Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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- Accuracy of prehospital triage protocols in select...
- Two hundred years since James Parkinson's essay on...
- Where we've gone “right” in the Parkinson's community
- Thyroid Cancer - Global API Manufacturers, Markete...
- Soft-diet feeding impairs neural transmission betw...
- Protecting Kids Against HPV Before Cancer Risk Inc...
- Chronic traumatic encephalopathy (CTE)
- Aims and Scope & Editorial Board
- Fay Hlubocky on Recognizing and Addressing Clinici...
- Surgical Management of Stage III (N2) Lung Cancer
- Current Pancreatic Cancer Guidelines Miss Targetab...
- Anticancer efficacy of the hypoxia-activated prodr...
- Vaccinating children against HPV could prevent can...
- A Hard Road | Couple's Net | Chandrama Anderson | ...
- An integrated approach to explore composition and ...
- Letters: Letters to the editor
- Hymenoptera-induced anaphylaxis: is it a mast cell...
- Climate changes and Hymenoptera venom allergy: are...
- Long-term epilepsy-associated tumor in the amygdal...
- A novel synthetic analogue of {omega}-3 17,18-epox...
- Characterization of the central neural projections...
- Structural transitions in conserved, ordered Becli...
- P2X7 receptor antagonism prevents IL-1{beta} relea...
- Conformational characterization of Nerve growth fa...
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Αυγ 10
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Ετικέτες
Πληροφορίες
Πέμπτη 10 Αυγούστου 2017
Accuracy of prehospital triage protocols in selecting severely injured patients: A systematic review
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Two hundred years since James Parkinson's essay on the shaking palsy—Have we made progress? Insights from the James Parkinson's 200 years course held in London, March 2017
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Where we've gone “right” in the Parkinson's community
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Thyroid Cancer - Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2017 - Markets Insider
Thyroid Cancer - Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2017 Markets Insider LONDON, Aug. 10, 2017 /PRNewswire/ -- DelveInsight's, Thyroid Cancer - Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2017" report provides comprehensive insights about marketed and Phase III products for the Thyroid Cancer. and more » |
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Soft-diet feeding impairs neural transmission between mitral cells and interneurons in the mouse olfactory bulb
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Tomohiro Noguchi, Chizuru Utsugi, Makoto Kashiwayanagi
(Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors. Release of GABA from inhibitory interneurons at the olfactory bulb induces inhibitory currents at the mitral cells, which are output neurons from the olfactory bulb. (Design) In the present study, we measured spontaneous inhibitory postsynaptic currents (sIPSCs) at the mitral cells of mice fed a soft diet in order to explore the effects of changes in texture of diets on neural function at the olfactory bulb. (Results) The soft-diet feeding extended the intervals between sIPSCs and reduced their peak amplitudes. (Conclusions) The present results suggest that soft-diet feeding in mice attenuates the neural functions of inhibitory interneurons at the olfactory bulb.
Graphical abstract
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Protecting Kids Against HPV Before Cancer Risk Increases - Newswise (press release)
Protecting Kids Against HPV Before Cancer Risk Increases Newswise (press release) However, the medical data clearly indicates that the HPV vaccine is extremely safe and highly effective at preventing cancers of the cervix, vagina, and vulva in women and cancers of the penis and anus in men; and oropharynx (tonsils) cancer in both sexes. |
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Chronic traumatic encephalopathy (CTE)
Chronic traumatic encephalopathy (CTE): a degenerative disease of the brain (form of brain damage) that occurs in athletes or others who have experienced repetitive concussions or other trauma to the brain. Some of the most common symptoms and signs of CTE can include memory loss, behavioral difficulties like difficulty with impulse control, impaired judgment, aggression, balance problems, a slow onset of dementia, and depression. Symptoms of CTE might be mistaken for symptoms due to the aging process or other conditions like Alzheimer's disease.
MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You
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Aims and Scope & Editorial Board
Publication date: July 2017
Source:Bioactive Carbohydrates and Dietary Fibre, Volume 11
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Fay Hlubocky on Recognizing and Addressing Clinician Burnout
In this interview we discuss the issue of burnout in oncology, including signs and risk factors, how it might affect patient care, and strategies for prevention. (Source: CancerNetwork)
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Surgical Management of Stage III (N2) Lung Cancer
This video reviews the role of surgery in patients with stage III (N2) non –small-cell lung cancer, highlighting some of the challenges in studying these patients and the need for multidisciplinary patient evaluations. (Source: CancerNetwork)
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Current Pancreatic Cancer Guidelines Miss Targetable Mutations
Germline mutations in pancreatic cancer susceptibility genes were commonly identified in a group of patients with pancreatic cancer who did not report a significant family history of cancer, according to the results of a single-center study. (Source: CancerNetwork)
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Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma
Abstract
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.
In this study, we investigated the cytotoxic activity of the hypoxia-activated prodrug evofosfamide against human osteosarcoma cells in vitro as a single agent and in combination with proapoptotic receptor agonist's dulanermin and drozitumab. We then assessed the anticancer activity of evofosfamide alone and in combination with drozitumab using a clinically relevant orthotopic mouse model of osteosarcoma and on subsequent pulmonary metastases. Evofosfamide as a single agent reduced tumor burden in bone and cooperated with drozitumab to protect bone from osteosarcoma-induced bone destruction while also reducing the incidence of pulmonary metastases and importantly, evofosfamide alone and in combination with drozitumab was not toxic to normal bone metabolism in vivo.
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Vaccinating children against HPV could prevent cancer risk in later life - News-Medical.net
Vaccinating children against HPV could prevent cancer risk in later life News-Medical.net However, the medical data clearly indicates that the HPV vaccine is extremely safe and highly effective at preventing cancers of the cervix, vagina, and vulva in women and cancers of the penis and anus in men; and oropharynx (tonsils) cancer in both sexes. and more » |
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A Hard Road | Couple's Net | Chandrama Anderson | Almanac Online | - The Almanac Online (blog)
A Hard Road | Couple's Net | Chandrama Anderson | Almanac Online | The Almanac Online (blog) I want to share an excerpt from another new book of mine: A Hard Road It's a story of cancer survival for patients and caregivers.We hope it will help you as you ... and more » |
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An integrated approach to explore composition and dynamics of cholesterol-rich membrane microdomains in sexual stages of malaria parasite [Research]
Membrane microdomains that include lipid rafts, are involved in key physiological and pathological processes and participate in the entry of endocellular pathogens. These assemblies, enriched in cholesterol and sphingolipids, form highly dynamic, liquid-ordered phases that can be separated from the bulk membranes thanks to their resistance to solubilization by non-ionic detergents. To characterize complexity and dynamics of detergent-resistant membranes of sexual stages of the rodent malaria parasite Plasmodium berghei, here we propose an integrated study of raft components based on proteomics, lipid analysis and bioinformatics. This analysis revealed unexpected heterogeneity and unexplored pathways associated with these specialized assemblies. Protein-protein relationships and protein-lipid co-occurrence were described through multi-component networks. The proposed approach can be widely applied to virtually every cell type in different contexts and perturbations, under physiological and/or pathological conditions.
