Full face ingenol mebutate for actinic keratosis: patient perspective

International Journal of Dermatology, EarlyView.


https://ift.tt/2CzrdFn

Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer

Abstract

Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms' tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints. All of the adverse events to DC vaccinations were tolerable under an adjuvant setting. The clinical response was stable disease in seven patients. Karnofsky Performance Scale scores were enhanced, and computed tomography scans revealed tumor shrinkage in three of seven patients. Human leukocyte antigen (HLA)/WT1-tetramer and cytoplasmic IFN-γ assays were used to examine the induction of a WT-1-specific immune response. The immunological responses to DC vaccination were significantly correlated with fewer myeloid-derived suppressor cells (P = 0.045) in the pretreated peripheral blood. These outcomes offered initial clinical evidence that the WT1 peptide-pulsed DC vaccination is a potential treatment for advanced cancer.

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Intralesional pentoxifylline injection in localized alopecia areata

Journal of Cosmetic Dermatology, EarlyView.


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Editorial Board w/barcode

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Table of Contents

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Hypertensive Waist and Lipid Accumulation Product as Predictors of Metabolic Syndrome

Metabolic Syndrome and Related Disorders, Ahead of Print.


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Relationship Between Obesity and Lumbar Spine Degeneration: A Cross-Sectional Study from the Fifth Korean National Health and Nutrition Examination Survey, 2010–2012

Metabolic Syndrome and Related Disorders, Ahead of Print.


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Contribution of Vaccination to the Reduction of Infectious Mortality in Ukraine in the Second Half of the 20th and Early 21st Century: A Comparative Population Based Study of the Dynamics and Structure of Infectious Mortality and Incidence

Viral Immunology, Ahead of Print.


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The steadily growing problem of lentigo maligna and lentigo maligna melanoma in Australia: Population‐based data on diagnosis and management

Australasian Journal of Dermatology, EarlyView.


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Anaesthesia care team improves outcomes in surgical patients compared with solo anaesthesiologist: An observational study

BACKGROUND In anaesthesiology, little attention has been drawn to the role of anaesthesia nurses as support personnel on quality of care. OBJECTIVES To compare the impact of anaesthesia by an anaesthesiologist alone (solo anaesthesiologist) or in combination with an anaesthesia nurse (anaesthesia care team) on 30-day postoperative mortality and hospital length of stay. RESULTS Anaesthesia was performed by solo anaesthesiologists in 2832 patients and by an anaesthesia care team in 2842 patients. The two groups were comparable in respect of sex and duration of anaesthesia but differed notably for age, American Society of Anesthesiologists' physical status score and type of surgery. Propensity score matching was performed by logistic regression to adjust for baseline differences between the two groups and 2095 pairs of perfectly matched patients were formed. The latter evidenced a significantly lower 30-day mortality rate for the anaesthesia care team compared with solo anaesthesiologists (0.76 vs. 1.56%, P = 0.0014). Length of hospital stay was also significantly reduced when an anaesthesia nurse was present (4.9 ± 10.1 vs. 5.6 ± 11.5 days, P = 0.0011). CONCLUSION Anaesthesia given by the combination of an anaesthesiologist and an anaesthesia nurse is associated with decreased 30-day postoperative mortality and shorter length of stay when compared with a solo anaesthesiologist. Even if without any demonstration of causality, this emphasises the benefits of the anaesthesia care team model. TRIAL REGISTRATION CCB 325201730849. Correspondence to Patrice Forget, Anaesthesiology and Perioperative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium Tel: +32 24773058; e-mail: forgetpatrice@yahoo.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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Androgens in Women: Hormone modulating therapies for skin disease (Part II)

Androgen-mediated cutaneous disorders (AMCDs) in women including acne, hirsutism, and female pattern hair loss (FPHL) can be treated with hormone-modulating therapies. In the second part of this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments utilized for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy.

