2,395 research outputs found

    The Road to Normalcy

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    Originally published in 1962. In The Road to Normalcy, Wesley M. Bagby explains how the election of 1920 contributed to momentous shifts in American politics by detailing why the major political parties abandoned sentiments that were widely accepted several years prior to the election. Prior to World War I, two significant streams of progressivism maintained center stage in American politics—the Progressive movement and the world peace movement. The war proved not to be prohibitively distracting for the Progressive movement, which carried on well into the war years. But the war also introduced new elements into American political life, such as the restriction of free speech, popular outbursts of intolerance and hatred encouraged by war propaganda, and a belief in the necessity and efficacy of violence. Many of these elements eroded the ideals undergirding the Progressive movement. The international peace movement reflected the spirit of idealistic internationalism that characterized the tenor of American foreign policy from the beginning to the end of the war. However, the election of 1920, the first presidential election after World War I, addressed the question of whether America would resume its progressive efforts at home and abroad following the war. The election ultimately stymied both political currents, proving to be an end for both the Progressive movement and the world peace movement

    Structural analysis of Salmonella enterica effector protein SopD

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    Salmonella outer protein D (SopD) is a type III secreted virulence effector protein from Salmonella enterica. Full-length SopD and SopD lacking 16 amino acids at the N-terminus (SopDDeltaN) have been expressed as fusions with GST in Escherichia coli, purified with a typical yield of 20-30 mg per litre of cell culture and crystallized. Biophysical characterization has been carried out mainly on SopDDeltaN. Analytical size exclusion chromatography shows that SopDDeltaN is monomeric and probably globular in aqueous solution. The secondary structure composition, calculated from the CD spectrum, is mixed (38% alpha-helix and 26% beta-strand). Sequence analysis indicates that SopD contains a coiled coil motif, as found in numerous other type III secretion system-associated proteins. This suggests that SopD has the potential for one or more heterotypic protein-protein interactions. Limited trypsin digestion of SopDDeltaN, monitored by both one-dimensional proton NMR spectroscopy and SDS-PAGE, shows that the protein has a large, protease-resistant core domain of 286 amino acid residues. This single-domain architecture suggests that SopD lacks a cognate chaperone. In crystallization trials, SopDDeltaN produced better crystals than either full-length SopD or trypsin-digested SopDDeltaN. Diffraction to 3.0 Angstrom resolution has so far been obtained from crystals of SopDDeltaN

    Fee-for-Placement in Level II Fieldwork: Prevalence and Context

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    Occupational therapy (OT) education has utilized fieldwork experiences to develop professional identity and clinical competency of entry-level OT practitioners since 1923. Level II OT fieldwork is viewed as a necessary and valuable experience by students, clinicians, and academicians. Despite the significant role fieldwork has in the formation of the future workforce, some educational programs report a shortage of OT fieldwork placement sites and the emergence of fee-for-placement fieldwork sites. The purpose of this study was to examine the prevalence and context of fee-for-placement for Level II OT fieldwork in the United States. Investigators surveyed master’s and doctoral level OT programs to examine their experience with requests for fee-for-placement fieldwork sites. The response rate was 32% (58 of 128 programs). Approximately two-thirds (67%, n=38) of respondents reported a decrease in number of Level II placement reservations. Eighty-two percent of programs reported encountering sites who requested fee-for-placement and almost half (43%, n=25) anticipated this trend to increase in the future. The majority of programs (89%, n=52) indicated they avoid placing students at fieldwork sites who charge for placement. The observed trend in fee-for-placement fieldwork may affect OT education by yielding significant implications related to finances, selection and placement processes, and compliance with professional values and ethics for programs and students. The concerns raised by the respondents may warrant a profession-wide consensus and direction toward addressing fieldwork shortages and fee-for-placements

    Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies

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    This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Delivery on 2009-08, available online: http://www.tandfonline.com/10.1517/17425240903085128.Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs specifically to the tumor cells without damaging healthy organs or tissues. Over the past several decades, efforts have been made to improve drug delivery technologies that target anticancer drugs specifically to tumor cells. It has been known for over four decades that the lymphatics are the first site of metastasis for most solid cancers; however, few efforts have been made to localize chemotherapies to lymphatic tissues. Trials of several systemic targeted drug delivery systems based on nanoparticles containing chemotherapeutic agents (e.g., liposomal doxorubicin) have shown similar antitumor activity but better patient tolerance compared with conventional formulations. Animal studies have demonstrated that nanoparticles made of natural or synthetic polymers and liposomal carriers have higher accumulation in the lymph nodes and surrounding lymphatics compared to conventional intravenous therapies. This combination has the potential to both reduce nonspecific organ toxicities and increase the chemotherapeutic dose to the most likely sites of locoregional cancer metastasis

    Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent

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    New lymphatic imaging technologies are needed to better assess immune function and cancer progression and treatment. Lymphatic uptake depends mainly on particle size (10–100 nm) and charge. The size of carriers for imaging and drug delivery can be optimized to maximize lymphatic uptake, localize chemotherapy to lymphatic metastases, and enable visualization of treatment deposition. Toward this end, female BALB/c mice were injected subcutaneously in the hind footpad or forearm with a series of six different molecular weight hyaluronan (HA) near-infrared dye (HA-IR820) conjugates (ca. 5–200 nm). Mice were imaged using whole body fluorescent imaging over two weeks. HA-IR820 fluorescence was clearly visualized in the draining lymphatic capillaries, and in the popliteal and iliac or axillary lymph nodes. The 74-kDa HA-IR820 had the largest lymph node area-under-the-curve. In contrast to prior reports, mice bearing limb tumors exhibited three-fold longer retention of 74-kDa HA-IR820 in the popliteal node compared to mice without tumors. HA conjugate kinetics and disposition can be specifically tailored by altering their molecular weight. The specific lymphatic uptake and increased nodal retention of HA conjugates indicate significant potential for development as a natural biopolymer for intralymphatic drug delivery and imaging

    Alexithymia, emotion processing and social anxiety in adults with ADHD

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    <p>Abstract</p> <p>Objective</p> <p>Given sparse research on the issue, this study sought to shed light upon the interactions of alexithymia, emotion processing, and social anxiety in adults with attention-deficit hyperactivity disorder (ADHD).</p> <p>Subjects and methods</p> <p>73 German adults with ADHD according to DSM-IV diagnostic criteria participated. We used the Toronto Alexithymia Scale (TAS-20) to assess alexithymia, the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) to assess different features of social anxiety, and we applied the German 'Experience of Emotions Scale' (SEE) to measure emotion processing.</p> <p>Results</p> <p>40% of the sample were found to meet the DSM-IV criteria of social anxiety disorder, and about 22% were highly alexithymic according to a TAS-20 total score ≥ 61; however, the mean TAS-20 total score of 50.94 ± 9.3 was not much higher than in community samples. Alexithymic traits emerged to be closely linked to emotion processing problems, particularly 'difficulty accepting own emotions', and to social anxiety features.</p> <p>Discussion/conclusion</p> <p>Our findings suggest interactions of alexithymia, emotion processing dysfunction, and social anxiety in adults with ADHD, which may entail the therapeutic implication to thoroughly instruct these patients to identify, accept, communicate, and regulate their emotions to aid reducing interaction anxiety.</p

    Lymphatic trafficking kinetics and near-infrared imaging using star polymer architectures with controlled anionic character

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    Targeted lymphatic delivery of nanoparticles for drug delivery and imaging is primarily dependent on size and charge. Prior studies have observed increased lymphatic uptake and retentions of over 48 hrs for negatively charged particles compared to neutral and positively charged particles. We have developed new polymeric materials that extend retention over a more pharmaceutically relevant 7-day period. We used whole body fluorescence imaging to observe in mice the lymphatic trafficking of a series of anionic star poly-(6-O-methacryloyl-D-galactose) polymer-NIR dye (IR820) conjugates. The anionic charge of polymers was increased by modifying galactose moieties in the star polymers with succinic anhydride. Increasing anionic nature was associated with enhanced lymphatic uptake up to a zeta potential of ca. -40 mV; further negative charge did not affect lymphatic uptake. Compared to the 20% acid-conjugate, the 40 to 90% acid-star-polymer conjugates exhibited a 2.5- to 3.5-fold increase in lymphatic uptake in both the popliteal and iliac nodes. The polymer conjugates exhibited node half-lives of 2 to 20 hrs in the popliteal nodes and 19 to 114 hrs in the deeper iliac nodes. These polymer conjugates can deliver drugs or imaging agents with rapid lymphatic uptake and prolonged deep-nodal retention; thus they may provide a useful vehicle for sustained intralymphatic drug delivery with low toxicity
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