100,395 research outputs found
Intramedullary headless compression screw fixation of the middle phalanx: tips, tricks, and pitfalls
No full textThis report emphasizes careful consideration of surgical technique for intramedullary screw fixation in middle phalanx fractures. Highlighting pitfalls, particularly with K -wire placement, it suggests the antegrade trans-articular approach as superior, urging further research for improved patient outcomes.The authors wish to thank Tim Vanmierlo and Bruno Vandekerckhove, for their assistance in this letter to the editor
Editorial: Cyclic Nucleotide Phosphodiesterases (PDEs) in Immune Regulation and Inflammation
No full textEditorial on the Research Topic Cyclic nucleotide phosphodiesterases (PDEs) in immune regulation and inflammation Cyclic nucleotides are involved in many cellular functions and well-established regulator of immune responses and inflammation. Leukocytes play a critical role in inflammation and its modulation. Function and regulation of different subpopulations of T cells, B cells and NK cells, as well as myeloid cells, such as neutrophils, monocytes, macrophages, and dendritic cells involve activation of the cAMP pathway. Additionally, interactions between leukocytes and endothelial cells are critical during inflammatory lesion formation and can be regulated by cAMP/cGMP signaling. Cyclic nucleotides are degraded by cyclic nucleotide phosphodiesterase (PDE) enzymes. PDEs are the only enzymes known to hydrolyze cAMP/ cGMP and thereby maintain spatial and temporal control over pools of cAMP/cGMP within distinct cellular compartments. PDEs are divided into 11 different gene families based on their specificity for cAMP or cGMP, structural similarity and mode of regulation. While PDEs have been recognized early as potential drug targets for anti-inflammatory drugs, bringing specific PDE inhibitors into clinical use has faced decades of challenges, mostly due to dose-limiting side effects. Major progress has been made with the approval and clinical use of select PDE4 inhibitors to treat major human inflammatory diseases. PDE4-selective inhibitors are used for oral treatment of chronic obstructive pulmonary disease, psoriatic arthritis and plaque psoriasis as well as a topical treatment for atopic dermatitis. Recent advances demonstrate a role for inflammation involved in many neurodegenerative pathologies. Due to the unique roles of specific PDE isoforms to control distinct pools of cyclic nucleotides in leukocytes, additional PDEs became a focus to study potentially novel therapeutics for inflammatory disorders. First, basic molecular functions of PDEs cell regulation are addressed. Kurelic et al. show that PDE2A is upregulated during activation of effector/conventional CD4 + T cells in vitro Kurelic et al. Combining selective inhibitors studies, approaches to induce accumulation of cGMP through various activators and elegant real time FRET imaging, they demonstrate an increase of cAMP in non-activated and a decrease of cAMP in activated effector/conventional CD4 + T cells, presumably dependent on the expression of PDE2A. These studies could explain context dependent regulation of effector/conventional T cell activation and function and provide the basis for developing new therapeutic approaches to T cell mediated autoimmune disorders. Chinn et al. identify PDE4B as the primary PDE expressed in dendritic cells (DCs) and demonstrate using DC-specific depletion of Gαs that dynamic, bidirectional regulation of PDE4B expression acts as a key homeostatic regulator of cAMP levels in DCs Chinn et al. They further show that inhibition of PDE4B in Gαs-depleted DCs decreased Th2 cell differentiation, which in concert with the known phenotype of DC-selective Gαs depletion in mice suggests PDE4B inhibition as a target for Th2-allergic asthma. Golshiri et al. highlighted the complexities of exploring PDE function in disease settings, in this case the role of PDE1 in a mouse knockout model of smooth muscle cell (SMC) agingThe editors of this Research Topic were funded by the NMSS, FWO, Fondation Charcot Stichting and the Smart Family Foundation.