https://ift.tt/2Nyjk47

Androgens in Women: Androgen mediated skin disease and patient evaluation (Part I)

Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, as well as in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), testosterone, dihydrotestosterone (DHT), and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL) – androgen mediated cutaneous disorders (AMCDs).

https://ift.tt/2ONNlSe

Flow mediated vasodilation assay indicates no endothelial dysfunction in hereditary angioedema patients with C1-inhibitor deficiency

Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare, potentially life-threatening disorder characterized by recurrent edematous attacks. The edema formation is the consequence of interaction of bradykinin and various vasoactive peptides with endothelium. Besides these agents, danazol, a modified testosterone derivative used in these patients to prevent edematous attacks, can also affect the function of the endothelium, since it shifts the blood lipid profile to a pro-atherogenic phenotype.

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From the Pages of AllergyWatch

John J. Oppenheimer, MD, Assistant Editor

https://ift.tt/2NyRzIE

Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of Antibody Repertoires [SYSTEMS IMMUNOLOGY]

Abs are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made Abs the primary class of biopharmaceuticals. Recently, it has become possible to query their immense natural diversity using next-generation sequencing of Ig gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 55 studies, covering more than half a billion Ab sequences across diverse immune states, organisms (primarily human and mouse), and individuals. We have sorted, cleaned, annotated, translated, and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at http://antibodymap.org. The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.

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Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative Myelopoiesis and Tissue Recovery following Ischemic Damage [INNATE IMMUNITY AND INFLAMMATION]

Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM)-generating myeloid cells, and persistent HSPC activity may drive chronic inflammation and impair tissue recovery. Although increased reactive oxygen species in the BM regulate HSPC functions, their roles in myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic damage are not well understood. In this paper, we report that deletion of Nox2 NADPH oxidase in mice results in persistent elevations in BM HSPC activity and levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model of hindlimb ischemia. Ischemic tissue damage induces oxidants in BM such as elevations of hydrogen peroxide and oxidized phospholipids, which activate redox-sensitive Lyn kinase in a Nox2-dependent manner. Moreover, during tissue recovery after ischemic injury, this Nox2-ROS–Lyn kinase axis is induced by Nox2 in neutrophils that home to the BM, which inhibits HSPC activity and inflammatory monocyte generation and promotes tissue regeneration after ischemic damage. Thus, oxidant signaling in the BM mediated by Nox2 in neutrophils regulates myelopoiesis of HSPCs to promote regeneration of damaged tissue.

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The Role of WNT Signaling in Mature T Cells: T Cell Factor Is Coming Home [BRIEF REVIEWS]

T cell factor, the effector transcription factor of the WNT signaling pathway, was so named because of the primary observation that it is indispensable for T cell development in the thymus. Since this discovery, the role of this signaling pathway has been extensively studied in T cell development, hematopoiesis, and stem cells; however, its functional role in mature T cells has remained relatively underinvestigated. Over the last few years, various studies have demonstrated that T cell factor can directly influence T cell function and the differentiation of Th1, Th2, Th17, regulatory T cell, follicular helper CD4⁺ T cell subsets, and CD8⁺ memory T cells. In this paper, we discuss the molecular mechanisms underlying these observations and place them in the general context of immune responses. Furthermore, we explore the implications and limitations of these findings for WNT manipulation as a therapeutic approach for treating immune-related diseases.

