Multifaceted contributions : health workers and smallpox eradication in India

Smallpox eradication in South Asia was a result of the efforts of many grades of health-workers. Working from within the confines of international organisations and government structures, the role of the field officials, who were of various nationalities and also drawn from the cities and rural enclaves of the countries in these regions, was crucial to the development and deployment of policies. However, the role of these personnel is often downplayed in official histories and academic histories, which highlight instead the roles played by a handful of senior officials within the World Health Organization and the federal governments in the sub-continent. This article attempts to provide a more rounded assessment of the complex situation in the field. In this regard, an effort is made to underline the great usefulness of the operational flexibility displayed by field officers, wherein lessons learnt in the field were made an integral part of deploying local campaigns; careful engagement with the communities being targeted, as well as the employment of short term workers from amongst them, was an important feature of this work

Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension

The ability to design and construct structures with atomic level precision is one of the key goals of nanotechnology. Proteins offer an attractive target for atomic design, as they can be synthesized chemically or biologically, and can self-assemble. However the generalized protein folding and design problem is unsolved. One approach to simplifying the problem is to use a repetitive protein as a scaffold. Repeat proteins are intrinsically modular, and their folding and structures are better understood than large globular domains. Here, we have developed a new class of synthetic repeat protein, based on the pentapeptide repeat family of beta-solenoid proteins. We have constructed length variants of the basic scaffold, and computationally designed de novo loops projecting from the scaffold core. The experimentally solved 3.56 ˚A resolution crystal structure of one designed loop matches closely the designed hairpin structure, showing the computational design of a backbone extension onto a synthetic protein core without the use of backbone fragments from known structures. Two other loop designs were not clearly resolved in the crystal structures and one loop appeared to be in an incorrect conformation. We have also shown that the repeat unit can accommodate whole domain insertions by inserting a domain into one of the designed loops

Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

Wenwu Xiao1, Juntao Luo2, Teesta Jain3, John Riggs3, Harry P Tseng1, Paul T Henderson3, Simon R Cherry4, Douglas Rowland4, Kit S Lam1,31Department of Biochemistry and Molecular Medicine, UC Davis Cancer Center, University of California Davis, Sacramento, CA; 2Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY; 3Department of Internal Medicine, Division of Hematology and Oncology, 4Department of Biomedical Engineering, UC Davis Cancer Center, University of California Davis, Davis, CABackground: A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel.Methods: The telodendrimer was covalently labeled with 125I and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively.Results: The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®). Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol.Conclusion: Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications.Keywords: telodendrimer, nanomicelle, paclitaxel, microSPECT/CT, imaging guided drug deliver

A skin abscess model for teaching incision and drainage procedures

<p>Abstract</p> <p>Background</p> <p>Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.</p> <p>Methods</p> <p>We developed a realistic model of skin abscess formation to demonstrate the technique of incision and drainage for educational purposes. The creation of this model is described in detail in this report.</p> <p>Results</p> <p>This model has been successfully used to develop and disseminate a multimedia video production for teaching this medical procedure. Clinical faculty and resident physicians find this model to be a realistic method for demonstrating abscess incision and drainage.</p> <p>Conclusion</p> <p>This manuscript provides a detailed description of our model of abscess incision and drainage for medical education. Clinical educators can incorporate this model into skills labs or demonstrations for teaching this basic procedure.</p

Orbital swelling as a first symptom in breast carcinoma diagnosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>The frequency of intra-orbital metastasis in systemic cancer is a controversial topic. Of all metastatic tumors to the orbit of the eye, breast carcinoma is considered to be the most prevalent. Orbital findings typically present themselves after the diagnosis of the primary tumor, with an average delay of three to six years. In spite of that, this study reports a case in which orbital manifestation was the initial symptom in breast carcinoma diagnosis.</p> <p>Case presentation</p> <p>A 66-year-old Italian Caucasian woman presented with a swelling located on the lower orbit of her right eye.</p> <p>Conclusions</p> <p>Previous cases report orbital manifestations discovered secondary to breast cancer. This case demonstrates that orbital symptoms may be the primary presentation of the disease. Orbital metastasis originating from breast cancer predicts widespread metastatic disease in other organs. In the presence of an ambiguous infiltrative orbital process, diagnostic examination of the breast is recommended.</p

Production Trends, Collaboration, and Main Topics of the Integrative and Complementary Oncology Research Area: A Bibliometric Analysis

Background: The prevalence of cancer has increased over time worldwide. Nevertheless, the number of deaths has been reduced during the past 2 decades. Thus, one-third of the cancer patients are users of complementary and alternative therapies, looking for other types of interventions. The main aim of the present study is to understand the current status of the research in integrative and complementary oncology. Three different aspects were analyzed: production trends, country collaboration, and leading research topics. Methods: The dataset was obtained from the documents indexed under the Integrative and Complementary Medicine category of the Web of Science database from 1976 to 2017. VOSviewer and SciMAT software were employed to perform the bibliometric analysis. Results: The Journal of Ethnopharmacology, China Medical University and the People’s Republic of China are the leading producers in the field. Regarding the collaboration, the United States and China present a close connection. The scientific community is focused on the following topics: apoptosis, breast cancer, oxidative stress, chemotherapy, and nuclear factor-Kappa-B (NF-Kappa-B). Conclusions: The present article shows potentially important information that allows understanding of the past, present, and future of research in integrative and complementary oncology. It is a useful evidence-based framework on which to base future research actions and academic directions

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.Includes Wellcome, BHF, MRC, BBSRC and NIHR