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Letters: Letters to the editor
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Hymenoptera-induced anaphylaxis: is it a mast cell driven hematological disorder?.
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Climate changes and Hymenoptera venom allergy: are there some connections?.
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Long-term epilepsy-associated tumor in the amygdala of a 16-year-old boy: report of a rare case having intranuclear filaments
Abstract
The term "long-term epilepsy-associated tumor (LEAT)" encompasses brain lesions associated with drug-resistant epilepsy over a long duration (≥2 years). Notably, some LEATs do not fit into any of the classifications of the World Health Organization (WHO). Herein, we report a LEAT that occurred in the left amygdala of a 16-year-old patient with intractable epilepsy. Histological examination of the resected amygdala revealed diffusely infiltrating tumor cells in the cortex. Perineuronal satellitosis and perivascular aggregation of tumor cells were apparent, along with mild nuclear enlargement and cytologic atypia. Tumor cells were positive for oligodendrocyte transcription factor 2 and neuronal markers including NeuN, neurofilaments, and synaptophysin, but were negative for CD34 and nestin. The most intriguing finding was intranuclear filaments, which appeared as rod- or needle-like shapes under high-power view. Ancillary ultrastructural analysis revealed thin filamentous intranuclear structures in tumor cells. Based on the glioneuronal nature of these cells as well as the infiltrative growth pattern, a diagnosis of LEAT was rendered that was deemed WHO grade I to II; however, the clinicopathological implications of the intranuclear inclusions remain unknown. The patient is currently alive and well without seizures.
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A novel synthetic analogue of {omega}-3 17,18-epoxy-eicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells [Research]
A saturated analog of the cytochrome P450–mediated -3-17,18-epoxide of -3-eicosapentaenoic acid (C20E) activated apoptosis in human triple-negative MDA-MB-231 breast cancer cells. This study evaluated the apoptotic mechanism of C20E. Increased cytosolic cytochrome c expression and altered expression of pro- and antiapoptotic B-cell lymphoma-2 proteins indicated activation of the mitochondrial pathway. Caspase-3 activation by C20E was prevented by pharmacological inhibition and silencing of the JNK and p38 MAP kinases (MAPK), upstream MAPK kinases MKK4 and MKK7, and the upstream MAPK kinase kinase apoptosis signal-regulating kinase 1 (ASK1). Silencing of the death receptor TNF receptor 1 (TNFR1), but not Fas, DR4, or DR5, and the adapters TRADD and TNF receptor–associated factor 2, but not Fas-associated death domain, prevented C20E-mediated apoptosis. B-cell lymphoma-2 homology 3–interacting domain death agonist (Bid) cleavage by JNK/p38 MAPK linked the extrinsic and mitochondrial pathways of apoptosis. In further studies, an antibody against the extracellular domain of TNFR1 prevented apoptosis by TNF-α but not C20E. These findings suggest that C20E acts intracellularly at TNFR1 to activate ASK1-MKK4/7-JNK/p38 MAPK signaling and to promote Bid-dependent mitochondrial disruption and apoptosis. In in vivo studies, tumors isolated from C20E-treated nu/nu mice carrying MDA-MB-231 xenografts showed increased TUNEL staining and decreased Ki67 staining, reflecting increased apoptosis and decreased proliferation, respectively. -3-Epoxy fatty acids like C20E could be incorporated into treatments for triple-negative breast cancers.—Dyari, H. R. E., Rawling, T., Chen, Y., Sudarmana, W., Bourget, K., Dwyer, J. M., Allison, S. E., Murray, M. A novel synthetic analogue of -3 17,18-epoxy-eicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells.
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Characterization of the central neural projections to brown, white, and beige adipose tissue [Research]
The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.—Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue.
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Structural transitions in conserved, ordered Beclin 1 domains essential to regulating autophagy [Cell Biology]
Beclin 1 (BECN1) is a key regulator of autophagy, a critical catabolic homeostasis pathway that involves the sequestration of cytoplasmic components by multilayered vesicles called autophagosomes, followed by lysosomal fusion and degradation. BECN1 is a core component of class III phosphatidylinositol-3-kinase complexes responsible for autophagosome nucleation. Without heterologous binding partners, BECN1 forms an antiparallel homodimer via its coiled-coil domain (CCD). However, the last 16 CCD residues, composing an overlap helix (OH), have been crystallized in two mutually exclusive states: either as part of the CCD or packed against the C-terminal lower case β-α-repeated, autophagy-specific domain (BARAD). Here, using circular dichroism (CD) spectroscopy, isothermal titration calorimetry (ITC), and small-angle X-ray scattering (SAXS), we show that in the homodimeric state, the OH transitions between these two different packing states, with the predominant state comprising the OH packed against the BARAD, contrary to expectations based on known BECN1 interactions with heterologous partners. We confirmed this observation by comparing the impact of mutating four residues that mediate packing of the OH against both the CCD and BARAD on structure and stability of the CCD, the OH+BARAD, and the two-domain CCD-BARAD. Lastly, we used cellular assays demonstrating that mutation of these OH-interface residues abrogates starvation-induced up-regulation of autophagy, but does not affect basal autophagy. In summary, we have identified a BECN1 helical region that transitions between packing as part of either one of two conserved domains, i.e. the CCD or the BARAD. Our findings have important implications for the relative stability of autophagy-inactive and autophagy-active BECN1 complexes.