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Bacterial Lipoproteins Constitute the TLR2-Stimulating Activity of Serum Amyloid A [INNATE IMMUNITY AND INFLAMMATION]

Studies comparing endogenous and recombinant serum amyloid A (SAA) have generated conflicting data on the proinflammatory function of these proteins. In exploring this discrepancy, we found that in contrast to commercially sourced recombinant human SAA1 (hSAA1) proteins produced in Escherichia coli, hSAA1 produced from eukaryotic cells did not promote proinflammatory cytokine production from human or mouse cells, induce Th17 differentiation, or stimulate TLR2. Proteomic analysis of E. coli–derived hSAA1 revealed the presence of numerous bacterial proteins, with several being reported or probable lipoproteins. Treatment of hSAA1 with lipoprotein lipase or addition of a lipopeptide to eukaryotic cell–derived hSAA1 inhibited or induced the production of TNF-α from macrophages, respectively. Our results suggest that a function of SAA is in the binding of TLR2-stimulating bacterial proteins, including lipoproteins, and demand that future studies of SAA employ a recombinant protein derived from eukaryotic cells.

https://ift.tt/2OhOUbC

Cutting Edge: Intracellular IFN-{beta} and Distinct Type I IFN Expression Patterns in Circulating Systemic Lupus Erythematosus B Cells [CUTTING EDGE]

In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN–stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-β. Single-cell analyses of transitional B cells isolated from SLE patients revealed distinct B cell subpopulations, including type I IFN producers, IFN responders, and mixed IFN producer/responder clusters. Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I IFNs that could stimulate HEK-Blue cells. Increased levels of IFN-β were detected in circulating B cells from SLE patients compared with controls and were significantly higher in African American patients with renal disease and in patients with autoantibodies. Together, the results identify type I IFN–producing and –responding subpopulations within the SLE B cell compartment and suggest that some patients may benefit from specific targeting of IFN-β.

https://ift.tt/2Ofo04c

Cardiotrophin-like Cytokine Increases Macrophage-Foam Cell Transition [INNATE IMMUNITY AND INFLAMMATION]

CLCF1 is a neurotrophic and B cell–stimulating factor belonging to the IL-6 family. Mutations in the gene coding for CLCF1 or its secretion partner CRLF1 lead to the development of severe phenotypes, suggesting important nonredundant roles in development, metabolism, and immunity. Although CLCF1 was shown to promote the proliferation of the myeloid cell line M1, its roles on myeloid activation remain underinvestigated. We characterized the effects of CLCF1 on myeloid cells with a focus on monocyte–macrophage and macrophage–foam cell differentiations. CLCF1 injections in mice resulted in a significant increase in CD11b⁺ circulating cells, including proinflammatory monocytes. Furthermore, CLCF1 activated STAT3 phosphorylation in bone marrow CD11b⁺ cells and in bone marrow–derived macrophages (BMDM). BMDM stimulated with CLCF1 produced a large array of proinflammatory factors comprising IL-6, IL-9, G-CSF, GM-CSF, IL-1β, IL-12, CCL5, and CX3CL1. The pattern of cytokines and chemokines released by CLCF1-treated BMDM led us to investigate the role of CLCF1 in foam cell formation. When pretreated with CLCF1, BMDM presented a marked SR-A1 upregulation, an increase in acetylated–low-density lipoprotein uptake, and an elevated triglyceride accumulation. CLCF1-induced SR-A1 upregulation, triglyceride accumulation, and acetylated–low-density lipoprotein uptake could be prevented using ruxolitinib, a JAK inhibitor, indicating that the effects of the cytokine on myeloid cells result from activation of the canonical JAK/STAT signaling pathway. Our data reveal novel biological roles for CLCF1 in the control of myeloid function and identify this cytokine as a strong inducer of macrophage–foam cell transition, thus bringing forward a new potential therapeutic target for atherosclerosis.

https://ift.tt/2OhOKB2

Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs [CUTTING EDGE]

Several heat shock proteins (HSPs) prime immune responses, which are, in part, a result of activation of APCs. APCs respond to these immunogenic HSPs by upregulating costimulatory molecules and secreting cytokines, including IL-1β. These HSP-mediated responses are central mediators in pathological conditions ranging from cancer, sterile inflammation associated with trauma, and rheumatoid arthritis. We tested in this study the requirement of inflammasomes in the release of IL-1β by one immunogenic HSP, gp96. Our results show that murine APCs activate NLRP3 inflammasomes in response to gp96 by K⁺ efflux. This is shown to initiate inflammatory conditions in vivo in the absence of additional known inflammasome activators or infection. These results document a novel mechanism by which proteins of endogenous origin, the HSPs, can modulate an inflammatory response following their release from aberrant cells.

