Potassium-Incorporated Titanium Oxide Nanoparticles Modulate Human Dendritic Cell Immune Response to Mycobacterium leprae

The two polar clinical forms of leprosy, termed tuberculoid and lepromatous, have polarized cellular immune responses with complex immunological distinctions. The predominance of DCs in tuberculoid leprosy has been reported, while the lepromatous pattern of illness is associated with weak activation of local populations of DCs. TiO2 nanoparticles have previously been shown to induce maturation of these cells, leading to an inflammatory response similar to adjuvant usage in vaccine administration. We aimed to evaluate the effect of potassium-incorporated Ti oxide nanostructures, namely KTiOxs, in the response of human monocyte-derived DCs to live M. leprae. Human monocytic cell line dual THP-1, which harbors two inducible reporter plasmid systems for transcription factor activation of NF-κB and interferon regulating factor (IRF), was treated with titanium control or with 1 mol/L KOH-treated Ti or 10 mol/L KOH for 24 h. Subsequently, cells were infected with M. leprae. KTiOx nanoparticles increase DC phagocytic activity without inflammation. KTiOx exposure of DCs led to an increase in IRF activation with modulation of the inflammatory response to live M. leprae. It also led to differential secretion of the critical components of innate immune response and the development of cell-mediated immunity against intracellular pathogens. This study demonstrates the effect of nanostructures of KTiOxs and the usefulness of nanoparticle technology in the in vitro activation of human DCs against an infectious disease with a puzzling immune spectrum. Our findings may prompt future therapeutic strategies, such as DC immunotherapy for disseminated and progressive lepromatous lesion

Experiential Learning Through Participatory Action Research in an Interdisciplinary Leadership Training Program

Background: Experience in multidisciplinary collaboration among healthcare providers, leaders in public health, and educators is essential to effectively address the diverse needs of children with intellectual and developmental disabilities (I/DD) and their families. Purpose: We describe three participatory action research (PAR) projects from an interdisciplinary training program, which used experiential learning to enhance leadership competencies and promote inclusive services. Trainees report their leadership growth as providers and advocates for children with I/DD using experiential learning through PAR. Approach: Trainees discuss their engagement with organizations serving children with I/DD and ways that experiential learning supported leadership skill development, commitment to inclusive person- and family-centered practices, and contributions to disability advocacy and support programs. Conclusion: PAR is a beneficial experiential learning approach to foster interdisciplinary collaboration through inclusive community engagement. Related training programs may adopt a similar approach to build leadership skills among professionals in health care, public health, and education, and promote optimal health outcomes for children with I/DD

Numerical determination of frequency behavior in cloaking structures based on L-C distributed networks with TLM method

This paper was published in Optic Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/OE.16.009344.The increasing interest in metamaterials with negative refractive index has been prompted by a variety of promising optical and microwave applications. Often, the resulting electromagnetic problems to be solve are not analytically derivable; therefore, numerical modeling must be employed and the Transmission Line Modeling (TLM) method constitutes a possible choice. After having greatly simplified the existing TLM techniques for the modeling of metamaterials, we propose in this paper to carry out a frequency study of cloaking structure.This work has been supported in part by the “Ministerio de Educación y Ciencia” of Spain under research projects No. FIS2004-03273 and FIS2007-63293, cofinanced with FEDER funds of the European Union

Adipose Tissue Therapeutics for Scar Rehabilitation after Thermal Injury

Background: Burn injuries are common and in the long term can lead to hypertrophic or keloid scars, pain and pruritus, limited mobility across joints, and disfigurement. Numerous reports suggest adipose derived tissues, including adipose derived stem cells (ADSCs) and processed lipoaspirate, can improve acutely healing wounds from a variety of etiologies including excisional, thermal, and radiation injuries by both secretion of growth factors and direct differentiation. There are many options for scar treatment, including laser therapy, silicone sheets, steroid injection, and even skin grafting however these techniques either lack optimal efficacy or involve significant cost and morbidity. Clinical case series suggest a beneficial effect of adipose tissues in improving scarred tissues, however this phenomenon has not been extensively studied in animal models especially in a thermal scar model. Objectives: (1) Determine if adipose tissue can accelerate and improve scar remodeling subacutely after acute wound healing has occurred. (2) Determine if the effect is related to adipose derived stem cells or other components of lipoaspirate. Methods: 50 CD1 nu/nu athymic mice received a standardized 70°C 10 second burn with a brass rod to the dorsal skin. Digital photographs and hyperspectral images were taken immediately following injury and serially over the study’s entirety. Burned skin reliably progressed through normal stages of wound healing to a scarred and granulating state. At six weeks post-burn animals received subcutaneous injection immediately beneath the scar with fresh human lipoaspirate (n=10), high dose hADSCs in matrigel (n=10), low dose hADSCs in matrigel (n=10), matrigel control (n=10), or were not injected (n=10). At 4 weeks post-injection (10 weeks post-burn) animals were sacrificed and tissue samples were harvested for histological molecular analysis. Results: Oxygenation and perfusion profiles from hyperspectral imaging and scar wound area correlated between groups suggesting methodological consistency of burns prior to any intervention. Oxygenated hemoglobin at 10 weeks in scars treated with lipoaspirate increased significantly more compared to 6-week pre-treatment baseline than all other groups (1.57x vs. 0.85x, p Conclusion: A consistent model of burn injury and scar maturation is described. Preliminary HSI and scar area data suggest scar improvement in lipoaspirate treated scars compared to ADSCs and controls