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P2X7 receptor antagonism prevents IL-1{beta} release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy [Immunology]
Salivary gland inflammation is a hallmark of Sjogrens syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome. Here, our results show that in primary mouse submandibular gland (SMG) epithelial cells, P2X7R activation also induces the assembly of the NLRP3 inflammasome and the maturation and release of IL-1β, a response that is absent in SMG cells isolated from mice deficient in P2X7Rs (P2X7R-/- ). P2X7R-mediated IL-1β release in SMG epithelial cells is dependent on transmembrane Na+ and/or K+ flux and the activation of heat shock protein 90 (HSP90), a protein required for the activation and stabilization of the NLRP3 inflammasome. Also, using the reactive oxygen species (ROS) scavengers N-acetyl cysteine and Mito-TEMPO, we determined that mitochondrial ROS are required for P2X7R-mediated IL-1β release. Lastly, in vivo administration of the P2X7R antagonist A438079 in the CD28-/-, IFNγ-/-, NOD.H-2h4 mouse model of salivary gland exocrinopathy ameliorated salivary gland inflammation and enhanced carbachol-induced saliva secretion. These findings demonstrate that P2X7R antagonism in vivo represents a promising therapeutic strategy to limit salivary gland inflammation and improve secretory function.
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Conformational characterization of Nerve growth factor-{beta} reveals that its regulatory pro-part domain stabilizes three loop regions in its mature part [Neurobiology]
Nerve growth factor-β (NGF) is essential for correct development of the nervous system. NGF exists both in a mature and a pro-form (proNGF). The two forms have opposing effects on neurons, in which NGF induces proliferation, while proNGF induces apoptosis via binding to a receptor complex of the common neurotrophine receptor (p75NTR) and Sortilin. Overexpression of both proNGF and Sortilin has been associated with several neurodegenerative diseases. Insights into the conformational differences between proNGF and NGF are central to a better understanding of the opposing mechanisms of action of NGF and proNGF on neurons. However, while the structure of NGF has been determined by X-ray crystallography, structural details for proNGF remain elusive. Here, using a sensitive MS-based analytical method to measure the hydrogen/deuterium exchange of proteins in solution, we analyzed the conformational properties of proNGF and NGF. We detected the presence of a localized higher-order structure in the pro-part of proNGF. Furthermore, by comparing the hydrogen/deuterium exchange in the mature part of NGF and proNGF, we found that the presence of the pro-part in proNGF causes a structural stabilization of three loop regions in the mature part, possibly through a direct molecular interaction. Moreover, using tandem MS analyses, we identified two N-linked and two O-linked glycosylations in the pro-part of proNGF. These results advance our knowledge of the conformational properties of proNGF and NGF and help provide a rationale for the diverse biological effects of NGF and proNGF at the molecular level.
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The ATAD2 Bromodomain Binds Different Acetylation Marks on the Histone H4 in Similar Fuzzy Complexes [Computational Biology]
Bromodomains are protein modules adopting conserved helix-bundle folds. Some bromodomain-containing proteins, such as ATPase family AAA domain-containing protein 2 (ATAD2), isoform A, have attracted much interest because they are overexpressed in many types of cancer. Bromodomains bind to acetylated lysine residues on histone tails and thereby facilitate the reading of the histone code. Epigenetic regulators in general have been implicated as indicators, mediators, or causes of a large number of diseases and disorders. To interfere with or modulate these processes, it is therefore of fundamental interest to understand the molecular mechanisms by which epigenetic regulation occurs. Here, we present results from molecular dynamics simulations of a doubly acetylated histone H4 peptide bound to the bromodomain of ATAD2 (ATAD2A hereafter). These simulations revealed how the flexibility of ATAD2A`s major loop, the so-called ZA loop, creates an adaptable interface that preserves the disorder of both peptide and loop in the bound state. We further demonstrate that the binding involves an almost identical average pattern of interactions irrespective of which acetyl mark is inserted into the pocket. In conjunction with a likely mechanism of electrostatically-driven recruitment, our simulation results highlight how the bromodomain is built toward promiscuous binding with low specificity. In conclusion, the simulations indicate that disorder and electrostatic steering function jointly to recruit ATAD2A to the histone core and that these fuzzy interactions may promote cooperativity between nearby epigenetic marks.
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Interaction of Munc18c and Syntaxin4 facilitates invadopodium formation and extracellular matrix invasion of tumour cells [Molecular Bases of Disease]
Tumor cell invasion involves targeted localization of proteins required for interactions of the extracellular matrix (ECM) and for proteolysis. The localization of many proteins during these cell-ECM interactions relies on membrane trafficking mediated in part by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The SNARE protein syntaxin4 (Stx4) is involved in the formation of invasive structures called invadopodia; however, it is unclear how Stx4 function is regulated during tumor cell invasion. Munc18c is known to regulate Stx4 activity, and here we show that Munc18c is required for Stx4-mediated invadopodium formation and cell invasion. Biochemical and microscopic analyses revealed a physical association between Munc18c and Stx4, which was enhanced during invadopodium formation, and that reduced Munc18c expression decreases invadopodium formation. We also found that an N-terminal Stx4-derived peptide associates with Munc18c, and inhibits endogenous interactions of Stx4 with synaptosome-associated protein 23 (SNAP23) and vesicle-associated membrane protein 2 (VAMP2). Furthermore, expression of the Stx4 N-terminal peptide decreased invadopodium formation and cell invasion in vitro. Of note, cells expressing the Stx4 N-terminal peptide exhibited impaired trafficking of membrane type-1 matrix metalloproteinase (MT1-MMP) and EGF receptor (EGFR) to the cell surface during invadopodium formation. Our findings implicate Munc18c as a regulator of Stx4-mediated trafficking of MT1-MMP and EGFR, advancing our understanding of the role of SNARE function in the localization of proteins that drive tumor cell invasion.
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Molecular mechanisms and genomic maps of DNA excision repair in E.coli and humans [DNA and Chromosomes]
Nucleotide excision repair is a major DNA repair mechanism in all cellular organisms. In this repair system the DNA damage is removed by concerted dual incisions bracketing the damage and at precise distance from the damage. Here, we review the basic mechanisms of excision repair in E.coli and humans and the recent genome-wide mapping of DNA damage and repair in these organisms at single-nucleotide resolution.