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In This Issue [IN THIS ISSUE]

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Cutting Edge: TGF-{beta} and Phosphatidylinositol 3-Kinase Signals Modulate Distinct Metabolism of Regulatory T Cell Subsets [CUTTING EDGE]

Murine Foxp3⁺ regulatory T cells (Tregs) differentiated in vitro (induced Tregs [iTregs]) in the presence of anti-inflammatory cytokine TGF-β rely predominantly upon lipid oxidation to fuel mitochondrial oxidative phosphorylation. Foxp3 expression underlies this metabolic preference, as it suppresses glycolysis and drives oxidative phosphorylation. In this study, we show that in contrast to iTregs, thymic-derived Tregs (tTregs), engage in glycolysis and glutaminolysis at levels comparable to effector T cells despite maintained Foxp3 expression. Interestingly, exposure of tTregs to the anti-inflammatory cytokine TGF-β represses PI3K-mediated mTOR signaling, inhibits glucose transporter and Hk2 expression, and reprograms their metabolism to favor oxidative phosphorylation. Conversely, replicating the effects of inflammation via elevation of PI3K signaling has minimal effects on tTregs but dramatically enhances the glycolysis of normally oxidative iTregs, resulting in reduction of Foxp3 expression. Collectively, these findings suggest both extrinsic and intrinsic factors govern the unique metabolic signature of Treg subsets.

https://ift.tt/2OjJJYY

IL-17A Attenuates IFN-{lambda} Expression by Inducing Suppressor of Cytokine Signaling Expression in Airway Epithelium [INNATE IMMUNITY AND INFLAMMATION]

IFN- is a cytokine expressed in epithelial tissues and plays a central role in antiviral mucosal immune response. The expression of IFN- in the airway is impaired in chronic airway diseases (e.g., asthma, chronic obstructive pulmonary disease), which renders patients susceptible to viral infection. IL-17A is associated with asthma and chronic obstructive pulmonary disease pathogenesis; however, IL-17A regulation of IFN- expression remains unclear. The aim of the current study is to clarify IL-17A–mediated regulatory mechanisms of IFN- expression in human airway epithelial cells. In this study, we have shown that polyinosinic:polycytidylic acid (polyI:C) and influenza A virus (IAV) infection increased IFN- expression at mRNA and protein levels in primary cultures of normal human bronchial epithelial cells, whereas IL-17A attenuated polyI:C- or IAV-induced IFN- expression. IFN- receptor 1 knockdown and a JAK inhibitor, ruxolitinib, attenuated polyI:C-induced IFN- expression, confirming that a positive autocrine feedback loop, the IFN- receptor–JAK–STAT pathway, was involved in IFN- expression. In Western blotting analysis, we demonstrated that polyI:C and IAV infection induced STAT1 phosphorylation in normal human bronchial epithelial cells, whereas IL-17A suppressed polyI:C- or IAV-mediated STAT1 phosphorylation. Furthermore, we found that cotreatment with IL-17A and polyI:C or IAV infection synergistically increased suppressor of cytokine signaling (SOCS)1 and SOCS3 expression. SOCS1 small interfering RNA and SOCS3 small interfering RNA negated the inhibitory effect of IL-17A in polyI:C-induced IFN- expression by restoring attenuated STAT1 phosphorylation. Taken together, these findings indicate that IL-17A attenuates virus-induced IFN- expression by enhancing SOCS1 and SOCS3 expression to inhibit autocrine signaling loops in human airway epithelial cells.

