinal tract is necessary to achieve optimal intake of nutrients and their bioefficacy. Although in vivo trials can provide insights on physiological responses of nutrients, in vitro assays are often applied as tools to understand specific mechanisms, or as prescreening methods to determine the factors associated with the uptake of food components in the gastrointestinal tract. In vitro assays are also often utilized to design novel or improved food delivery systems. In this review the available approaches to study delivery and uptake of food bioactives and the associated challenges are discussed. For an in depth understanding of food processing in the gastrointestinal tract, it is necessary to apply multidisciplinary methodologies, at the interface between materials science, chemistry, physics and biology.

Electronic Nicotine Delivery Systems (ENDS): What Nurses Need to Know.

PubMed

Essenmacher, Carol; Naegle, Madeline; Baird, Carolyn; Vest, Bridgette; Spielmann, Rene; Smith-East, Marie; Powers, Leigh

Efforts to decrease adverse effects of tobacco use are affected by emergence of new nicotine delivery products. Advertising, product promotion, and social media promote use of these products, yet a lack of evidence regarding safety leaves nurses unprepared to counsel patients. To critically evaluate current research, reviews of literature, expert opinion, and stakeholder policy proposals on use and safety of electronic nicotine delivery systems (ENDS). A targeted examination of literature generated by key stakeholders and subject matter experts was conducted using key words, modified by risk factors, and limited to the past 8 years. Current knowledge gaps in research literature and practice implications of the literature are discussed. The safety of ENDS is questionable and unclear. There are clear health risks of nicotine exposure to developing brains. Potential health risks of ENDS secondhand emissions exposure exist. Using ENDS to facilitate total tobacco cessation is not proven.

Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

PubMed Central

Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

2014-01-01

The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

Controlled Dual Growth Factor Delivery From Microparticles Incorporated Within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification.

PubMed

Dang, Phuong N; Dwivedi, Neha; Phillips, Lauren M; Yu, Xiaohua; Herberg, Samuel; Bowerman, Caitlin; Solorio, Loran D; Murphy, William L; Alsberg, Eben

2016-02-01

Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-β1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-β1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-β1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis and osteogenesis with regard to endochondral bone formation in high-density stem cell systems through the controlled presentation of inductive factors from incorporated microparticles. This work lays the foundation for a rapidly implantable tissue engineering system that promotes bone repair via endochondral ossification, a pathway that can delay the need for a functional vascular network and has an intrinsic ability to promote angiogenesis. The modular nature of this system lends well to using different cell types and/or growth factors to induce endochondral bone formation, as well as the production of other tissue types. ©AlphaMed Press.

E-commerce and its Impact on Logistics Requirements

NASA Astrophysics Data System (ADS)

Zákorová, Eva

2017-05-01

The contribution will focus on the development of e-commerce. The extent of the development of internet by age category will be assessed and the development of this factor will be monitored by correlation analysis. Analysis of logistics operators will be performed in the field courier, express and parcel shipments. Market competitiveness B2C will focus on flexibility in delivery, evening delivery or on weekends, term delivery (increasing the cost of tracking shipments and their records), use and offering banking products with secure payment system, readiness deliver the goods via its own fueling point. On the contrary, legal provision regulating the entrance to the parking are, entrance into pedestrian zone service may limit or prevent.

Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration.

PubMed

Tarafder, Solaiman; Koch, Alia; Jun, Yena; Chou, Conrad; Awadallah, Mary R; Lee, Chang H

2016-04-25

Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF's bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing cartridges during a single printing process. Spatially controlled delivery of GFs, with a prolonged release, guided formation of multi-tissue interfaces from bone marrow derived mesenchymal stem/progenitor cells (MSCs). To investigate efficacy of the micro-precise delivery system embedded in 3D printed scaffold, temporomandibular joint (TMJ) disc scaffolds were fabricated with micro-precise spatiotemporal delivery of CTGF and TGFβ3, mimicking native-like multiphase fibrocartilage. In vitro, TMJ disc scaffolds spatially embedded with CTGF/TGFβ3-μS resulted in formation of multiphase fibrocartilaginous tissues from MSCs. In vivo, TMJ disc perforation was performed in rabbits, followed by implantation of CTGF/TGFβ3-μS-embedded scaffolds. After 4 wks, CTGF/TGFβ3-μS embedded scaffolds significantly improved healing of the perforated TMJ disc as compared to the degenerated TMJ disc in the control group with scaffold embedded with empty μS. In addition, CTGF/TGFβ3-μS embedded scaffolds significantly prevented arthritic changes on TMJ condyles. In conclusion, our micro-precise spatiotemporal delivery system embedded in 3D printing may serve as an efficient tool to regenerate complex and inhomogeneous tissues.

Nursing Services Delivery Theory: an open system approach

PubMed Central

Meyer, Raquel M; O’Brien-Pallas, Linda L

2010-01-01

meyer r.m. & o’brien-pallas l.l. (2010)Nursing services delivery theory: an open system approach. Journal of Advanced Nursing66(12), 2828–2838. Aim This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. Background The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a ‘black box’ that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. Data sources A search of CINAHL and Business Source Premier for the years 1980–2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. Discussion The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. Implications for nursing The Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. Conclusion The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. PMID:20831573

[Impact on environmental factors on the reproductive system and fetal development].

PubMed

Dulskiene, Virginija; Maroziene, Ligita

2002-01-01

A literature review discusses the effect of selected environmental factors on women reproductive system, fetal development and growth. According to recent reports, 2-3% of newborns have congenital malformations. These malformations are caused by interaction of genetic and environmental factors. Exposure of paternal or maternal organisms to environmental hazards may damage germ cells or interfere fetal development, resulting in malformation of various organ systems. Since environmental hazards exposures are complex, it is difficult to establish the primary effect of single factor. Factors, that are known to increase the risk of congenital malformations, preterm delivery or spontaneous abortion, are classified into five groups--psychological, social, biological, physical and chemical factors. The governments of most counties recognize the effect of hazardous environmental factors on public health as global problem. World Health Organization encourages researches, aimed at evaluation of various environmental factors impact on health of pregnant women and their offsprings.

Social Cultural Factors Influencing Appointment of Headteachers in Primary Schools in Eldoret East Sub-County, Kenya

ERIC Educational Resources Information Center

Suter, Esther J.

2017-01-01

Headteachers' position is at the critical point of which all the mechanism of Education system: planning, delivery and management rest. The purpose of the study was to investigate social cultural factors influencing appointment of headteachers in primary schools in Eldoret East Sub-County, Uasin Gishu County. The target population comprised of 275…

Tribological investigation of a functional medical textile with lubricating drug-delivery finishing.

PubMed

Gerhardt, L-C; Lottenbach, R; Rossi, R M; Derler, S

2013-08-01

Textile-based drug delivery systems have a high potential for innovative medical and gerontechnological applications. In this study, the tribological behaviour and lubrication properties of a novel textile with drug delivery function/finishing was investigated by means of friction experiments that simulated cyclic dynamic contacts with skin under dry and wet conditions. The textile drug delivery system is based on a loadable biopolymer dressing on a polyester (PES) woven fabric. The fabrics were finished with low (LC) and highly cross-linked (HC) polysaccharide dressings and investigated in the unloaded condition as well as loaded with phytotherapeutic substances. The mechanical resistance and possible abrasion of the functional coatings on the textile substrate were assessed by friction measurements and scanning electron microscopical analyses. Under dry contact conditions, all investigated fabrics (PES substrate alone and textiles with loaded and unloaded dressings) showed generally low friction coefficients (0.20-0.26). Under wet conditions, the measured friction coefficients were typically higher (0.34-0.51) by a factor of 1.5-2. In the wet condition, both loaded drug delivery textiles exhibited 7-29% lower friction (0.34-0.41) than the PES fabric with unloaded dressings (0.42-0.51), indicating pronounced lubrication effects. The lubrication effects as well as the abrasion resistance of the studied textiles with drug delivery function depended on the degree of dilution of the phytotherapeutic substances. Lubricating formulations of textile-based drug delivery systems which reduce friction against the skin might be promising candidates for advanced medical textile finishes in connection with skin care and wound (decubitus ulcer) prevention. Copyright © 2013 Elsevier B.V. All rights reserved.

Absorption sites of orally administered drugs in the small intestine.

PubMed

Murakami, Teruo

2017-12-01

In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

What contributes to disparities in the preterm birth rate in European countries?

PubMed Central

Delnord, Marie; Blondel, Béatrice; Zeitlin, Jennifer

2015-01-01

Purpose of review In countries with comparable levels of development and healthcare systems, preterm birth rates vary markedly – a range from 5 to 10% among live births in Europe. This review seeks to identify the most likely sources of heterogeneity in preterm birth rates, which could explain differences between European countries. Recent findings Multiple risk factors impact on preterm birth. Recent studies reported on measurement issues, population characteristics, reproductive health policies as well as medical practices, including those related to subfertility treatments and indicated deliveries, which affect preterm birth rates and trends in high-income countries. We showed wide variation in population characteristics, including multiple pregnancies, maternal age, BMI, smoking, and percentage of migrants in European countries. Summary Many potentially modifiable population factors (BMI, smoking, and environmental exposures) as well as health system factors (practices related to indicated preterm deliveries) play a role in determining preterm birth risk. More knowledge about how these factors contribute to low and stable preterm birth rates in some countries is needed for shaping future policy. It is also important to clarify the potential contribution of artifactual differences owing to measurement. PMID:25692506

The Dynamics of Community Health Care Consolidation: Acquisition of Physician Practices

PubMed Central

Christianson, Jon B; Carlin, Caroline S; Warrick, Louise H

2014-01-01

Context Health care delivery systems are becoming increasingly consolidated in urban areas of the United States. While this consolidation could increase efficiency and improve quality, it also could raise the cost of health care for payers. This article traces the consolidation trajectory in a single community, focusing on factors influencing recent acquisitions of physician practices by integrated delivery systems. Methods We used key informant interviews, supplemented by document analysis. Findings The acquisition of physician practices is a process that will be difficult to reverse in the current health care environment. Provider revenue uncertainty is a key factor driving consolidation, with public and private attempts to control health care costs contributing to that uncertainty. As these efforts will likely continue, and possibly intensify, community health care systems now are less consolidated than they will be in the future. Acquisitions of multispecialty and primary care practices by integrated delivery systems follow a common process, with relatively predictable issues relating to purchase agreements, employment contracts, and compensation. Acquisitions of single-specialty practices are less common, with motivations for acquisitions likely to vary by specialty type, group size, and market structure. Total cost of care contracting could be an important catalyst for practice acquisitions in the future. Conclusions In the past, market and regulatory forces aimed at controlling costs have both encouraged and rewarded the consolidation of providers, with important new developments likely to create momentum for further consolidation, including acquisitions of physician practices. PMID:25199899

The dynamics of community health care consolidation: acquisition of physician practices.

PubMed

Christianson, Jon B; Carlin, Caroline S; Warrick, Louise H

2014-09-01

Health care delivery systems are becoming increasingly consolidated in urban areas of the United States. While this consolidation could increase efficiency and improve quality, it also could raise the cost of health care for payers. This article traces the consolidation trajectory in a single community, focusing on factors influencing recent acquisitions of physician practices by integrated delivery systems. We used key informant interviews, supplemented by document analysis. The acquisition of physician practices is a process that will be difficult to reverse in the current health care environment. Provider revenue uncertainty is a key factor driving consolidation, with public and private attempts to control health care costs contributing to that uncertainty. As these efforts will likely continue, and possibly intensify, community health care systems now are less consolidated than they will be in the future. Acquisitions of multispecialty and primary care practices by integrated delivery systems follow a common process, with relatively predictable issues relating to purchase agreements, employment contracts, and compensation. Acquisitions of single-specialty practices are less common, with motivations for acquisitions likely to vary by specialty type, group size, and market structure. Total cost of care contracting could be an important catalyst for practice acquisitions in the future. In the past, market and regulatory forces aimed at controlling costs have both encouraged and rewarded the consolidation of providers, with important new developments likely to create momentum for further consolidation, including acquisitions of physician practices. © 2014 Milbank Memorial Fund.

Effect of delivery condition on desorption rate of ZrCo metal hydride bed for fusion fuel cycle

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

Kang, H.G.; Yun, S.H.; Chung, D.

2015-03-15

For the safety of fusion fuel cycle, hydrogen isotope gases including tritium are stored as metal hydride form. To satisfy fueling requirement of fusion machine, rapid delivery from metal hydride bed is one of major factors for the development of tritium storage and delivery system. Desorption from metal hydride depends on the operation scenario by pressure and temperature control of the bed. The effect of operation scenario and pump performance on desorption rate of metal hydride bed was experimentally investigated using ZrCo bed. The results showed that the condition of pre-heating scenario before actual delivery of gas affected the deliverymore » performance. Different pumps were connected to desorption line from bed and the effect of pump capacity on desorption rate were also found to be significant. (authors)« less

Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

NASA Astrophysics Data System (ADS)

Xue, Jingwei; Zhao, Zekai; Zhang, Lei; Xue, Lingjing; Shen, Shiyang; Wen, Yajing; Wei, Zhuoyuan; Wang, Lu; Kong, Lingyi; Sun, Hongbin; Ping, Qineng; Mo, Ran; Zhang, Can

2017-07-01

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.

Numbers, systems, people: how interactions influence integration. Insights from case studies of HIV and reproductive health services delivery in Kenya.

PubMed

Mayhew, Susannah H; Sweeney, Sedona; Warren, Charlotte E; Collumbien, Martine; Ndwiga, Charity; Mutemwa, Richard; Lut, Irina; Colombini, Manuela; Vassall, Anna

2017-11-01

Drawing on rich data from the Integra evaluation of integrated HIV and reproductive-health services, we explored the interaction of systems hardware and software factors to explain why some facilities were able to implement and sustain integrated service delivery while others were not. This article draws on detailed mixed-methods data for four case-study facilities offering reproductive-health and HIV services between 2009 and 2013 in Kenya: (i) time-series client flow, tracking service uptake for 8841 clients; (ii) structured questionnaires with 24 providers; (iii) in-depth interviews with 17 providers; (iv) workload and facility data using a periodic activity review and cost-instruments; and (v) contextual data on external activities related to integration in study sites. Overall, our findings suggested that although structural factors like stock-outs, distribution of staffing and workload, rotation of staff can affect how integrated care is provided, all these factors can be influenced by staff themselves: both frontline and management. Facilities where staff displayed agency of decision making, worked as a team to share workload and had management that supported this, showed better integration delivery and staff were able to overcome some structural deficiencies to enable integrated care. Poor-performing facilities had good structural integration, but staff were unable to utilize this because they were poorly organized, unsupported or teams were dysfunctional. Conscientious objection and moralistic attitudes were also barriers.Integra has demonstrated that structural integration is not sufficient for integrated service delivery. Rather, our case studies show that in some cases excellent leadership and peer-teamwork enabled facilities to perform well despite resource shortages. The ability to provide support for staff to work flexibly to deliver integrated services and build resilient health systems to meet changing needs is particularly relevant as health systems face challenges of changing burdens of disease, climate change, epidemic outbreaks and more. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Biomimetic transport and rational drug delivery.

PubMed

Ranney, D F

2000-01-15

Medicine and pharmaceutics are encountering critical needs and opportunities for transvascular drug delivery that improves site targeting and tissue permeation by mimicking natural tissue addressing and transport mechanisms. This is driven by the accelerated development of genomic agents requiring targeted controlled release. Although rationally designed for in vitro activity, such agents are not highly effective in vivo, due to opsonization and degradation by plasma constituents, and failure to transport across the local vascular endothelium and tissue matrix. A growing knowledge of the addresses of the body can be applied to engineer "Bio-Logically" staged delivery systems with sequential bioaddressins complementary to the discontinuous compartments encountered--termed discontinuum pharmaceutics. Effective tissue targeting is accomplished by leukocytes, bacteria, and viruses. We are increasingly able to mimic their bioaddressins by genomic means. Approaches described in this commentary include: (a) endothelial-directed adhesion mediated by oligosaccharides and carbohydrates (e.g. dermatan sulfate as a mimic of sulfated CD44) and peptidomimetics interacting with adhesins, selectins, integrins, hyaluronans, and locally induced growth factors (e.g. vascular endothelial growth factor, VEGF) and coagulation factors (e.g. factor VIII antigen); (b) improved tissue permeation conferred by hydrophilically "cloaked" carrier systems; (c) "uncloaking" by matrix dilution or selective triggering near the target cells; and (d) target binding-internalization by terminally exposed hydrophobic moieties, cationic polymers, and receptor-binding lectins, peptides, or carbohydrates. This commentary also describes intermediate technology solutions (e.g. "hybrid drugs"), and highlights the high-resolution, dynamic magnetic resonance imaging and radiopharmaceutical imaging technologies plus the groups and organizations capable of accelerating these important initiatives.

Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis

NASA Astrophysics Data System (ADS)

Yu-Wai-Man, Cynthia; Tagalakis, Aristides D.; Manunta, Maria D.; Hart, Stephen L.; Khaw, Peng T.

2016-02-01

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats.

PubMed

Haidar, Ziyad S; Hamdy, Reggie C; Tabrizian, Maryam

2010-04-01

A hybrid, localized and release-controlled delivery system for bone growth factors consisting of a liposomal core incorporated into a shell of alternating layer-by-layer self-assembled natural polyelectrolytes has been formulated. Hydrophilic, monodisperse, spherical and stable cationic nanoparticles (< or =350 nm) with an extended shelf-life resulted. Cytocompatibility was previously assayed with MC3T3-E1.4 mouse preosteoblasts showing no adverse effects on cell viability. In this study, the in vivo biocompatibility of unloaded and loaded nanoparticles with osteogenic protein-1 or OP-1 was investigated. Young male Wistar rats were injected intramuscularly and monitored over a period of 10 weeks for signs of inflammation and/or adverse reactions. Blood samples (600 microL/collection) were withdrawn followed by hematological and biochemical analysis. Body weight changes over the treatment period were noted. Major organs were harvested, weighed and examined histologically for any pathological changes. Finally, the injection site was identified and examined immunohistochemically. Overall, all animals showed no obvious toxic health effects, immune responses and/or change in organ functions. This hybrid core-shell nanoparticulate delivery system localizes the effect of the released bioactive load within the site of injection in muscle with no significant tissue distress. Hence, a safe and promising carrier for therapeutic growth factors and possibly other biomolecules is presented. 2009 Elsevier Ltd. All rights reserved.

Highlights in Endocytosis of Nanostructured Systems.

PubMed

Voltan, Aline R; Alarcon, Kaila M; Fusco-Almeida, Ana M; Soares, Christiane P; Mendes-Giannini, Maria J S; Chorilli, Marlus

2017-01-01

The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanostructured systems. The most commonly studied routes of cellular uptake are phagocytosis, macro-pinocytosis, clathrinmediated endocytosis, caveolin-mediated endocytosis, and clathrin and caveolinindependent endocytosis. The mechanism utilised by NSs for cellular entry depends on factors such as cell type and its physicochemical properties. Currently, with the development of drugs-loaded onto NSs, it has been possible to increase the therapeutic index against few diseases. The NSs can deliver the active drug at locations that conventional drugs cannot, thereby minimising unwanted side effects. On cellular entry of NSs, there is a possibility of an endosomal escape of the contents into the cytoplasm, a mechanism that can be exploited so that NSs can migrate intra-cellularly and deliver the drug to the target of interest. Designing endolysosomal escape strategy is not an easy task, but it is critical for the optimal pharmacological action on the target tissue. The cellular uptake of drugs is a very important factor in therapy. Although NSs have emerged as effective drug delivery vehicle for treatment of diseases, it is crucial to understand the mechanism of NSs endocytosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells

PubMed Central

Hindriksen, Sanne; Bramer, Arne J.; Truong, My Anh; Vromans, Martijn J. M.; Post, Jasmin B.; Verlaan-Klink, Ingrid; Snippert, Hugo J.; Lens, Susanne M. A.

2017-01-01

The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC). We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B. PMID:28640891

In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

PubMed

Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

2015-07-01

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Agile delivery of protein therapeutics to CNS.

PubMed

Yi, Xiang; Manickam, Devika S; Brynskikh, Anna; Kabanov, Alexander V

2014-09-28

A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Agile Delivery of Protein Therapeutics to CNS

PubMed Central

Yi, Xiang; Manickam, Devika S.; Brynskikh, Anna; Kabanov, Alexander V.

2014-01-01

A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics. PMID:24956489

Synthetic Tumor Networks for Screening Drug Delivery Systems

PubMed Central

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Garson, Charles J.; Mills, Ivy R.; Matar, Majed M.; Fewell, Jason G.; Pant, Kapil

2015-01-01

Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle’s physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of “leaky vessels”. Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

PubMed

Garbayo, E; Ansorena, E; Blanco-Prieto, M J

2013-11-01

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Organizational context, systems change, and adopting treatment delivery systems in the criminal justice system.

PubMed

Taxman, Faye S; Henderson, Craig E; Belenko, Steven

2009-08-01

The correctional system does not include service provision as a primary goal, even though individuals in prison, jail, and on probation/parole have large unmet substance abuse treatment needs. In response to mandates in the U.S. Constitution for basic health care, services are provided for incarcerated offenders, but generally do not include substance abuse treatment. The system does little to extend any type of health care service to individuals in community settings. This leaves the majority of offenders (6 million under community supervision in the U.S.) basically unattended, even with substance abuse disorders that are four times greater than the general public. The challenge of adapting the correctional system to be part of an integrated service provision system - working in conjunction with the public and private community-based service delivery sector - has intrigued researchers and policy makers over the last two decades. A series of articles using data from the National Criminal Justice Treatment Practices survey have examined factors that influence the adoption of a myriad of substance abuse treatment services for offender populations in various settings. These articles explore the factors that affect adoption and implementation, and provide guidance on issues relevant to organizational change and a dual mission of correctional agencies to advance public safety and public health. This special issue of Drug and Alcohol Dependence is devoted to understanding organizational constructs and factors to improve health outcomes for offenders.

The global nephrology workforce: emerging threats and potential solutions!

PubMed

Sharif, Muhammad U; Elsayed, Mohamed E; Stack, Austin G

2016-02-01

Amidst the rising tide of chronic kidney disease (CKD) burden, the global nephrology workforce has failed to expand in order to meet the growing healthcare needs of this vulnerable patient population. In truth, this shortage of nephrologists is seen in many parts of the world, including North America, Europe, Australia, New Zealand, Asia and the African continent. Moreover, expert groups on workforce planning as well as national and international professional organizations predict further reductions in the nephrology workforce over the next decade, with potentially serious implications. Although the full impact of this has not been clearly articulated, what is clear is that the delivery of care to patients with CKD may be threatened in many parts of the world unless effective country-specific workforce strategies are put in place and implemented. Multiple factors are responsible for this apparent shortage in the nephrology workforce and the underpinning reasons may vary across health systems and countries. Potential contributors include the increasing burden of CKD, aging workforce, declining interest in nephrology among trainees, lack of exposure to nephrology among students and residents, rising cost of medical education and specialist training, increasing cultural and ethnic disparities between patients and care providers, increasing reliance on foreign medical graduates, inflexible work schedules, erosion of nephrology practice scope by other specialists, inadequate training, reduced focus on scholarship and research funds, increased demand to meet quality of care standards and the development of new care delivery models. It is apparent from this list that the solution is not simple and that a comprehensive evaluation is required. Consequently, there is an urgent need for all countries to develop a policy framework for the provision of kidney disease services within their health systems, a framework that is based on accurate projections of disease burden, a full understanding of the internal care delivery systems and a framework that is underpinned by robust health intelligence on current and expected workforce numbers required to support the delivery of kidney disease care. Given the expected increases in global disease burden and the equally important increase in many established kidney disease risk factors such as diabetes and hypertension, the organization of delivery and sustainability of kidney disease care should be enshrined in governmental policy and legislation. Effective nephrology workforce planning should be comprehensive and detailed, taking into consideration the structure and organization of the health system, existing care delivery models, nephrology workforce practices and the size, quality and success of internal nephrology training programmes. Effective training programmes at the undergraduate and postgraduate levels, adoption of novel recruitment strategies, flexible workforce practices, greater ownership of the traditional nephrology landscape and enhanced opportunities for research should be part of the implementation process. Given that many of the factors that impact on workforce capacity are generic across countries, cooperation at an international level would be desirable to strengthen efforts in workforce planning and ensure sustainable models of healthcare delivery.

The global nephrology workforce: emerging threats and potential solutions!

PubMed Central

Sharif, Muhammad U.; Elsayed, Mohamed E.; Stack, Austin G.

2016-01-01

Amidst the rising tide of chronic kidney disease (CKD) burden, the global nephrology workforce has failed to expand in order to meet the growing healthcare needs of this vulnerable patient population. In truth, this shortage of nephrologists is seen in many parts of the world, including North America, Europe, Australia, New Zealand, Asia and the African continent. Moreover, expert groups on workforce planning as well as national and international professional organizations predict further reductions in the nephrology workforce over the next decade, with potentially serious implications. Although the full impact of this has not been clearly articulated, what is clear is that the delivery of care to patients with CKD may be threatened in many parts of the world unless effective country-specific workforce strategies are put in place and implemented. Multiple factors are responsible for this apparent shortage in the nephrology workforce and the underpinning reasons may vary across health systems and countries. Potential contributors include the increasing burden of CKD, aging workforce, declining interest in nephrology among trainees, lack of exposure to nephrology among students and residents, rising cost of medical education and specialist training, increasing cultural and ethnic disparities between patients and care providers, increasing reliance on foreign medical graduates, inflexible work schedules, erosion of nephrology practice scope by other specialists, inadequate training, reduced focus on scholarship and research funds, increased demand to meet quality of care standards and the development of new care delivery models. It is apparent from this list that the solution is not simple and that a comprehensive evaluation is required. Consequently, there is an urgent need for all countries to develop a policy framework for the provision of kidney disease services within their health systems, a framework that is based on accurate projections of disease burden, a full understanding of the internal care delivery systems and a framework that is underpinned by robust health intelligence on current and expected workforce numbers required to support the delivery of kidney disease care. Given the expected increases in global disease burden and the equally important increase in many established kidney disease risk factors such as diabetes and hypertension, the organization of delivery and sustainability of kidney disease care should be enshrined in governmental policy and legislation. Effective nephrology workforce planning should be comprehensive and detailed, taking into consideration the structure and organization of the health system, existing care delivery models, nephrology workforce practices and the size, quality and success of internal nephrology training programmes. Effective training programmes at the undergraduate and postgraduate levels, adoption of novel recruitment strategies, flexible workforce practices, greater ownership of the traditional nephrology landscape and enhanced opportunities for research should be part of the implementation process. Given that many of the factors that impact on workforce capacity are generic across countries, cooperation at an international level would be desirable to strengthen efforts in workforce planning and ensure sustainable models of healthcare delivery. PMID:26798456

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

PubMed

Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

2016-09-01

The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Factors associated with different types of birth attendants for home deliveries: an analysis of the cross-sectional 2010 South Sudan household survey

PubMed Central

Mugo, Ngatho S.; Agho, Kingsley E.; Zwi, Anthony B.; Dibley, Michael J.

2016-01-01

Background In South Sudan, birth deliveries attended by unskilled birth attendants put the mothers and their newborns at increased risk of perinatal morbidity and mortality. The aim of this study was to identify factors associated with delivery by unskilled birth attendants or by unassisted delivery. Design We examined data for 2,767 (weighted total) women aged 15–49 years who delivered at home 2 years prior to the South Sudan Household Health Survey 2010. Multinomial logistic regression analyses were used to identify factors associated with delivery by unskilled birth attendants or by unassisted delivery. Results The prevalence of delivery by unskilled birth attendants was 19% [95% confidence interval (CI) 17.0, 20.5], by skilled birth attendants (SBAs) was 45% (95% CI 42.4, 47.0), and by unassisted delivery was 36% (95% CI 34.2, 38.6). After adjusting for potential confounders, the following factors were associated with the increased odds for unassisted delivery or delivery by an unskilled birth attendant: mothers with no schooling, who did not attend antenatal care (ANC) during pregnancy, who had lower quality of ANC services, from poor households, or who had no prior knowledge about obstetric danger signs. Conclusions We found that non-utilization of maternal health care services, such as ANC, was significantly associated with unattended birth delivery or delivery by unskilled health providers. The increased uptake of SBAs at delivery will require easier access to ANC services, health promotion on the importance and benefits of SBAs for delivery, targeting both mothers and their families, and the training and deployment of more SBAs across the country. PMID:27473675

Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering.

PubMed

Jia, Yang; Fan, Ming; Chen, Huinan; Miao, Yuting; Xing, Lian; Jiang, Bohong; Cheng, Qifan; Liu, Dongwei; Bao, Weikang; Qian, Bin; Wang, Jionglu; Xing, Xiaodong; Tan, Huaping; Ling, Zhonghua; Chen, Yong

2015-11-15

Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation

PubMed Central

Sleep, Eduard; McClendon, Mark T.; Preslar, Adam T.; Chen, Charlotte H.; Sangji, M. Hussain; Pérez, Charles M. Rubert; Haynes, Russell D.; Meade, Thomas J.; Blau, Helen M.; Stupp, Samuel I.

2017-01-01

Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice. PMID:28874575

Defining the Content of the Undergraduate Systems Analysis and Design Course as Measured by a Survey of Instructors

ERIC Educational Resources Information Center

Burns, Timothy J.

2011-01-01

There are many factors that make the undergraduate systems analysis and design course somewhat enigmatic in its purpose, and therefore equivocal in its delivery. The purpose of this research is to learn, specifically, what instructors are teaching in their systems analysis and design courses. This paper reports the results of a survey and follow…

FACTORS ASSOCIATED WITH UPTAKE OF SKILLED ATTENDANTS' SERVICES DURING CHILD DELIVERY IN GARISSA TOWN, KENYA.