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The Unintended Mitochondrial Uncoupling Effects of the FDA Approved Anti-Helminth Drug Nitazoxanide Mitigates Experimental Parkinsonism in Mice [Bioenergetics]
Mitochondria plays a primary role in the pathophysiology of Parkinson's disease (PD) and small molecules that counteract the initial stages of disease may offer therapeutic benefit. In this regard, we have examined whether the off-target effects of the FDA approved anti-helminth drug, nitazoxanide (NTZ) on mitochondrial respiration could possess any therapeutic potential for PD. Results indicate that MPP+ induced loss in oxygen consumption rate (OCR) and ATP production by mitochondria were ameliorated by NTZ in real-time by virtue of its mild-uncoupling effect. Pretreatment of cells with NTZ mitigated MPP+ induced loss in mitochondrial OCR and ROS. Similarly, addition of NTZ to cells pre-treated with MPP+ could reverse block in mitochondrial OCR and ROS induced by MPP+ in realtime. The observed effects of NTZ were found to be transient and reversible as removal of NTZ from incubation medium restored the mitochondrial respiration to that of controls. Apoptosis induced by MPP+ was ameliorated by NTZ in a dose-dependent manner. In vivo results demonstrated that oral administration of NTZ (50 mg/kg) in an acute MPTP mouse model of PD conferred significant protection against the loss of TH positive neurons of Substantia nigra. Based on the above observations we believe that repurposing of NTZ for PD may offer therapeutic benefit.
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Decorin-Evoked Paternally Expressed Gene 3 (PEG3) is an Upstream Regulator of the Transcription Factor EB (TFEB) in Endothelial Cell Autophagy [Cell Biology]
Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires Paternally Expressed Gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of TFEB, a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in HUVEC and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMPK, a major decorin-activated energy sensor kinase prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient and energy independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB.
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Atomic-Resolution Map of the Interactions between an Amyloid Inhibitor Protein and Amyloid Beta (A{beta}) Peptides in the Monomer and Protofibril States [Protein Structure and Folding]
Self-association of amyloid beta (Aβ) peptides is a hallmark of Alzheimer's disease and serves as a general prototype for amyloid formation. A key endogenous inhibitor of Aβ self-association is Human Serum Albumin (HSA), which binds ~90% of plasma Aβ. However, the exact molecular mechanism by which HSA binds Aβ monomers and protofibrils is not fully understood. Here, using dark-state exchange saturation transfer (DEST) NMR and relaxation experiments, complemented by morphological characterization, we mapped the HSA-Aβ interactions at atomic resolution by examining HSA's effects on Aβ monomers and soluble high-molecular weight oligomeric protofibrils. We found that HSA binds both monomeric and protofibrillar Aβ, but the affinity of HSA for Aβ monomers is lower than for Aβ protofibrils (Kd ~ sub-mM vs. μM), yet physiologically relevant owing to the ~0.6 - 0.7 mM plasma HSA concentration. In both Aβ protofibrils and monomers, HSA targets key Aβ self-recognition sites spanning the β strands found in cross-β protofibril structures, leading to a net switch from direct to tethered contacts between the monomeric Aβ and the protofibril surface. These HSA-Aβ interactions are isoform specific, as the Aβ monomer - HSA interactions were weaker for Aβ (1-42) than for Aβ (1-40). In addition, the HSA-induced perturbations of the monomer / protofibrils pseudo-equilibrium extended to the C-terminal residues in the Aβ (1-42) isoform but not in Aβ (1-40). These results provide an unprecedented view of how albumin interacts with Aβ and illustrate the potential of DEST NMR in mapping the interactions between amyloid-inhibitory proteins and amyloidogenic peptides.
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Acrylic stent to aid placement of footplate of palatal distractor during surgically-assisted rapid palatal expansion
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K.F.B. Payne, L. Dewhurst, G. Robinson, B. Edwards, K. McVeigh
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Simple method of covering maxillectomy defects with lyophilised amniotic membrane
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K. Hazarika, A.K. Adhyapok, S.C. Debnath, K. Malik
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Should patients take vitamin D before mandibular operations?
Publication date: Available online 10 August 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): N. Syed, G.A. Chiu, P. Korczak
Vitamin D deficiency is endemic in the United Kingdom (UK), particularly in high-risk groups. We report the outcomes of patients with low concentrations of the vitamin who had complications after reduction of mandibular fractures or osteotomy, and those who were screened preoperatively. A deficiency can be diagnosed with a simple and inexpensive blood test, and in the UK the cost of a vitamin D tablet is about £0.04/tablet/day. Patients at risk of a deficiency should be screened before mandibular operations, and those listed for orthognathic surgery or replacement of the temporomandibular joint should be asked to take a supplement before operation.
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Metabolic characterization and RNA profiling reveal glycolytic dependence of pro-fibrotic phenotype of alveolar macrophages in lung fibrosis
Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis. We found that alveolar macrophages from both bleomycin and active TGF-β1 induced fibrotic mouse lungs demonstrated a primarily pro-fibrotic M2-like profile that was distinct from the well-defined M1 or any of the M2 subtypes. More importantly, we found that fibrotic lung alveolar macrophages assumed augmented glycolysis, which was likely attributed to enhanced expression of multiple key glycolytic mediators. We also found that fatty acid oxidation was upregulated in these cells. However, the pro-fibrotic M2-like profile of fibrotic lung alveolar macrophages was not dependent on fatty acid oxidation and synthesis or lipolysis, but instead on glycolysis, in contrast to the typical IL-4 induced macrophages M(IL-4). Additionally, glutaminolysis, a key metabolic program that has been implicated in numerous pathologies, was not required for the pro-fibrotic M2-like phenotype of these macrophages. In summary, our study identifies a unique expression and metabolic profile in alveolar macrophages from fibrotic lungs and suggests glycolytic inhibition as an effective anti-fibrotic strategy in treating lung fibrosis.
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PRESERVED RIGHT VENTRICULAR INTEGRITY IN A NEW TELEMETRIC RAT MODEL OF SEVERE PULMONARY HYPERTENSION
Telemetric monitoring of hemodynamic parameters has become an established standard in experimental models of pulmonary arterial hypertension (PAH). To that purpose, a dedicated catheter is usually implanted through the right ventricular wall of study animals. Drawbacks of this standard technique are: obtained pressures are from the right ventricle and therefore only surrogates for pulmonary arterial pressures, and furthermore, right ventricular myocardium is always damaged to a certain degree. To overcome shortcomings of standard hemodynamic assessment, we modified an established rat model, where severe PAH is induced by left-sided pneumonectomy plus monocrotaline injection. We describe here a novel telemetry catheter implantation technique, where the device is advanced into the pulmonary artery via the remaining stump, and the transmitter is placed in a subcutaneous pocket. A total of 105 rats were operated with a median implantation time of 50 (30-88)min and an excellent perioperative survival of 93%. After monocrotaline induction on day 7, animals developed severe PAH with mean pressures of 75.9 ±18.6 mmHg (systolic), 55.0 ±18.0 mmHg (mean) and 42.1 ±21.3 mmHg (diastolic) after four weeks. Post-mortem, the animals showed severe right ventricular hypertrophy and histological analysis confirmed excessive medial hypertrophy and intimal hyperplasia, both characteristic features of human PAH. Comparison of the new telemetric model with standard microtip catheterization did not show relevant measurement differences. We established the first experimental animal model for PAH with preserved right ventricular integrity that allows direct telemetric monitoring of real-time systolic, mean and diastolic pressures in the main pulmonary artery of freely moving rats.