https://ift.tt/2OhORws

Bronchial Allergen Challenge of Patients with Atopic Asthma Triggers an Alarmin (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa [ALLERGY AND OTHER HYPERSENSITIVITIES]

The alarmin cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play a critical role in asthma pathogenesis by inducing mucosal Th2-type cytokine production. Although environmental exposure to aeroallergens has been proposed as an alarmin trigger in asthma, there has been no systematic parallel study of the effects of allergen exposure on the expression of these cytokines in the airways of human asthmatics. Using single and sequential double immunohistochemistry, we evaluated the numbers and phenotypes of IL-25–, IL-33–, and TSLP-immunoreactive cells in sections of bronchial biopsies from mild atopic asthmatics (n = 16) before and 24 h after allergen inhalational challenge. Allergen challenge highly increased expression of baseline immunoreactivity for IL-25, IL-33, and TSLP, both in the bronchial epithelium and submucosa (p < 0.001), to a degree that correlated with the extent of the late phase of airway obstruction. Aside from epithelial cells, the principal source of immunoreactivity for all three alarmins, TSLP, and IL-33 immunoreactivity colocalized principally with endothelial cells and mast cells, neutrophils, and fibroblasts, whereas IL-25 immunoreactivity colocalized principally with eosinophils as well as endothelial cells, mast cells, and fibroblasts. The data implicate that allergen challenge directly increases airway alarmin expression in atopic asthmatics to a degree correlating with increase late-phase airway obstruction, affirming these molecules as potential molecular targets for the inhibition of allergen-induced airway inflammation and obstruction.

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Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium [INNATE IMMUNITY AND INFLAMMATION]

Baculovirus (BV), an enveloped insect virus with a circular dsDNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. In this study, we show that BV administration in BALB/c mice not only provides complete protection against a subsequent Plasmodium berghei sporozoite infection for up to 7 d after the injection but also eliminates existing liver-stage parasites completely. The elimination of sporozoites by BV was superior to that by primaquine, and this effect occurred in a TLR9-independent manner. At 6 h after BV administration, IFN-α and IFN- were robustly produced in the serum, and RNA transcripts of IFN-stimulated genes were markedly upregulated in the liver compared with control mice. The in vivo passive transfer of serum after BV administration effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite-killing mechanism is downstream of the type I IFN signaling pathway. These findings provide evidence that BV-induced, fast-acting innate immunity completely kills liver-stage parasites and, thus, may lead to new malaria drug and vaccine strategies.

https://ift.tt/2OhONgc

TLR9 and IL-1R1 Promote Mobilization of Pulmonary Dendritic Cells during Beryllium Sensitization [ALLERGY AND OTHER HYPERSENSITIVITIES]

Metal-induced hypersensitivity is driven by dendritic cells (DCs) that migrate from the site of exposure to the lymph nodes, upregulate costimulatory molecules, and initiate metal-specific CD4⁺ T cell responses. Chronic beryllium disease (CBD), a life-threatening metal-induced hypersensitivity, is driven by beryllium-specific CD4⁺ Th1 cells that expand in the lung-draining lymph nodes (LDLNs) after beryllium exposure (sensitization phase) and are recruited back to the lung, where they orchestrate granulomatous lung disease (elicitation phase). To understand more about how beryllium exposures impact DC function during sensitization, we examined the early events in the lung and LDLNs after pulmonary exposure to different physiochemical forms of beryllium. Exposure to soluble or crystalline forms of beryllium induced alveolar macrophage death/release of IL-1α and DNA, enhanced migration of CD80^hi DCs to the LDLNs, and sensitized HLA-DP2 transgenic mice after single low-dose exposures, whereas exposures to insoluble particulate forms beryllium did not. IL-1α and DNA released by alveolar macrophages upregulated CD80 on immature BMDC via IL-1R1 and TLR9, respectively. Intrapulmonary exposure of mice to IL-1R and TLR9 agonists without beryllium was sufficient to drive accumulation of CD80^hi DCs in the LDLNs, whereas blocking both pathways prevented accumulation of CD80^hi DCs in the LDLNs of beryllium-exposed mice. Thus, in contrast to particulate forms of beryllium, which are poor sensitizers, soluble or crystalline forms of beryllium promote death of alveolar macrophages and their release of IL-1α and DNA, which act as damage-associated molecular pattern molecules to enhance DC function during beryllium sensitization.