PubMed

Abikar, R A; Karama, M; Ng'ang'a, Z W

2013-11-01

To identify the factors that are associated with uptake of skilled delivery services during child delivery among women of reproductive age in Garissa town. Cross sectional study. Garissa town. Three hundred and thirty four women aged 15-49 years who had had at least one delivery in their lifetime were asked about the type of delivery services they had during their last child delivery. The study found that 47% of the last deliveries women were attended by skilled persons and the rest of the deliveries were provided by TBAs. The predictors of skilled delivery uptake in this study were found to be; having knowledge on skilled delivery service providers (AOR = 17.2; 95% CI: 1.05-281.12; p = 0.046), child deliveries numbering one to three (AOR = 116.95; 95% CI: 26.68-512.64; p = 0.001) and four to six (AOR = 16.75; 95% CI: 4.44-62.87; p = 0.001), presence of previous delivery complication (AOR = 11.71; 95% CI: 3.96-34.60; p = 0.001), disapproval of TBA services (AOR = 27.19; 95% CI: 6.67-110.76; p = 0.001), lack of preference for gender of skilled delivery service provider (AOR = 6.51; 95% CI: 1.08-39.37; p = 0.041), and positive view on service related factors such as time to nearest facility (AOR = 3.91; 95% CI: 1.24-12.34; p = 0.020), hygiene (AOR = 5.03; 95% CI: 1.49-17.05; p = 0.009) and operation time of health facility (AOR = 4.67; 95% CI: 1.59-13.76; p = 0.005). The findings show that cultural and maternal factors as well as quality of services at facility level play major role in determining uptake of skilled services among women in Garissa as compared to social demographic and economic factors.

Large-Scale Educational Telecommunications Systems for the U.S.: An Analysis of Educational Needs and Technological Opportunities.

ERIC Educational Resources Information Center

Morgan, Robert P.; And Others

Opportunities for utilizing large-scale educational telecommunications delivery systems to aid in meeting needs of U.S. education are extensively analyzed in a NASA-funded report. Status, trends, and issues in various educational subsectors are assessed, along with current use of telecommunications and technology and factors working for and…

Systems Impact: Issues and Trends in Improving School Outcomes for All Learners through Multitier Instructional Models

ERIC Educational Resources Information Center

Chard, David J.

2013-01-01

The majority of school districts implementing response to intervention use a systemwide, multitier model of delivery. This article describes the common features of multitier models and discusses the emerging evidence of their effectiveness. In addition, specific factors that schools should consider to enhance effective implementation of systemic,…

Care delivery for Filipino Americans using the Neuman systems model.

PubMed

Angosta, Alona D; Ceria-Ulep, Clementina D; Tse, Alice M

2014-04-01

Filipino Americans are at risk of coronary heart disease due to the presence of multiple cardiometabolic factors. Selecting a framework that addresses the factors leading to coronary heart disease is vital when providing care for this population. The Neuman systems model is a comprehensive and wholistic framework that offers an innovative method of viewing clients, their families, and the healthcare system across multiple dimensions. Using the Neuman systems model, advanced practice nurses can develop and implement interventions that will help reduce the potential cardiovascular problems of clients with multiple risk factors. The authors in this article provides insight into the cardiovascular health of Filipino Americans and has implications for nurses and other healthcare providers working with various Southeast Asian groups in the United States.

From nano- to macro-scale: nanotechnology approaches for spatially controlled delivery of bioactive factors for bone and cartilage engineering.

PubMed

Santo, Vítor E; Gomes, Manuela E; Mano, João F; Reis, Rui L

2012-07-01

The field of biomaterials has advanced towards the molecular and nanoscale design of bioactive systems for tissue engineering, regenerative medicine and drug delivery. Spatial cues are displayed in the 3D extracellular matrix and can include signaling gradients, such as those observed during chemotaxis. Architectures range from the nanometer to the centimeter length scales as exemplified by extracellular matrix fibers, cells and macroscopic shapes. The main focus of this review is the application of a biomimetic approach by the combination of architectural cues, obtained through the application of micro- and nanofabrication techniques, with the ability to sequester and release growth factors and other bioactive agents in a spatiotemporal controlled manner for bone and cartilage engineering.

Creating Welcoming Spaces for Lesbian, Gay, Bisexual, and Transgender (LGBT) Patients: An Evaluation of the Health Care Environment.

PubMed

McClain, Zachary; Hawkins, Linda A; Yehia, Baligh R

2016-01-01

Health outcomes are affected by patient, provider, and environmental factors. Previous studies have evaluated patient-level factors; few focusing on environment. Safe clinical spaces are important for lesbian, gay, bisexual, and transgender (LGBT) communities. This study evaluates current models of LGBT health care delivery, identifies strengths and weaknesses, and makes recommendations for LGBT spaces. Models are divided into LGBT-specific and LGBT-embedded care delivery. Advantages to both models exist, and they provide LGBT patients different options of healthcare. Yet certain commonalities must be met: a clean and confidential system. Once met, LGBT-competent environments and providers can advocate for appropriate care for LGBT communities, creating environments where they would want to seek care.

Factors affecting the choice of type of delivery with breast feeding in Iranian mothers.

PubMed

Sharifi, Farangis; Nouraei, Soheila; Sharifi, Nader

2017-09-01

This study assessed the factors affecting the choice of type of delivery with breast feeding in Iranian mothers. This Cross section descriptive analytic study was performed using a random sampling technique, using data from 400 pregnant women who attended the maternity centers in Borazjan and Kazerun in Iran in 2014. A questionnaire covering demographic characteristics, mode of delivery and postpartum conditions was completed for each mother. Descriptive analysis and Chi square test were used along with SPSS 23 software to statistically analyze the data and p-value less than 0.05 was considered for statistical significance. In this study, the rate of normal delivery and cesarean operation are considered equal. In the main factors influencing the choice of delivery, mothers' education level (p=0.028) and pregnancy status (p=0.041) showed a significant relationship. Although no significant association between child nutrition with the type of delivery was found, duration of breastfeeding with the type of delivery showed significant association (p=0.046). Although cesarean delivery in many cases is life-saving for mother and fetus; in addition to medical indications, parents with higher education and pregnancy status are also important factors in increasing the rate of cesarean section compared to vaginal delivery. Babies of mothers with normal delivery had a longer time of breastfeeding. Further studies in Iran are necessary, regarding the reasons for high cesarean section and their outcomes.

Production of bioinspired and rationally designed polymer hydrogels for controlled delivery of therapeutic proteins

NASA Astrophysics Data System (ADS)

Kim, Sung Hye

Hydrogel systems for controlled delivery therapeutic growth factors have been developed in a wide spectrum of strategies: these systems aim for the release of growth factors via a passive diffusion, electrostatic interaction, degradation of hydrogels, and responsiveness to external stimuli. Heparin, a highly sulfated glycosaminoglycan (GAG), was employed for a targeted delivery system of vascular endothelial growth factor (VEGF) to endothelial cells overexpressing a relevant receptor VEGFR-2. Addition of dimeric VEGF to 4-arm star-shaped poly(ethylene glycol) (PEG) immobilized with low-molecular weight heparin (LMWH) afforded a non-covalently assembled hydrogel via interaction between heparin and VEGF, with storage modulus 10 Pa. The release of VEGF and hydrogel erosion reached maximum 100 % at day 4 in the presence of VEGFR-2 overexpressing pocine aortic endothelial cell (PAE/KDR), while those of 80% were achieved via passive release at day 5 in the presence of PAE cell lacking VEGFR-2 or in the absence of cell, indicating that the release of VEGF was in targeted manner toward cell receptor. The proliferation of PAE/KDR in the presence of [PEG-LMWH/VEGF] hydrogel was greater by ca. 30% at day 4 compared to that of PAE, confirming that the release of VEGF was in response to the cellular demand. The phosphorylation fraction of VEGFR-2 on PAE/KDR was greater in the presence of [PEG-LMWH/VEGF] hydrogel, increasing from 0.568 at day 1 to 0.790 at day 4, whereas it was maintained at 0.230 at day 4 in the presence of [PEG-LMWH] hydrogel. This study has proven that this hydrogel, assembled via bio-inspired non-covalent interaction, liberating VEGFon celluar demand to target cell, eroding upon VEGF release, and triggering endothelial cell proliferation, could be used in multiple applications including targeted delivery and angiogenesis. Heparin has been widely exploited in growth factor delivery systems owing to its ability to bind many growth factors through the flexible patterns of functional groups. However, heterogeneity in the composition and in the polydispersity of heparin has been problematic in controlled delivery system and thus motivated the development of homogeneous heparin mimics. Peptides of appropriate sequence and chemical function have therefore recently emerged as potential replacements for heparin in select applications. Studied was the assessment of the binding affinities of multiple sulfated peptides (SPs) for a set of heparin-binding peptides (HBPs) and for VEGF; these binding partners have application in the selective immobilization of proteins and in hydrogel formation through non-covalent interactions. Sulfated peptides were produced via solid-phase methods, and their affinity for the HBPs and VEGF was assessed via affinity liquid chromatography (ALC), surface plasmon resonance (SPR), and in select cases, isothermal titration calorimetry (ITC). The shortest peptide, SPa, showed the highest affinity binding of HBPs and VEGF165 in both ALC and SPR measurements, with slight exceptions. Of the investigated HBPs, a peptide based on the heparin-binding domain of human platelet factor 4 showed greatest binding affinities toward all of the SPs, consistent with its stronger binding to heparin. The affinity between SPa and PF4ZIP was indicated via SPR ( KD = 5.27 muM) and confirmed via ITC (KD = 8.09 muM). The binding by SPa of both VEGF and HBPs suggests its use as a binding partner to multiple species, and the use of these interactions in assembly of materials. Given that the peptide sequences can be varied to control binding affinity and selectivity, opportunities are also suggested for the production of a wider array of matrices with selective binding and release properties useful for biomaterials applications. Hydrogel consisting of SPa was formed via a covalent Michael Addition reaction between maleimide- and thiol-terminated multi-arm PEGs and Cys-SPa. The mechanical property of hydrogel was tunable from ca. 186 to 1940 Pa. by varing the cross-linking density, suggesting its flexible applications depending on matrix needs. The non-anti-coagulative property of SPa, assessed via activated partial thromboplastin time (APTT) and HeptestRTM in comparison to LMWH, implied its usefulness in applications without excessive bleeding. The VEGF released from [PEG-SPa] hydrogel showed up to ca. 400% greater bioactivity on proliferation of human umbilical vein endothelical cell (HUVEC) compared to the VEGF incubated in solution for the same period: this was significantly higher than that of [PEG] hydrogel (ca. 280%), suggesting the SPa may protect the bioactivity of VEGF when bound. The release of dual growth factor, i.e. VEGF and fibroblast growth factor-2 (FGF-2), were investigated on [PEG-SPa] hydrogel: the release of bFGF was lower than that of VEGF due to weaker binding affinity to matrix-bound SPa. The HUVEC culture on dual growth factor loaded [PEG-SPa] showed that the synergistic effects of dual system in select concentrations, suggesting the opportunity of manipulating cell responses. Given that sulfated peptides for various binding targets with desired affinity can be identified, applications are suggested in multiple growth factors delivery where an integrated action of multiple growth factors is required, such as angiogenesis.

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

Anti-Cancer Drug Delivery Using Carbohydrate-Based Polymers.

PubMed

Ranjbari, Javad; Mokhtarzadeh, Ahad; Alibakhshi, Abbas; Tabarzad, Maryam; Hejazi, Maryam; Ramezani, Mohammad

2018-02-12

Polymeric drug delivery systems in the form of nanocarriers are the most interesting vehicles in anticancer therapy. Among different types of biocompatible polymers, carbohydrate-based polymers or polysaccharides are the most common natural polymers with complex structures consisting of long chains of monosaccharide or disaccharide units bound by glycosidic linkages. Their appealing properties such as availability, biocompatibility, biodegradability, low toxicity, high chemical reactivity, facile chemical modification and low cost led to their extensive applications in biomedical and pharmaceutical fields including development of nano-vehicles for delivery of anti-cancer therapeutic agents. Generally, reducing systemic toxicity, increasing short half-lives and tumor localization of agents are the top priorities for a successful cancer therapy. Polysaccharide-based or - coated nanosystems with respect to their advantageous features as well as accumulation in tumor tissue due to enhanced permeation and retention (EPR) effect can provide promising carrier systems for the delivery of noblest impressive agents. Most challenging factor in cancer therapy was the toxicity of anti-cancer therapeutic agents for normal cells and therefore, targeted delivery of these drugs to the site of action can be considered as an interesting therapeutic strategy. In this regard, several polysaccharides exhibited selective affinity for specific cell types, and so they can act as a targeting agent in drug delivery systems. Accordingly, different aspects of polysaccharide applications in cancer treatment or diagnosis were reviewed in this paper. In this regard, after a brief introduction of polysaccharide structure and its importance, the pharmaceutical usage of carbohydrate-based polymers was considered according to the identity of accompanying active pharmaceutical agents. It was also presented that the carbohydrate based polymers have been extensively considered as promising materials in the design of efficient nanocarriers for anti-cancer biopharmaceuticals including peptide and proteins or nucleic acid-based therapeutics. Then, the importance of various polysaccharide co-polymers in the drug delivery approaches was illustrated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing, China

PubMed Central

Song, Geng; Wei, Yu-Mei; Zhu, Wei-Wei; Yang, Hui-Xia

2017-01-01

Background: The cesarean section rate (CSR) has been a main concern worldwide. The present study aimed to investigate the CSR in Beijing, China, and to analyze the related factors of CS delivery. Methods: An observational study was conducted in 15 medical centers in Beijing using a systemic cluster sampling method. In total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to examine differences between two groups, and related factors of the CSR were examined by multivariable logistic regression. Results: The CSR was 41.9% (4471/10,671) in singleton primiparae. Women who were more than 35 years old had a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561–9.816, P < 0.001). Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640–2.584, P < 0.001). The excessive weight gain group had a 1.4-fold increased risk of CS delivery compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289–1.568, P < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood glucose women. Women who were born in rural areas had a lower risk of CS delivery than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625–0.775, P < 0.001). The risk of CS delivery gradually increased with a decreasing education level. Neonates weighing 3000–3499 g had the lowest CSR (36.2%). Neonates weighing <2500 g had a 2-fold increased risk of CS delivery compared with neonates weighing 3000–3499 g (OR = 2.020, 95% CI = 1.537–2.656, P < 0.001). Neonates weighing ≥4500 g had an 8.3-fold increased risk of CS delivery compared with neonates weighing 3000–3499 g (OR = 8.313, 95% CI = 4.436–15.579, P < 0.001). Conclusions: Maternal age, prepregnancy body mass index, gestational weight gain, blood glucose levels, residence, education level, and singleton fetal birth weight are all factors that might significantly affect the CSR. PMID:29052558

Public-private delivery of insecticide-treated nets: a voucher scheme in Volta Region, Ghana

PubMed Central

Kweku, Margaret; Webster, Jayne; Taylor, Ian; Burns, Susan; Dedzo, McDamien

2007-01-01

Background Coverage of vulnerable groups with insecticide-treated nets (ITNs) in Ghana, as in the majority of countries of sub-Saharan Africa is currently low. A voucher scheme was introduced in Volta Region as a possible sustainable delivery system for increasing this coverage through scale-up to other regions. Successful scale-up of public health interventions depends upon optimal delivery processes but operational research for delivery processes in large-scale implementation has been inadequate. Methods A simple tool was developed to monitor numbers of vouchers given to each health facility, numbers issued to pregnant women by the health staff, and numbers redeemed by the distributors back to the management agent. Three rounds of interviews were undertaken with health facility staff, retailers and pregnant women who had attended antenatal clinic (ANC). Results During the one year pilot 25,926 vouchers were issued to eligible women from clinics, which equates to 50.7% of the 51,658 ANC registrants during this time period. Of the vouchers issued 66.7% were redeemed by distributors back to the management agent. Initially, non-issuing of vouchers to pregnant women was mainly due to eligibility criteria imposed by the midwives; later in the year it was due to decisions of the pregnant women, and supply constraints. These in turn were heavily influenced by factors external to the programme: current household ownership of nets, competing ITN delivery strategies, and competition for the limited number of ITNs available in the country from major urban areas of other regions. Conclusion Both issuing and redemption of vouchers should be monitored as factors assumed to influence voucher redemption had an influence on issuing, and vice versa. More evidence is needed on how specific contextual factors influence the success of voucher schemes and other models of delivery of ITNs. Such an evidence base will facilitate optimal strategic decision making so that the delivery model with the best probability of success within a given context is implemented. Rigorous monitoring has an important role to play in the successful scaling-up of delivery of effective public health interventions. PMID:17274810

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

[Support of the nursing process through electronic nursing documentation systems (UEPD) – Initial validation of an instrument].

PubMed

Hediger, Hannele; Müller-Staub, Maria; Petry, Heidi

2016-01-01

Electronic nursing documentation systems, with standardized nursing terminology, are IT-based systems for recording the nursing processes. These systems have the potential to improve the documentation of the nursing process and to support nurses in care delivery. This article describes the development and initial validation of an instrument (known by its German acronym UEPD) to measure the subjectively-perceived benefits of an electronic nursing documentation system in care delivery. The validity of the UEPD was examined by means of an evaluation study carried out in an acute care hospital (n = 94 nurses) in German-speaking Switzerland. Construct validity was analyzed by principal components analysis. Initial references of validity of the UEPD could be verified. The analysis showed a stable four factor model (FS = 0.89) scoring in 25 items. All factors loaded ≥ 0.50 and the scales demonstrated high internal consistency (Cronbach's α = 0.73 – 0.90). Principal component analysis revealed four dimensions of support: establishing nursing diagnosis and goals; recording a case history/an assessment and documenting the nursing process; implementation and evaluation as well as information exchange. Further testing with larger control samples and with different electronic documentation systems are needed. Another potential direction would be to employ the UEPD in a comparison of various electronic documentation systems.

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Nanotechnology for protein delivery: Overview and perspectives.

PubMed

Yu, Mikyung; Wu, Jun; Shi, Jinjun; Farokhzad, Omid C

2016-10-28

Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape. Development of effective protein delivery strategies is therefore essential to further enhance therapeutic outcomes to enable widespread medical applications. This review discusses the advantages and limitations of marketed and developmental-stage protein delivery strategies, and provides a focused overview of recent advances in nanotechnology platforms for the systemic delivery of therapeutic proteins. In addition, we also highlight nanoparticle-mediated non-invasive administration approaches (e.g., oral, nasal, pulmonary, and transdermal routes) for protein delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Viruses, Artificial Viruses and Virus-Based Structures for Biomedical Applications.

PubMed

van Rijn, Patrick; Schirhagl, Romana

2016-06-01

Nanobiomaterials such as virus particles and artificial virus particles offer tremendous opportunities to develop new biomedical applications such as drug- or gene-delivery, imaging and sensing but also improve understanding of biological mechanisms. Recent advances within the field of virus-based systems give insights in how to mimic viral structures and virus assembly processes as well as understanding biodistribution, cell/tissue targeting, controlled and triggered disassembly or release and circulation times. All these factors are of high importance for virus-based functional systems. This review illustrates advances in mimicking and enhancing or controlling these aspects to a high degree toward delivery and imaging applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spray-congealed microparticles for drug delivery - an overview of factors influencing their production and characteristics.

PubMed

Oh, Ching Mien; Guo, Qiyun; Wan Sia Heng, Paul; Chan, Lai Wah

2014-07-01

In any manufacturing process, the success of producing an end product with the desired properties and yield depends on a range of factors that include the equipment, process and formulation variables. It is the interest of manufacturers and researchers to understand each manufacturing process better and ascertain the effects of various manufacturing-associated factors on the properties of the end product. Unless the manufacturing process is well understood, it would be difficult to set realistic limits for the process variables and raw material specifications to ensure consistently high-quality and reproducible end products. Over the years, spray congealing has been used to produce particulates by the food and pharmaceutical industries. The latter have used this technology to develop specialized drug delivery systems. In this review, basic principles as well as advantages and disadvantages of the spray congealing process will be covered. Recent developments in spray congealing equipment, process variables and formulation variables such as the matrix material, encapsulated material and additives will also be discussed. Innovative equipment designs and formulations for spray congealing have emerged. Judicious choice of atomizers, polymers and additives is the key to achieve the desired properties of the microparticles for drug delivery.

Tailored Educational Approaches for Consumer Health: A Model to Address Health Promotion in an Era of Personalized Medicine.

PubMed

Cohn, Wendy F; Lyman, Jason; Broshek, Donna K; Guterbock, Thomas M; Hartman, David; Kinzie, Mable; Mick, David; Pannone, Aaron; Sturz, Vanessa; Schubart, Jane; Garson, Arthur T

2018-01-01

To develop a model, based on market segmentation, to improve the quality and efficiency of health promotion materials and programs. Market segmentation to create segments (groups) based on a cross-sectional questionnaire measuring individual characteristics and preferences for health information. Educational and delivery recommendations developed for each group. General population of adults in Virginia. Random sample of 1201 Virginia residents. Respondents are representative of the general population with the exception of older age. Multiple factors known to impact health promotion including health status, health system utilization, health literacy, Internet use, learning styles, and preferences. Cluster analysis and discriminate analysis to create and validate segments. Common sized means to compare factors across segments. Developed educational and delivery recommendations matched to the 8 distinct segments. For example, the "health challenged and hard to reach" are older, lower literacy, and not likely to seek out health information. Their educational and delivery recommendations include a sixth-grade reading level, delivery through a provider, and using a "push" strategy. This model addresses a need to improve the efficiency and quality of health promotion efforts in an era of personalized medicine. It demonstrates that there are distinct groups with clearly defined educational and delivery recommendations. Health promotion professionals can consider Tailored Educational Approaches for Consumer Health to develop and deliver tailored materials to encourage behavior change.

Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region.

PubMed

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Hamano, Nobuhito; Li, Shyh-Dar; Chougule, Mahavir; Shoyele, Sunday A; Gupta, Umesh; Ajazuddin; Alexander, Amit

2018-06-01

Brain is supposed to be the most complicated part of the body which is very far from the reach of drug moieties. The drug entry in to the brain region depends upon various factors, and among those, the blood-brain-barrier remains the most prominent one. This barrier restricts the entry of almost all the drug and most of the essential biological components like proteins, peptides, etc. and hinders treatment of the CNS disorders. Alzheimer Disease (AD) is one such brain disorder, more specifically a neurodegenerative disorder which primarily affects the older adults. Areas covered: From solubility enhancement to targeted delivery, the nanoparticulate system became the answer for almost all the criticality related to drug delivery. Hence, nanoparticulate drug carrier system has been widely utilizing to remove the hurdles of brain drug delivery. Keeping this in mind, we have underlined the proficiencies of the nanocarrier systems which claim to improve the drug efficacy for the treatment of the AD. Expert opinion: The nanotechnological approaches are highly exploited by the researchers to enhance the drug permeation across the BBB to improve its bioavailability and efficacy by protecting the drug from peripheral degradation. However, still in this area of drug targeting provides vast scope for discoveries towards the enhancement of drug efficacy through surface modifications, site specification, reduced toxicity of the nanocarrier system and so on.

Regional Multiteam Systems in Cancer Care Delivery

PubMed Central

Monson, John R.T.; Rizvi, Irfan; Savastano, Ann; Green, James S.A.; Sevdalis, Nick

2016-01-01

Teamwork is essential for addressing many of the challenges that arise in the coordination and delivery of cancer care, especially for the problems that are presented by patients who cross geographic boundaries and enter and exit multiple health care systems at various times during their cancer care journeys. The problem of coordinating the care of patients with cancer is further complicated by the growing number of treatment options and modalities, incompatibilities among the vast variety of technology platforms that have recently been adopted by the health care industry, and competing and misaligned incentives for providers and systems. Here we examine the issue of regional care coordination in cancer through the prism of a real patient journey. This article will synthesize and elaborate on existing knowledge about coordination approaches for complex systems, in particular, in general and cancer care multidisciplinary teams; define elements of coordination derived from organizational psychology and human factors research that are applicable to team-based cancer care delivery; and suggest approaches for improving multidisciplinary team coordination in regional cancer care delivery and avenues for future research. The phenomenon of the mobile, multisystem patient represents a growing challenge in cancer care. Paradoxically, development of high-quality, high-volume centers of excellence and the ease of virtual communication and data sharing by using electronic medical records have introduced significant barriers to effective team-based cancer care. These challenges urgently require solutions. PMID:27650833

Factors Influencing the Use of Information and Communication Technology (ICT) in Teaching and Learning Computer Studies in Ohaukwu Local Government Area of Ebonyi State-Nigeria

ERIC Educational Resources Information Center

Agbo, Igwe Sylvester

2015-01-01

Research studies in the past years show that Information and Communication Technology is an effective means for boasting educational opportunities, but most teachers neither use this technology as an instructional delivery system nor integrate technology into their curriculum. Studies reveal a number of factors influencing teachers' decisions to…

The Gentrification of Public Welfare.

ERIC Educational Resources Information Center

Dattalo, Patrick

1992-01-01

Notes that public welfare agencies are serving middle-class Americans. Examines six factors that may contribute to gentrification of public welfare agencies: growing demands for services from nontraditional clients; restructuring of public welfare's service delivery system; declining resources; increasing emphasis on child protective services;…

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.

PubMed

Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

2017-01-01

Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.

Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects

PubMed Central

Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

2017-01-01

Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin αvβ3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer. PMID:28331317

Uniform Surface Modification of 3D Bioglass®-Based Scaffolds with Mesoporous Silica Particles (MCM-41) for Enhancing Drug Delivery Capability

PubMed Central

Boccardi, Elena; Philippart, Anahí; Juhasz-Bortuzzo, Judith A.; Beltrán, Ana M.; Novajra, Giorgia; Vitale-Brovarone, Chiara; Spiecker, Erdmann; Boccaccini, Aldo R.

2015-01-01

The design and characterization of a new family of multifunctional scaffolds based on bioactive glass (BG) of 45S5 composition for bone tissue engineering and drug delivery applications are presented. These BG-based scaffolds are developed via a replication method of polyurethane packaging foam. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which act as an in situ drug delivery system. These sub-micron spheres are characterized by large surface area and pore volume with a narrow pore diameter distribution. The solution used for the synthesis of the silica mesoporous particles was designed to obtain a high-ordered mesoporous structure and spherical shape – both are key factors for achieving the desired controlled drug release. The MCM-41 particles were synthesized directly inside the BG-based scaffolds, and the drug-release capability of this combined system was evaluated. Moreover, the effect of MCM-41 particle coating on the bioactivity of the BG-based scaffolds was assessed. The results indicate that it is possible to obtain a multifunctional scaffold system characterized by high and interconnected porosity, high bioactivity, and sustained drug delivery capability. PMID:26594642

Polymeric biomaterials for nerve regeneration applications: From promoting cellular organization to the delivery of bioactive molecules

NASA Astrophysics Data System (ADS)

Delgado-Rivera, Roberto L.

Thousands of new cases of injury to the central nervous system (CNS) occur each year in the USA and all over the world. However, despite recent advances, at present there is no cure for the resulting paraplegia or quadriplegia. This research is directed towards engineering biomaterial platforms to promote cellular organization at the surface of polymer scaffolds that will be conducive to proper regeneration of injured CNS. In addition, the formulation of a delivery system for neuroactive molecules using polymer-based materials will be evaluated to establish its potential to treat CNS disorders. Initial studies involved the chemical modification of an electrospun nonwoven matrix of nanofibers with fibroblast growth factor 2 (FGF-2). Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, that FGF-2 modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of damaged tissue following CNS injury or disease. Subsequent research efforts focused on a novel micropatterning technique called microscale plasma-initiated patterning (microPIP). This patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. FGF-2 and laminin-1 were applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. In this work it, was possible to demonstrate that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization. Finally, a microsphere system capable of encapsulating proteins while minimizing the mechanisms of protein degradation and providing a controlled release was investigated. Microspheres were comprised of a salicylic-acid based poly(anhydride-ester) (PAE), a biodegradable polymer that incorporates salicylic acid into the polymer backbone (PolyAspirin). The use of microspheres formulated from PolyAspirin as a delivery vehicle can be advantageous due its ability of performing a dual delivery; biomolecule (protein) and drug. By combining these two properties, it will be possible to release neurotrophic factors to induce a biological response while mitigating inflammatory pathways due to the localized delivery of salicylic acid.

Integrated model for pricing, delivery time setting, and scheduling in make-to-order environments

NASA Astrophysics Data System (ADS)

Garmdare, Hamid Sattari; Lotfi, M. M.; Honarvar, Mahboobeh

2018-03-01

Usually, in make-to-order environments which work only in response to the customer's orders, manufacturers for maximizing the profits should offer the best price and delivery time for an order considering the existing capacity and the customer's sensitivity to both the factors. In this paper, an integrated approach for pricing, delivery time setting and scheduling of new arrival orders are proposed based on the existing capacity and accepted orders in system. In the problem, the acquired market demands dependent on the price and delivery time of both the manufacturer and its competitors. A mixed-integer non-linear programming model is presented for the problem. After converting to a pure non-linear model, it is validated through a case study. The efficiency of proposed model is confirmed by comparing it to both the literature and the current practice. Finally, sensitivity analysis for the key parameters is carried out.

Systems and Components Fuel Delivery System, Water Delivery System, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

[Anaemia in pregnancy and in the immediate postpartum period. Prevalence and risk factors in pregnancy and childbirth].