Lipoaspirate and Adipose Stem Cells as Potential Therapeutics for Chronic Scars

Introduction: Burn injuries can lead to hypertrophic or keloid scars, causing pain and long lasting mobility issues. Current therapies are often unsatisfactory, costly, or morbid. Prior studies suggest adipose derived stem cells (ADSCs) and lipoaspirate can improve scar outcomes of acute thermal wounds. Clinical reports suggest lipoaspirate and ADSCs can improve chronic burn scar remodeling. However, this has not been extensively studied in animal models. We sought to determine if adipose tissue can improve chronic scar remodeling and to compare the effects of ADSCs and processed lipoaspirate. Methods: 50 CD1 nu/nu athymic mice received a standardized deep partial-thickness thermal burn. Scars matured for 6 weeks. Photographs and perfusion measurements by hyperspectral imaging (HSI) were taken over the entire study. Lipoaspirate and ADSCs (SVF and ex-vivo culture with flow cytometry confirmation) were obtained from a discarded human pannus specimen. After 6 weeks, animals received a 0.6cc subcutaneous graft beneath the scar of either: human lipoaspirate processed with the Coleman technique, high-dose (106) hADSCs in Matrigel, low-dose (104) hADSCs in Matrigel, Matrigel only, or not injected (n=10 per group). At 10 weeks, animals were sacrificed and scar tissue was harvested for histological and molecular analysis. Results: HSI oxygenated hemoglobin values in lipoaspirate treated scars increased significantly more compared to 6-week pre-treatment baseline than all other groups (p \u3c 0.05). Planimetry analysis showed reduction in wound area in lipoaspirate treated mice compared to control groups (p \u3c 0.01). Blood vessel density quantification on Masson’s trichrome stains suggests increased density in lipoaspirate treated scars versus controls (p \u3c 0.01). Conclusion: HSI, blood vessel density, and scar analysis suggest improvement in lipoaspirate treated scars compared to controls. Preliminary molecular data offers some insight to this trend. No effect was seen with ADSCs at either concentration at the analyzed timepoints. Molecular analyses are ongoing to investigate cellular mechanisms in regulating scar remodeling

Generation of Functional Human Adipose Tissue in Mice from Primed Progenitor Cells

Adipose tissue (AT) is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes cell death, leading to inflammation, calcification, and requirement for further revision surgery. Previously, we have found that mesenchymal progenitor cells within human AT can proliferate in three-dimensional culture under proangiogenic conditions. These cells (primed ADipose progenitor cells, PADS) robustly differentiate into adipocytes in vitro (ad-PADS). The goal of this study is to determine whether ad-PADS can form structured AT in vivo, with potential for use in surgical applications. Grafts formed from ad-PADS were compared to grafts formed from AT obtained by liposuction after implantation into nude mice. Graft volume was measured by microcomputed tomography scanning, and the functionality of cells within the graft was assessed by quantifying circulating human adiponectin. The degree of graft vascularization by donor or host vessels and the content of human or mouse adipocytes within the graft were measured using species-specific endothelial and adipocyte-specific quantitative real time polymerase chain reaction probes, and histochemistry with mouse and human-specific lectins. Our results show that ad-PADS grafted subcutaneously into nude mice induce robust vascularization from the host, continue to increase in volume over time, express the human adipocyte marker PLIN1 at levels comparable to human AT, and secrete increasing amounts of human adiponectin into the mouse circulation. In contrast, grafts composed of AT fragments obtained by liposuction become less vascularized, develop regions of calcification and decreased content of PLIN1, and secrete lower amounts of adiponectin per unit volume. Enrichment of liposuction tissue with ad-PADS improves vascularization, indicating that ad-PADS may be proangiogenic. Mechanistically, ad-PADS express an extracellular matrix gene signature that includes elements previously associated with small vessel development (COL4A1). Thus, through the formation of a proangiogenic environment, ad-PADS can form functional AT with capacity for long-term survival, and can potentially be used to improve outcomes in reconstructive and regenerative medicine

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an ‘implementation gap’. At a policy level, the design of internationally salient solutions that are able to address AMR’s interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise ‘good’ antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scale

Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin with Current Modulation

Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3′ terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels

The C Allele of rs5743836 Polymorphism in the Human TLR9 Promoter Links IL-6 and TLR9 Up-Regulation and Confers Increased B-Cell Proliferation

In humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression, leading to exacerbated cellular responses to CpG, including IL-6 production and B-cell proliferation. Our study uncovers a role for the rs5743836 polymorphism in B-cell biology with implications on TLR9-mediated diseases and on the therapeutic usage of TLR9 agonists/antagonists