We express our gratitude to all the authors who have contributed to this Research Topic and to the reviewers for their valuable work
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Brown seaweed food supplementation
Get PDFMultiple health benefits have been ascribed to brown seaweeds that are used traditionally as dietary component mostly in Asia. This systematic review summarizes information on the impact of brown seaweeds or components on inflammation, and inflammation-related pathologies, such as allergies, diabetes mellitus and obesity. We focus on oral supplementation thus intending the use of brown seaweeds as food additives. Despite the great diversity of experimental systems in which distinct species and compounds were tested for their effects on inflammation and immunity, a remarkably homogeneous picture arises. The predominant effects of consumption of brown seaweeds or compounds can be classified into three categories: (1) inhibition of reactive oxygen species, known to be important drivers of inflammation; (2) regulation, i.e., in most cases inhibition of pro-inflammatory NF-κB signaling; (3) modulation of adaptive immune responses, in particular by interfering with T-helper cell polarization. Over the last decades, several inflammation-related diseases have increased substantially. These include allergies and autoimmune diseases as well as morbidities associated with lifestyle and aging. In this light, further development of brown seaweeds and seaweed compounds as functional foods and nutriceuticals might contribute to combat these challenges.</p
Release-regulating sphingosine 1-phosphate 1/3 receptors in cortical synaptosomes and gliosomesof mice suffering from experimental autoimmune encephalomyelitis: impact of fingolimod.
No full textFully Threaded Versus Partially Threaded Intramedullary Headless Compression Screw Fixation for Proximal Third Fractures of the Proximal Phalanx: A Biomechanical Study
No full textFully threaded versus partially threaded intramedullary headless compression screw fixation for proximal third fractures of the proximal phalanx: a biomechanical study.-Manuscript Draft-Manuscript Number: JHS-D-24-00450R2 Article Type: Full Length Article Abstract: Purpose The purpose of this study was to compare the maximal elastic force and deformation resistance of two commonly used headless compression screw systems-a fully threaded 2.5mm screw and a partially threaded screw of the same dimensions-in a cadaveric model of a human transverse proximal third fracture of the proximal phalanx. Methods Six fresh frozen cadavers were used, and the proximal phalanges of the index, long, and ring fingers of both hands were dissected. A proximal third transverse osteotomy was created, and screws were inserted in an antegrade direction. The three-point bending load-to-failure test measured the maximal elastic force and deformation resistance of each bone-screw construct. Results The fully threaded screw demonstrated a maximal elastic force of 121N and a deformation resistance of 134N/mm. The partially threaded screw showed superior performance with a maximal elastic force of 165N and deformation resistance of 166N/mm. The bone-screw construct with the fully threaded screw had a mean maximal elastic force of 155.2N compared to 101.8N in the construct with the partially threaded screw. Deformation resistance was 145.2N/mm for fully threaded screws and 98.6N/mm for partially threaded screws. Conclusions Fully threaded intramedullary headless compression screw fixation provides superior maximal elastic force and deformation resistance compared to partially threaded intramedullary headless compression screw fixation in transverse proximal third fractures of the proximal phalanx. Clinical Relevance The findings indicate that fully threaded intramedullary headless compression screw fixation may offer enhanced stability for treating proximal third fractures of the proximal Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporatio
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses
Get PDFBruno, O., Fedele, E., Prickaerts, J., Parker, L. A., Canepa, E., Brullo, C., Cavallero, A., Gardella, E., Balbi, A., Domenicotti, C., Bollen, E., Gijselaers, H. J. M., Vanmierlo, T., Erb, K., Limebeer, C. L., Argellati, F., Marinari, U. M., Pronzato, M. A., & Ricciarelli, R. (2011). GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses. British Journal of Pharmacology, 164, 2054-2063. doi: 10.1111/j.1476-5381.2011.01524.xBACKGROUND AND PURPOSE
Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde
derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-b (Ab) levels.
EXPERIMENTAL APPROACH
To measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Ab peptides were measured in hippocampal tissues and cultured N2a cells by ELISA.
KEY RESULTS
GEBR-7b increased hippocampal cAMP, did not influence Ab levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents.
CONCLUSION AND IMPLICATIONS
Our results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
Get PDFIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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