PubMed

Urquizu I Brichs, Xavier; Rodriguez Carballeira, Mónica; García Fernández, Antonio; Perez Picañol, Emilio

2016-05-20

The objective of the study was to assess the prevalence of anaemia in the immediate postpartum period (48-72hours), determine the risk factors and the value of haemoglobin before birth to reduce postpartum anaemia. A prospective, observational and longitudinal study that included 1,426 women who delivered consecutively and agreed to participate in the study. Different variables, analytical, epidemiological, foetal and maternal symptoms were studied. The prevalence of anaemia in the postpartum period was 49.7%. The most important risk factors were antepartum anaemia and type of delivery. The types of delivery most influencing postpartum anaemia were, forceps (82.3%), the ventouse 67%, cesarean section (58,2%) and vaginal delivery (37.2%). In the multivariate study was found as the most important independent risk factors, the haemoglobin in the delivery day (OR 6.16, CI: 3.73 to 10.15) and instrumental delivery (OR: 4.61, CI: 3.44 to 6, 19). Other independent risk factors were haemoglobin in the third trimester, episiotomy and perineal tears, ethnicity, birth weight, parity and intra/postpartum complications. Anaemia in the immediate postpartum is a prevalent problem. The factors most associated postpartum anaemia were antepartum anaemia and instrumental delivery. If patients arrive at the day of delivery with haemoglobins≥12,6g/dl and were restricted to necessary instrumented deliveries and cesarean sections, episiotomies and we could avoid perineal tears we can decrease anaemia in the immediate postpartum period very significantly. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Nursing Services Delivery Theory: an open system approach.

PubMed

Meyer, Raquel M; O'Brien-Pallas, Linda L

2010-12-01

This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a 'black box' that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. A search of CINAHL and Business Source Premier for the years 1980-2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. THE Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. © 2010 Blackwell Publishing Ltd.

Risk factors for cesarean section and instrumental vaginal delivery after successful external cephalic version.

PubMed

de Hundt, Marcella; Vlemmix, Floortje; Bais, Joke M J; de Groot, Christianne J; Mol, Ben Willem; Kok, Marjolein

2016-01-01

Aim of this article is to examine if we could identify factors that predict cesarean section and instrumental vaginal delivery in women who had a successful external cephalic version. We used data from a previous randomized trial among 25 hospitals and their referring midwife practices in the Netherlands. With the data of this trial, we performed a cohort study among women attempting vaginal delivery after successful ECV. We evaluated whether maternal age, gestational age, parity, time interval between ECV and delivery, birth weight, neonatal gender, and induction of labor were predictive for a vaginal delivery on one hand or a CS or instrumental vaginal delivery on the other hand. Unadjusted and adjusted odds ratios were calculated with univariate and multivariate logistic regression analysis. Among 301 women who attempted vaginal delivery after a successful external cephalic version attempt, the cesarean section rate was 13% and the instrumental vaginal delivery rate 6%, resulting in a combined instrumental delivery rate of 19%. Nulliparity increased the risk of cesarean section (OR 2.7 (95% CI 1.2-6.1)) and instrumental delivery (OR 4.2 (95% CI 2.1-8.6)). Maternal age, gestational age at delivery, time interval between external cephalic version and delivery, birth weight and neonatal gender did not contribute to the prediction of failed spontaneous vaginal delivery. In our cohort of 301 women with a successful external cephalic version, nulliparity was the only one of seven factors that predicted the risk for cesarean section and instrumental vaginal delivery.

Labor induction and cesarean delivery: A prospective cohort study of first births in Pennsylvania, USA.

PubMed

Kjerulff, Kristen H; Attanasio, Laura B; Edmonds, Joyce K; Kozhimannil, Katy B; Repke, John T

2017-09-01

Mode of delivery at first childbirth largely determines mode of delivery at subsequent births, so it is particularly important to understand risk factors for cesarean delivery at first childbirth. In this study, we investigated risk factors for cesarean delivery among nulliparous women, with focus on the association between labor induction and cesarean delivery. A prospective cohort study of 2851 nulliparous women with singleton pregnancies who attempted vaginal delivery at hospitals in Pennsylvania, 2009-2011, was conducted. We used nested logistic regression models and multiple mediational analyses to investigate the role of three groups of variables in explaining the association between labor induction and unplanned cesarean delivery-the confounders of maternal characteristics and indications for induction, and the mediating (intrapartum) factors-including cervical dilatation, labor augmentation, epidural analgesia, dysfunctional labor, dystocia, fetal intolerance of labor, and maternal request of cesarean during labor. More than a third of the women were induced (34.3%) and 24.8% underwent cesarean delivery. Induced women were more likely to deliver by cesarean (35.9%) than women in spontaneous labor (18.9%), unadjusted OR 2.35 (95% CI 1.97-2.79). The intrapartum factors significantly mediated the association between labor induction and cesarean delivery (explaining 76.7% of this association), particularly cervical dilatation <3 cm at hospital admission, fetal intolerance of labor, and dystocia. The indications for labor induction only explained 6.2%. Increased risk of cesarean delivery after labor induction among nulliparous women is attributable mainly to lower cervical dilatation at hospital admission and higher rates of labor complications. © 2017 Wiley Periodicals, Inc.

Clinical indications for cesarean delivery among women living with female genital mutilation.

PubMed

Rodriguez, Maria I; Say, Lale; Abdulcadir, Jasmine; Hindin, Michelle J

2017-10-01

To compare primary indications for cesarean delivery among patients with different female genital mutilation (FGM) status. The present secondary analysis included data from women who underwent trial of labor resulting in cesarean delivery at 28 obstetric centers in six African countries between November 1, 2001, and March 31, 2003. Associations between cesarean delivery indications and FGM status were assessed using descriptive statistics and multivariable multinomial logistic regression. Data from 1659 women (480 patients with no type of FGM and 1179 patients with FGM [any type]) were included; cesarean delivery indications were collapsed into five categories (fetal indications, maternal factors, stage 1 arrest, stage 2 arrest, and other). The incidence of a clear medical indication for cesarean delivery did not differ between the groups (P=0.320). Among patients without a clear indication for cesarean delivery, women with FGM were more likely to have undergone cesarean delivery for maternal factors (adjusted relative risk ratio [aRRR] 3.92, 95% confidence interval [CI] 1.3-11.71), stage 1 arrest (aRRR 7.74, 95% CI 1.33-45.07), stage 2 arrest (aRRR 6.63, 95% CI 3.74-11.73), or other factors (aRRR 2.41, 95% CI 1.04-5.60) rather than fetal factors compared with women who had no type of FGM. Among women with unclear medical indications, FGM was associated with cesarean delivery being performed for maternal factors or arrest disorders. © 2017 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

The Risk Factors That Predict Chronic Hypertension After Delivery in Women With a History of Hypertensive Disorders of Pregnancy

PubMed Central

Hwang, Ji-won; Park, Sung-Ji; Oh, Soo-young; Chang, Sung-A.; Lee, Sang-Chol; Park, Seung Woo; Kim, Duk-Kyung

2015-01-01

Abstract Hypertensive disorders of pregnancy (HDP) is one of the most important lethal complications in pregnant mothers. It is also associated with the subsequent development of chronic hypertension. The objective of this study was to identify the clinical risk factors of postpartum chronic hypertension in women diagnosed with HDP. Six hundred patients as HDP, who diagnosed and followed-up at least 6 month after delivery, were included in the study. We divided the included subjects in 2 groups based on the development of postpartum chronic hypertension: presenting with the chronic hypertension, “case group” (n = 41) and without chronic hypertension, “control group” (n = 559). Clinical and demographic factors were evaluated. By multiple regression analysis, early onset hypertension with end-organ dysfunction, smoking, higher prepregnancy body mass index (BMI), and comorbidities, systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APLS), were associated with progression to chronic hypertension in the postpartum period. The value of area under the curves (AUC) for the 5 models, that generated to combine the significant factors, increased from 0.645 to 0.831, which indicated improved prediction of progression to the chronic hypertension. Additional multivariate analysis revealed significant specific risk factors. This retrospective single hospital-based study demonstrated that the clinical risk factors, that is early onset hypertension with end-organ dysfunction, smoking, and higher prepregnancy BMI, were significant independent predictors of chronic hypertension in women after delivery. Identification of risk factors allowed us to narrow the subject field for monitoring and managing high blood pressure in the postpartum period. PMID:26496291

Maternal mortality in India: current status and strategies for reduction.

PubMed

Prakash, A; Swain, S; Seth, A

1991-12-01

The causes (medical, reproductive factors, health care delivery system, and socioeconomic factors) of maternal mortality in India and strategies for reducing maternal mortality are presented. Maternal mortality rates (MMR) are very high in Asia and Africa compared with Northern Europe's 4/100,000 live births. An Indian hospital study found the MMR to be 4.21/1000 live births. 50-98% of maternal deaths are caused by direct obstetric causes (hemorrhage, infection, and hypertensive disorders, ruptured uterus, hepatitis, and anemia). 50% of maternal deaths due to sepsis are related to illegal induced abortion. MMR in India has not declined significantly in the past 15 years. Age, primi and grande multiparity, unplanned pregnancy, and related illegal abortion are the reproductive causes. In 1985 WHO reported that 63-80% of maternal deaths due to direct obstetric causes and 88-98% of all maternal deaths could probably have been prevented with proper handling. In India, coordination between levels in the delivery system and fragmentation of care account for the poor quality of maternal health care. Mass illiteracy is another cause. Effective strategies for reducing the MMR are 1) to place a high priority on maternal and child health (MCH) services and integrate vertical programs (e.g., family planning) related to MCH; 2) to give attention to care during labor and delivery, which is the most critical period for complications; 3) to provide community-based delivery huts which can provide a clean and safe delivery place close to home, and maternity waiting rooms in hospitals for high risk mothers; 4) to improve the quality of MCH care at the rural community level (proper history taking, palpation, blood pressure and fetal heart screening, risk factor screening, and referral); 5) to improve quality of care at the primary health care level (emergency care and proper referral); 6) to include in the postpartum program MCH and family planning services; 7) to examine the feasibility of a national blood transfusion service network; 8) to improve transportation; 9) to educate young girls on health and sex; 10) to informally educate the masses on MCH; 11) to focus obstetrics and gynecology training primarily on practical skills in management of labor and delivery; 12) to research reproductive behavior; and 13) to assure every women the right to safe motherhood.

Emerging Educational Technology: Assessing the Factors that Influence Instructors' Acceptance in Information Systems and Other Classrooms

ERIC Educational Resources Information Center

Ball, Diane M.; Levy, Yair

2008-01-01

Over the past decade there has been a shift in the emphasis of Internet-based emerging educational technology from use in online settings to supporting face-to-face and mixed delivery classes. Although emerging educational technology integration in the classroom has been led by information systems (IS) instructors, the technology acceptance and…

A Response to "Social Privilege, Social Justice, and Group Counseling: An Inquiry": Social Privilege--Counselors' Competence with Systemically Determined Inequalities

ERIC Educational Resources Information Center

Roysircar, Gargi

2008-01-01

The literature is extensive about explanatory behavioral and social effects with an individual or micro focus. A somewhat less programmatic literature exits in social justice that considers systemic or macro factors: for example, mental health service and its structures that perpetuate inequity and disparity in service delivery. Social privilege…

Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.

PubMed

Rodríguez-Nogales, C; Garbayo, E; Carmona-Abellán, M M; Luquin, M R; Blanco-Prieto, M J

2016-02-01

The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Gastroretentive drug delivery systems for therapeutic management of peptic ulcer.

PubMed

Garg, Tarun; Kumar, Animesh; Rath, Goutam; Goyal, Amit K

2014-01-01

A peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease (PUD), is a very common chronic disorder of the stomach which is mainly caused by damage or impairment of the stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and blood flow to mucosa play an important role in causing peptic ulcers. In this review article, our main focus is on some important gastroretentive drug delivery systems (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, superporous hydrogel, and magnetic systems) which will be helpful in gastroretention of different dosage forms for treatment of peptic ulcer. GRDDS provides a mean for controlled release of compounds that are absorbed by active transport in the upper intestine. It also enables controlled delivery for paracellularly absorbed drugs without a decrease in bioavailability. The above approaches are specific for targeting and leading to a marked improvement in the quality of life for a large number of patients. In the future, it is expected that they will become of growing significance, finally leading to improved efficiencies of various types of pharmacotherapies.

Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

PubMed Central

Chen, Yulin; Ma, Ping; Gui, Shuangying

2014-01-01

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

The Smart Drug Delivery System and Its Clinical Potential

PubMed Central

Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

2016-01-01

With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

FACTORS AFFECTING THE DEPOSITION OF AEROSOLIZED INSULIN

EPA Science Inventory

Abstract
Background
The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their...

Health promotion interventions to prevent early childhood human influenza at the household level: a realist review to identify implications for programmes in Hong Kong.

PubMed

Lam, Winsome; Dawson, Angela; Fowler, Cathrine

2015-04-01

To identify factors affecting the delivery of health promotion interventions to prevent early childhood human influenza at the household level. Yearly, influenza epidemics seriously affect all age groups, particularly those with weakened immune systems, including children. Influenza is transmitted easily from person to person through droplet and direct contact. Maintaining personal hygiene, avoiding close contact with the infected person and proper hand washing are recommended as the most effective means of preventing the transmission of influenza. However, it is not clear what programme-related mechanisms and contexts are crucial to the successful delivery of interventions in the home. This study systematically reviewed published research studies to identify factors influencing the effective delivery of health promotion programmes targeting influenza in a household. Realist review. A realist review methodology was selected to examine what interventions are effective in preventing and managing influenza at the household level and in what circumstances. A structured search of the peer-reviewed primary research literature was undertaken using a defined search protocol. Eight studies were retrieved for the analysis. Mechanisms impacting on intervention delivery were identified, including timing of implementation, programme reach, organisational and healthcare worker involvement, mode and place of delivery, contact with infected person, health practice compliance and sustainability at home. These findings suggest contextual factors that could be identified through ecological approaches to health promotion that are crucial for policymakers to consider when designing interventions. The active involvement of community nurses through an integrated household visiting programme may help to better deliver family-based health promotion interventions to prevent illnesses such as influenza in children. © 2014 John Wiley & Sons Ltd.

A potential pathophysiological role for galectins and the renin-angiotensin system in preeclampsia.

PubMed

Blois, Sandra M; Dechend, Ralf; Barrientos, Gabriela; Staff, Anne Cathrine

2015-01-01

This review discusses a potential role of galectins and the renin-angiotensin system (RAS) in the pathophysiology of preeclampsia (PE). Preeclampsia affects between 3 and 5 % of all pregnancies and is a heterogeneous disease, which may be caused by multiple factors. The only cure is the delivery of the placenta, which may result in a premature delivery and baby. Probably due to its heterogeneity, PE studies in human have hitherto only led to the identification of a limited number of factors involved in the pathogenesis of the disease. Animal models, particularly in mice and rats, have been used to gain further insight into the molecular pathology behind PE. In this review, we discuss the picture emerging from human and animal studies pointing to galectins and the RAS being associated with the PE syndrome and affecting a broad range of cellular signaling components. Moreover, we review the epidemiological evidence for PE increasing the risk of future cardiovascular disease later in life.

Synthesis of EF24-tripeptide chloromethyl ketone: a novel curcumin-related anticancer drug delivery system.

PubMed

Sun, Aiming; Shoji, Mamoru; Lu, Yang J; Liotta, Dennis C; Snyder, James P

2006-06-01

The blood coagulation cascade includes a step in which the soluble protein, factor VIIa (fVIIa), complexes with its transmembrane receptor, tissue factor (TF). The fVIIa/TF protein-protein complex is subsequently drawn into the cell by endocytosis. The observation that TF is aberrantly and abundantly expressed on many cancer cells offers an opportunity to specifically target those cells with an effective anticancer drug. Thus, we propose a new drug delivery system, drug-linker-Phe-Phe-Arg-mk-fVIIa, which can associate with TF on the surface of cancer cells, but release the cytotoxic agent in the cytoplasm. Synthetic procedures have been developed for the preparation of phenylalanine-phenylalanine-arginine chloromethyl ketone, (FFRck) followed by coupling with the cytotoxin EF24 and subsequently fVIIa to give EF-24-FFRmk-fVIIa. When breast cancer cells (MDA-MB-231) and human melanoma cells (RPMI-7951) are treated with the complex, the cells are arrested to a greater extent than EF24 alone by comparison with controls.

Defining community readiness for the implementation of a system of care.

PubMed

Behar, Lenore B; Hydaker, William M

2009-11-01

Developing systems of care for children with emotional disorders requires changes in the organization and delivery of services. Using concept mapping, the authors conducted a study to define factors of a community's readiness to make such changes. Participants were from 25 of 27 federally-funded, advanced sites, plus a panel of experts. The participants completed three tasks: brainstorming, rating, and sorting. This process produced eight factors: Leadership, Network of Local Partners, Shared Goals, Collaboration, Families and Youth as Partners, Accountability, Evaluation, and Plans to Expand Services. Understanding factors that contribute to successful implementation should help communities identify and make needed changes.

Understanding patient willingness to recommend and return: a strategy for prioritizing improvement opportunities.

PubMed

Burroughs, T E; Davies, A R; Cira, J C; Dunagan, W C

1999-06-01

Beginning in April 1995, an ongoing, comprehensive measurement system has been developed and refined at BJC Health System, a regional integrated delivery and financing system serving the St Louis metropolitan area, mid-Missouri, and Southern Illinois, to assess patient satisfaction with inpatient treatment, outpatient treatment, outpatient surgery, and emergency care. This system has provided the mechanism for identifying opportunities, setting priorities, and monitoring the impact of improvement initiatives. Satisfaction with key components of the care process among 23,361 patients (7,083 inpatients, 8,885 patients undergoing outpatient tests/procedures, 5,356 patients undergoing outpatient surgery, and 2,037 patients receiving emergency care) at 15 BJC Health System facilities was assessed through weekly surveys administered in April 1995 through December 1996. Structural equation models were developed to identify the key predictors of patient advocation-willingness to return for or recommend care. Across all venues of care the compassion provided to patients had the strongest relationship to patient advocation. Within each venue of care, however, a slightly different set of secondary factors emerged. The resulting models provided important information to help prioritize competing improvement opportunities in BJC Health System. In one hospital, a general medicine unit working for several years with little success to improve its patient satisfaction decided to focus on two primary factors predicting patient advocation: nursing care delivery and compassionate care. Root cause analysis was used to determine why two items-staff willingness to help with questions/concerns and clear explanation about tests and procedures-were rated low. On the basis of feedback from phone interviews with discharged patients, the care delivery process was changed to encourage patients to ask questions. Across the next two quarters, this unit experienced significant improvements in both targeted items. The significance of compassionate care and care delivery again speaks not only to the importance of the technical quality of clinical care but also to the customer-focused way in which this care was provided. After the primary predictors of patient advocation were identified, management was able to strategically focus improvement initiatives to maximize their impact. Across the organization, improvement teams scanned their data to find key factors where performance was lacking. Once these key opportunities were identified, the teams developed potential solutions and launched initiatives to improve their performance. Results suggest that some core issues are of extreme importance to patients regardless of whether they are receiving care in an inpatient, outpatient, or emergency setting. The compassion with which care is provided appears to be the most important factor in influencing patient intentions to recommend/return, regardless of the setting in which care is provided.

In Situ Forming Polymeric Drug Delivery Systems

PubMed Central

Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.

2009-01-01

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility.

PubMed

Kulkarni, Jayesh A; Cullis, Pieter R; van der Meel, Roy

2018-04-23

Genetic drugs based on RNA or DNA have remarkable therapeutic potential as virtually any disease can be treated by silencing a pathological gene, expressing a beneficial protein, or by editing defective genes. However, therapies based on nucleic acid polymers require sophisticated delivery systems to deliver these macromolecules to the interior of target cells. In this study, we review progress in developing nonviral lipid nanoparticle (LNP) delivery systems that have attractive properties, including ease of manufacture, reduced immune responses, multidosing capabilities, larger payloads, and flexibility of design. LNP systems represent the most advanced delivery systems for genetic drugs as it is expected that an LNP-short interfering RNA (siRNA) formulation will receive clinical approval from the Food and Drug Administration (FDA) in 2018 for treatment of the hereditary condition transthyretin-mediated amyloidosis, a fatal condition for which there is currently no treatment. This achievement is largely due to the development of optimized ionizable cationic lipids, arguably the most important factor in the clinical success of LNP-siRNA. In addition, we highlight potential LNP applications, including targeting tissues beyond the liver and therapeutic approaches based on messenger RNA or Clustered Regularly Interspaced Short Palindromic Repeats/Cas.

Biocompatible medical implant materials with binding sites for a biodegradable drug-delivery system

PubMed Central

Al-Dubai, Haifa; Pittner, Gisela; Pittner, Fritz; Gabor, Franz

2011-01-01

Feasibility studies have been carried out for development of a biocompatible coating of medical implant materials allowing the binding of biodegradable drug-delivery systems in a way that their reloading might be possible. These novel coatings, able to bind biodegradable nanoparticles, may serve in the long run as drug carriers to mediate local pharmacological activity. After biodegradation of the nanoparticles, the binding sites could be reloaded with fresh drug-delivering particles. As a suitable receptor system for the nanoparticles, antibodies are anchored. The design of the receptor is of great importance as any bio- or chemorecognitive interaction with other components circulating in the blood has to be avoided. Furthermore, the binding between receptor and the particles has to be strong enough to keep them tightly bound during their lifetime, but on the other hand allow reloading after final degradation of the particles. The nanoparticles suggested as a drug-delivery system for medical implants can be loaded with different pharmaceuticals such as antibiotics, growth factors, or immunosuppressives. This concept may enable the changing of medication, even after implantation of the medical device, if afforded by patients’ needs. PMID:24198488

Care Delivery for Filipino Americans Using the Neuman Systems Model

PubMed Central

Angosta, Alona D.; Ceria-Ulep, Clementina D.; Tse, Alice M.

2016-01-01

Filipino Americans are at risk of coronary heart disease due to the presence of multiple cardiometabolic factors. Selecting a framework that addresses the factors leading to coronary heart disease is vital when providing care for this population. The Neuman systems model is a comprehensive and wholistic framework that offers an innovative method of viewing clients, their families, and the healthcare system across multiple dimensions. Using the Neuman systems model, advanced practice nurses can develop and implement interventions that will help reduce the potential cardiovascular problems of clients with multiple risk factors. The authors in this article provides insight into the cardiovascular health of Filipino Americans and has implications for nurses and other healthcare providers working with various Southeast Asian groups in the United States. PMID:24740949

Determinants of Skilled Delivery Assistance in a Rural Population: Findings from an HDSS Site of Rural West Bengal, India.

PubMed

Ghosh, Saswata; Siddiqui, Md Zakaria; Barik, Anamitra; Bhaumik, Sunil

2015-11-01

This study examines the determinants of utilisation of skilled birth attendants (SBAs) amongst 2886 rural women in the state of West Bengal, India, using data from a survey of 2012-2013 conducted by the Birbhum Health and Demographic Surveillance System. Multilevel logit regression models were estimated and qualitative investigations conducted to understand the determinants of utilisation of SBAs in rural West Bengal. Among women who delivered their last child during the 3 years preceding the survey, 69.1 % of deliveries were assisted by SBAs, while 30.9 % were home deliveries without any SBA assistance. Multivariate analysis revealed that apart from socio-demographic and economic factors (such as household affluence, women's education, birth order, uptake of comprehensive ANC check-ups, advice regarding danger signs of pregnancy and household's socio-religious affiliation), supply side factors, such as availability of skilled birth attendants in the village and all-weather roads, have significant effect on seeking skilled assistance. Our findings also show that unobserved factors at village level independently influence uptake of SBA-assisted delivery. The present findings emphasise that both demand and supply side intervention strategies are essential prerequisites to enhance skilled birth attendance. Ample communication is observed at the individual level, but improving community level outreach and advocacy activities could generate further demand. SBAs can be better integrated by accommodating the socio-religious needs of local communities, such as providing female doctors and doctors with similar socio-religious backgrounds.

Recurrent shoulder dystocia: is it predictable?

PubMed

Kleitman, Vered; Feldman, Roi; Walfisch, Asnat; Toledano, Ronen; Sheiner, Eyal

2016-11-01

To examine the course and outcome of deliveries occurring in women who previously experienced shoulder dystocia. In addition, recurrent shoulder dystocia risk factors were assessed. A retrospective cohort analysis comparing all singleton deliveries with and without shoulder dystocia in their preceding delivery was conducted. Independent predictors of recurrent shoulder dystocia were investigated using a multiple logistic regression model. Of the 201,422 deliveries included in the analysis, 307 occurred in women with a previous shoulder dystocia (0.015 %). Women with a history of shoulder dystocia were more likely to be older, experienced higher rates of gestational diabetes mellitus, polyhydramnios, prolonged second stage, operative delivery and macrosomia (>4000 g) in the following delivery. Previous shoulder dystocia was found to be an independent risk factor for recurrent shoulder dystocia (OR = 6.1, 95 % CI 3.2-11.8, p value <0.001) in the multivariable regression analysis. Shoulder dystocia is an independent risk factor for recurrent shoulder dystocia. Deliveries in women with a history of shoulder dystocia are characterized by higher rates of operative delivery, prolonged second stage of labor and macrosomia.

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

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

Briquez, Priscilla S.; Hubbell, Jeffrey A.; Martino, Mikaël M.

2015-08-01

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localizationmore » of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.« less

e-Healthcare in India: critical success factors for sustainable health systems.

PubMed

Taneja, Udita; Sushil

2007-01-01

As healthcare enterprises seek to move towards an integrated, sustainable healthcare delivery model an IT-enabled or e-Healthcare strategy is being increasingly adopted. In this study we identified the critical success factors influencing the effectiveness of an e-Healthcare strategy in India. The performance assessment criteria used to measure effectiveness were increasing reach and reducing cost of healthcare delivery. A survey of healthcare providers was conducted. Analytic Hierarchy Process (AHP) and Interpretive Structural Modeling (ISM) were the analytical tools used to determine the relative importance of the critical success factors in influencing effectiveness of e-Healthcare and their interplay with each other. To succeed in e-Healthcare initiatives the critical success factors that need to be in place are appropriate government policies, literacy levels, and telecommunications and power infrastructure in the country. The focus should not be on the IT tools and biomedical engineering technologies as is most often the case. Instead the nontechnology factors such as healthcare provider and consumer mindsets should be addressed to increase acceptance of, and enhance the effectiveness of, sustainable e-Healthcare services.

The next step in gene delivery: molecular engineering of adeno-associated virus serotypes.

PubMed

Wang, Jinhui; Faust, Susan M; Rabinowitz, Joseph E

2011-05-01

Delivery is at the heart of gene therapy. Viral DNA delivery systems are asked to avoid the immune system, transduce specific target cell types while avoiding other cell types, infect dividing and non-dividing cells, insert their cargo within the host genome without mutagenesis or to remain episomal, and efficiently express transgenes for a substantial portion of a lifespan. These sought-after features cannot be associated with a single delivery system, or can they? The Adeno-associated virus family of gene delivery vehicles has proven to be highly malleable. Pseudotyping, using AAV serotype 2 terminal repeats to generate designer shells capable of transducing selected cell types, enables the packaging of common genomes into multiple serotypes virions to directly compare gene expression and tropism. In this review the ability to manipulate this virus will be examined from the inside out. The influence of host cell factors and organism biology including the immune response on the molecular fate of the viral genome will be discussed as well as differences in cellular trafficking patterns and uncoating properties that influence serotype transduction. Re-engineering the prototype vector AAV2 using epitope insertion, chemical modification, and molecular evolution not only demonstrated the flexibility of the best-studied serotype, but now also expanded the tool kit for molecular modification of all AAV serotypes. Current AAV research has changed its focus from examination of wild-type AAV biology to the feedback of host cell/organism on the design and development of a new generation of recombinant AAV delivery vehicles. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy". Copyright © 2010 Elsevier Ltd. All rights reserved.

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

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

J Torin Huzil; S Sivaloganathan; M Kohandel

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein andmore » nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.« less

A non-invasive system for delivering neural growth factors across the blood-brain barrier: a review.

PubMed

Granholm, A C; Albeck, D; Bäckman, C; Curtis, M; Ebendal, T; Friden, P; Henry, M; Hoffer, B; Kordower, J; Rose, G M; Söderström, S; Bartus, R T

1998-01-01

Intraventricular administration of nerve growth factor (NGF) in rats has been shown to reduce age-related atrophy of central cholinergic neurons and the accompanying memory impairment, as well as protect these neurons against a variety of perturbations. Since neurotrophins do not pass the blood-brain barrier (BBB) in significant amounts, a non-invasive delivery system for this group of therapeutic molecules needs to be developed. We have utilized a carrier system, consisting of NGF covalently linked to an anti-transferrin receptor antibody (OX-26), to transport biologically active NGF across the BBB. The biological activity of this carrier system was tested using in vitro bioassays and intraocular transplants; we were able to demonstrate that cholinergic markers in both developing and aged intraocular septal grafts were enhanced by intravenous delivery of the OX-26-NGF conjugate. In subsequent experiments, aged (24 months old) Fischer 344 rats received intravenous injections of the OX-26-NGF conjugate for 6 weeks, resulting in a significant improvement in spatial learning in previously impaired rats, but disrupting the learning ability of previously unimpaired rats. Neuroanatomical analyses showed that OX-26-NGF conjugate treatment resulted in a significant increase in cholinergic cell size as well as an upregulation of both low and high affinity NGF receptors in the medial septal region of rats initially impaired in spatial learning. Finally, OX-26-NGF was able to protect striatal cholinergic neurons against excitotoxicity and basal forebrain cholinergic neurons from degeneration associated with chemically-induced loss of target neurons. These results indicate the potential utility of the transferrin receptor antibody delivery system for treatment of neurodegenerative disorders with neurotrophic substances.

The Information Processing Role of the Informal and Quasi-Formal Support Systems among the Hispanic Elderly: Implications for the Delivery of Formal Social Services.