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Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus
Infants born prematurely often require supplemental oxygen that contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV) infection. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with influenza A virus (IAV (A/Hong Kong/X31) H3N2) as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescently expressing reporter strain of H1N1 IAV (A/Puerto Rico/8/34 mCherry, PR8 mCherry) to evaluate whether it also altered early infection of the respiratory epithelium. Like HKx31, neonatal hyperoxia increased morbidity and mortality of adult mice infected with PR8-mCherry. Whole lung imaging and histology suggested a modest increase in mCherry expression in adult mice exposed to neonatal hyperoxia when compared to room air exposed animals. However, this did not reflect an increase in airway or alveolar epithelial infection when mCherry + cells were identified and quantified by flow cytometry. Instead, a modest increase in the number of CD45+ macrophages expressing mCherry was detected. While neonatal hyperoxia does not alter early epithelial infection to IAV, it may increase the activity of macrophages towards infected cells thereby enhancing early epithelial injury.
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Aquaporin 1-mediated changes in pulmonary arterial smooth muscle cell migration and proliferation involve {beta}-catenin
Exposure to hypoxia induces migration and proliferation of pulmonary arterial smooth muscle cells (PASMCs), leading to vascular remodeling and contributing to the development of hypoxic pulmonary hypertension. The mechanisms controlling PASMC growth and motility are incompletely understood, although aquaporin 1 plays an important role. In tumor, kidney and stem cells, AQP1 has been shown to interact with β-catenin, a dual function protein that activates the transcription of crucial target genes (i.e., c-Myc and cyclin D1) related to cell migration and proliferation. Thus, the goal of this study was to examine mechanisms by which AQP1 mediates PASMC migration and proliferation, with a focus on β-catenin. Using primary rat PASMCs from resistance level pulmonary arteries infected with adenoviral constructs containing GFP (control; AdGFP), wild-type AQP1 (AdAQP1) or AQP1 with the C-terminal tail deleted (AdAQP1M), we demonstrated that increasing AQP1 expression using AdAQP1 upregulated β-catenin protein levels and the expression (mRNA and protein) of the known β-catenin targets, c-Myc and cyclin D1. In contrast, infection with AdAQP1M had no effect on any of these variables. Using silencing approaches to reduce β-catenin levels prevented both hypoxia- and AQP1-induced migration and proliferation of PASMCs. Thus, our results indicate that elevated AQP1 levels upregulate β-catenin protein levels, via a mechanism requiring the AQP1 C-terminal tail, enhancing expression of β-catenin targets and promoting PASMC proliferation and migration.
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Benefits of Oxytocin Administration in Obstructive Sleep Apnea
Activation of oxytocin receptors has shown benefits in animal models of Obstructive Sleep Apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. 8 patients diagnosed with OSA were administered intranasal oxytocin (40 i.u.). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability were assessed. Oxytocin significantly increased indices of parasympathetic activity, including heart rate variability, total sleep time, and the Post-Polysommogram Sleep Assessment (PPSA) score, an index of self-reported sleep satisfaction. Although the Apnea-Hypopnea Index (AHI) was not significantly changed with oxytocin administration, when apnea and hypopnea events were compared independently, the frequency of hypopneas, but not apneas, were significantly (p<.005) decreased with oxytocin treatment. Both apneas and hypopneas were significantly shortened in duration with oxytocin treatment. Oxytocin treatment significantly decreased the percent of apnea and hypopnea events that were accompanied with an arousal. Oxytocin administration has the potential to restore cardiorespiratory homeostasis and reduce some clinically important (objective and patient-reported) adverse events that occur with OSA. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory and autonomic function in OSA patients.
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CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms
Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to-mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effects of a CYP2E1 inhibitor on development of RIPF were evaluated by in vivo studies. Taken together, the results of the present study suggest that CYP2E1 is an important mediator of RIPF development that functions by increasing cellular ER stress and ROS levels.
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LungMAP: The Molecular Atlas of Lung Development Program
The National Heart Lung and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic crosstalk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, data coordinating center and human tissue repository will provide high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross-correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of datasets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains over 5000 high resolution lung images, transcriptomic, proteomic, and lipidomic data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database and portal development and upcoming features that will enhance the LungMAP experience for a community of users.
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Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation
A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known. Here, we postulate that the OGG1 signaling pathway differentially altered the levels of small regulatory RNAs and increased the expression of T helper 2 (Th2) cytokines in ragweed pollen extract (RWPE)-challenged lungs. To determine this, the lungs of sensitized mice expressing or lacking OGG1 were challenged with RWPE and/or with OGG1's excision product 8-oxoG. The responses in lungs were assessed by next-generation sequencing, as well as various molecular and histological approaches. The results showed that RWPE challenge induced oxidative burst, damage to DNA and activated OGG1 signaling, resulting in the differential expression of 84 microRNAs, which then exacerbated antigen-driven allergic inflammation and histological changes in the lungs. The exogenous administration of the down-regulated let-7b-p3 mimetic or inhibitors of up-regulated miR23a or miR27a decreased eosinophil recruitment, mucus and collagen production via controlling the expression of IL4, IL5, and IL13. Together, these data demonstrate the roles of OGG1 signaling in the regulation of antigen-driven allergic immune responses via differential expressions of microRNAs upstream of Th2 cytokines and eosinophils.