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Haptoglobin Is a Divergent MASP Family Member That Neofunctionalized To Recycle Hemoglobin via CD163 in Mammals [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

In mammals, haptoglobin (Hp) is an acute-phase plasma protein that binds with high affinity to hemoglobin (Hb) released by intravascular hemolysis. The resultant Hp–Hb complexes are bound and cleared by the scavenger receptor CD163, limiting Hb-induced oxidative damage. In this study, we show that Hp is a divergent member of the complement-initiating MASP family of proteins, which emerged in the ancestor of jawed vertebrates. We demonstrate that Hp has been independently lost from multiple vertebrate lineages, that characterized Hb-interacting residues of mammals are poorly conserved in nonmammalian species maintaining Hp, and that the extended loop 3 region of Hp, which mediates CD163 binding, is present only in mammals. We show that the Hb-binding ability of cartilaginous fish (nurse shark, Ginglymostoma cirratum; small-spotted catshark, Scyliorhinus canicula; and thornback ray, Raja clavata) and teleost fish (rainbow trout, Oncorhynchus mykiss) Hp is species specific, and where binding does occur it is likely mediated through a different structural mechanism to mammalian Hp. The continued, high-level expression of Hp in cartilaginous fishes in which Hb binding is not evident signals that Hp has (an)other, yet unstudied, role(s) in these species. Previous work indicates that mammalian Hp also has secondary, immunomodulatory functions that are independent of Hb binding; our work suggests these may be remnants of evolutionary more ancient functions, retained after Hb removal became the primary role of Hp in mammals.

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Remarkably Robust Antiviral Immune Response despite Combined Deficiency in Caspase-8 and RIPK3 [IMMUNE REGULATION]

Caspase-8 (Casp8)–mediated signaling triggers extrinsic apoptosis while suppressing receptor-interacting protein kinase (RIPK) 3–dependent necroptosis. Although Casp8 is dispensable for the development of innate and adaptive immune compartments in mice, the importance of this proapoptotic protease in the orchestration of immune response to pathogens remains to be fully explored. In this study, Casp8^–/–Ripk3^–/– C57BL/6 mice show robust innate and adaptive immune responses to the natural mouse pathogen, murine CMV. When young, these mice lack lpr-like lymphoid hyperplasia and accumulation of either B220⁺CD3⁺ or B220^–CD3⁺CD4⁺ and CD8⁺ T cells with increased numbers of immature myeloid cells that are evident in older mice. Dendritic cell activation and cytokine production drive both NK and T cell responses to control viral infection in these mice, suggesting that Casp8 is dispensable to the generation of antiviral host defense. Curiously, NK and T cell expansion is amplified, with greater numbers observed by 7 d postinfection compared with either Casp8^+/–Ripk3^–/– or wild type (Casp8^+/+Ripk3^+/+) littermate controls. Casp8 and RIPK3 are natural targets of virus-encoded cell death suppressors that prevent infected cell apoptosis and necroptosis, respectively. It is clear from the current studies that the initiation of innate immunity and the execution of cytotoxic lymphocyte functions are all preserved despite the absence of Casp8 in responding cells. Thus, Casp8 and RIPK3 signaling is completely dispensable to the generation of immunity against this natural herpesvirus infection, although the pathways driven by these initiators serve as a crucial first line for host defense within virus-infected cells.