ERIC Educational Resources Information Center

Starrett, Richard A.; And Others

The study examined relationships among factors influencing utilization of social services by Hispanic elderly, particularly factors categorized as: (1) informal, such as support groups of family, kin, neighbors, friends, and (2) quasi-formal, such as church groups. Thirty-seven variables and data selected from a 1979-80 15-state survey of 1,805…

WHY DO YOU NEED TO USE A CARIES RISK ASSESSMENT PROTOCOL TO PROVIDE AN EFFECTIVE CARIES PREVENTIVE REGIME?

PubMed

Afuakwah, Charles; Welbury, Richard

2015-11-01

Clinical guidelines recommend an individual is given a caries risk status based on analysis of defined clinical and social criteria before implementing a tailored preventive plan. Improve documentation of caries risk assessment (CRA) in a general dental practice setting, using a systems-based approach to quality improvement methods. Investigate the impact of quality improvement efforts on subsequent design and delivery of preventive care. Identify barriers to delivery of CRA and provision of preventive care. Data for patients aged 0-16 years was collected over two cycles using standard audit methodology. The first cycle was a retrospective analysis (n = 400) using random sampling. The second cycle a prospective analysis (n = 513) using consecutive sampling over a 15-week period. Five staff meetings with feedback occurred between cycles. In cycle one, no specific CRA system was identified. CRA status was not stated widely, risk factors were not analysed and there was variation with respect to the prescription and delivery of preventive strategies. These discrepancies were demonstrable for all four participating dentists and at all ages. In cycle two, 100% recorded CRA. All risk factors were analysed and individual caries risk was correctly annotated. There was 100% compliance with the protocol for preventive plans. The use of CRA improved documentation of caries risk status. This has improved subsequent prescription of age specific evidence-based preventive care appropriate to the risk status of that individual. Barriers were identified to the delivery of CRA and the provision of comprehensive preventive care by the dentists and other healthcare professionals.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

A review of drug delivery systems for capsule endoscopy.

PubMed

Munoz, Fredy; Alici, Gursel; Li, Weihua

2014-05-01

The development of a highly controllable drug delivery system (DDS) for capsule endoscopy has become an important field of research due to its promising applications in therapeutic treatment of diseases in the gastrointestinal (GI) tract and drug absorption studies. Several factors need to be considered to establish the minimum requirements for a functional DDS. Environmental factors of the GI tract and also pharmaceutical factors can help determine the requirements to be met by a DDS in an endoscopic capsule. In order to minimize the influence of such factors on the performance of an effective DDS, at least two mechanisms should be incorporated into a capsule endoscope: an anchoring mechanism to control the capsule position and a drug release mechanism to control variables such as the drug release rate, number of doses and amount of drug released. The implementation of such remotely actuated mechanisms is challenging due to several constraints, including the limited space available in a swallowable capsule endoscope and the delicate and complex environment within the GI tract. This paper presents a comprehensive overview of existing DDS. A comparison of such DDS for capsule endoscopy based on the minimum DDS requirements is presented and future work is also discussed. Copyright © 2013 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.

Release of Cyclic Phosphatidic Acid from Gelatin-based Hydrogels Inhibit Colon Cancer Cell Growth and Migration

PubMed Central

Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

2012-01-01

Microparticle and nanoparticle formulations are widely used to improve the bioavailability of low-solubility drugs and as vehicles for organ- and tissue-specific targeted drug delivery. We investigated the effect of a novel, controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on human colon cancer cell line functions. We encapsulated cPA in gelatin-based hydrogels and examined its ability to inhibit the viability and migration of HT-29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). The hydrogel delivery system prolonged cPA release into the culture medium. Accordingly, cPA-hydrogel microspheres substantially inhibited LPA-induced PPARγ activity and cell growth and migration compared with that of cells cultured with cPA alone. Thus, hydrogel microspheres are a potential system for stable and efficient delivery of bioactive lipids such as cPA and may offer a new strategy for targeted colon cancer treatment. PMID:23008752

PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect.

PubMed

Acharya, Sarbari; Sahoo, Sanjeeb K

2011-03-18

As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. Copyright © 2010 Elsevier B.V. All rights reserved.

Matrix Metalloproteinase Responsive Delivery of Myostatin Inhibitors.

PubMed

Braun, Alexandra C; Gutmann, Marcus; Ebert, Regina; Jakob, Franz; Gieseler, Henning; Lühmann, Tessa; Meinel, Lorenz

2017-01-01

The inhibition of myostatin - a member of the transforming growth factor (TGF-β) family - drives regeneration of functional skeletal muscle tissue. We developed a bioresponsive drug delivery system (DDS) linking release of a myostatin inhibitor (MI) to inflammatory flares of myositis to provide self-regulated MI concentration gradients within tissues of need. A protease cleavable linker (PCL) - responding to MMP upregulation - is attached to the MI and site-specifically immobilized on microparticle surfaces. The PCL disintegrated in a matrix metalloproteinase (MMP) 1, 8, and particularly MMP-9 concentration dependent manner, with MMP-9 being an effective surrogate biomarker correlating with the activity of myositis. The bioactivity of particle-surface bound as well as released MI was confirmed by luciferase suppression in stably transfected HEK293 cells responding to myostatin induced SMAD phosphorylation. We developed a MMP-responsive DDS for MI delivery responding to inflammatory flare of a diseased muscle matching the kinetics of MMP-9 upregulation, with MMP-9 kinetics matching (patho-) physiological myostatin levels. ᅟ: Graphical Abstract Schematic illustration of the matrix metalloproteinase responsive delivery system responding to inflammatory flares of muscle disease. The protease cleavable linker readily disintegrates upon entry into the diseased tissue, therby releasing the mystatin inhibitor.

Decision making in childbirth: the influence of traditional structures in a Ghanaian village.

PubMed

Jansen, I

2006-03-01

The regional health administration of the Brong-Ahafo Region in Ghana identified that although informed about the advantages of both aspects of care, pregnant women made use of antenatal services but not of the supervised delivery. Quantitative studies have identified economic factors that influence the decisions of pregnant women. To describe and understand the traditional structures of childbirth in Kwame Danso/Ghana and to explore why the pregnant women do not make use of supervised deliveries in the modern institutions. A mini-ethnographic study, using participant observation and ethnographic interviews. Cultural and social factors have a significant influence on the decisions related to childbirth. One of the most important factors identified was that the responsible persons for decisions related to a delivery were the older female relatives, rather than the mothers themselves. Older females used rational judgements to weigh up the possibilities of risks, interests and advantages related to their cultural, spiritual and social system. Other factors were staff behaviour that was characterized as unfriendly and lacking for respect as to the living conditions and thinking of the pregnant women in the village. Ethnographic research provided an understanding of traditional structures that have an influence on the decisions and behaviour of the community related to childbirth. Appreciation of these structures enabled health promotion and structured health services to be delivered in a more culturally appropriate way.

Planning Communication Networks to Deliver Educational Services.

ERIC Educational Resources Information Center

Ballard, Richard J.; Eastwood, Lester F., Jr.

As companion to the more general document Telecommunications Media for the Delivery of Educational Programming , this report concentrates on the technical and economic factors affecting the design of only one class of educational networks, dedicated coaxial cable systems. To provide illustrations, possible single and dual dedicated cable networks…

Understanding ADHD from a Biopsychosocial-Cultural Framework: A Case Study

ERIC Educational Resources Information Center

Pham, Andy V.

2015-01-01

The biopsychosocial-cultural framework is a systemic and multifaceted approach to assessment and intervention that takes into account biological, psychological, and socio-cultural factors that influence human functioning and service delivery. Although originally developed to assess physical health and medical illness, this contemporary model can…

Risk factors for unscheduled delivery in patients with placenta accreta.

PubMed

Bowman, Zachary S; Manuck, Tracy A; Eller, Alexandra G; Simons, Marilee; Silver, Robert M

2014-03-01

Patients with suspected placenta accreta have improved outcomes with scheduled delivery. Our objective was to identify risk factors for unscheduled delivery in patients with suspected placenta accreta. This was a cohort study of women with antenatally suspected placenta accreta. Women who delivered prior to a planned delivery date were compared with women who had a scheduled delivery. Data were analyzed using a Student t test, χ(2), logistic regression, and survival analyses. Variables included in the analyses were episodes of antenatal vaginal bleeding, preterm premature rupture of membranes (PPROM), uterine contractions, prior cesarean deliveries, interpregnancy interval, parity, and patient demographic factors. A value of P < .05 was considered significant. Seventy-seven women with antenatal suspicion for placenta accreta were identified. Thirty-eight (49.4%) had an unscheduled delivery. Demographics were similar between groups. Unscheduled patients delivered earlier (mean 32.3 vs 35.7 weeks, P < .001) and were significantly more likely to have had vaginal bleeding (86.8% vs 35.9%, P < .001) and uterine activity (47.4% vs 2.6%, P < .001). Each episode of antenatal vaginal bleeding was associated with an increased risk of unscheduled delivery (adjusted odds ratio, 3.8; 95% confidence interval, 1.8-7.8). Risk of earlier delivery was even greater when associated with PPROM (P < .001). Among women with suspected placenta accreta, those with antenatal vaginal bleeding were more likely to require unscheduled delivery. This risk increases further in the setting of PPROM and/or uterine contractions. These clinical factors should be considered when determining the optimal delivery gestational age for women with placental accreta. Copyright © 2014 Mosby, Inc. All rights reserved.

A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration.

PubMed

Xu, Yanyi; Fu, Minghuan; Li, Zhihong; Fan, Zhaobo; Li, Xiaofei; Liu, Ying; Anderson, Peter M; Xie, Xiaoyun; Liu, Zhenguo; Guan, Jianjun

2016-02-01

Stem cell therapy is one of the most promising strategies to restore blood perfusion and promote muscle regeneration in ischemic limbs. Yet its therapeutic efficacy remains low owing to the inferior cell survival under the low oxygen and nutrient environment of the injured limbs. To increase therapeutic efficacy, high rates of both short- and long-term cell survival are essential, which current approaches do not support. In this work, we hypothesized that a high rate of short-term cell survival can be achieved by introducing a prosurvival environment into the stem cell delivery system to enhance cell survival before vascularization is established; and that a high rate of long-term cell survival can be attained by building a proangiogenic environment in the system to quickly vascularize the limbs. The system was based on a biodegradable and thermosensitive poly(N-Isopropylacrylamide)-based hydrogel, a prosurvival and proangiogenic growth factor bFGF, and bone marrow-derived mesenchymal stem cells (MSCs). bFGF can be continuously released from the system for 4weeks. The released bFGF significantly improved MSC survival and paracrine effects under low nutrient and oxygen conditions (0% FBS and 1% O2) in vitro. The prosurvival effect of the bFGF on MSCs was resulted from activating cell Kruppel-like factor 4 (KLF4) pathway. When transplanted into the ischemic limbs, the system dramatically improved MSC survival. Some of the engrafted cells were differentiated into skeletal muscle and endothelial cells, respectively. The system also promoted the proliferation of host cells. After only 2weeks of implantation, tissue blood perfusion was completely recovered; and after 4weeks, the muscle fiber diameter was restored similarly to that of the normal limbs. These pronounced results demonstrate that the developed stem cell delivery system has a potential for ischemic limb regeneration. Stem cell therapy is a promising strategy to restore blood perfusion and promote muscle regeneration in ischemic limbs. Yet its therapeutic efficacy remains low owing to the inferior cell survival under the ischemic environment of the injured limbs. To increase therapeutic efficacy, high rate of cell survival is essential, which current approaches do not support. In this work, we tested the hypothesis that a stem cell delivery system that can continuously release a prosurvival and proangiogenic growth factor will promote high rates of cell survival in the ischemic limbs. The prosurvival effect could augment cell survival before vascularization is established, while the proangiogenic effect could stimulate quick angiogenesis to achieve long-term cell survival. Meanwhile, the differentiation of stem cells into endothelial and myogenic lineages, and cell paracrine effects will enhance vascularization and muscle regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease.

PubMed

Maslov, Mikhail; Foianini, Stephan; Lovich, Mark

2017-10-01

Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically. Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD. Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.

Silk hydrogels for sustained ocular delivery of anti-vascular endothelial growth factor (anti-VEGF) therapeutics.

PubMed

Lovett, Michael L; Wang, Xiaoqin; Yucel, Tuna; York, Lyndsey; Keirstead, Marc; Haggerty, Linda; Kaplan, David L

2015-09-01

Silk hydrogels were formulated with anti-vascular endothelial growth factor (anti-VEGF) therapeutics for sustained ocular drug delivery. Using silk fibroin as a vehicle for delivery, bevacizumab-loaded hydrogel formulations demonstrated sustained release of 3 months or greater in experiments in vitro as well as in vivo using an intravitreal injection model in Dutch-belted rabbits. Using both standard dose (1.25mg bevacizumab/50 μL injection) and high dose (5.0mg bevacizumab/50 μL injection) hydrogel formulations, release concentrations were achieved at day 90 that were equivalent or greater than those achieved at day 30 with the positive standard dose control (single injection (50 μL) of 1.25mg bevacizumab solution), which is estimated to be the therapeutic threshold based on the current dosage administration schedule of 1 injection/month. These gels also demonstrated signs of biodegradation after 3 months, suggesting that repeated injections may be possible (e.g., one injection every 3-6 months or longer). Due to its pharmacokinetic and biodegradation profiles, this delivery system may be used to reduce the frequency of dosing for patients currently enduring treatment using bevacizumab or other anti-VEGF therapeutics. Copyright © 2015 Elsevier B.V. All rights reserved.

Online Course Delivery: An Empirical Investigation of Factors Affecting Student Satisfaction

ERIC Educational Resources Information Center

Beqiri, Mirjeta S.; Chase, Nancy M.; Bishka, Atena

2010-01-01

The authors investigated potential factors impacting students' satisfaction with online course delivery using business students as participants. The findings suggest that the student who would be more satisfied with the delivery of online courses fits the following profile: graduate, married, resides more than 1 mile away from campus, and male.…

Integrated multisystem analysis in a mental health and criminal justice ecosystem.

PubMed

Falconer, Erin; El-Hay, Tal; Alevras, Dimitris; Docherty, John; Yanover, Chen; Kalton, Alan; Goldschmidt, Yaara; Rosen-Zvi, Michal

2014-01-01

Patients with a serious mental illness often receive care that is fragmented due to reduced availability of or access to resources, and inadequate, discontinuous, and uncoordinated care across health, social services, and criminal justice organizations. These gaps in care may lead to increased mental health disease burden and relapse, as well as repeated incarcerations. Further, the complex health, social service, and criminal justice ecosystem within which the patient may be embedded makes it difficult to examine the role of modifiable risk factors and delivered services on patient outcomes, particularly given that agencies often maintain isolated sets of relevant data. Here we describe an approach to creating a multisystem analysis that derives insights from an integrated data set including patient access to case management services, medical services, and interactions with the criminal justice system. We combined data from electronic systems within a US mental health ecosystem that included mental health and substance abuse services, as well as data from the criminal justice system. We applied Cox models to test the associations between delivery of services and re-incarceration. Using this approach, we found an association between arrests and crisis stabilization services in this population. We also found that delivery of case management or medical services provided after release from jail was associated with a reduced risk for re-arrest. Additionally, we used machine learning to train and validate a predictive model linking non-modifiable and modifiable risk factors and outcomes. A predictive model, constructed using elastic net regularized logistic regression, and considering age, past arrests, mental health diagnosis, as well as use of a jail diversion program, outpatient, medical and case management services predicted the probability of re-arrests with fair accuracy (AUC=.67). By modeling the complex interactions between risk factors, service delivery and outcomes, we may better enable systems of care to meet patient needs and improve outcomes.

Race, biology, and health care: reassessing a relationship.

PubMed

Byrd, W M

1990-01-01

Recent reports reaffirm huge disparities in the health of blacks compared to other Americans. These disparities persist in part because of the current attempt by health policy makers to frame racially based health differences in non-racial terms. Yet an historical analysis shows that since ancient times, blacks have been the victims of racism in the biomedical sciences; health-system discrimination and deprivation; and later, medical and scientific exploitation. Race- and class-based structuring of the health delivery system has combined with other factors, including physicians' attitudes conditioned by their participation in slavery, and the scientific myth of black biological and intellectual inferiority, to establish a "slave health deficit" that has never been corrected. Until the persistent institutional racism and racial discrimination in health policy, health delivery, and medical educational systems are eradicated, African-Americans will continue to experience poor health outcome.

The Impact of Youth and Family Risk Factors on Service Recommendations and Delivery in a School-Based System of Care

PubMed Central

Whitson, Melissa L.; Connell, Christian M.; Bernard, Stanley; Kaufman, Joy S.

2010-01-01

The present study examines the impact of child and family risk factors on service access for youth and families in a school-based system of care. Regression analyses examined the relationships between risk factors and services recommended, services received, and dosage of services received. Logistic regression analyses examined the relationship between risk factors and whether or not youth received specific types of services within the system of care. Results revealed that youth with a personal or family history of substance use had more services recommended than youth without these risk factors, while youth with a family history of substance use received more services. Youth with a history of substance use received a significantly higher dosage of services overall. Finally, history of family mental illness was associated with receiving mental health and operational services (e.g., family advocacy, emergency funds). Implications and limitations are discussed. PMID:20165927

Variability in Nose-to-Lung Aerosol Delivery

PubMed Central

Walenga, Ross L; Tian, Geng; Hindle, Michael; Yelverton, Joshua; Dodson, Kelley; Longest, P. Worth

2014-01-01

Nasal delivery of lung targeted pharmaceutical aerosols is ideal for drugs that need to be administered during high flow nasal cannula (HFNC) gas delivery, but based on previous studies losses and variability through both the delivery system and nasal cavity are expected to be high. The objective of this study was to assess the variability in aerosol delivery through the nose to the lungs with a nasal cannula interface for conventional and excipient enhanced growth (EEG) delivery techniques. A database of nasal cavity computed tomography (CT) scans was collected and analyzed, from which four models were selected to represent a wide range of adult anatomies, quantified based on the nasal surface area-to-volume ratio (SA/V). Computational fluid dynamics (CFD) methods were validated with existing in vitro data and used to predict aerosol delivery through a streamlined nasal cannula and the four nasal models at a steady state flow rate of 30 L/min. Aerosols considered were solid particles for EEG delivery (initial 0.9 μm and 1.5 μm aerodynamic diameters) and conventional droplets (5 μm) for a control case. Use of the EEG approach was found to reduce depositional losses in the nasal cavity by an order of magnitude and substantially reduce variability. Specifically, for aerosol deposition efficiency in the four geometries, the 95% confidence intervals (CI) for 0.9 and 5 μm aerosols were 2.3-3.1 and 15.5-66.3%, respectively. Simulations showed that the use of EEG as opposed to conventional methods improved delivered dose of aerosols through the nasopharynx, expressed as penetration fraction (PF), by approximately a factor of four. Variability of PF, expressed by the coefficient of variation (CV), was reduced by a factor of four with EEG delivery compared with the control case. Penetration fraction correlated well with SA/V for larger aerosols, but smaller aerosols showed some dependence on nasopharyngeal exit hydraulic diameter. In conclusion, results indicated that the EEG technique not only improved lung aerosol delivery, but largely eliminated variability in both nasal depositional loss and lung PF in a newly developed set of nasal airway models. PMID:25308992

Advancement in integrin facilitated drug delivery.

PubMed

Arosio, Daniela; Casagrande, Cesare

2016-02-01

The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.

PubMed

Zhou, Chengxin; Robert, Marie-Claude; Kapoulea, Vassiliki; Lei, Fengyang; Stagner, Anna M; Jakobiec, Frederick A; Dohlman, Claes H; Paschalis, Eleftherios I

2017-01-01

Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS). The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.

Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction.

PubMed

Gyöngyösi, Mariann; Hemetsberger, Rayyan; Posa, Aniko; Charwat, Silvia; Pavo, Noemi; Petnehazy, Ors; Petrasi, Zsolt; Pavo, Imre J; Hemetsberger, Hani; Benedek, Imre; Benedek, Teodora; Benedek, Istvan; Kovacs, Istvan; Kaun, Christoph; Maurer, Gerald

2010-04-01

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1alpha) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8 +/- 1.2 x 10(6)) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22 +/- 4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1alpha was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1alpha expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1alpha increased immediately post-MI (from 278 +/- 127 to 631 +/- 375 pg/ml, p < 0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1alpha significantly (p < 0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1alpha expression in the infarcted area was higher in Group IM than in Group IC or S (1,963 +/- 586 vs. 1,307 +/- 392 vs. 271 +/- 110 activity per square millimeter, respectively, p < 0.05), while the border zone contained similarly lower level of HIF-1alpha, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1alpha was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1alpha. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1alpha more effectively than does intracoronary delivery.

Delivery should happen soon and my pain will be reduced: understanding women's perception of good delivery care in India.

PubMed

Bhattacharyya, Sanghita; Srivastava, Aradhana; Avan, Bilal Iqbal

2013-11-22

Understanding a woman's perspective and her needs during childbirth and addressing them as part of quality-improvement programmes can make delivery care safe, affordable, and respectful. It has been pointed out that the patient's judgement on the quality and goodness of care is indispensible to improving the management of healthcare systems. The objective of the study is to understand the aspects of care that women consider important during childbirth. Individual in-depth interviews (IDIs) and focus-group discussions (FGDs) with women who recently delivered were the techniques used. Seventeen IDIs and four FGDs were conducted in Jharkhand state in east India between January and March 2012. Women who had normal deliveries with live births at home and in primary health centres were included. To minimise recall bias, interviews were conducted within 42 days of childbirth. Using the transcripts of interviews, the data were analysed thematically. Aspects of care most commonly cited by women to be important were: availability of health providers and appropriate medical care (primarily drugs) in case of complications; emotional support; privacy; clean place after delivery; availability of transport to reach the institution; monetary incentives that exceed expenses; and prompt care. Other factors included kind interpersonal behaviour, cognitive support, faith in the provider's competence, and overall cleanliness of the facility and delivery room. Respondents belonging to low socio-economic strata with basic literacy levels might not understand appropriate clinical aspects of care, but they want care that is affordable and accessible, along with privacy and emotional support during delivery. The study highlighted that healthcare quality-improvement programmes in India need to include non-clinical aspects of care as women want to be treated humanely during delivery--they desire respectful treatment, privacy, and emotional support. Further research into maternal satisfaction could be made more policy relevant by assessing the relative strength of various factors in influencing maternal satisfaction; this could help in prioritising appropriate interventions for improved quality of care (QoC).

Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma

PubMed Central

Varshosaz, Jaleh; Farzan, Maryam

2015-01-01

Hepatocellular carcinoma (HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorable systemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs (siRNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and siRNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited side-effects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is over-expressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and non-viral siRNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic siRNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and siRNA-based therapeutics in HCC and discussed in detail in this article. PMID:26576089

The Latina paradox: an opportunity for restructuring prenatal care delivery.

PubMed

McGlade, Michael S; Saha, Somnath; Dahlstrom, Marie E

2004-12-01

Latina mothers in the United States enjoy surprisingly favorable birth outcomes despite their social disadvantages. This "Latina paradox" is particularly evident among Mexican-born women. The social and cultural factors that contribute to this paradox are maintained by community networks--informal systems of prenatal care that are composed of family, friends, community members, and lay health workers. This informal system confers protective factors that provide a behavioral context for healthy births. US-born Latinas are losing this protection, although it could be maintained with the support of community-based informal care systems. We recommend steps to harness the benefits of informal systems of prenatal care in Latino communities to meet the increasing needs of pregnant Latina women.

SU-E-T-100: Designing a QA Tool for Enhance Dynamic Wedges Based On Dynalog Files

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

Yousuf, A; Hussain, A

2014-06-01

Purpose: A robust quality assurance (QA) program for computer controlled enhanced dynamic wedge (EDW) has been designed and tested. Calculations to perform such QA test is based upon the EDW dynamic log files generated during dose delivery. Methods: Varian record and verify system generates dynamic log (dynalog) files during dynamic dose delivery. The system generated dynalog files contain information such as date and time of treatment, energy, monitor units, wedge orientation, and type of treatment. It also contains the expected calculated segmented treatment tables (STT) and the actual delivered STT for the treatment delivery as a verification record. These filesmore » can be used to assess the integrity and precision of the treatment plan delivery. The plans were delivered with a 6 MV beam from a Varian linear accelerator. For available EDW angles (10°, 15°, 20°, 25°, 30°, 45°, and 60°) Varian STT values were used to manually calculate monitor units for each segment. It can also be used to calculate the EDW factors. Independent verification of fractional MUs per segment was performed against those generated from dynalog files. The EDW factors used to calculate MUs in TPS were dosimetrically verified in solid water phantom with semiflex chamber on central axis. Results: EDW factors were generated from the STT provided by Varian and verified against practical measurements. The measurements were in agreement of the order of 1 % to the calculated EDW data. Variation between the MUs per segment obtained from dynalog files and those manually calculated was found to be less than 2%. Conclusion: An efficient and easy tool to perform routine QA procedure of EDW is suggested. The method can be easily implemented in any institution without a need for expensive QA equipment. An error of the order of ≥2% can be easily detected.« less

Service readiness, health facility management practices, and delivery care utilization in five states of Nigeria: a cross-sectional analysis.

PubMed

Gage, Anastasia J; Ilombu, Onyebuchi; Akinyemi, Akanni Ibukun

2016-10-06

Existing studies of delivery care in Nigeria have identified socioeconomic and cultural factors as the primary determinants of health facility delivery. However, no study has investigated the association between supply-side factors and health facility delivery. Our study analyzed the role of supply-side factors, particularly health facility readiness and management practices for provision of quality maternal health services. Using linked data from the 2005 and 2009 health facility and household surveys in the five states in which the Community Participation for Action in the Social Sector (COMPASS) project was implemented, indices of health service readiness and management were developed based on World Health Organization guidelines. Multilevel logistic regression models were run to determine the association between these indices and health facility delivery among 2710 women aged 15-49 years whose last child was born within the five years preceding the surveys and who lived in 51 COMPASS LGAs. The health facility delivery rate increased from 25.4 % in 2005 to 44.1 % in 2009. Basic amenities for antenatal care provision, readiness to deliver basic emergency obstetric and newborn care, and management practices supportive of quality maternal health services were suboptimal in health facilities surveyed and did not change significantly between 2005 and 2009. The LGA mean index of basic amenities for antenatal care provision was more positively associated with the odds of health facility delivery in 2009 than in 2005, and in rural than in urban areas. The LGA mean index of management practices was associated with significantly lower odds of health facility delivery in rural than in urban areas. The LGA mean index of facility readiness to deliver basic emergency obstetric and neonatal care declined slightly from 5.16 in 2005 to 3.98 in 2009 and was unrelated to the odds of health facility delivery. Supply-side factors appeared to play a role in health facility delivery after controlling for socio-demographic factors. Improving uptake of delivery care would require greater attention to rural-urban inequities and health facility management practices, and to increasing the number of health facilities with fundamental elements for delivery of basic emergency obstetric and neonatal care.

In Vitro Comparison of Aerosol Delivery Using Different Face Masks and Flow Rates With a High-Flow Humidity System.

PubMed

Lin, Hui-Ling; Harwood, Robert J; Fink, James B; Goodfellow, Lynda T; Ari, Arzu

2015-09-01

Aerosol drug delivery to infants and small children is influenced by many factors, such as types of interface, gas flows, and the designs of face masks. The purpose of this in vitro study was to evaluate aerosol delivery during administration of gas flows across the range used clinically with high-flow humidity systems using 2 aerosol masks. A spontaneous lung model was used to simulate an infant/young toddler up to 2 y of age and pediatric breathing patterns. Nebulized salbutamol by a vibrating mesh nebulizer positioned at the inlet of a high-flow humidification system at gas flows of 3, 6, and 12 L/min was delivered via pediatric face masks to a pediatric face mannequin attached to a filter. Aerosol particle size distribution exiting the vibrating mesh nebulizer and at the mask position distal to the heated humidifier with 3 flows was measured with a cascade impactor. Eluted drug from the filters and the impactor was analyzed with a spectrophotometer (n = 3). Statistical analysis was performed by analysis of variance with a significant level of P < .05. The inhaled mass was between 2.8% and 8.1% among all settings and was significantly lower at 12 L/min (P = .004) in the pediatric model. Drug delivery with pediatric breathing was greater than with infant breathing (P = .004). The particle size distribution of aerosol emitted from the nebulizer was larger than the heated humidified aerosol exiting the tubing (P = .002), with no difference between the 3 flows (P = .10). The flows of gas entering the mask and breathing patterns influence aerosol delivery, independent of the face mask used. Aerosol delivery through a high-flow humidification system via mask could be effective with both infant and pediatric breathing patterns. Copyright © 2015 by Daedalus Enterprises.

Hidden Costs of Hospital Based Delivery from Two Tertiary Hospitals in Western Nepal.

PubMed

Acharya, Jeevan; Kaehler, Nils; Marahatta, Sujan Babu; Mishra, Shiva Raj; Subedi, Sudarshan; Adhikari, Bipin

2016-01-01

Hospital based delivery has been an expensive experience for poor households because of hidden costs which are usually unaccounted in hospital costs. The main aim of this study was to estimate the hidden costs of hospital based delivery and determine the factors associated with the hidden costs. A hospital based cross-sectional study was conducted among 384 post-partum mothers with their husbands/house heads during the discharge time in Manipal Teaching Hospital and Western Regional Hospital, Pokhara, Nepal. A face to face interview with each respondent was conducted using a structured questionnaire. Hidden costs were calculated based on the price rate of the market during the time of the study. The total hidden costs for normal delivery and C-section delivery were 243.4 USD (US Dollar) and 321.6 USD respectively. Of the total maternity care expenditures; higher mean expenditures were found for food & drinking (53.07%), clothes (9.8%) and transport (7.3%). For postpartum women with their husband or house head, the total mean opportunity cost of "days of work loss" were 84.1 USD and 81.9 USD for normal delivery and C-section respectively. Factors such as literate mother (p = 0.007), employed house head (p = 0.011), monthly family income more than 25,000 NRs (Nepalese Rupees) (p = 0.014), private hospital as a place of delivery (p = 0.0001), C-section as a mode of delivery (p = 0.0001), longer duration (>5days) of stay in hospital (p = 0.0001), longer distance (>15km) from house to hospital (p = 0.0001) and longer travel time (>240 minutes) from house to hospital (p = 0.007) showed a significant association with the higher hidden costs (>25000 NRs). Experiences of hidden costs on hospital based delivery and opportunity costs of days of work loss were found high. Several socio-demographic factors, delivery related factors (place and mode of delivery, length of stay, distance from hospital and travel time) were associated with hidden costs. Hidden costs can be a critical factor for many poor and remote households who attend the hospital for delivery. Current remuneration (10-15 USD for normal delivery, 30 USD for complicated delivery and 70 USD for caesarean section delivery) for maternity incentive needs to account the hidden costs by increasing it to 250 USD for normal delivery and 350 USD for C-section. Decentralization of the obstetric care to remote and under-privileged population might reduce the economic burden of pregnant women and can facilitate their attendance at the health care centers.