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Endothelial cell-related autophagic pathways in Sugen/hypoxia-exposed pulmonary arterial hypertensive rats
Pulmonary arterial hypertension (PAH) is characterized by progressive obstructive remodeling of pulmonary arteries. However, no reports have described the causative role of the autophagic pathway in pulmonary vascular endothelial cell (EC) alterations associated with PAH. This study investigated the time-dependent role of the autophagic pathway in pulmonary vascular ECs and pulmonary vascular EC kinesis in a severe PAH rat model (Sugen/Hypoxia rat) and evaluated whether timely induction of the autophagic pathway by rapamycin improves PAH. Hemodynamic and histological examinations as well as flow cytometry of pulmonary vascular EC-related autophagic pathways and pulmonary vascular EC kinetics in lung cell suspensions were performed. The time-dependent and therapeutic effects of rapamycin on the autophagic pathway were also assessed. Sugen/Hypoxia rats treated with the vascular endothelial growth factor receptor blocker SU5416 showed increased right ventricular systolic pressure (RVSP) and numbers of obstructive vessels due to increased pulmonary vascular remodeling. The expression of the autophagic marker LC3 in ECs also changed in a time-dependent manner, in parallel with proliferation and apoptotic markers as assessed by flow cytometry. These results suggest the presence of crosstalk between pulmonary vascular remodeling and the autophagic pathway, especially in small vascular lesions. Moreover, treatment of Sugen/Hypoxia rats with rapamycin after SU5416 injection activated the autophagic pathway and improved the balance between cell proliferation and apoptosis in pulmonary vascular ECs to reduce RVSP and pulmonary vascular remodeling. These results suggested that the autophagic pathway can suppress PAH progression and that rapamycin-dependent activation of the autophagic pathway could ameliorate PAH.
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Pulmonary function in patients with eosinophilic chronic rhinosinusitis
Source:Auris Nasus Larynx
Author(s): Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki
ObjectiveThere is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients.MethodsPulmonary function was measured in 53 patients with eosinophilic chronic rhinosinusitis with asthma, 58 patients with eosinophilic chronic rhinosinusitis without asthma, and 30 patients with non-eosinophilic chronic rhinosinusitis. The diagnosis of chronic rhinosinusitis was based on the definition in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012. Eosinophilic chronic rhinosinusitis was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system. The relationship between pulmonary function and clinical parameters was assessed. These parameters included radiographic severity of chronic rhinosinusitis, peripheral blood eosinophil percentage, serum total immunoglobulin E level, and eosinophilic infiltration in nasal polyps.ResultsThe pulmonary function of the patients with eosinophilic chronic rhinosinusitis was significantly affected. The eosinophilic chronic rhinosinusitis patients had more peripheral airway obstruction as compared to the patients with non-eosinophilic chronic rhinosinusitis.ConclusionOur findings indicated latent obstructive lung function changes in the eosinophilic chronic rhinosinusitis patients. The patients with eosinophilic chronic rhinosinusitis should be carefully monitored in order to detect lung diseases.
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Variations in the labyrinthine segment of facial nerve canal revealed by high-resolution computed tomography
Source:Auris Nasus Larynx
Author(s): Aiyan Jin, Peng Xu, Fengqin Qu
ObjectiveTo study variations in the labyrinthine segment of fallopian canal and the associated middle and inner ear malformations.MethodThe high-resolution computed tomography (HRCT) images of the temporal bone in 24 patients with congenital variations in the labyrinthine segment of fallopian canal were analyzed retrospectively. The length of labyrinthine segment of the facial nerve and angle of the first genu of 10 normal subjects were also measured. Based on the original axial images, multi-planar reformation (MPR) and curved-planar reformation (CPR) images of bilateral ossicular chains, inner ear structure and fallopian canal were reconstructed. HRCT features of congenital variations in the labyrinthine segment of the facial nerve were analyzed, including its beginning site, dehiscence, length, angle of the first genu and the associated middle and inner ear malformations.ResultsAmong the normal subjects, the length of labyrinthine segment of the facial nerve was 3.56±0.41mm, and angle of the first genu was 71.87±8.09°. Five types of variations in the labyrinthine segment of the facial nerve were found in 45 ears of 24 cases, including dehiscence in geniculate fossa in 25 ears, anteromedial displacement at the beginning site in 27 ears (widening of Bill's bar in 7 cases), enlargement of the angle of the first genu in 30 ears with an average value of 107.2° (96.0–126.0°), increase of length in 30 ears with an average length of 6.8mm (5.2–8.3mm) and bifurcation in one ear. Associated middle ear malformation in 6 ears and inner ear malformation in 36 ears were also found.ConclusionA variety of congenital variations may occur in the labyrinthine segment of the facial nerve and they are often associated with middle or inner ear malformations, which can be clearly displayed by HRCT with MPR or CPR images.
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P-REX1 amplification promotes progression of cutaneous melanoma via the PAK1/P38/MMP-2 pathway
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN.
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Modified hybrid fixation using absorbable plate and screw for mandibular advancement surgery
The purpose of this study was to examine the skeletal stability of mandibular advancement after sagittal split ramus osteotomy (SSRO) with modified hybrid fixation using absorbable plates and screws.
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Can electromagnetic-navigated maxillary positioning replace occlusional splints in orthognathic surgery? A clinical pilot study
Because of the inaccuracy of intermaxillary splints in orthognathic surgery, intraoperative guidance via a real time navigation system might represent a suitable method for enhancing the precision of maxillary positioning. Therefore, in this clinical trial, maxillary repositioning after Le Fort I osteotomy was guided splintless by an electromagnetic navigation system.
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Clinical prognostic factors of salivary adenoid cystic carcinoma: A single-center analysis of 61 patients
Adenoid cystic carcinomas are rare malignant tumors of the salivary glands. They are characterized by a high rate of local recurrence, late distant metastasis and a poor disease-free survival. In this study, we analysed a series of 61 patients who were all treated at the University of Göttingen over a period of 21.0 years.
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Prevalence and drug susceptibility pattern of group B Streptococci (GBS) among pregnant women attending antenatal care (ANC) in Nekemte Referral Hospital (NRH), Nekemte, Ethiopia
The main objective of this study was to determine the prevalence and drug susceptibility pattern of group B Streptococci (GBS) among pregnant women. The specific objectives include; (1) To determine the prevalenc...
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Seroprevalence of influenza A and B viruses among unvaccinated children in the United Arab Emirates: a cross-sectional study
Young children are at increased risk of severe influenza disease and, thus, are good candidates for receiving annual vaccination. Nevertheless, the influenza vaccine is infrequently given to children in our re...
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Development and characterization of microsatellite markers for diploid populations of the wind-pollinated herb Mercurialis annua
Mercurialis annua is a wind-pollinated annual plant that has long been used as a model for the study of ploidy and sexual-systems evolution. However, no molecular markers are yet avail...