Factors of influence and social correlates of parturition in captive Campbell's monkeys: Case study and breeding data.

PubMed

Lemasson, Alban; Jubin, Ronan; Bec, Philippe; Hausberger, Martine

2017-05-01

How nonhuman primates deal with birth, at the moment of delivery, and during the following days, remains poorly explored because of the unpredictability of this event, particularly for forest-dwelling arboreal species. Available studies highlight intra- and interspecific variation which suggest flexibility of the timing of delivery, of behavior associated with labor contractions and parturition, and the social context and ambient noise surrounding delivery. Here, we present the findings of a two-decade survey of reproduction in a population of captive Campbell's monkeys. Analysis of 34 births (with a female-biased sex ratio) showed that deliveries occurred systematically at night and more frequently during week-ends and in fall (September-November). This suggests the existence of both circadian and infradian biological rhythms. We present the first detailed description of a birth for this species and its short-term social consequences. In line with previous findings for other monkeys and apes, labor (estimated by unusual stretching postures) and parturition were rapid, and delivery occurred in a clear social and vocal context. During the following days, the new mother became the center of attention of for young (kin and non-kin) females and rose through the hierarchy. We discuss socio-ecological factors, notably captivity conditions and the high degree of tolerance in the species' social system, and confirm the existence of both "rigidity" and "flexibility" in the primates' adaptive reproductive strategies. © 2017 Wiley Periodicals, Inc.

Risk and protective factors for obstetric anal sphincter injuries: A retrospective nationwide study.

PubMed

Marschalek, Marie-Louise; Worda, Christof; Kuessel, Lorenz; Koelbl, Heinz; Oberaigner, Willi; Leitner, Hermann; Marschalek, Julian; Husslein, Heinrich

2018-03-14

In view of the reported increase in obstetric anal sphincter injuries, the objective of this study was to evaluate the incidence of such injuries over time and the associated risk and protective factors. This was a retrospective cohort study from a national database of 168 137 primiparous women with term, singleton, cephalic, vaginal delivery between 2008 and 2014. The main outcome measure was obstetric anal sphincter injury. A multivariate regression model was used to identify risk and protective factors. Age >19 years, birthweight >4000 g, and operative vaginal delivery were independent risk factors for obstetric anal sphincter injuries. Mediolateral episiotomy increased the risk for obstetric anal sphincter injuries in spontaneous vaginal birth (number needed to harm 333), whereas it was protective in vacuum delivery (number needed to treat 50). From 2008 to 2014, there was an increase in the rate of obstetric anal sphincter injuries (2.1% vs 3.1%, P < .01), vacuum deliveries (12.1% vs 12.8%, P < .01), and cesarean delivery after labor (17.1% vs 19.4%, P < .01), while forceps deliveries (0.4% vs 0.1%, P < .01) and episiotomy rate decreased (35.9% vs 26.4%, P < .01). Episiotomy may be a risk or protective factor depending on the type of episiotomy and the clinical setting in which it is used. Our study supports a restrictive use of mediolateral episiotomy in spontaneous vaginal deliveries. In vacuum deliveries mediolateral episiotomy may help prevent obstetric anal sphincter injuries. © 2018 the Authors. Birth published by Wiley Periodicals, Inc.

Where are we on the diffusion curve? Trends and drivers of primary care physicians' use of health information technology.

PubMed

Audet, Anne-Marie; Squires, David; Doty, Michelle M

2014-02-01

To describe trends in primary care physicians' use of health information technology (HIT) between 2009 and 2012, examine practice characteristics associated with greater HIT capacity in 2012, and explore factors such as delivery system and payment reforms that may affect adoption and functionality. We used data from the 2012 and 2009 Commonwealth Fund International Health Policy Surveys of Primary Care Physicians. The data were collected in both years by postal mail between March and July among a nationally representative sample of primary care physicians in the United States. We compared primary care physicians' HIT capacity in 2009 and 2012. We employed multivariable logistic regression to analyze whether participating in an integrated delivery system, sharing resources and support with other practices, and being eligible for financial incentives were associated with greater HIT capacity in 2012. Primary care physicians' HIT capacity has significantly expanded since 2009, although solo practices continue to lag. Practices that are part of an integrated delivery system or share resources with other practices have higher rates of electronic medical record (EMR) adoption, multifunctional HIT, electronic information exchange, and electronic access for patients. Receiving or being eligible for financial incentives is associated with greater adoption of EMRs and information exchange. Federal efforts to increase adoption have coincided with a rapid increase in HIT capacity. Delivery system and payment reforms and federally funded extension programs could offer promising pathways for further diffusion. © Health Research and Educational Trust.

Use of liposomes as injectable-drug delivery systems.

PubMed

Ostro, M J; Cullis, P R

1989-08-01

The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive approval for marketing in the early 1990s. Liposomal encapsulation of drugs represents a new drug delivery system that appears to offer important therapeutic advantages over existing methods of drug delivery.

Analysis of correlation factors and pregnancy outcomes of hypertensive disorders of pregnancy - a secondary analysis of a random sampling in Beijing, China.

PubMed

Zhu, Yu-Chun; Yang, Hui-Xia; Wei, Yu-Mei; Zhu, Wei-Wei; Meng, Wen-Ying; Wang, Yong-Qing; Shang, Li-Xin; Cai, Zhen-Yu; Ji, Li-Ping; Wang, Yun-Feng; Sun, Ying; Liu, Jia-Xiu; Wei, Li; Sun, Yu-Feng; Zhang, Xue-Ying; Luo, Tian-Xia; Chen, Hai-Xia; Yu, Li-Jun

2017-03-01

We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China. This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA). The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group. In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.

Librarian instruction-delivery modality preferences for professional continuing education

PubMed Central

Lynn, Valerie A.; Bose, Arpita; Boehmer, Susan J.

2010-01-01

Objectives: Attending professional continuing education (CE) is an important component of librarianship. This research study identified librarians' preferences in delivery modalities of instruction for professional CE. The study also identified influential factors associated with attending CE classes. Methods: Five instruction-delivery modalities and six influential factors were identified for inclusion in an online survey. The survey completed by members of the American Library Association (ALA), Special Libraries Association (SLA), and Medical Library Association (MLA) provided the data for analysis of librarian preferences and influential factors. Results: The majority of respondents were MLA members, followed by ALA and SLA members. Librarians from all three library associations preferred the face-to-face instructional modality. The most influential factor associated with the decision to attend a professional CE class was cost. Conclusions: All five instruction-delivery modalities present useful structures for imparting professional CE. As librarians' experience with different modalities increases and as technology improves, preferences in instruction delivery may shift. But at present, face-to-face remains the most preferred modality. Based on the results of this study, cost was the most influential factor associated with attending a CE class. This may change as additional influential factors are identified and analyzed in future studies. PMID:20098656

Librarian instruction-delivery modality preferences for professional continuing education.

PubMed

Lynn, Valerie A; Bose, Arpita; Boehmer, Susan J

2010-01-01

Attending professional continuing education (CE) is an important component of librarianship. This research study identified librarians' preferences in delivery modalities of instruction for professional CE. The study also identified influential factors associated with attending CE classes. Five instruction-delivery modalities and six influential factors were identified for inclusion in an online survey. The survey completed by members of the American Library Association (ALA), Special Libraries Association (SLA), and Medical Library Association (MLA) provided the data for analysis of librarian preferences and influential factors. The majority of respondents were MLA members, followed by ALA and SLA members. Librarians from all three library associations preferred the face-to-face instructional modality. The most influential factor associated with the decision to attend a professional CE class was cost. All five instruction-delivery modalities present useful structures for imparting professional CE. As librarians' experience with different modalities increases and as technology improves, preferences in instruction delivery may shift. But at present, face-to-face remains the most preferred modality. Based on the results of this study, cost was the most influential factor associated with attending a CE class. This may change as additional influential factors are identified and analyzed in future studies.

The Effect of Leadership on the Delivery of Information Technology Systems

ERIC Educational Resources Information Center

Daly, Edward William

2012-01-01

Effective leadership is an important factor contributing to the successful implementation and operation of information products and services. The quantitative study examined the thoughts of IT upper management and employees in the private, public, and nonprofits institutions. The study assessed the memberships of the Association of Information…

75 FR 10229 - Application for Presidential Permit; Champlain Hudson Power Express, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

.... electric power supply system under normal and contingency conditions, and any other factors that DOE may... Power Express, Inc. AGENCY: Office of Electricity Delivery and Energy Reliability, DOE. ACTION: Notice of application. SUMMARY: Champlain Hudson Power Express, Inc. (CHPEI) has applied for a Presidential...

Advances in Web-Based Education: Personalized Learning Environments

ERIC Educational Resources Information Center

Magoulas, George, Ed.; Chen, Sherry, Ed.

2006-01-01

Advances in technology are increasingly impacting the way in which curriculum is delivered and assessed. The emergence of the Internet has offered learners a new instructional delivery system that connects them with educational resources. "Advances in Web-Based Education: Personalized Learning Environments" covers a wide range of factors that…

Reviews and syntheses: Effects of permafrost thaw on Arctic aquatic ecosystems

NASA Astrophysics Data System (ADS)

Vonk, J. E.; Tank, S. E.; Bowden, W. B.; Laurion, I.; Vincent, W. F.; Alekseychik, P.; Amyot, M.; Billet, M. F.; Canário, J.; Cory, R. M.; Deshpande, B. N.; Helbig, M.; Jammet, M.; Karlsson, J.; Larouche, J.; MacMillan, G.; Rautio, M.; Anthony, K. M. Walter; Wickland, K. P.

2015-12-01

The Arctic is a water-rich region, with freshwater systems covering about 16 % of the northern permafrost landscape. Permafrost thaw creates new freshwater ecosystems, while at the same time modifying the existing lakes, streams, and rivers that are impacted by thaw. Here, we describe the current state of knowledge regarding how permafrost thaw affects lentic (still) and lotic (moving) systems, exploring the effects of both thermokarst (thawing and collapse of ice-rich permafrost) and deepening of the active layer (the surface soil layer that thaws and refreezes each year). Within thermokarst, we further differentiate between the effects of thermokarst in lowland areas vs. that on hillslopes. For almost all of the processes that we explore, the effects of thaw vary regionally, and between lake and stream systems. Much of this regional variation is caused by differences in ground ice content, topography, soil type, and permafrost coverage. Together, these modifying factors determine (i) the degree to which permafrost thaw manifests as thermokarst, (ii) whether thermokarst leads to slumping or the formation of thermokarst lakes, and (iii) the manner in which constituent delivery to freshwater systems is altered by thaw. Differences in thaw-enabled constituent delivery can be considerable, with these modifying factors determining, for example, the balance between delivery of particulate vs. dissolved constituents, and inorganic vs. organic materials. Changes in the composition of thaw-impacted waters, coupled with changes in lake morphology, can strongly affect the physical and optical properties of thermokarst lakes. The ecology of thaw-impacted lakes and streams is also likely to change; these systems have unique microbiological communities, and show differences in respiration, primary production, and food web structure that are largely driven by differences in sediment, dissolved organic matter, and nutrient delivery. The degree to which thaw enables the delivery of dissolved vs. particulate organic matter, coupled with the composition of that organic matter and the morphology and stratification characteristics of recipient systems will play an important role in determining the balance between the release of organic matter as greenhouse gases (CO2 and CH4), its burial in sediments, and its loss downstream. The magnitude of thaw impacts on northern aquatic ecosystems is increasing, as is the prevalence of thaw-impacted lakes and streams. There is therefore an urgent need to quantify how permafrost thaw is affecting aquatic ecosystems across diverse Arctic landscapes, and the implications of this change for further climate warming.

Meeting global health challenges through operational research and management science

PubMed Central

2011-01-01

Abstract This paper considers how operational research and management science can improve the design of health systems and the delivery of health care, particularly in low-resource settings. It identifies some gaps in the way operational research is typically used in global health and proposes steps to bridge them. It then outlines some analytical tools of operational research and management science and illustrates how their use can inform some typical design and delivery challenges in global health. The paper concludes by considering factors that will increase and improve the contribution of operational research and management science to global health. PMID:21897489

Meeting global health challenges through operational research and management science.

PubMed

Royston, Geoff

2011-09-01

This paper considers how operational research and management science can improve the design of health systems and the delivery of health care, particularly in low-resource settings. It identifies some gaps in the way operational research is typically used in global health and proposes steps to bridge them. It then outlines some analytical tools of operational research and management science and illustrates how their use can inform some typical design and delivery challenges in global health. The paper concludes by considering factors that will increase and improve the contribution of operational research and management science to global health.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

NASA Astrophysics Data System (ADS)

Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Risk factors for the breakdown of perineal laceration repair after vaginal delivery.

PubMed

Williams, Meredith K; Chames, Mark C

2006-09-01

The purpose of this study was to identify risk factors that are associated with the breakdown of perineal laceration repair in the postpartum period. We conducted a retrospective, case-control study to review perineal laceration repair breakdown in patients who were delivered between September 1995 and February 2005 at the University of Michigan. Bivariate analysis with chi-square test and t-test and stepwise logistic regression analysis were performed. Fifty-nine cases and 118 control deliveries were identified from a total of 14,124 vaginal deliveries. Risk factors were longer second stage of labor (142 vs 87 minutes; P = .001), operative vaginal delivery (odds ratio, 3.6; 95% CI, 1.8-7.3), mediolateral episiotomy (odds ratio, 6.9; 95% CI, 2.6-18.7), third- or fourth-degree laceration (odds ratio, 3.1; 95% CI, 1.5-6.4), and meconium-stained amniotic fluid (odds ratio, 3.0; 95% CI, 1.1-7.9). Previous vaginal delivery was protective (odds ratio, 0.38; 95% CI, 0.18-0.84). Logistic regression showed the most significant factor to be an interaction between operative vaginal delivery and mediolateral episiotomy (odd ratio, 6.36; 95% CI, 2.18-18.57). The most significant events were mediolateral episiotomy, especially in conjunction with operative vaginal delivery, third- and fourth-degree lacerations, and meconium.

Controlled, sustained release of proteins via an injectable, mineral-coated microsphere delivery vehicle

NASA Astrophysics Data System (ADS)

Franklin-Ford, Travelle

Hydroxyapatite interfaces have demonstrated strong protein binding and protein selection from a passing solution and can serve as a biocompatible carrier for controlled protein delivery. Hydroxyapatite is a major component of long bones and tooth enamel and is the most stable of all calcium phosphate isoforms in aqueous solutions at physiologic pH, providing a sensitive chromatographic mechanism for separating proteins. Here we describe an approach to create a synthetic hydroxyapatite coating through a biomimetic, heterogeneous nucleation from a modified simulated body fluid--supersaturated with calcium and phosphate ions on the surface of injectable polymer microspheres. We are able to bind and release bioactive growth factors into a variety of in vitro and in vivo conditions, demonstrating the functionality and advantage of the biomaterial. Creating a hydroxyapatite layer on the Poly(D,L-lactide-co-glycolide) (PLG) microsphere surface, avails the microsphere interior for another application that will not compete with protein binding and release. Encapsulating an imaging agent within the aqueous phase of the emulsion provides a visual reference for the injectable therapy upon microsphere fabrication. Another advantage of this system is that the mineral coating and subsequent protein binding is not compromised by the encapsulated imaging agent. This dual function delivery vehicle is not only advantageous for spatial tracking therapeutic applications, but also determining the longevity of the delivery vehicle once injected. In the broader sense, providing a mechanism to image and track our temporally controlled, sustained delivery system gives more evidence to support the effects of released protein on in vivo responses (bioactivity) and locate microspheres within different biological systems.

Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain.

PubMed

Rodriguez, A L; Bruggeman, K F; Wang, Y; Wang, T Y; Williams, R J; Parish, C L; Nisbet, D R

2018-03-01

Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells. Copyright © 2017 John Wiley & Sons, Ltd.

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

PubMed

Bhaskar, Sonu; Tian, Furong; Stoeger, Tobias; Kreyling, Wolfgang; de la Fuente, Jesús M; Grazú, Valeria; Borm, Paul; Estrada, Giovani; Ntziachristos, Vasilis; Razansky, Daniel

2010-03-03

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.

Perceptions of barriers and facilitators to health behavior change among veteran cancer survivors.

PubMed

Beehler, Gregory P; Rodrigues, Amy E; Kay, Morgan A; Kiviniemi, Marc T; Steinbrenner, Lynn

2014-09-01

This study aimed to identify barriers and facilitators to health behavior change related to body size in a sample of veteran cancer survivors. A qualitative study was conducted with a sample of 35 male and female cancer survivors receiving care at a Veterans Administration comprehensive cancer center. Participants completed individual interviews regarding barriers and facilitators to lifestyle change and responded to a brief questionnaire regarding current health behaviors. Participants reported suboptimal adherence to recommended health behavior goals and the majority were overweight or obese (80%). Qualitative analysis revealed numerous barriers and facilitators to health behavior change across six broad categories: environmental factors, health services delivery factors, health-related factors, factors related to attitudes toward change, factors related to enacting change, and motivational factors. Veteran cancer survivors were impacted by common barriers to change affecting the general population, cancer-specific factors related to personal diagnosis and treatment history, and health service delivery factors related to the Veterans Administration health care system. There are many barriers and facilitators that exist in diverse domains for veteran cancer survivors, each of which offers unique challenges and opportunities for improving engagement in behavior change following cancer diagnosis and treatment. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Spatial analysis of choice of place of delivery in Nigeria.

PubMed

Gayawan, Ezra

2014-06-01

Access to quality healthcare during childbirth is a crucial factor for taming maternal and child mortality and morbidity. Increasing this access in developing countries depends on understanding the factors influencing maternal healthcare decision at a geographical location. This study analyzes spatial pattern in choice of place of delivery in Nigeria. Data analyzed came from Nigerian Demographic and Health Survey data set. The choice of place delivery was considered a multi-categorical response and a multinomial logistic regression model used to evaluate spatial variations in choosing a particular place to deliver against home delivery. Results show a north-south divide in choosing health facilities against homes for delivery. The likelihood of institutional delivery was significantly lower for women residing in Bayelsa and the majority of the states in northern Nigeria. As women advance in age, they have more likelihood of having institutional deliveries. Other contributing factors that favor institutional deliveries include use of antenatal care services, urban dwelling, mass media and parity. Usage of mass media to campaign for institutional deliveries particularly in northern Nigeria, among younger women and those of higher parity; encouraging the use of antenatal services and even distribution of health facilities making them easily accessible to rural women are important for enhancing chances of institutional deliveries. Also, state-specific policies in this regard are indispensable. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors influencing non-institutional deliveries in afghanistan: secondary analysis of the afghanistan mortality survey 2010.

PubMed

Azimi, Mohammad Daud; Najafizada, Said Ahmad Maisam; Khaing, Inn Kynn; Hamajima, Nobuyuki

2015-02-01

Home delivery in unhygienic environments is common among Afghan women; only one third of births are delivered at health facilities. Institutional delivery is central to reducing maternal mortality. The factors associated with place of delivery among women in Afghanistan were examined using the Afghanistan Mortality Survey 2010 (AMS 2010), which was open to researchers. The AMS 2010 data were collected through an interviewer-led questionnaire from 18,250 women. Odds ratio (OR) and 95% confidence interval (CI) of non-institutional delivery were estimated by logistic regression analysis. When age at survey, education, parity, residency, antenatal care frequency, remoteness, wealth and regions were adjusted, the OR of non-institutional delivery was 8.37 (95% CI, 7.47-9.39) for no antenatal care relative to four or more antenatal care visits, 4.07 (95% CI, 3.45-4.80) for poorest household relative to women from richest household, 2.02 (95% CI, 1.43-2.84) for no education relative to higher education, 1.78 (95% CI, 1.52-2.09) for six or more deliveries relative to one delivery, and 1.50 (95% CI, 1.36-1.67) for rural relative to urban residency. Since antenatal care was strongly associated with non-institutional delivery after adjustment of the other factors, antenatal care service may promote institutional deliveries, which can reduce maternal mortality ratio in Afghanistan.

Advanced Materials and Processing for Drug Delivery: The Past and the Future

PubMed Central

Zhang, Ying; Chan, Hon Fai; Leong, Kam W.

2012-01-01

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

Prevalence and factors associated with non-utilization of healthcare facility for childbirth in rural and urban Nigeria: Analysis of a national population-based survey.

PubMed

Adewuyi, Emmanuel O; Zhao, Yun; Auta, Asa; Lamichhane, Reeta

2017-08-01

The aim of this study was to assess the rural-urban differences in the prevalence and factors associated with non-utilization of healthcare facility for childbirth (home delivery) in Nigeria. Dataset from the Nigeria demographic and health survey, 2013, disaggregated by rural-urban residence were analyzed with appropriate adjustment for the cluster sampling design of the survey. Factors associated with home delivery were identified using multivariable logistic regression analysis. In rural and urban residence, the prevalence of home delivery were 78.3% and 38.1%, respectively ( p < 0.001). The lowest prevalence of home delivery occurred in the South-East region for rural residence (18.6%) and the South-West region for urban residence (17.9%). The North-West region had the highest prevalence of home delivery, 93.6% and 70.5% in rural and urban residence, respectively. Low maternal as well as paternal education, low antenatal attendance, being less wealthy, the practice of Islam, and living in the North-East, North-West and the South-South regions increased the likelihood of home delivery in both rural and urban residences. Whether in rural or urban residence, birth order of one decreased the likelihood of home delivery. In rural residence only, living in the North-Central region increased the chances of home delivery. In urban residence only, maternal age ⩾ 36 years decreased the likelihood of home delivery, while 'Traditionalist/other' religion and maternal age < 20 years increased it. The prevalence of home delivery was much higher in rural than urban Nigeria and the associated factors differ to varying degrees in the two residences. Future intervention efforts would need to prioritize findings in this study.

Determinants of ambulance response time: A study in Sabah, Malaysia

NASA Astrophysics Data System (ADS)

Chin, Su Na; Cheah, Phee Kheng; Arifin, Muhamad Yaakub; Wong, Boh Leng; Omar, Zaturrawiah; Yassin, Fouziah Md; Gabda, Darmesah

2017-04-01

Ambulance response time (ART) is one of the standard key performance indicators (KPI) in measuring the emergency medical services (EMS) delivery performances. When the mean time of ART of EMS system reaches the KPI target, it shows that the EMS system performs well. This paper considers the determinants of ART, using data sampled from 967 ambulance runs in a government hospital in Sabah. Multiple regression analysis with backward elimination was proposed for the identification of significant factors. Amongst the underlying factors, travel distance, age of patients, type of treatment and peak hours were identified to be significantly affecting ART. Identifying factors that influence ART helps the development of strategic improvement planning for reducing the ART.

Three-factor anonymous authentication and key agreement scheme for Telecare Medicine Information Systems.

PubMed

Arshad, Hamed; Nikooghadam, Morteza

2014-12-01

Nowadays, with comprehensive employment of the internet, healthcare delivery services is provided remotely by telecare medicine information systems (TMISs). A secure mechanism for authentication and key agreement is one of the most important security requirements for TMISs. Recently, Tan proposed a user anonymity preserving three-factor authentication scheme for TMIS. The present paper shows that Tan's scheme is vulnerable to replay attacks and Denial-of-Service attacks. In order to overcome these security flaws, a new and efficient three-factor anonymous authentication and key agreement scheme for TMIS is proposed. Security and performance analysis shows superiority of the proposed scheme in comparison with previously proposed schemes that are related to security of TMISs.

Factors affecting institutional delivery in rural Chitwan district of Nepal: a community-based cross-sectional study.

PubMed

Shah, Rajani; Rehfuess, Eva A; Maskey, Mahesh K; Fischer, Rainald; Bhandari, Prem B; Delius, Maria

2015-02-13

Health facility delivery is considered a critical strategy to improve maternal health. The Government of Nepal is promoting institutional delivery through different incentive programmes and the establishment of birthing centres. This study aimed to identify the socio-demographic, socio-cultural, and health service-related factors influencing institutional delivery uptake in rural areas of Chitwan district, where high rates of institutional deliveries co-exist with a significant proportion of home deliveries. This community-based cross-sectional study was conducted in six rural Village Development Committees of Chitwan district, which are characterised by relatively low institutional delivery rates and the availability of birthing centres. The study area represents both hilly and plain areas of Chitwan. A total of 673 mothers who had given birth during a one-year-period were interviewed using a structured questionnaire. Univariate and multivariable logistic regression analysis using stepwise backward elimination was performed to identify key factors affecting institutional delivery. Adjusting for all other factors in the final model, advantaged caste/ethnicity [aOR: 1.98; 95% CI: 1.15-3.42], support for institutional delivery by the husband [aOR: 19.85; 95% CI: 8.53-46.21], the decision on place of delivery taken jointly by women and family members [aOR: 5.43; 95% CI: 2.91-10.16] or by family members alone [aOR: 4.61; 95% CI: 2.56-8.28], birth preparations [aOR: 1.75; 95% CI: 1.04-2.92], complications during the most recent pregnancy/delivery [aOR: 2.88; 95% CI: 1.67-4.98], a perception that skilled health workers are always available [aOR: 2.70; 95% CI: 1.20-6.07] and a birthing facility located within one hour's travelling distance [aOR: 2.15; 95% CI: 1.26-3.69] significantly increased the likelihood of institutional delivery. On the other hand, not knowing about the adequacy of physical facilities significantly decreased the likelihood of institutional delivery [aOR: 0.14; 95% CI: 0.05-0.41]. With multiple incentives present, the decision to deliver in a health facility is affected by a complex interplay of socio-demographic, socio-cultural, and health service-related factors. Family decision-making roles and a husband's support for institutional delivery exert a particularly strong influence on the place of delivery, and this should be emphasized in the health policy as well as development and implementation of maternal health programmes in Nepal.

Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma.

PubMed

Liang, Chao; Li, Fangfei; Wang, Luyao; Zhang, Zong-Kang; Wang, Chao; He, Bing; Li, Jie; Chen, Zhihao; Shaikh, Atik Badshah; Liu, Jin; Wu, Xiaohao; Peng, Songlin; Dang, Lei; Guo, Baosheng; He, Xiaojuan; Au, D W T; Lu, Cheng; Zhu, Hailong; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

2017-12-01

Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Addressing health system barriers to access to and use of skilled delivery services: perspectives from Ghana.

PubMed

Ganle, John Kuumuori; Fitzpatrick, Raymond; Otupiri, Easmon; Parker, Michael

2016-10-01

Poor access to and use of skilled delivery services have been identified as a major contributory factor to poor maternal and newborn health in sub-Saharan African countries, including Ghana. However, many previous studies that examine norms of childbirth and care-seeking behaviours have focused on identifying the norms of non-use of services, rather than factors, that can promote service use. Based on primary qualitative research with a total of 185 expectant and lactating mothers, and 20 healthcare providers in six communities in Ghana, this paper reports on strategies that can be used to overcome health system barriers to the use of skilled delivery services. The strategies identified include expansion and redistribution of existing maternal health resources and infrastructure, training of more skilled maternity caregivers, instituting special programmes to target women most in need, improving the quality of maternity care services provided, improving doctor-patient relationships in maternity wards, promotion of choice, protecting privacy and patient dignity in maternity wards and building partnerships with traditional birth attendants and other non-state actors. The findings suggest the need for structural changes to maternity clinics and routine nursing practices, including an emphasis on those doctor-patient relational practices that positively influence women's healthcare-seeking behaviours. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Implementing injury surveillance systems alongside injury prevention programs: evaluation of an online surveillance system in a community setting.

PubMed

Ekegren, Christina L; Donaldson, Alex; Gabbe, Belinda J; Finch, Caroline F

Previous research aimed at improving injury surveillance standards has focused mainly on issues of data quality rather than upon the implementation of surveillance systems. There are numerous settings where injury surveillance is not mandatory and having a better understanding of the barriers to conducting injury surveillance would lead to improved implementation strategies. One such setting is community sport, where a lack of available epidemiological data has impaired efforts to reduce injury. This study aimed to i) evaluate use of an injury surveillance system following delivery of an implementation strategy; and ii) investigate factors influencing the implementation of the system in community sports clubs. A total of 78 clubs were targeted for implementation of an online injury surveillance system (approximately 4000 athletes) in five community Australian football leagues concurrently enrolled in a pragmatic trial of an injury prevention program called FootyFirst. System implementation was evaluated quantitatively, using the RE-AIM framework, and qualitatively, via semi-structured interviews with targeted-users. Across the 78 clubs, there was 69% reach, 44% adoption, 23% implementation and 9% maintenance. Reach and adoption were highest in those leagues receiving concurrent support for the delivery of FootyFirst. Targeted-users identified several barriers and facilitators to implementation including personal (e.g. belief in the importance of injury surveillance), socio-contextual (e.g. understaffing and athlete underreporting) and systems factors (e.g. the time taken to upload injury data into the online system). The injury surveillance system was implemented and maintained by a small proportion of clubs. Outcomes were best in those leagues receiving concurrent support for the delivery of FootyFirst, suggesting that engagement with personnel at all levels can enhance uptake of surveillance systems. Interview findings suggest that increased uptake could also be achieved by educating club personnel on the importance of recording injuries, developing clearer injury surveillance guidelines, increasing club staffing and better remunerating those who conduct surveillance, as well as offering flexible surveillance systems in a range of accessible formats. By increasing the usage of surveillance systems, data will better represent the target population and increase our understanding of the injury problem, and how to prevent it, in specific settings.

The Costs and Their Determinant of Cesarean Section and Vaginal Delivery: An Exploratory Study in Chongqing Municipality, China

PubMed Central

He, Zhifei; Cheng, Zhaohui; Wu, Tailai; Zhou, Yan; Chen, Junguo; Fu, Qian

2016-01-01

Objectives. This study aims to analyze the cesarean section (CS) rates and vaginal delivery rates in tertiary hospitals of China, explore the costs of two different deliveries, and examine the relative influencing factors of the costs in both CS and vaginal deliveries. Methods. 30,168 anonymized obstetric medical cases were selected from three sample tertiary hospitals in Chongqing Municipality from 2011 to 2013. Chi-square test was used to compare the distributions of CS and vaginal deliveries under different indicators. Mann–Whitney test and Kruskal-Wallis test were adopted to analyze the differences under different items. Multiple linear regression was used to determine the influencing factors of the costs of different delivery modes. Results. (1) The rates of CS were 69%, 65.5%, and 59.2% in the three sample tertiary hospitals in Chongqing from 2011 to 2013. (2) The costs and the length of stay of CS were greater than those of vaginal delivery, which had significant differences (P < 0.005). (3) The areas, length of stay, age, medical insurance, and modes of delivery were the influencing factors of both CS and vaginal delivery costs. Discussion. The high CS rates in China must be paid significant attention. The indicators of two modes of delivery should be regulated strictly. CS rate reduction and saving medical resources will be the benefits if vaginal delivery is chosen by pregnant women. PMID:27995142

Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

PubMed Central

Lee, Andrew S.; Inayathullah, Mohammed; Lijkwan, Maarten A.; Zhao, Xin; Sun, Wenchao; Park, Sujin; Hong, Wan Xing; Parekh, Mansi B.; Malkovskiy, Andrey V.; Lau, Edward; Qin, Xulei; Pothineni, Venkata Raveendra; Sanchez-Freire, Verónica; Zhang, Wendy Y.; Kooreman, Nigel G.; Ebert, Antje D.; Chan, Charles K. F.; Nguyen, Patricia K.; Rajadas, Jayakumar; Wu, Joseph C.

2018-01-01

Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen–dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy. PMID:29721363

Inter-institutional Variation in Use of Caesarean Delivery for Labour Dystocia.

PubMed

Riddell, Corinne A; Hutcheon, Jennifer A; Strumpf, Erin C; Abenhaim, Haim A; Kaufman, Jay S

2017-11-01

To establish the degree of variation across hospitals in the use of Caesarean delivery for the indication of labour dystocia before and after accounting for maternal, fetal, and hospital characteristics. This study was a retrospective, population-based cohort study of nulliparous women delivering term singletons in cephalic position following labour. Delivery visits were extracted from three provincial perinatal registries in the Canadian provinces of Ontario, Alberta, and British Columbia, from 2008-2012. Crude hospital-specific rates of Caesarean delivery for labour dystocia were reported, and these rates were then stabilized to account for hospitals with low delivery volumes. Rates were then adjusted for maternal, fetal, and hospital characteristics using hierarchical logistic regression. Among 403 205 women delivering at 170 hospitals, the overall Caesarean delivery rate was 21.0%, and the rate of Caesarean delivery for labour dystocia was 12.7%, indicating that 60% of all Caesarean deliveries were performed in part for this indication. The middle 95% of hospitals had Caesarean delivery rates for labour dystocia ranging from 4.5% to 24.7%. Differences in maternal case mix and hospital characteristics explained only a small proportion of this variation (95% central range 6.3%-21.7%). Considerable inter-hospital variation in rates of Caesarean delivery for labour dystocia remained after accounting for differences in maternal and hospital factors. Reporting systems that monitor variation in inter-institutional rates should incorporate stabilization and adjustment for case-mix differences and consider indication-specific rates of Caesarean delivery to more fairly compare hospital performance and better target interventions to reduce Caesarean delivery for specific indications. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

What is the role of community capabilities for maternal health? An exploration of community capabilities as determinants to institutional deliveries in Bangladesh, India, and Uganda.

PubMed

Paina, Ligia; Vadrevu, Lalitha; Hanifi, S M Manzoor Ahmed; Akuze, Joseph; Rieder, Rachel; Chan, Kitty S; Peters, David H

2016-11-15

While community capabilities are recognized as important factors in developing resilient health systems and communities, appropriate metrics for these have not yet been developed. Furthermore, the role of community capabilities on access to maternal health services has been underexplored. In this paper, we summarize the development of a community capability score based on the Future Health System (FHS) project's experience in Bangladesh, India, and Uganda, and, examine the role of community capabilities as determinants of institutional delivery in these three contexts. We developed a community capability score using a pooled dataset containing cross-sectional household survey data from Bangladesh, India, and Uganda. Our main outcome of interest was whether the woman delivered in an institution. Our predictor variables included the community capability score, as well as a series of previously identified determinants of maternal health. We calculate both population-averaged effects (using GEE logistic regression), as well as sub-national level effects (using a mixed effects model). Our final sample for analysis included 2775 women, of which 1238 were from Bangladesh, 1199 from India, and 338 from Uganda. We found that individual-level determinants of institutional deliveries, such as maternal education, parity, and ante-natal care access were significant in our analysis and had a strong impact on a woman's odds of delivering in an institution. We also found that, in addition to individual-level determinants, greater community capability was significantly associated with higher odds of institutional delivery. For every additional capability, the odds of institutional delivery would increase by up to almost 6 %. Individual-level characteristics are strong determinants of whether a woman delivered in an institution. However, we found that community capability also plays an important role, and should be taken into account when designing programs and interventions to support institutional deliveries. Consideration of individual factors and the capabilities of the communities in which people live would contribute to the vision of supporting people-centered approaches to health.

Health Care Reform: Impact on Total Joint Replacement.

PubMed

Chambers, Monique C; El-Othmani, Mouhanad M; Saleh, Khaled J

2016-10-01

The US health care system has been fragmented for more than 40 years; this model created a need for modification. Sociopoliticomedical system-related factors led to the Affordable Care Act (ACA) and a restructuring of health care provision/delivery. The ACA increases access to high-quality "affordable care" under cost-effective measures. This article provides a comprehensive review of health reform and the motivating factors that drive policy to empower arthroplasty providers to effectively advocate for the field of orthopedics as a whole, and the patients served. Copyright © 2016 Elsevier Inc. All rights reserved.

Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

PubMed

Popilski, Hen; Stepensky, David

2015-05-01

Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

Winner of the society for biomaterials student award in the Ph.D. category for the annual meeting of the society for biomaterials, april 11-14, 2018, Atlanta, GA: Development of a bimodal, in situ crosslinking method to achieve multifactor release from electrospun gelatin.

PubMed

Kishan, Alysha; Walker, Taneidra; Sears, Nick; Wilems, Thomas; Cosgriff-Hernandez, Elizabeth

2018-05-01

To better mimic native tissue microenvironments, current efforts have moved beyond single growth factor delivery to more complex multiple growth factor delivery with distinct release profiles. Electrospun gelatin, a widely investigated drug delivery vehicle, requires postprocessing crosslinking techniques that generate a mesh with uniform crosslinking density, limiting the ability to deliver multiple factors at different rates. Herein, we describe a method to independently control release of multiple factors from a single electrospun gelatin mesh. Two in situ crosslinking modalities, photocrosslinking of methacyrlated gelatin and reactive crosslinking of gelatin with a diisocyanate, are coelectrospun to generate distinct fiber populations with different crosslinking chemistry and density in a single mesh. The photocrosslinked gelatin-methacrylate resulted in a relatively rapid release of a model protein (48 ± 12% at day 1, 96 ± 3% at day 10) due to diffusion of embedded protein from the crosslinked fibers. The reactive crosslinking system displayed a more sustained release (7 ± 5% at day 1, 33 ± 2% at day 10) that was attributed to the conjugation of protein to gelatin with the diisocyanate, requiring degradation of gelatin prior to diffusion out of the fibers. Both modalities displayed tunable release profiles. Subsequent release studies of a cospun mesh with two different crosslinked fiber populations confirmed that the cospun mesh displayed multifactor release with independent release profiles. Overall, this bimodal, in situ crosslinking approach enables the delivery of multiple factors with distinct release kinetics from a single mesh and is expected to have broad utility in tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1155-1164, 2018. © 2018 Wiley Periodicals, Inc.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Contributing factors of pregnant women's beliefs towards mode of delivery: a cross-sectional study from Iran.

PubMed

Zamani-Alavijeh, Fereshteh; Araban, Marzieh; Hassanzadeh, Akbar; Makhouli, Khadije

2018-01-01

Delivery is a critical event in every woman's life. Under some medical conditions, women sometimes undergo a cesarean section to save the life of themselves and their infant. Understanding the factors associated with choosing the type of delivery leads to more effective health interventions and the promotion of maternal and newborn health. The aim of this study is to determine contributing factors in pregnant women's beliefs toward the mode of delivery in a sample of women referring to Hojatieh Hospital in Isfahan, Iran. This cross-sectional study was conducted in September 2016 on 200 pregnant women (gestational age 30-37 weeks) referred to Hojatieh Hospital in Isfahan, Iran. The inclusion criteria of this study included healthy pregnancy and having no known cases (heart, pulmonary, and renal disease) and pregnancy complications (spotting, bleeding, headache, blurred vision), and willingness of pregnant women to complete the questionnaire. Data were collected through an eight-part questionnaire consisting of demographic factors, delivery intention, knowledge, perceived self-efficacy, attitude, perceived social, and private support in the presence of the researcher and the outcome of delivery were asked 2 weeks after the due date of delivery during a telephone call. Data were analyzed using SPSS16 software, independent t-test, chi-square, and logistic regression. There was no significant differences between the mean scores of knowledge and private social support among individuals with two types of delivery ( P  > 0.05), but the mean scores of perceived self-efficacy and public social support in women who gave birth normal were significantly higher than those of women who gave birth by cesarean section ( P  < 0.05). The findings of this study showed that attitude and perceived self-efficacy were the most important predictors of delivery mode. Therefore, education based on the items included in these factors might be useful for choosing the delivery mode. The results might be used in evidence based midwifery practices in low and middle income countries to promote normal delivery and perhaps maternal health index.

Vascular dysfunction in preeclampsia.

PubMed

Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

2014-01-01

Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review. © 2013 John Wiley & Sons Ltd.

Double incontinence in a cohort of nulliparous pregnant women.

PubMed

Espuña-Pons, Montserrat; Solans-Domènech, Maite; Sánchez, Emília

2012-11-01

To estimate the frequency of double incontinence, and to identify associated risk factors during pregnancy and postpartum in previously continent nulliparous women. A cohort study in healthy, nulliparous, continent pregnant women, attending the public healthcare system of Catalonia (Spain) was designed. The field work was conducted during the control visits of pregnancy, at the time of delivery, and in the postpartum. Double incontinence was defined as a situation in which participants reported simultaneously urinary incontinence (UI) and anal incontinence with the help of a self-administered questionnaire. Prevalence rates, and their corresponding confidence intervals (95% CI), were calculated, as well as the impact on daily life. Multivariable logistic regressions in pregnancy and postpartum were estimated to assess the association of potential risk factors. The prevalence rate of double incontinence during pregnancy was 8.6% (95% CI: 7.0-10.3). Age over 35 years, and family history of UI were associated to a higher risk of double incontinence. After delivery, the prevalence rate decreased to 3.5% (95% CI: 2.4-4.6); only 6.7% of women with double incontinence in pregnancy had a persistency of their symptoms in early postpartum. Instrumental vaginal deliveries carried 2.2 times more risk of double incontinence than spontaneous ones. Episiotomy implied a higher risk for double incontinence. Symptoms of double incontinence are prevalent during first pregnancy; age and other intrinsic factors may favor the occurrence of double incontinence throughout gestation, while instrumental delivery and episiotomy increase the risk of double incontinence in the postpartum period. Copyright © 2012 Wiley Periodicals, Inc.

Determinants of use of supervised delivery care under Ghana's fee exemption policy for maternal healthcare: the case of the Central Region.

PubMed

Asante-Sarpong, Henrietta; Owusu, Adobea Yaa; Saravanan, Sheela; Appiah, Ernest; Abu, Mumuni

2016-07-19

Improving access to supervised and emergency obstetric care resources through fee reduction/exemption maternity care initiatives has been touted as one major strategy to avoiding preventable maternal deaths. Evaluations on the effect of Ghana's fee exemption policy for maternal healthcare have largely focused on how it has influenced health outcomes and patterns of use of supervised care with little attention to understanding the main factors influencing use. This study therefore sought to explore the main individual and health system factors influencing use of delivery care services under the policy initiative in the Central Region. A cross-sectional study was conducted using 412 mothers with children aged less than one year in one largely rural and another largely urban districts in the Central Region of Ghana from September to December 2013. Data were collected using a questionnaire survey on the socio-demographic characteristics of mothers, their knowledge and use of care under the fee free policy. Chi-square and Binary Logistic Regression tests were used to evaluate the main determinants of delivery care use under the policy. Out of the 412 mothers interviewed, 268 (65 %) reported having delivered their most recent birth under the fee exemption policy even though awareness about the policy was almost universal 401 (97.3 %) among respondents. Utilization however differed for the two study districts. Respondents in the Cape Coast Metropolis (largely urban) used delivery service more (75.7 %) than those in the largely rural Assin North Municipal area (54.4 %). Binary logistic regression results identified maternal age, parity, religion, place of residence, awareness and knowledge about the fee exemption policy for maternal healthcare as significantly associated with the likelihood of delivery care use under the policy. The likelihood of using supervised delivery care under the policy was lower for mothers aged 20-29 compared to those in the age bracket of 40-49 (Odds ratio (OR) = 0.069, p = 0.003). For their index (last child), mothers who already had 1, 2 or 3 births were more likely to deliver under the policy than those with five or more births. Mothers living in urban areas were 3.79 times more likely to use delivery services under the policy than those living in rural areas (OR = 3.793, p = 0.000). The likelihood of using delivery services under the policy was higher for mothers who were aware and had full knowledge of the total benefit package of the policy (OR = 13.820, p = 0.022 and OR = 2.985, p = 0.001 for awareness and full knowledge respectively). Delivery service use under the free maternal healthcare policy is relatively low (65 %) when compared with nearly universal awareness (97.3 %) about the policy. Factors influencing delivery service use under the policy operate at both individual and policy implementation levels. Effective interventions to improve delivery service use under the policy should target the underlying individual and health policy implementation factors identified in the study.

Mesoporous silica nanoparticles for bioadsorption, enzyme immobilisation, and delivery carriers

NASA Astrophysics Data System (ADS)

Popat, Amirali; Hartono, Sandy Budi; Stahr, Frances; Liu, Jian; Qiao, Shi Zhang; Qing (Max) Lu, Gao

2011-07-01

Mesoporous silica nanoparticles (MSNs) provide a non-invasive and biocompatible delivery platform for a broad range of applications in therapeutics, pharmaceuticals and diagnosis. The creation of smart, stimuli-responsive systems that respond to subtle changes in the local cellular environment are likely to yield long term solutions to many of the current drug/gene/DNA/RNA delivery problems. In addition, MSNs have proven to be promising supports for enzyme immobilisation, enabling the enzymes to retain their activity, affording them greater potential for wide applications in biocatalysis and energy. This review provides a comprehensive summary of the advances made in the last decade and a future outlook on possible applications of MSNs as nanocontainers for storage and delivery of biomolecules. We discuss some of the important factors affecting the adsorption and release of biomolecules in MSNs and review of the cytotoxicity aspects of such nanomaterials. The review also highlights some promising work on enzyme immobilisation using mesoporous silica nanoparticles.

A MEMS Electrochemical Bellows Actuator for Fluid Metering Applications

PubMed Central

Sheybani, Roya; Gensler, Heidi; Meng, Ellis

2013-01-01

We present a high efficiency wireless MEMS electrochemical bellows actuator capable of rapid and repeatable delivery of boluses for fluid metering and drug delivery applications. Nafion®-coated Pt electrodes were combined with Parylene bellows filled with DI water to form the electrolysis-based actuator. The performance of actuators with several bellows configurations was compared for a range of applied currents (1-10 mA). Up to 75 boluses were delivered with an average pumping flow rate of 114.40 ± 1.63 μL/min. Recombination of gases into water, an important factor in repeatable and reliable actuation, was studied for uncoated and Nafion®-coated actuators. Real-time pressure measurements were conducted and the effects of temperature, physiological back pressure, and drug viscosity on delivery performance were investigated. Lastly, we present wireless powering of the actuator using a class D inductive powering system that allowed for repeatable delivery with less than 2% variation in flow rate values. PMID:22833156

Peptide-chaperone-directed transdermal protein delivery requires energy.

PubMed

Ruan, Renquan; Jin, Peipei; Zhang, Li; Wang, Changli; Chen, Chuanjun; Ding, Weiping; Wen, Longping

2014-11-03

The biologically inspired transdermal enhanced peptide TD1 has been discovered to specifically facilitate transdermal delivery of biological macromolecules. However, the biological behavior of TD1 has not been fully defined. In this study, we find that energy is required for the TD1-mediated transdermal protein delivery through rat and human skins. Our results show that the permeation activity of TD1-hEGF, a fusion protein composed of human epidermal growth factor (hEGF) and the TD1 sequence connected with a glycine-serine linker (GGGGS), can be inhibited by the energy inhibitor, rotenone or oligomycin. In addition, adenosine triphosphate (ATP), the essential energetic molecule in organic systems, can effectively facilitate the TD1 directed permeation of the protein-based drug into the skin in a dose-dependent fashion. Our results here demonstrate a novel energy-dependent permeation process during the TD1-mediated transdermal protein delivery that could be valuable for the future development of promising new transdermal drugs.

Characteristics Associated With Severe Perineal and Cervical Lacerations During Vaginal Delivery

PubMed Central

Landy, Helain J.; Laughon, S. Katherine; Bailit, Jennifer; Kominiarek, Michelle A.; Gonzalez-Quintero, Victor Hugo; Ramirez, Mildred; Haberman, Shoshana; Hibbard, Judith; Wilkins, Isabelle; Branch, D. Ware; Burkman, Ronald T.; Gregory, Kimberly; Hoffman, Matthew K.; Learman, Lee A.; Hatjis, Christos; VanVeldhuisen, Paul C.; Reddy, Uma M.; Troendle, James; Sun, Liping; Zhang, Jun

2011-01-01

Objective To characterize potentially modifiable risk factors for third- or fourth-degree perineal lacerations and cervical lacerations in a contemporary U.S. obstetric practice. Methods The Consortium on Safe Labor collected electronic medical records from 19 hospitals within 12 institutions (228,668 deliveries from 2002 to 2008). Information on patient characteristics, prenatal complications, labor and delivery data, and maternal and neonatal outcomes were collected. Only women with successful vaginal deliveries of cephalic singletons at 34 weeks of gestation or later were included; we excluded data from sites lacking information about lacerations at delivery and deliveries complicated by shoulder dystocia; 87,267 and 71,170 women were analyzed for third- or fourth-degree and cervical lacerations, respectively. Multivariable logistic regressions were used to adjust for other factors. Results Third- or fourth-degree lacerations occurred in 2,516 women (2,223 nulliparous [5.8%], 293 [0.6%] multiparous) and cervical lacerations occurred in 536 women (324 nulliparous [1.1%], 212 multiparous [0.5%]). Risks for third or fourth-degree lacerations included nulliparity (7.2-fold risk), being Asian or Pacific Islander, increasing birth weight, operative vaginal delivery, episiotomy, and longer second stage of labor. Increasing body mass index was associated with fewer lacerations. Risk factors for cervical lacerations included young maternal age, vacuum vaginal delivery, and oxytocin use among multiparous women, and cerclage regardless of parity. Conclusion Our large cohort of women with severe obstetric lacerations reflects contemporary obstetric practices. Nulliparity and episiotomy use are important risk factors for third- or fourth-degree lacerations. Cerclage increases the risk for cervical lacerations. Many identified risk factors may not be modifiable. PMID:21343766

Persistent stress urinary incontinence during pregnancy and one year after delivery; its prevalence, risk factors and impact on quality of life in Taiwanese women: An observational cohort study.

PubMed

Lin, Yi-Hao; Chang, Shuenn-Dhy; Hsieh, Wu-Chiao; Chang, Yao-Lung; Chueh, Ho-Yen; Chao, An-Shine; Liang, Ching-Chung

2018-06-01

The study was to investigate the prevalence and risk factors of stress urinary incontinence (SUI) and its impact on the quality of life during pregnancy and 12 months after delivery. 866 women delivering their newborns at a tertiary hospital were recruited. All women were asked to complete several questionnaires including demographic and obstetric data, Short Form 12 health survey (SF-12), Urogenital Distress Inventory Short Form (UDI-6), and Incontinence Impact Questionnaire Short Form (IIQ-7). All women were interviewed via telephone to answer the same questionnaires at 12 months postpartum. There were 446 (51.5%) self-reported SUI women during pregnancy. Out of 560 women delivered vaginally, 70 (12.5%) had SUI at 12 months postpartum; in 306 women undergoing Cesarean delivery, 22 (7.2%) experienced SUI 12 months after delivery. Risk factors of SUI during pregnancy included body weight and body mass index at first visit. At 12 months postpartum, parity stood out as the risk factor of persistent SUI in vaginal delivery group, but no significant risk factor was found in Cesarean group. Women with SUI during pregnancy featured worse mental component summary (MCS) score of SF-12, compared to women without SUI. At 12 months postpartum, women with persistent SUI in vaginal delivery group had higher mean UDI-6 and IIQ-7 scores than those without SUI. Persistent SUI is more prevalent in the vaginal delivery group than Cesarean group. Both SUI during pregnancy and after childbirth have negative impact on the quality of life in women undergoing vaginal delivery. Copyright © 2018. Published by Elsevier B.V.

Cereal transformation through particle bombardment

NASA Technical Reports Server (NTRS)

Casas, A. M.; Kononowicz, A. K.; Bressan, R. A.; Hasegawa, P. M.; Mitchell, C. A. (Principal Investigator)

1995-01-01

The review focuses on experiments that lead to stable transformation in cereals using microprojectile bombardment. The discussion of biological factors that affect transformation examines target tissues and vector systems for gene transfer. The vector systems include reporter genes, selectable markers, genes of agronomic interest, and vector constructions. Other topics include physical parameters that affect DNA delivery, selection of stably transformed cells and plant regeneration, and analysis of gene expression and transmission to the progeny.

Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

PubMed

Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

2017-10-01

Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled Fabrication of Gelatin Nanoparticles as Drug Carriers

NASA Astrophysics Data System (ADS)

Jahanshahi, M.; Sanati, M. H.; Minuchehr, Z.; Hajizadeh, S.; Babaei, Z.

2007-08-01

In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Protein nanoparticles (BSA, HAS and gelatin) generally vary in size from 50-300 nm and they hold certain advantages such as greater stability during storage, stability in vivo, non-toxicity, non-antigen and ease to scale up during manufacture over the other drug delivery systems. The primary structure of gelatin offers many possibilities for chemical modification and covalent drug attachment. Here nanoparticles of gelatin type A were prepared by a two-step desolvation method as a colloidal drug delivery system and the essential parameters in fabrication were considered. Gelatin was dissolved in 25 mL distilled water under room temperature range. Then acetone was added to the gelatin solution as a desolvating agent to precipitate the high molecular weight (HMW) gelatin. The supernatant was discarded and the HMW gelatin re-dissolved by adding 25 mL distilled water and stirring at 600 rpm. Acetone were added drop-wise to form nanoparticles. At the end of the process, glutaraldehyde solution was used for preparing nanoparticles as a cross-linking agent, and stirred for 12h at 600 rpm. For purification stage we use centrifuge with 600rpm for 3 times. The objective of the present study is consideration of some factors such as temperature, gelatin concentration, agitation speed and the amount of acetone and their effects on size and distribution of nanoparticles. Among the all conditions, 60° C, 50 mg/ml gelatin concentration, 75 ml acetone had the best result and the nanoparticle size was under 170 nm. The effect of these factors for synthesis of gelatine nanoparticle is strongly discussed.

A squeeze-type osmotic tablet for controlled delivery of nifedipine.

PubMed

Park, Jung Soo; Shin, Jun Hyun; Lee, Dong Hun; Kim, Moon Suk; Rhee, John M; Lee, Hai Bang; Khang, Gilson

2008-01-01

Osmotic delivery systems are based on osmotic driving force. Nifedipine tablets, available under the trade names Procardia XL (Pfizer) and Adalat (Bayer), are commercialized drug-delivery systems of an elemental osmotic pump that the push-pull osmotic tablet operates successfully in delivering water-insoluble drugs. For the improvement of the release pattern and the solubility of the drug, we developed a squeeze-type osmotic tablet (SQT) for nifedipine as a model drug. The SQT was composed of one or more ring type of squeeze-push layer (squeeze-disc) and a centered drug core. Squeeze-discs were stacked up with different physicochemical properties with gradient such as viscosity, swelling ratio and water absorption ratio using the osmotic agents from a disc of bottom to top. The present work investigated the effect of different preparation factors, such as hydrophilic polymers, the molecular weight of polymers, coating process, orifice size and types of excipient on release performance of nifedipine. With the purpose of delivering water-insoluble nifedipine at an approximate zero-order rate and step-function rate for 24 h, SQT has been successfully prepared, and significantly improved in the release rate and patterns in comparison with the Adalat push-pull system in vitro release features.

New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects.

PubMed

Ei Thu, Hnin; Hussain, Zahid; Shuid, Ahmad Nazrun

2018-01-01

Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing.

PubMed

Gašperlin, Mirjana; Gosenca, Mirjam

2011-07-01

One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants. This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously. A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.

Interaction between drug delivery vehicles and cells under the effect of shear stress.

PubMed

Godoy-Gallardo, M; Ek, P K; Jansman, M M T; Wohl, B M; Hosta-Rigau, L

2015-09-01

Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs while, at the same time, allowing for drug release to be triggered through a diverse range of physical and chemical cues. While these advances are impressive, the field has been lacking behind in translating these systems into the clinic, mainly due to low predictability of in vitro and rodent in vivo models. An important factor within the complex and dynamic human in vivo environment is the shear flow observed within our circulatory system and many other tissues. Within this review, recent advances to leverage microfluidic devices to better mimic these conditions through novel in vitro assays are summarized. By grouping the discussion in three prominent classes of DDVs (lipidic and polymeric particles as well as inorganic nanoparticles), we hope to guide researchers within drug delivery into this exciting field and advance a further implementation of these assay systems within the development of DDVs.

Edible Nanoemulsions as Carriers of Active Ingredients: A Review.

PubMed

Salvia-Trujillo, Laura; Soliva-Fortuny, Robert; Rojas-Graü, M Alejandra; McClements, D Julian; Martín-Belloso, Olga

2017-02-28

There has been growing interest in the use of edible nanoemulsions as delivery systems for lipophilic active substances, such as oil-soluble vitamins, antimicrobials, flavors, and nutraceuticals, because of their unique physicochemical properties. Oil-in-water nanoemulsions consist of oil droplets with diameters typically between approximately 30 and 200 nm that are dispersed within an aqueous medium. The small droplet size usually leads to an improvement in stability, gravitational separation, and aggregation. Moreover, the high droplet surface area associated with the small droplet size often leads to a high reactivity with biological cells and macromolecules. As a result, lipid digestibility and bioactive bioavailability are usually higher in nanoemulsions than conventional emulsions, which is an advantage for the development of bioactive delivery systems. In this review, the most important factors affecting nanoemulsion formation and stability are highlighted, and a critical analysis of the potential benefits of using nanoemulsions in food systems is presented.

Nanoparticles and direct immunosuppression

PubMed Central

Ngobili, Terrika A

2016-01-01

Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

Sickle cell anemia: the impact of discovery, politics, and business.

PubMed

Xie, Lai-Hua; Doye, Angelia A; Conley, Eric; Gwathmey, Judith K

2013-11-01

Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that our novel formulation lowered the dosage requirements by 50%-75%, allowed for less frequent and shorter treatment durations, eliminating the need for a pump and the standard multi-night administration of DFO. In an iron-overloaded rat model, LDFO reduced iron in the liver, and also improved cardiac function. The lower dosage and improved safety profile makes our novel LDFO delivery system a highly desirable new therapy. Meanwhile, this system will also provide an ideal model for studying the mechanism of Fe overload-induced arrhythmias. The political and economic factors related to health care disparities are also discussed.

Ewing's Sarcoma: Development of RNA Interference-Based Therapy for Advanced Disease

PubMed Central

Simmons, Olivia; Maples, Phillip B.; Senzer, Neil; Nemunaitis, John

2012-01-01

Ewing's sarcoma tumors are associated with chromosomal translocation between the EWS gene and the ETS transcription factor gene. These unique target sequences provide opportunity for RNA interference(i)-based therapy. A summary of RNAi mechanism and therapeutically designed products including siRNA, shRNA and bi-shRNA are described. Comparison is made between each of these approaches. Systemic RNAi-based therapy, however, requires protected delivery to the Ewing's sarcoma tumor site for activity. Delivery systems which have been most effective in preclinical and clinical testing are reviewed, followed by preclinical assessment of various silencing strategies with demonstration of effectiveness to EWS/FLI-1 target sequences. It is concluded that RNAi-based therapeutics may have testable and achievable activity in management of Ewing's sarcoma. PMID:22523703

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

3D axon growth by exogenous electrical stimulus and soluble factors.