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Preventive medicine as a first- or second-choice course: a cross-sectional survey into students’ motivational differences and implications for information provision
Challenges in recruiting and retaining medical staff in preventive medical specialties have recently been the subject of numerous studies. To improve selection procedures, it is important to understand the car...
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Nanoemulsion Formulation of a Novel Taxoid DHA-SBT-1214 Inhibits Prostate Cancer Stem Cell-Induced Tumor Growth
The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane® and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells.
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Rare Diseases on the Plastic Surgery In-Service Training Examination
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Book Review: Deep Sternal Wound Infections
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Efficacy and Safety of the Babysitter Procedure With Different Percentages of Partial Neurectomy
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The Impact of Physician Assistants on a Breast Reconstruction Practice: Outcomes and Cost Analysis
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Shared Medical Appointments for Adolescent Breast Reduction
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The “Sandwich Therapy”: A Microsurgical Integrated Approach for Presternal Keloid Treatment
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Female-to-Male Chest Reconstruction: A Review of Technique and Outcomes
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Complications After Body Contouring Surgery in Postbariatric Patients
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Mastering Lymphatic Microsurgery: A New Training Model in Living Tissue
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On-Top Index Pollicization After a Partial Amputation of a Syndactylized Hypoplastic Thumb in a Patient With Townes-Brocks Syndrome
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Quality Measures in Breast Reconstruction: A Systematic Review
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Acrylic stent to aid placement of footplate of palatal distractor during surgically-assisted rapid palatal expansion
We describe a modification that ensures the correct placement of the footplate of a palatal distractor during surgically-assisted rapid palatal expansion (SARPE). The Synthes™ transpalatal distractor (DePuy Synthes, Oberdorf, Switzerland) is a modular system consisting of a central barrel and two footplates that are screwed into bone to produce a "bone-borne" distraction force.1 An advantage of the system is the ability to change the size of the central barrel (small: 16–24mm; medium: 20–36mm; large: 24–48mm) mid-way through treatment to increase the distance of distraction.
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Simple method of covering maxillectomy defects with lyophilised amniotic membrane
Prosthetic rehabilitation and flap reconstruction are the main methods used to obliterate maxillectomy defects. Although cost-effective, prosthetic rehabilitation has limitations such as discomfort from the foreign body, poor retention in large defects, and the need for frequent readjustment. Flap reconstruction costs more, and surgeons need to be highly skilled with a well trained operating team. We describe a simple method to apply lyophilised amniotic membrane in subtotal maxillectomy defects, which helps to epithelialise the entire defect within a short space of time.
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Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2
Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2
British Journal of Cancer advance online publication, August 10 2017. doi:10.1038/bjc.2017.243
Authors: Nicola Cirillo, David J Morgan, Maria Carmela Pedicillo, Antonio Celentano, Lorenzo Lo Muzio, Michael J McCullough & Stephen S Prime
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Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy
Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy
British Journal of Cancer advance online publication, August 10 2017. doi:10.1038/bjc.2017.253
Authors: Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill & Andrew Haydon
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Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A
Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A
British Journal of Cancer advance online publication, August 10 2017. doi:10.1038/bjc.2017.263
Authors: Siti Aminah Abdul Rahim, Anne Dirkse, Anais Oudin, Anne Schuster, Jill Bohler, Vanessa Barthelemy, Arnaud Muller, Laurent Vallar, Bassam Janji, Anna Golebiewska & Simone P Niclou
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Cone beam computed tomography-based cephalometric norms for Brazilian adults
This study established cone beam computed tomography (CBCT)-based cephalometric norms for Brazilian adults, including the assessment of sexual dimorphism. An observer performed McNamara's cephalometric analysis twice on 60 CBCT datasets acquired from patients with a normal dental occlusion, divided equally into two groups by sex. Welch's t-test was applied to assess differences between the sexes in hard tissue cephalometric measurements, and Dahlberg's formula was used to calculate measurement error introduced by the observer.
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An aggressive and fatal craniofacial group A Streptococcus infection resulting from a minimally displaced orbital floor fracture
While sharp, penetrating trauma is often associated with group A Streptococcus (GAS) infections and subsequent necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS), there are scant reports in the oral and maxillofacial surgery literature regarding blunt, non-penetrating trauma in association with these conditions. With a clinical course that initially appears relatively benign following blunt trauma, NF can progress swiftly through the fascial planes and may quickly become life-threatening if the oral and maxillofacial surgeon fails to recognize some of the critical pathognomonic signs.
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Vertical platysma myocutaneous flap reconstruction for oral defects using three different incision designs: experience with 68 cases
This study evaluated the effects of three different incision designs for the vertical platysma myocutaneous flap (VPMF): apron, MacFee, and T-shaped. This flap was used for the reconstruction of intraoral defects following cancer ablation in selected patients. Sixty-eight cases of VPMF reconstruction were assessed: the apron incision was used in 28, MacFee incision in 22, and T-shaped incision in 18. With regard to postoperative outcomes, there were 26 cases of flap survival and two of partial necrosis with the apron incision; 20 of survival and two of partial necrosis with the MacFee incision; 15 of survival and three of partial necrosis with the T-shaped incision.
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Previously successful dental implants can fail when patients commence anti-resorptive therapy—a case series
This article reports a type of localized osteonecrosis that can occur in patients who have had successful osseointegrated implants for many years and then commence anti-resorptive therapy. Eleven female patients were identified who had successful implant insertion, but who were placed on anti-resorptive therapy (bisphosphonates or denosumab) several years later and developed osteonecrosis around the implants. In each case, the osteonecrosis occurred only around the implants and not around the patient's remaining teeth.
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Two-stage reconstruction of the severely deficient alveolar ridge: bone graft followed by alveolar distraction osteogenesis
Distraction osteogenesis for the augmentation of severe alveolar bone deficiency has gained popularity during the past two decades. In cases where the vertical bone height is not sufficient to create a stable transport segment, performing alveolar distraction osteogenesis (ADO) is not possible. In these severe cases, a two-stage treatment protocol is suggested: onlay bone grafting followed by ADO. An iliac crest onlay bone graft followed by ADO was performed in 13 patients: seven in the mandible and six in the maxilla.
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The expression and correlation of Hsp 70 and Hsp 27 in serous middle ear effusion fluids of pediatric patients-a preliminary study
Several cytokines and innate immune-associated molecules are present in middle ear effusions, but damage-associated molecular patterns (DAMPs) in middle ear effusion have not been studied. Therefore, we evaluated the role of heat shock proteins (Hsps) in the development of otitis media with effusion (OME).