PubMed

Tang-Schomer, Min D

2018-01-01

Axon growth and alignment are fundamental processes during nervous system development and neural regeneration after injury. The present study investigates the effects of exogenous stimulus of electrical signals and soluble factors on axon 3D growth, using a silk protein material-based 3D brain tissue model. Electrical stimulus was delivered via embedded gold wires positioned at the interface of the scaffold region and the center matrix gel-filled region, spanning the axon growth area. This setup delivered applied electrical field directly to growing axons, and the effects were compared to micro-needle assisted local delivery of soluble factors of extracellular (ECM) components and neurotrophins. Dissociated rat cortical neurons were exposed to an alternating field of 80 mV/mm at 0.5 Hz to 2 kHz or soluble factors for up to 4 days, and evaluated by of β III-tubulin immunostaining, confocal imaging and 3D neurite tracing. 0.5-20 Hz were found to promote axon growth, with 2 Hz producing the biggest effect of ∼30% axon length increase compared to control cultures. Delivery of ECM components of laminin and fibronectin resulted significantly greater axon initial length increases compared to neurotrophic factors, such as BDNF, GDNF, NGF and NT3 (all at 1 μM). Though axon lengths under 2 Hz stimulation and LN or FN exposure were statistically similar, significant AC-induced axon alignment was found under all frequencies tested. The effects included perpendicular orientation of axons trespassing an electrode, large populations of aligned axon tracts in parallel to the field direction with a few perpendicularly aligned along the middle point of the EF. These findings are consistent with the hypothesis that an electrode in AC field could act as an alternating cathode that attracts the growing tip of the axon. These results demonstrate the use of alternating electric field stimulation to direct axon 3D length growth and orientation. Our study provides basis for further optimizing stimulation parameters, in conjunction of delivery of growth promoting soluble factors to direct axon growth in a brain mimetic 3D environment. This system provides a platform for studying the effects of exogenous signals on nervous system development and for testing neuromodulation approaches for neurological diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Missed opportunities to improve the health of postpartum women: high rates of untreated hypertension in rural Tanzania

PubMed Central

Larson, Elysia; Rabkin, Miriam; Mbaruku, Godfrey M.; Mbatia, Redempta; Kruk, Margaret E.

2017-01-01

Objectives To assess the prevalence of high blood pressure amongst postpartum women in rural Tanzania, and to explore factors associated with hypertension prevalence, awareness of their own hypertension, treatment, and control. Methods We conducted a cross-sectional study of 1,849 women in Tanzania’s Pwani Region who delivered a child in the prior year. We measured blood pressure, administered a structured questionnaire, and assessed factors associated with hypertension (HTN) prevalence, women’s awareness of their own HTN, treatment, and control of HTN using bivariable and multivariable logistic regressions. Findings 26.7% of women had high blood pressure and/or were taking antihypertensive medication. Women were on average 27.5 years old (range 15–54). Nearly all women (99.5%) reported contact with the health system during their pregnancy and delivery, with 97.0% reporting at least one antenatal care visit, 81.4% reporting facility delivery, and an overall average of 5.2 visits for their own care in the past year. Only 23.5% of those with HTN were aware of their diagnosis, 17.4% were taking medication, and only 10.5% had controlled blood pressure. In multivariable analysis, facility delivery, health insurance, and increased distance from a hospital were associated with increased likelihood of HTN awareness; facility delivery and hospital distance were associated with current hypertensive treatment; younger age and increased hospital distance were associated with control of HTN. Conclusion The prevalence of high blood pressure in this postpartum population was high, and despite frequent recent contacts with the health system, awareness, treatment and control of HTN were low. These findings highlight an important missed opportunity to improve women’s health during antenatal and postnatal care. PMID:28120288

Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

DOT National Transportation Integrated Search

2012-05-16

This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

Acceptance of lean redesigns in primary care: A contextual analysis.

PubMed

Hung, Dorothy; Gray, Caroline; Martinez, Meghan; Schmittdiel, Julie; Harrison, Michael I

Lean is a leading change strategy used in health care to achieve short-term efficiency and quality improvement while promising longer-term system transformation. Most research examines Lean intervention to address isolated problems, rather than to achieve broader systemic changes to care delivery. Moreover, no studies examine contextual influences on system-wide Lean implementation efforts in primary care. The aim of this study was to identify contextual factors most critical to implementing and scaling Lean redesigns across all primary care clinics in a large, ambulatory care delivery system. Over 100 interviews and focus groups were conducted with frontline physicians, clinical staff, and operational leaders. Data analysis was guided by a modified Consolidated Framework for Implementation Research (CFIR), a popular implementation science framework. On the basis of expert recommendations, the modified framework targets factors influencing the implementation of process redesigns. This modified framework, the CFIR-PR, informed our identification of contextual factors that most impacted Lean acceptance among frontline physicians and staff. Several domains identified by the CFIR-PR were critical to acceptance of Lean redesigns. Regarding the implementation process acceptance was influenced by time and intensity of exposure to changes, "top-down" versus "bottom-up" implementation styles, and degrees of employee engagement in developing new workflows. Important factors in the inner setting were the clinic's culture and style of leadership, along with availability of information about Lean's effectiveness. Last, implementation efforts were impacted by individual and team characteristics regarding changed work roles and related issues of professional identity, authority, and autonomy. This study underscores the need for change leaders to consider the contextual factors that surround efforts to implement Lean in primary care. As Lean redesigns are scaled across a system, special attention is warranted with respect to the implementation approach, internal clinic setting, and implications for professional roles and identities of physicians and staff.

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

48 CFR 815.304-70 - Evaluation factor commitments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SDVOSBs; (2) Use past performance in meeting SDVOSB subcontracting goals as a non-price evaluation factor... as an evaluation factor when competitively negotiating the award of contracts or task or delivery... competitively negotiating the award of contracts or task or delivery orders. (b) If an offeror proposes to use...

Strategies in Development and Delivery of Nanotechnology Based Cosmetic Products.

PubMed

Ahmad, Usama; Ahmad, Zeeshan; Khan, Ahmed Abdullah; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees

2018-03-26

The science of formulation involving cosmetic ingredients has always been a challenge since the release of active components greatly depends upon the carrier system involved and the selectivity of skin barrier. The principle obstacle of the skin resides in the epidermis and it's hard for many active components to cross it. The formulation related factors like size of particles, viscosity and lipophilicity of the components also play an important role in permeation of the dermal composition. Though widely used; conventional creams and gels still struggle in terms of success. This work focuses on nano based formulation strategies for successful delivery of cosmetic agents. Novel strategies like nanoemulsion, nanogels, liposomes, aquasomes, niosomes, dendrimers and fullerenes have paved way for successful delivery of dermal formulations to desire depths in the skin. © Georg Thieme Verlag KG Stuttgart · New York.

Risk Factors Associated with Preterm Delivery after Fetoscopic Laser Surgery for Twin Twin Transfusion Syndrome

PubMed Central

PAPANNA, Ramesha; BLOCK-ABRAHAM, Dana; Mann, Lovepreet K; BUHIMSCHI, Irina A.; BEBBINGTON, Michael; GARCIA, Elisa; KAHLEK, Nahla; HARMAN, Christopher; JOHNSON, Anthony; BASCHAT, Ahmet; MOISE, Kenneth J.

2014-01-01

OBJECTIVE Despite improved perinatal survival following fetoscopic laser surgery (FLS) for twin twin transfusion syndrome (TTTS), prematurity remains an important contributor to perinatal mortality and morbidity. The objective of the study was to identify risk factors for complicated preterm delivery after FLS. STUDY DESIGN Retrospective cohort study of prospectively collected data on maternal/fetal demographics and pre-operative, operative and post-operative variables of 459 patients treated in 3 U.S. fetal centers. Multivariate linear regression was performed to identify significant risk factors associated with preterm delivery, which was cross-validated using K-fold method. Multivariate logistic regression was performed to identify risk factors for early vs. late preterm delivery based on median gestational age at delivery of 32 weeks. RESULTS There were significant differences in case selection and outcomes between the centers. After controlling for the center of surgery, a multivariate analysis indicated a lower maternal age at procedure, history of previous prematurity, shortened cervical length, use of amnioinfusion, 12 Fr cannula diameter, lack of a collagen plug placement and iatrogenic preterm premature rupture of membranes (iPPROM) were significantly associated with a lower gestational age at delivery. CONCLUSION Specific fetal/maternal and operative variables are associated with preterm delivery after FLS for the treatment of TTTS. Further studies to modify some of these variables may decrease the perinatal morbidity after laser therapy. PMID:24013922

Proposal of a service delivery integration index of home care for older persons: application in several European cities

PubMed Central

Henrard, Jean-Claude; Ankri, Joël; Frijters, Dinnus; Carpenter, Iain; Topinkova, Eva; Garms-Homolova, Vjenka; Finne-Soveri, Harriett; Sørbye, Liv Wergeland; Jónsson, Palmi V.; Ljunggren, Gunnar; Schroll, Marianne; Wagner, Cordula; Bernabei, Roberto

2006-01-01

Abstract Purpose To propose an integration index of home care delivery to older persons, to study its validity and to apply it to home care services of European cities. Theory Home care delivery integration was based on two dimensions referring to process-centred integration and organisational structure approach. Method Items considered as part of both dimensions according to an expert consensus (face validity) were extracted from a standardised questionnaire used in “Aged in Home care” (AdHoc) study to capture basic characteristics of home care services. Their summation leads to a services' delivery integration index. This index was applied to AdHoc services. A factor analysis was computed in order to empirically test the validity of the theoretical constructs. The plot of the settings was performed. Results Application of the index ranks home care services in four groups according to their score. Factor analysis identifies a first factor which opposes working arrangement within service to organisational structure bringing together provisions for social care. A second factor corresponds to basic nursing care and therapies. Internal consistency for those three domains ranges from 0.78 to 0.93. When plotting the different settings different models of service delivery appear. Conclusion The proposed index shows that behind a total score several models of care delivery are hidden. Comparison of service delivery integration should take into account this heterogeneity. PMID:17006549

[Choice of type of delivery: factors reported by puerperal woman].

PubMed

Nascimento, Raquel Ramos Pinto do; Arantes, Sandra Lucia; Souza, Eunice Delgado Cameron de; Contrera, Luciana; Sales, Ana Paula Assis

2015-01-01

To know the factors listed by puerperal woman that influenced the choice in type of delivery. Qualitative research, developed with 25 puerperal women in a University Hospital of Mato Grosso do Sul, between September and November 2014. A semi-structured interview was used for data collection and the Collective Subject Discourse was used to organize and tabulate the data collected. The Collective Subject Discourses resulted in the following categories: Desire for the type of delivery; Respect for the chosen type of delivery and Factors that influenced the choice. Most of the women interviewed (76%) expressed a preference for normal birth due to rapid recovery, less pain and suffering. The influence of family members, previous experience with childbirth, professional-customer interaction and internet information influenced the type of delivery chosen, which reinforces the importance of health education since the pre-natal stage, highlighting the need to equip women to perform a conscious choice.

Adenoviral modification of mouse brain derived endothelial cells, bEnd3, to induce apoptosis by vascular endothelial growth factor.

PubMed

Mitsuuchi, Y; Powell, D R; Gallo, J M

2006-02-09

A second generation genetically-engineered cell-based drug delivery system, referred to as apoptotic-induced drug delivery (AIDD), was developed using endothelial cells (ECs) that undergo apoptosis upon binding of vascular endothelial growth factor (VEGF) to a Flk-1:Fas fusion protein (FF). This new AIDD was redesigned using mouse brain derived ECs, bEnd3 cells, and an adenovirus vector in order to enhance and control the expression of FF. The FF was tagged with a HA epitope (FFHA) and designed to be coexpressed with green fluorescence protein (GFP) by the regulation of cytomegalovirus promoters in the adenovirus vector. bEnd3 cells showed favorable coexpression of FFHA and GFP consistent with the multiplicity of infection of the adenovirus. Immunofluorescence analysis demonstrated that FFHA was localized at the plasma membrane, whereas GFP was predominantly located in the cytoplasm of ECs. Cell death was induced by VEGF, but not by platelet derived growth factor or fibroblast growth factor in a dose-dependent manner (range 2-20 ng/ml), and revealed caspase-dependent apoptotic profiles. The FFHA expressing bEnd3 cells underwent apoptosis when cocultured with a glioma cell (SF188V+) line able to overexpress VEGF. The combined data indicated that the FFHA adenovirus system can induce apoptotic signaling in ECs in response to VEGF, and thus, is an instrumental modification to the development of AIDD.

Patient Involvement in Safe Delivery: A Qualitative Study.

PubMed

Olfati, Forozun; Asefzadeh, Saeid; Changizi, Nasrin; Keramat, Afsaneh; Yunesian, Masud

2015-09-28

Patient involvement in safe delivery planning is considered important yet not widely practiced. The present study aimed at identifythe factors that affect patient involvementin safe delivery, as recommended by parturient women. This study was part of a qualitative research conducted by content analysis method and purposive sampling in 2013.The data were collected through 63 semi-structured interviews in4 hospitalsand analyzed using thematic content analysis. The participants in this research were women before discharge and after delivery. Findings were analyzed using Colaizzi's method. Four categories of factors that could affect patient involvement in safe delivery emerged from our analysis: patient-related (true and false beliefs, literacy, privacy, respect for patient), illness-related (pain, type of delivery, patient safety incidents), health care professional-relatedand task-related factors (behavior, monitoring &training), health care setting-related (financial aspects, facilities). More research is needed to explore the factors affecting the participation of mothers. It is therefore, recommended to: 1) take notice of mother education, their husbands, midwives and specialists; 2) provide pregnant women with insurance coverage from the outset of pregnancy, especially during prenatal period; 3) form a labor pain committee consisting of midwives, obstetricians, and anesthesiologists in order to identify the preferred painless labor methods based on the existing facilities and conditions, 4) carry out research on observing patients' privacy and dignity; 5) pay more attention on the factors affecting cesarean.

Futurescapes: evidence expectations in the USA for comparative effectiveness research for drugs in 2020.

PubMed

Messner, Donna A; Mohr, Penny; Towse, Adrian

2015-08-01

Explore key factors influencing future expectations for the production of evidence from comparative effectiveness research for drugs in the USA in 2020 and construct three plausible future scenarios. Semistructured key informant interviews and three rounds of modified Delphi with systematic scenario-building methods. Most influential key factors were: health delivery system integration; electronic health record development; exploitation of very large databases and mixed data sources; and proactive patient engagement in research. The scenario deemed most likely entailed uneven development of large integrated health systems with pockets of increased provider risk for patient care, enhanced data collection systems, changing incentives to do comparative effectiveness research and new opportunities for evidence generation partnerships.

Health of the American Indian. Report of a Regional Task Force.

ERIC Educational Resources Information Center

Michal, Mary L.; And Others

Good health is the result of such factors as sanitation, adequate housing and clothing, nutritional food, and a health delivery system which protects against contagious diseases by immunization, provides for early detection and treatment, provides health education to promote practices that will prevent diseases, and gives services in a culturally…

Online Help Systems

DTIC Science & Technology

1989-09-07

online materials (and the concomitant increase in the cost for hardcopy materials) will make online delivery the marketing choice. In sum, medium of...involved in programming, marketing , human factors research, training, and business management. Job Titles of Online Help Designers Job Title...of Company Senior Research Librarian Advisory Information Developer Research Staff Assistant Marketing Manager Manager of Online Documentation Table

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PubMed

Jones, Jason J; Chu, Jeffrey; Graham, Jacob; Zaluski, Serge; Rocha, Guillermo

2016-01-01

The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

Nuclear delivery of recombinant OCT4 by chitosan nanoparticles for transgene-free generation of protein-induced pluripotent stem cells.

PubMed

Tammam, Salma; Malak, Peter; Correa, Daphne; Rothfuss, Oliver; Azzazy, Hassan M E; Lamprecht, Alf; Schulze-Osthoff, Klaus

2016-06-21

Protein-based reprogramming of somatic cells is a non-genetic approach for the generation of induced pluripotent stem cells (iPSCs), whereby reprogramming factors, such as OCT4, SOX2, KLF4 and c-MYC, are delivered as functional proteins. The technique is considered safer than transgenic methods, but, unfortunately, most protein-based protocols provide very low reprogramming efficiencies. In this study, we developed exemplarily a nanoparticle (NP)-based delivery system for the reprogramming factor OCT4. To this end, we expressed human OCT4 in Sf9 insect cells using a baculoviral expression system. Recombinant OCT4 showed nuclear localization in Sf9 cells indicating proper protein folding. In comparison to soluble OCT4 protein, encapsulation of OCT4 in nuclear-targeted chitosan NPs strongly stabilized its DNA-binding activity even under cell culture conditions. OCT4-loaded NPs enabled cell treatment with high micromolar concentrations of OCT4 and successfully delivered active OCT4 into human fibroblasts. Chitosan NPs therefore provide a promising tool for the generation of transgene-free iPSCs.

Critical success factor (CSF) service delivery for tahfiz institution teaching & learning environment

NASA Astrophysics Data System (ADS)

Ridza, B. H.; Jalil, R. A.; Sipan, I.; Nukman, Y.

2017-11-01

The exceptional existence of tahfiz institutions (TI) by a government and the private sector in Malaysia indicates that tahfiz education at par to fill mainstream education. Nevertheless, the level of TI facilities management (FM) provided is unstandardized since its infrastructure and establishment is initiated by the varied background of TI organizer. Thus, the effectiveness of TI education system is immeasurable. The significance of this research is to explore the critical success factor (CSF) of service delivery for TI teaching and learning environment. This research adopts both qualitative and quantitative method through survey instrument in order to review and analyze to achieve the research goal. The findings showed several important criteria for a transformation of TI education teaching and learning environment such top management of TI needs to be more responsible in providing better FM practice to achieve efficiency of manpower in providing a conducive learning environment for students for producing excellent huffaz. Thus, TI education system needs to have clear standard guidelines in operating their activities in producing huffaz that capable implement Islamic knowledge to the development of the country.

Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study.

PubMed

Roberts, Christine L; Algert, Charles S; Morris, Jonathan M; Ford, Jane B

2015-10-05

Since the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia. Population-based record linkage study utilising linked birth and hospital records. A cohort of 1,076,122 deliveries in New South Wales, Australia, 2001-2012. Pregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome. From 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.9-18.4%) and labour inductions by 10% (24.8-27.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ≥35 years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20 years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38 weeks gestation and were steepest from 41 weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery. It appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk factors for hypertension were relatively more likely to be selected for early delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

High ANC coverage and low skilled attendance in a rural Tanzanian district: a case for implementing a birth plan intervention.

PubMed

Magoma, Moke; Requejo, Jennifer; Campbell, Oona M R; Cousens, Simon; Filippi, Veronique

2010-03-19

In Tanzania, more than 90% of all pregnant women attend antenatal care at least once and approximately 62% four times or more, yet less than five in ten receive skilled delivery care at available health units. We conducted a qualitative study in Ngorongoro district, Northern Tanzania, in order to gain an understanding of the health systems and socio-cultural factors underlying this divergent pattern of high use of antenatal services and low use of skilled delivery care. Specifically, the study examined beliefs and behaviors related to antenatal, labor, delivery and postnatal care among the Maasai and Watemi ethnic groups. The perspectives of health care providers and traditional birth attendants on childbirth and the factors determining where women deliver were also investigated. Twelve key informant interviews and fifteen focus group discussions were held with Maasai and Watemi women, traditional birth attendants, health care providers, and community members. Principles of the grounded theory approach were used to elicit and assess the various perspectives of each group of participants interviewed. The Maasai and Watemi women's preferences for a home birth and lack of planning for delivery are reinforced by the failure of health care providers to consistently communicate the importance of skilled delivery and immediate post-partum care for all women during routine antenatal visits. Husbands typically serve as gatekeepers of women's reproductive health in the two groups - including decisions about where they will deliver- yet they are rarely encouraged to attend antenatal sessions. While husbands are encouraged to participate in programs to prevent maternal-to-child transmission of HIV, messages about the importance of skilled delivery care for all women are not given emphasis. Increasing coverage of skilled delivery care and achieving the full implementation of Tanzania's Focused Antenatal Care Package in Ngorongoro depends upon improved training and monitoring of health care providers, and greater family participation in antenatal care visits.

High ANC coverage and low skilled attendance in a rural Tanzanian district: a case for implementing a birth plan intervention

PubMed Central

2010-01-01

Background In Tanzania, more than 90% of all pregnant women attend antenatal care at least once and approximately 62% four times or more, yet less than five in ten receive skilled delivery care at available health units. We conducted a qualitative study in Ngorongoro district, Northern Tanzania, in order to gain an understanding of the health systems and socio-cultural factors underlying this divergent pattern of high use of antenatal services and low use of skilled delivery care. Specifically, the study examined beliefs and behaviors related to antenatal, labor, delivery and postnatal care among the Maasai and Watemi ethnic groups. The perspectives of health care providers and traditional birth attendants on childbirth and the factors determining where women deliver were also investigated. Methods Twelve key informant interviews and fifteen focus group discussions were held with Maasai and Watemi women, traditional birth attendants, health care providers, and community members. Principles of the grounded theory approach were used to elicit and assess the various perspectives of each group of participants interviewed. Results The Maasai and Watemi women's preferences for a home birth and lack of planning for delivery are reinforced by the failure of health care providers to consistently communicate the importance of skilled delivery and immediate post-partum care for all women during routine antenatal visits. Husbands typically serve as gatekeepers of women's reproductive health in the two groups - including decisions about where they will deliver- yet they are rarely encouraged to attend antenatal sessions. While husbands are encouraged to participate in programs to prevent maternal-to-child transmission of HIV, messages about the importance of skilled delivery care for all women are not given emphasis. Conclusions Increasing coverage of skilled delivery care and achieving the full implementation of Tanzania's Focused Antenatal Care Package in Ngorongoro depends upon improved training and monitoring of health care providers, and greater family participation in antenatal care visits. PMID:20302625

Application of modelling and nanotechnology-based approaches: The emergence of breakthroughs in theranostics of central nervous system disorders.

PubMed

Hassanzadeh, Parichehr; Atyabi, Fatemeh; Dinarvand, Rassoul

2017-08-01

The limited efficiency of the current treatment options against the central nervous system (CNS) disorders has created increasing demands towards the development of novel theranostic strategies. The enormous research efforts in nanotechnology have led to the production of highly-advanced nanodevices and biomaterials in a variety of geometries and configurations for targeted delivery of genes, drugs, or growth factors across the blood-brain barrier. Meanwhile, the richness or reliability of data, drug delivery methods, therapeutic effects or potential toxicity of nanoparticles, occurrence of the unexpected phenomena due to the polydisperse or polymorphic nature of nanomaterials, and personalized theranostics have remained as challenging issues. In this respect, computational modelling has emerged as a powerful tool for rational design of nanoparticles with optimized characteristics including the selectivity, improved bioactivity, and reduced toxicity that might lead to the effective delivery of therapeutic agents. High-performance simulation techniques by shedding more light on the dynamical behaviour of neural networks and pathomechanisms of CNS disorders may provide imminent breakthroughs in nanomedicine. In the present review, the importance of integration of nanotechnology-based approaches with computational techniques for targeted delivery of theranostics to the CNS has been highlighted. Copyright © 2017. Published by Elsevier Inc.

Micelle-like Nanoparticles as Carriers for DNA and siRNA

PubMed Central

Navarro, Gemma; Pan, Jiayi; Torchilin, Vladimir P.

2015-01-01

Gene therapy represents a potential efficient approach of disease prevention and therapy. However, due to their poor in vivo stability, gene molecules need to be associated with delivery systems to overcome extracellular and intracellular barriers and allow access to the site of action. Cationic polymeric nanoparticles are popular carriers for small interfering RNA (siRNA) and DNA-based therapeutics for which efficient and safe delivery are important factors that need to be optimized. Micelle-like nanoparticles (MNP) (half micelles, half polymeric nanoparticles) can overcome some of the disadvantages of such cationic carriers by unifying in one single carrier the best of both delivery systems. In this review, we will discuss how the unique properties of MNP including self-assembly, condensation and protection of nucleic acids, improved cell association and gene transfection, and low toxicity may contribute to the successful application of siRNA- and DNA-based therapeutics into the clinic. Recent developments of MNP involving the addition of stimulus-sensitive functions to respond specifically to pathological or externally applied “triggers” (e.g., temperature, pH or enzymatic catalysis, light, or magnetic fields) will be discussed. Finally, we will overview the use of MNP as two-in-one carriers for the simultaneous delivery of different agents (small molecules, imaging agents) and nucleic acid combinations. PMID:25557580

Specific gene delivery to liver sinusoidal and artery endothelial cells.

PubMed

Abel, Tobias; El Filali, Ebtisam; Waern, Johan; Schneider, Irene C; Yuan, Qinggong; Münch, Robert C; Hick, Meike; Warnecke, Gregor; Madrahimov, Nodir; Kontermann, Roland E; Schüttrumpf, Jörg; Müller, Ulrike C; Seppen, Jurgen; Ott, Michael; Buchholz, Christian J

2013-09-19

Different types of endothelial cells (EC) fulfill distinct tasks depending on their microenvironment. ECs are therefore difficult to genetically manipulate ex vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary liver cell cultures. Upon systemic injection, strong reporter gene expression was detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs (LSECs) but not Kupffer cells, which were mainly transduced by nontargeted LVs. Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery of the erythropoietin gene with mCD105-LV resulted in substantially increased erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs. Interestingly, when applied at higher dose and in absence of target cells in the liver, huCD105-LV transduced ECs of a human artery transplanted into the descending mouse aorta. The data demonstrate for the first time targeted gene delivery to specialized ECs upon systemic vector administration. This strategy offers novel options to better understand the physiological functions of ECs and to treat genetic diseases such as those affecting blood factors.

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

PubMed Central

Khalin, Igor; Alyautdin, Renad; Kocherga, Ganna; Bakar, Muhamad Abu

2015-01-01

Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. PMID:25995632

Impact of managed care on healthcare delivery practices: the perception of healthcare administrators and clinical practitioners.

PubMed

Tietze, Mari F

2003-01-01

Managed care has introduced changes, such as cost effectiveness, access to care, and quality of care, to many components of the U.S. healthcare delivery system. These changes have affected how healthcare administrators and clinical practitioners perceive the impact of managed care on healthcare delivery practices. A survey was initiated to explore whether the perceptions of administrators differed from those of practitioners and to discover which organizational variables could explain the difference. A descriptive, cross-sectional survey design was used for the target population of administrators and practitioners in high, moderate, and low managed-care-penetration markets. Two investigator-developed instruments--the Managed Care Perceptions Inventory (MCPI) and the MCPI-Demographic--and an intact centralization of decision-making assessment subscale were used for data collection. Administrators had a statistically significant, more positive perception of the impact of managed care on healthcare delivery than did practitioners. When the distinction between administrator and practitioner was not used as a grouping factor, managed care market penetration, nonprofit status, and years in current employment position were factors that had statistically significant associations with a more positive perception of managed care. Based on these findings, both administrators and practitioners have a role in maintaining awareness regarding their perceptions and should work collaboratively to address issues of concern. Similarly, promoting trust and commitment at the organizational level is important. Recommendations for further research are also provided.

Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases.

PubMed

Matsui, Akitsugu; Uchida, Satoshi; Ishii, Takehiko; Itaka, Keiji; Kataoka, Kazunori

2015-10-28

Gene therapy is a promising approach for treating diseases that are closely associated with excessive apoptosis, because the gene can effectively and sustainably introduce anti-apoptotic factors into cells. However, DNA delivery poses the risk of random genomic integration, leading to overexpression of the delivered gene and cancer development. Messenger RNA (mRNA) can evade integration events in target cells. We examined the use of mRNA-based therapeutics for introducing anti-apoptotic factors by using a mouse model of fulminant hepatitis. For introducing mRNA into the liver, a synthesised polymer-based carrier of polyplex nanomicelles was used for hydrodynamic intravenous injection. Using GFP as a reporter, we demonstrate that mRNA delivery induced efficient protein expression in almost 100% of liver cells, while plasmid DNA (pDNA) delivery provided a smaller percentage of GFP-positive cells. Analyses using Cy5-labelled mRNA and pDNA revealed that efficient expression by mRNA was attributed to a simple intracellular mechanism, without the need for nuclear entry. Consistent with this observation, Bcl-2 mRNA was more effective on reducing apoptosis in the liver of mice with fulminant hepatitis than Bcl-2 pDNA. Therefore, mRNA-based therapeutics combined with an effective delivery system such as polyplex nanomicelles is a promising treatment for intractable diseases associated with excessive apoptosis.

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

Erythrocytes-based synthetic delivery systems: transition from conventional to novel engineering strategies.

PubMed

Bhateria, Manisha; Rachumallu, Ramakrishna; Singh, Rajbir; Bhatta, Rabi Sankar

2014-08-01

Erythrocytes (red blood cells [RBCs]) and artificial or synthetic delivery systems such as liposomes, nanoparticles (NPs) are the most investigated carrier systems. Herein, progress made from conventional approach of using RBC as delivery systems to novel approach of using synthetic delivery systems based on RBC properties will be reviewed. We aim to highlight both conventional and novel approaches of using RBCs as potential carrier system. Conventional approaches which include two main strategies are: i) directly loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas novel approaches exploit structural, mechanical and biological properties of RBCs to design synthetic delivery systems through various engineering strategies. Initial attempts included coupling of antibodies to liposomes to specifically target RBCs. Knowledge obtained from several studies led to the development of RBC membrane derived liposomes (nanoerythrosomes), inspiring future application of RBC or its structural features in other attractive delivery systems (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater potential. In conclusion, this review dwells upon comparative analysis of various conventional and novel engineering strategies in developing RBC based drug delivery systems, diversifying their applications in arena of drug delivery. Regardless of the challenges in front of us, RBC based delivery systems offer an exciting approach of exploiting biological entities in a multitude of medical applications.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

PubMed Central

Ko, Young Tag; Choi, Dong-Kug

2018-01-01

Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. PMID:29588585

Is prophylaxis required for delivery in women with factor VII deficiency?