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Post-analytical stability of 23 common chemistry and immunochemistry analytes in incurred samples
Publication date: Available online 10 August 2017
Source:Clinical Biochemistry
Author(s): Betina Klint Nielsen, Tina Frederiksen, Lennart Friis-Hansen, Pia Bükmann Larsen
BackgroundStorage of blood samples after centrifugation, decapping and initial sampling allows ordering of additional blood tests. The pre-analytic stability of biochemistry and immunochemistry analytes has been studied in detail, but little is known about the post-analytical stability in incurred samples.MethodsWe examined the stability of 23 routine analytes on the Dimension Vista® (Siemens Healthineers, Denmark): 42–60 routine samples in lithium-heparin gel tubes (Vacutainer, BD, USA) were centrifuged at 3000×g for 10min. Immediately after centrifugation, initial concentration of analytes were measured in duplicate (t=0). The tubes were stored decapped at room temperature and re-analyzed after 2, 4, 6, 8 and 10h in singletons. The concentration from reanalysis were normalized to initial concentration (t=0). Internal acceptance criteria for bias and total error were used to determine stability of each analyte. Additionally, evaporation from the decapped blood collection tubes and the residual platelet count in the plasma after centrifugation were quantified.Results and conclusionWe report a post-analytical stability of most routine analytes of ≥8h and do therefore – with few exceptions – suggest a standard 8hour-time limit for reordering and reanalysis of analytes in incurred samples.
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Model analysis of bidirectional interference in two-stage labeled-ligand immunoassays
Publication date: Available online 10 August 2017
Source:Clinical Biochemistry
Author(s): Eleanor R. Lewin, Amitava Dasgupta, Roland Valdes, Douglas F. Stickle
ObjectivesImmunoassays involving sample incubation followed by a wash step prior to introduction of labeled analyte are potentially subject to both positive and negative interference (bidirectional interference) by a competing ligand. We examine this phenomenon from a theoretical standpoint using a mathematical model for sequential-step immunoassays in the presence of interferent.Design & methodsCompetitive binding to antibody between analyte and interferent was modeled for sequential-step immunoassays. A primary assumption was that the ratio of affinity constants between the intended analyte and the interferent reflected the ratio of dissociation rate constants, with the higher dissociation rate constant for the lesser affinity ligand.ResultsRelationships of parameters (relative affinity constants, relative concentrations) for analyte and interferent were determined for conditions in which bidirectional interference can occur, for both steady-state and non-steady-state sample incubation conditions. Non-steady state sample incubation conditions can enhance the effects of an interferent. Homogeneous assay formats utilizing labeled ligand without a wash step can also demonstrate bidirectional interference, but positive interference is favored under such formats.ConclusionsModel calculations demonstrate the theoretical basis for bidirectional interference in two-stage immunoassays. Results delineate constraints on conditions in which bidirectional interference can occur.
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The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population
Publication date: Available online 10 August 2017
Source:Clinical Biochemistry
Author(s): Anne Greiser, Theresa Winter, Hala Mahfoud, Anders Kallner, Till Ittermann, Annette Masuch, Norbert Lubenow, Thomas Kohlmann, Andreas Greinacher, Matthias Nauck, Astrid Petersmann
ObjectivesDetermination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.Design & MethodsCTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.ResultsThe 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.ConclusionWhile the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.
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The expression and correlation of Hsp 70 and Hsp 27 in serous middle ear effusion fluids of pediatric patients-a preliminary study
Several cytokines and innate immune-associated molecules are present in middle ear effusions, but damage-associated molecular patterns (DAMPs) in middle ear effusion have not been studied. Therefore, we evaluated the role of heat shock proteins (Hsps) in the development of otitis media with effusion (OME).
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Aesthetic and hearing rehabilitation in patients with bilateral microtia-atresia
To evaluate the safety and efficacy of auricle reconstruction and active transcutaneous bone-conduction implantation in patients with bilateral microtia-atresia.
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【About us】"Canon Transition News" has been added.
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Breakfast habits, dairy product consumption, physical activity, and their associations with body mass index in children aged 6–18
Abstract
The purpose of this study was to determine breakfast habits, dairy product consumption, and physical activity and their relations with body mass index (BMI) in schoolchildren and adolescents. This cross-sectional, school-based study was performed with children aged 6–18 years. Height and weight were measured, and a BMI z-score was calculated for each child. Breakfast consumption frequency, intake of milk and other dairy products, physical activity habits, and mothers' employment status were assessed via a self-report questionnaire. Multiple linear regression analysis was used to estimate the association between these habits and BMI z-scores. Seven thousand one hundred sixteen children were included, 3445 (48.4%) female, with a mean age of 11.7 ± 2.7 years (5.8–18.9). Of these, 62.6% had breakfast every day. Boys ate breakfast daily significantly more often than girls (64.5 and 60.7%, respectively; p < 0.001). The percentage of children eating breakfast daily decreased with age (79.1% at 6–11 vs. 52.1% at 12–18 years, p < 0.001). Sixty-four (0.9%) children consumed no dairy products. Milk intake was negatively and significantly associated with BMI z-score (β = − 0.103, p < 0.001). Cheese consumption and the mother being employed were positively and significantly associated with BMI z-score (β = 0.517, p < 0.001, and β = 0.172, p < 0.001, respectively). Children engaging in physical activity had higher BMI z-score values than others (0.22 ± 0.01 vs. 0.12 ± 0.02, p < 0.001). Prevalence of overweight/obese was higher among children of working mothers compared to those of unemployed mothers (respectively, 29.3, 23.3%, p < 0.001).
Conclusions: Skipping breakfast was associated with overweight/obesity in schoolchildren and adolescents, while milk consumption exhibited a protective effect.
What is known? • Dietary interventions should be incorporated into a multidisciplinary strategy for obesity prevention. • Most studies of habitual physical activity in children suggest that the overweight and obese children are less active. |
What is new? • Milk consumption seems to have a protective effect against overweight/obesity, irrespective of yogurt or cheese consumption. • Children engaging in greater physical activity had higher body mass index values than others. |
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Publication date: 1 May 2019 Source: Talanta, Volume 196 Author(s): Ruiqing Long, Te Li, Chaoying Tong, Lihui Wu, Shuyun Shi Abstract...
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Oral Cancer Rapid Test Kit Market Rugged Expansion Foreseen by 2024 MilTech Oral cancer is one of the largest group of cancers ...
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