PubMed Central

Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

2013-01-01

Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

Is prophylaxis required for delivery in women with factor VII deficiency?

PubMed

Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

2013-11-01

Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

Vaginismus as an independent risk factor for cesarean delivery.

PubMed

Goldsmith, Tomer; Levy, Amalia; Sheiner, Eyal; Goldsmith, Tomer; Levy, Amalia; Sheiner, Eyal

2009-10-01

The present study was aimed to investigate pregnancy outcome of patients with vaginismus, and specifically the relationship between vaginismus and cesarean delivery. A population based study comparing all pregnancies in patients with and without vaginismus was conducted. Patients lacking prenatal care were excluded from the analysis. Deliveries occurred during the years 1988-2007. A multivariate logistic regression model, with backward elimination, was constructed to find independent risk factors associated with vaginismus. During the study period there were 192,954 deliveries, of which 118 occurred in patients with vaginismus. Patients with vaginismus tended to be younger (26.04+/-4.89 vs. 28.61+/-5.83; p < 0.001) and delivered smaller children (3024.2+/-517 g vs. 3160.9+/-576 g; p = 0.01) when compared with patients without vaginismus. Patients with vaginismus had higher rates of infertility treatments (5.9%vs. 2.7%, odds ratio [OR] 2.3; 95% confidence interval [CI] 1.1-4.9; p = 0.04) and labor induction (37.3%vs. 27.4%, OR 1.6; 95% CI 1.1-2.3; p = 0.02), vacuum extraction (9.3%vs. 2.8%, OR 3.6, 95% CI 1.9-6.7; p < 0.001), and cesarean delivery (39.0%vs. 14.5%, OR 3.8; 95% CI 2.6-5.5; p < 0.001) when compared with the comparison group. Even after controlling for possible confounders associated with cesarean delivery such as previous cesarean delivery, pathological presentations, and fetal distress, vaginismus remained as an independent risk factor for cesarean delivery (OR 7.1; 95% CI 4.5-11.1; p < 0.001). Vaginismus is an independent risk factor for cesarean delivery.

Integrated delivery systems focus on service delivery after capitation efforts stall.

PubMed

2005-03-01

Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

Mode of anaesthesia for preterm Caesarean delivery: secondary analysis from the Maternal–Fetal Medicine Units Network Caesarean Registry†‡

PubMed Central

Butwick, A. J.; El-Sayed, Y. Y.; Blumenfeld, Y. J.; Osmundson, S. S.; Weiniger, C. F.

2015-01-01

Background Preterm delivery is often performed by Caesarean section. We investigated modes of anaesthesia and risk factors for general anaesthesia among women undergoing preterm Caesarean delivery. Methods Women undergoing Caesarean delivery between 24+0 and 36+6 weeks' gestation were identified from a multicentre US registry. The mode of anaesthesia was classified as neuraxial anaesthesia (spinal, epidural, or combined spinal and epidural) or general anaesthesia. Logistic regression was used to identify patient characteristic, obstetric, and peripartum risk factors associated with general anaesthesia. Results Within the study cohort, 11 539 women had preterm Caesarean delivery; 9510 (82.4%) underwent neuraxial anaesthesia and 2029 (17.6%) general anaesthesia. In our multivariate model, African-American race [adjusted odds ratio (aOR)=1.9; 95% confidence interval (CI)=1.7–2.2], Hispanic ethnicity (aOR=1.5; 95% CI=1.2–1.8), other race (aOR=1.4; 95% CI=1.1–1.9), and haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia (aOR=2.8; 95% CI=2.2–3.5) were independently associated with receiving general anaesthesia for preterm Caesarean delivery. Women with an emergency Caesarean delivery indication had the highest odds for general anaesthesia (aOR=3.5; 95% CI=3.1–3.9). For every 1 week decrease in gestational age at delivery, the adjusted odds of general anaesthesia increased by 13%. Conclusions In our study cohort, nearly one in five women received general anaesthesia for preterm Caesarean delivery. Although potential confounding by unmeasured factors cannot be excluded, our findings suggest that early gestational age at delivery, emergent Caesarean delivery indications, hypertensive disease, and non-Caucasian race or ethnicity are associated with general anaesthesia for preterm Caesarean delivery. PMID:25956901

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Y-piece temperature and humidification during mechanical ventilation.

PubMed

Solomita, Mario; Daroowalla, Feroza; Leblanc, Deniese S; Smaldone, Gerald C

2009-04-01

Practitioners often presume there is adequate humidification in the ventilator circuit if the Y-piece is at a specified temperature, but control of Y-piece temperature may be inadequate to ensure adequate humidification. In an in vitro bench model we measured water-vapor delivery with several heated humidification setups and a wide range of minute volume (V (E)) values. The setup included a condenser, hygrometry, and thermometer. First, we calibrated the system with a point-source humidifier and water pump. Then we tested the water-vapor delivery during non-heated-wire humidification and during heated-wire humidification with a temperature gradient of +3 degrees C, 0 degrees C, and -3 degrees C between the humidifier and the Y-piece. We compared the results to 2 recommended humidification values: 100% saturated (absolute humidity 44 mg H(2)O/L) gas at 37 degrees C (saturated/37 degrees C); and 75% saturated (absolute humidity 33 mg H(2)O/L), which is the humidity recommended by the International Organization for Standardization (the ISO standard). In all the experiments the setup was set to provide 35 degrees C at the Y-piece. Our method for measuring water-vapor delivery closely approximated the amount delivered by a calibrated pump, but slightly underestimated the water-vapor delivery in all the experiments and the whole V (E) range. At all V (E) values, water-vapor delivery during non-heated-wire humidification matched or exceeded saturated/37 degrees C and was significantly greater than that during heated-wire humidification. During heated-wire humidification, water-vapor delivery varied with the temperature gradient and did not reach saturated/37 degrees C at V (E) > 6 L/min. Water-vapor delivery with the negative temperature gradient was below the ISO standard. Maintaining temperature at one point in the inspiratory circuit (eg, Y-piece), does not ensure adequate water-vapor delivery. Other factors (humidification system, V (E), gradient setting) are critical. At a given temperature, humidification may be significantly higher or lower than expected.

State of science: human factors and ergonomics in healthcare.

PubMed

Hignett, Sue; Carayon, Pascale; Buckle, Peter; Catchpole, Ken

2013-01-01

The past decade has seen an increase in the application of human factors and ergonomics (HFE) techniques to healthcare delivery in a broad range of contexts (domains, locations and environments). This paper provides a state of science commentary using four examples of HFE in healthcare to review and discuss analytical and implementation challenges and to identify future issues for HFE. The examples include two domain areas (occupational ergonomics and surgical safety) to illustrate a traditional application of HFE and the area that has probably received the most research attention. The other two examples show how systems and design have been addressed in healthcare with theoretical approaches for organisational and socio-technical systems and design for patient safety. Future opportunities are identified to develop and embed HFE systems thinking in healthcare including new theoretical models and long-term collaborative partnerships. HFE can contribute to systems and design initiatives for both patients and clinicians to improve everyday performance and safety, and help to reduce and control spiralling healthcare costs. There has been an increase in the application of HFE techniques to healthcare delivery in the past 10 years. This paper provides a state of science commentary using four illustrative examples (occupational ergonomics, design for patient safety, surgical safety and organisational and socio-technical systems) to review and discuss analytical and implementation challenges and identify future issues for HFE.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

PubMed

Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

Heparin-binding peptide amphiphile supramolecular architectures as platforms for angiogenesis and drug delivery

NASA Astrophysics Data System (ADS)

Chow, Lesleyann W.

A fascinating phenomenon in nature is the self-assembly of molecules into a functional, hierarchical structure. In the past decade, the Stupp Laboratory has developed several classes of self-assembling biomaterials, one of which is the synthetic peptide amphiphile (PA). Self-assembling PAs are attractive and versatile biomolecules that can be customized for specific applications in regenerative medicine. In particular, a heparin-binding peptide amphiphile (HBPA) containing a specific heparin-binding peptide sequence was used here to induce angiogenesis and serve as a delivery vehicle for growth factors and small hydrophobic molecules. Throughout this dissertation, the HBPA/heparin system is used in different architectures for a variety of regenerative medicine applications. In one aspect of this work, hybrid scaffolds made from HBPA/heparin gelled on a poly(L-lactic acid) (PLLA) fiber mesh were used to promote angiogenesis to facilitate pancreatic islet transplantation for the treatment of type 1 diabetes. Delivery of growth factors with HBPA/PLLA scafflolds increased vessel density in vivo and correlated with improved transplant outcomes in a streptozotocin-induced diabetic mouse model. Soluble HBPA nanofiber architectures were also useful for islet transplantation applications. These nanofibers were used at concentrations below gelation to deliver growth factors into the dense islet cell aggregate, promoting cell survival and angiogenesis in vitro. The nanostructures infiltrated the islets and promoted the retention of heparin and growth factors within the islet. Another interesting growth factor release system discussed here is the HBPA membrane structure. HBPA was found to self-assemble with hyaluronic acid, a large biopolymer found in the body, into macroscopic, hierarchically-ordered membranes. Heparin was incorporated into these membranes and affected the membrane's mechanical properties and growth factor release. Human mesenchymal stem cells were also shown to attach and maintain viability on these membranes. Finally, HBPA nanofibers were used to control the release of small hydrophobic molecules. HBPA nanofiber gels released nitric oxide (NO) to inhibit neointimal hyperplasia, a major cause for vascular graft or stent failure. HBPA/heparin gels were shown to prolong the release of NO generated from NO donors, significantly reducing neointimal hyperplasia in injured carotid arteries in vivo.

Attachment of nanoparticulate drug-release systems on poly(ε-caprolactone) nanofibers via a graftpolymer as interlayer.

PubMed

de Cassan, Dominik; Sydow, Steffen; Schmidt, Nadeschda; Behrens, Peter; Roger, Yvonne; Hoffmann, Andrea; Hoheisel, Anna Lena; Glasmacher, Birgit; Hänsch, Robert; Menzel, Henning

2018-03-01

Electrospun poly(ε-caprolactone) (PCL) fiber mats are modified using a chitosan grafted with PCL (CS-g-PCL), to improve the biological performance and to enable further modifications. The graft copolymer is immobilized by the crystallization of the PCL grafts on the PCL fiber surface as binding mechanism. In this way, the surface of the fibers is covered with chitosan bearing cationic amino groups, which allow adsorption of oppositely charged nanoparticulate drug-delivery systems. The modification of the fiber mats and the attachment of the drug delivery systems are easy and scalable dip processes. The process is also versatile; it is possible to attach different polymeric and inorganic nanoparticulate drug-release systems of cationic or anionic nature. The modifications are verified using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). As proof of principle, the release of ciprofloxacin from silica nanoparticles attached to the modified fiber mats is shown; however, the method is also suited for other biologically active substances including growth factors. The initial cellular attachment and proliferation as well as vitality of the cells is improved by the modification with CS-g-PCL and is further influenced by the type of the drug delivery system attached. Hence, this method can be used to transfer PCL fiber mats into bioactive implants for in-situ tissue engineering applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Insulin Patch Pumps: Their Development and Future in Closed-Loop Systems

PubMed Central

Bohannon, Nancy J.V.

2010-01-01

Abstract Steady progress is being made toward the development of a so-called “artificial pancreas,” which may ultimately be a fully automated, closed-loop, glucose control system comprising a continuous glucose monitor, an insulin pump, and a controller. The controller will use individualized algorithms to direct delivery of insulin without user input. A major factor propelling artificial pancreas development is the substantial incidence of—and attendant patient, parental, and physician concerns about—hypoglycemia and extreme hyperglycemia associated with current means of insulin delivery for type 1 diabetes mellitus (T1DM). A successful fully automated artificial pancreas would likely reduce the frequency of and anxiety about hypoglycemia and marked hyperglycemia. Patch-pump systems (“patch pumps”) are likely to be used increasingly in the control of T1DM and may be incorporated into the artificial pancreas systems of tomorrow. Patch pumps are free of tubing, small, lightweight, and unobtrusive. This article describes features of patch pumps that have been approved for U.S. marketing or are under development. Included in the review is an introduction to control algorithms driving insulin delivery, particularly the two major types: proportional integrative derivative and model predictive control. The use of advanced algorithms in the clinical development of closed-loop systems is reviewed along with projected next steps in artificial pancreas development. PMID:20515308

School-based vaccination programmes: a systematic review of the evidence on organisation and delivery in high income countries.

PubMed

Perman, Sarah; Turner, Simon; Ramsay, Angus I G; Baim-Lance, Abigail; Utley, Martin; Fulop, Naomi J

2017-03-14

Many countries have recently expanded their childhood immunisation programmes. Schools are an increasingly attractive setting for delivery of these new immunisations because of their ability to reach large numbers of children in a short period of time. However, there are organisational challenges to delivery of large-scale vaccination programmes in schools. Understanding the facilitators and barriers is important for improving the delivery of future school-based vaccination programmes. We undertook a systematic review of evidence on school-based vaccination programmes in order to understand the influence of organisational factors on the delivery of programmes. Our eligibility criteria were studies that (1) focused on childhood or adolescent vaccination programmes delivered in schools; (2) considered organisational factors that influenced the preparation or delivery of programmes; (3) were conducted in a developed or high-income country; and (4) had been peer reviewed. We searched for articles published in English between 2000 and 2015 using MEDLINE and HMIC electronic databases. Additional studies were identified by searching the Cochrane Library and bibliographies. We extracted data from the studies, assessed quality and the risk of bias, and categorised findings using a thematic framework of eight organisational factors. We found that most of the recent published literature is from the United States and is concerned with the delivery of pandemic or seasonal flu vaccination programmes at a regional (state) or local level. We found that the literature is largely descriptive and not informed by the use of theory. Despite this, we identified common factors that influence the implementation of programmes. These factors included programme leadership and governance, organisational models and institutional relationships, workforce capacity and roles particularly concerning the school nurse, communication with parents and students, including methods for obtaining consent, and clinic organisation and delivery. This is the first time that information has been brought together on the organisational factors influencing the delivery of vaccination programmes in school-based settings. An understanding of these factors, underpinned by robust theory-informed research, may help policy-makers and managers design and deliver better programmes. We identified several gaps in the research literature to propose a future research agenda, informed by theories of implementation and organisational change.

Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles

NASA Astrophysics Data System (ADS)

Colby, Aaron H.; Liu, Rong; Schulz, Morgan D.; Padera, Robert F.; Colson, Yolonda L.; Grinstaff, Mark W.

2016-01-01

Drug dose, high local target tissue concentration, and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian, and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed, and paclitaxel) with limited results. Here, we show that a “two-step” nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the separate administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional “drug-alone” administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.

The Effect of Different Delivery Conditions on the Accelerated Degradation of Structural Steel in the Coal Mine Environment / Wpływ Różnego Stanu Dostawy Na Przyspieszoną Degradację Stali Konstrukcyjnej W Środowisku Kopalnianym

NASA Astrophysics Data System (ADS)

Pawłowski, Bogdan; Bała, Piotr

2012-12-01

The main objective of this work was to determine the effect of different delivery conditions on the accelerated degradation of structural steels used for lifting beams (rails) of the monorail transport systems. Some of these rails, made of the same steel grade as others, undergoes accelerated corrosion in the coal mine environment. Corrosion degradation occurs much faster (more than two times faster), comparing to the same steel grade rails operated under the same conditions but with different microstructures. However, all the provided rails meet the requirements of appropriate standards for steel on the lifting beams of the monorail transport systems. The investigations were carried out on rails made of the same steel grade but with different microstructures and showed that the main factor influencing the accelerated corrosion degradation of tested steels is the delivery condition, so-called "as rolled" condition. The greatest resistance to the accelerated corrosion showed rails in the normalized or normalizing rolling condition.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Novel ex vivo protocol using porcine vagina to assess drug permeation from mucoadhesive and colloidal pharmaceutical systems.

PubMed

Pereira, Maíra N; Reis, Thaiene A; Matos, Breno N; Cunha-Filho, Marcílio; Gratieri, Taís; Gelfuso, Guilherme M

2017-10-01

Local treatment of vaginal diseases presents advantages over systemic treatments and the interaction of the drug delivery systems with the biological tissue is a key factor for a successful vaginal topical therapy. Conventional protocols for permeation studies have high variability and fail in distinguishing drug penetration from mucoadhesive or colloidal drug delivery systems from conventional formulations, as tissue interaction is normally under estimated. The protocol presented in this paper is a simplified ex vivo vertical model, in which formulations are placed in hung porcine vaginas with the objective of mimicking a condition closer to the biological circumstance, specifically considering the possible leak from the vaginal canal in the vertical position. The results indicate the proposed method was capable of differentiating formulations performances and histological evaluation showed mucosa structures are preserved during this new assay. Therefore, the ex vivo method can be considered reliable for approaching the physiological situation in comparative studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Is measurement of cervical length an accurate predictive tool in women with a history of preterm delivery who present with threatened preterm labor?

PubMed

Melamed, N; Hiersch, L; Meizner, I; Bardin, R; Wiznitzer, A; Yogev, Y

2014-12-01

To determine whether sonographically measured cervical length is an effective predictive tool in women with threatened preterm labor and a history of past spontaneous preterm delivery. This was a retrospective cohort study of all women with singleton pregnancies who presented with preterm labor at less than 34 + 0 weeks' gestation and underwent sonographic measurement of cervical length in a tertiary medical center between 2007 and 2012. The accuracy of cervical length in predicting preterm delivery was compared between women with and those without a history of spontaneous preterm delivery. Women with risk factors for preterm delivery other than a history of preterm delivery were excluded from both groups. Overall, 1023 women who presented with preterm labor met the study criteria, of whom 136 (13.3%) had a history of preterm delivery (past-PTD group) and 887 (86.7%) had no risk factors for preterm delivery (low-risk group). The rate of preterm delivery was significantly higher for women with a history of preterm delivery (36.8% vs 22.5%; P < 0.001). Cervical length was significantly correlated with the examination-to-delivery interval in low-risk women (r = 0.32, P < 0.001) but not in women who had had a previous preterm delivery (r = 0.07, P = 0.4). On multivariable analysis, cervical length was independently associated with the risk of preterm delivery for women in the low-risk group but not for women with a history of previous preterm delivery. For women with previous preterm delivery who presented with threatened preterm labor, cervical length failed to distinguish between those who did and those who did not deliver prematurely (area under the receiver-operating characteristics curve range, 0.475-0.506). When using standardized thresholds, the sensitivity and specificity of cervical length for the prediction of preterm delivery were significantly lower in women with previous preterm delivery than in women with no risk factors for preterm delivery. Cervical length appears to be of limited value in the prediction of preterm delivery among women with threatened preterm labor who are at high risk for preterm delivery owing to a history of spontaneous preterm delivery in a previous pregnancy. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hasan, Tayyaba

2016-03-01

This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

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.

Quality correction factors of composite IMRT beam deliveries: theoretical considerations.

PubMed

Bouchard, Hugo

2012-11-01

In the scope of intensity modulated radiation therapy (IMRT) dosimetry using ionization chambers, quality correction factors of plan-class-specific reference (PCSR) fields are theoretically investigated. The symmetry of the problem is studied to provide recommendable criteria for composite beam deliveries where correction factors are minimal and also to establish a theoretical limit for PCSR delivery k(Q) factors. The concept of virtual symmetric collapsed (VSC) beam, being associated to a given modulated composite delivery, is defined in the scope of this investigation. Under symmetrical measurement conditions, any composite delivery has the property of having a k(Q) factor identical to its associated VSC beam. Using this concept of VSC, a fundamental property of IMRT k(Q) factors is demonstrated in the form of a theorem. The sensitivity to the conditions required by the theorem is thoroughly examined. The theorem states that if a composite modulated beam delivery produces a uniform dose distribution in a volume V(cyl) which is symmetric with the cylindrical delivery and all beams fulfills two conditions in V(cyl): (1) the dose modulation function is unchanged along the beam axis, and (2) the dose gradient in the beam direction is constant for a given lateral position; then its associated VSC beam produces no lateral dose gradient in V(cyl), no matter what beam modulation or gantry angles are being used. The examination of the conditions required by the theorem lead to the following results. The effect of the depth-dose gradient not being perfectly constant with depth on the VSC beam lateral dose gradient is found negligible. The effect of the dose modulation function being degraded with depth on the VSC beam lateral dose gradient is found to be only related to scatter and beam hardening, as the theorem holds also for diverging beams. The use of the symmetry of the problem in the present paper leads to a valuable theorem showing that k(Q) factors of composite IMRT beam deliveries are close to unity under specific conditions. The theoretical limit k(Q(pcsr),Q(msr) ) (f(pcsr),f(msr) )=1 is determined based on the property of PCSR deliveries to provide a uniform dose in the target volume. The present approach explains recent experimental observations and proposes ideal conditions for IMRT reference dosimetry. The result of this study could potentially serve as a theoretical basis for reference dosimetry of composite IMRT beam deliveries or for routine IMRT quality assurance.

A Survey on the Preference of Sustained Glaucoma Drug Delivery Systems by Singaporean Chinese Patients: A Comparison Between Subconjunctival, Intracameral, and Punctal Plug Routes.

PubMed

Chan, Hiok Hong; Wong, Tina T; Lamoureux, Ecosse; Perera, Shamira

2015-09-01

To investigate the acceptance and preferences rates of 3 sustained drug delivery systems in glaucoma patients. A cross-sectional study involving 250 Chinese patients recruited from outpatient glaucoma clinics in Singapore using an interviewer-administered survey. Beliefs toward medicines, eye drops, illness perception, medication adherence, and health literacy were assessed using validated questionnaires. After receiving standard information on the 3 sustained drug delivery systems, that is, subconjunctival, intracameral, and punctal routes; each route's acceptance and attitudes were determined. The subconjunctival (acceptance: 61.6%, n=154), intracameral (acceptance: 57.2%, n=143), and punctal (acceptance: 63.2%, n=158) routes were willing to be accepted by the majority of the interviewed patients. Among those, 78.6%, 79.1%, and 78.5% were willing to pay an equal or higher cost compared with their current eye drops for the subconjunctival, intracameral, and punctal plug routes, respectively. Independent factors associated with the acceptance for subconjunctival, intracameral, and punctal plug routes included: male sex (P=0.007, 0.014, 0.046, respectively), patients not on health care subsidies (P=0.022, 0.002, 0.016, respectively), and bilateral glaucoma disease (P=0.003, 0.013, 0.004, respectively). A total of 120 (48.0%) patients ranked punctal plug placement as the preferred route for sustained drug delivery followed by subconjunctival (n=76, 30.4%) and intracameral (n=54, 21.6%) routes. Sustained drug delivery for the medical treatment of glaucoma is an acceptable alternative to daily eye drop administration by most Singaporean Chinese individuals in this study. Male patients, nonsubsidized patients, and those with bilateral glaucoma were independently associated with preference of these 3 alternative routes of administration to traditional glaucoma drops.

Intracavitary Therapeutics for Pleural Malignancies.

PubMed

Murthy, Vivek; Mangalick, Keshav; Sterman, Daniel H

2018-03-01

Pleural malignancies remain a serious therapeutic challenge, and are frequently refractory to standard treatment; however, they have the advantage of occurring in an enclosed cavity readily accessible for examination, biopsy, and serial sampling. Novel therapeutics can be administered via intracavitary delivery to maximize efficacy by targeting the site of involvement and potentially mitigating the adverse effects of systemic therapies. The easy accessibility of the pleural space lends itself well to repeated sampling and analysis to determine efficacy and toxicity of a given treatment paradigm. These factors support the rationale for delivery of novel therapeutics directly into the pleural space. Copyright © 2017 Elsevier Inc. All rights reserved.

ENTRY IN THE ADHD DRUGS MARKET: WELFARE IMPACT OF GENERICS AND ME-TOO'S*

PubMed Central

Bokhari, Farasat A S; Fournier, Gary M

2013-01-01

Recent decades have seen a growth in treatments for attention deficit hyperactivity disorder (ADHD) including many branded and generic drugs. In the early 2000's, new drug entry dramatically altered market shares. We estimate a demand system for ADHD drugs and assess the welfare impact of new drugs. We find that entry induced large welfare gains by reducing prices of substitute drugs, and by providing alternative delivery mechanisms for existing molecules. Our results suggest that the success of follow-on patented drugs may come from unanticipated innovations like delivery mechanisms, a factor ignored by proposals to retard new follow-on drug approvals. PMID:25821242

Tissue engineering skeletal muscle for orthopaedic applications

NASA Technical Reports Server (NTRS)

Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

2002-01-01

With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

Factors Associated with Teacher Delivery of a Classroom-Based Tier 2 Prevention Program

ERIC Educational Resources Information Center

Sutherland, Kevin S; Conroy, Maureen A; McLeod, Bryce D; Algina, James; Kunemund, Rachel L

2018-01-01

Teachers sometimes struggle to deliver evidence based programs designed to prevent and ameliorate chronic problem behaviors of young children with integrity. Identifying factors associated with variations in the quantity and quality of delivery is thus an important goal for the field. This study investigated factors associated with teacher…

Online, Instructional Television and Traditional Delivery: Student Characteristics and Success Factors in Business Statistics

ERIC Educational Resources Information Center

Dotterweich, Douglas P.; Rochelle, Carolyn F.

2012-01-01

Distance education has surged in recent years while research on student characteristics and factors leading to successful outcomes has not kept pace. This study examined characteristics of regional university students in undergraduate Business Statistics and factors linked to their success based on three modes of delivery - Online, Instructional…

Is prenatal urethral descent a risk factor for urinary incontinence during pregnancy and the postpartum period?

PubMed

Pizzoferrato, Anne-Cécile; Fauconnier, Arnaud; Bader, Georges; de Tayrac, Renaud; Fort, Julie; Fritel, Xavier

2016-07-01

Obstetric trauma during childbirth is considered a major risk factor for postpartum urinary incontinence (UI), particularly stress urinary incontinence. Our aim was to investigate the relation between postpartum UI, mode of delivery, and urethral descent, and to define a group of women who are particularly at risk of postnatal UI. A total of 186 women were included their first pregnancy. Validated questionnaires about urinary symptoms during pregnancy, 2 and 12 months after delivery, were administered. Urethral descent was assessed clinically and by ultrasound at inclusion. Multivariate logistic regression analysis was used to determine the risk factors for UI during pregnancy, at 2 months and 1 year after first delivery. The prevalence of UI was 38.6, 46.5, 35.6, and 34.4 % at inclusion, late pregnancy, 2 months postpartum, and 1 year postpartum respectively. No significant association was found between UI at late pregnancy and urethral descent assessed clinically or by ultrasound. The only risk factor for UI at 2 months postpartum was UI at inclusion (OR 6.27 [95 % CI 2.70-14.6]). The risk factors for UI at 1 year postpartum were UI at inclusion (6.14 [2.22-16.9]), body mass index (BMI), and urethral descent at inclusion, assessed clinically (7.21 [2.20-23.7]) or by ultrasound. The mode of delivery was not associated with urethral descent. Prenatal urethral descent and UI during pregnancy are risk factors for UI at 1 year postpartum. These results indicate that postnatal UI is more strongly influenced by susceptibility factors existing before first delivery than by the mode of delivery.

Maternal and neonatal factors associated with mode of delivery under a universal newborn hearing screening programme in Lagos, Nigeria

PubMed Central

Olusanya, Bolajoko O; Solanke, Olumuyiwa A

2009-01-01

Background Emerging evidence from a recent pilot universal newborn hearing screening (UNHS) programme suggests that the burden of obstetric complications associated with mode of delivery is not limited to maternal and perinatal mortality but may also include outcomes that undermine optimal early childhood development of the surviving newborns. However, the potential pathways for this association have not been reported particularly in the context of a resource-poor setting. This study therefore set out to establish the pattern of delivery and the associated neonatal outcomes under a UNHS programme. Methods A cross-sectional study in which all consenting mothers who delivered in an inner-city tertiary maternity hospital in Lagos, Nigeria from May 2005 to December 2007 were enrolled during the UNHS programme. Socio-demographic, obstetric and neonatal factors independently associated with vaginal, elective and emergency caesarean deliveries were determined using multinomial logistic regression analyses. Results Of the 4615 mothers enrolled, 2584 (56.0%) deliveries were vaginal, 1590 (34.4%) emergency caesarean and 441 (9.6%) elective caesarean section. Maternal age, parity, social class and all obstetric factors including lack of antenatal care, maternal HIV and multiple gestations were associated with increased risk of emergency caesarean delivery compared with vaginal delivery. Only parity, lack of antenatal care and prolonged/obstructed labour were associated with increased risk of emergency compared with elective caesarean delivery. Infants delivered by vaginal method or by emergency caesarean section were more likely to be associated with the risk of sensorineural hearing loss but less likely to be associated with hyperbilirubinaemia compared with infants delivered by elective caesarean section. Emergency caesarean delivery was also associated with male gender, low five-minute Apgar scores and admission into special care baby unit compared with vaginal or elective caesarean delivery. Conclusions The vast majority of caesarean delivery in this population occur as emergencies and are associated with socio-demographic factors as well as several obstetric complications. Mode of delivery is also associated with the risk of sensorineural hearing loss and other adverse birth outcomes that lie on the causal pathways for potential developmental deficits. PMID:19732443

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.

Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application

PubMed Central

Wu, Chengtie; Chang, Jiang

2012-01-01

The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition–structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. PMID:23741607

Effect of Vaccine Administration Modality on Immunogenicity and Efficacy

PubMed Central

Zhang, Lu; Wang, Wei; Wang, Shixia

2016-01-01

Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239