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Correction: IL-4 Regulates Bim Expression and Promotes B Cell Maturation in Synergy with BAFF Conferring Resistance to Cell Death at Negative Selection Checkpoints [CORRECTIONS]

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Presenilin 1 Regulates NF-{kappa}B Activation via Association with Breakpoint Cluster Region and Casein Kinase II [IMMUNE REGULATION]

We recently reported that NF-B–mediated inflammation caused by breakpoint cluster region (BCR) is dependent on the α subunit of casein kinase II (CK2α) complex. In the current study, we demonstrate that presenilin 1 (Psen1), which is a catalytic component of the -secretase complex and the mutations of which are known to cause familial Alzheimer disease, acts as a scaffold of the BCR–CK2α–p65 complex to induce NF-B activation. Indeed, Psen1 deficiency in mouse endothelial cells showed a significant reduction of NF-B p65 recruitment to target gene promoters. Conversely, Psen1 overexpression enhanced reporter activation under NF-B responsive elements and IL-6 promoter. Furthermore, the transcription of NF-B target genes was not inhibited by a -secretase inhibitor, suggesting that Psen1 regulates NF-B activation in a manner independent of -secretase activity. Mechanistically, Psen1 associated with the BCR–CK2α complex, which is required for phosphorylation of p65 at serine 529. Consistently, TNF-α–induced phosphorylation of p65 at serine 529 was significantly decreased in Psen1-deficient cells. The association of the BCR–CK2α–p65 complex was perturbed in the absence of Psen1. These results suggest that Psen1 functions as a scaffold of the BCR–CK2α–p65 complex and that this signaling cascade could be a novel therapeutic target for various chronic inflammation conditions, including those in Alzheimer disease.

https://ift.tt/2Oi0oMo

{beta}1 Integrins Are Required To Mediate NK Cell Killing of Cryptococcus neoformans [INFECTIOUS DISEASE AND HOST RESPONSE]

Cryptococcus neoformans is a fungal pathogen that causes fatal meningitis and pneumonia. During host defense to Cryptococcus, NK cells directly recognize and kill C. neoformans using cytolytic degranulation analogous to killing of tumor cells. This fungal killing requires independent activation of Src family kinase (SFK) and Rac1-mediated pathways. Recognition of C. neoformans requires the natural cytotoxicity receptor, NKp30; however, it is not known whether NKp30 activates both signal transduction pathways or whether a second receptor is involved in activation of one of the pathways. We used primary human NK cells and a human NK cell line and found that NKp30 activates SFK -> PI3K but not Rac1 cytotoxic signaling, which led to a search for the receptor leading to Rac1 activation. We found that NK cells require integrin-linked kinase (ILK) to activate Rac1 for effective fungal killing. This observation led to our identification of β1 integrin as an essential anticryptococcal receptor. These findings demonstrate that multiple receptors, including β1 integrins and NKp30 and their proximal signaling pathways, are required for recognition of Cryptococcus, which activates a central cytolytic antimicrobial pathway leading to fungal killing.

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Bmi1 Regulates I{kappa}B{alpha} Degradation via Association with the SCF Complex [IMMUNE REGULATION]

Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination complex PRC1 in the nucleus with no evidently direct link to the NF-B pathway. In this study, we report a novel function of Bmi1: its regulation of IBα ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-B–mediated gene expression in vitro and a NF-B–mediated mouse model of arthritis in vivo. Mechanistic analysis showed that Bmi1 associated with the SCF ubiquitination complex via its N terminus and with phosphorylation by an IKKα/β-dependent pathway, leading to the ubiquitination of IBα. These effects on NF-B–related inflammation suggest Bmi1 in the SCF complex is a potential therapeutic target for various diseases and disorders, including autoimmune diseases.

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D-Glycero-{beta}-D-Manno-Heptose 1-Phosphate and D-Glycero-{beta}-D-Manno-Heptose 1,7-Biphosphate Are Both Innate Immune Agonists [INNATE IMMUNITY AND INFLAMMATION]

d-Glycero-β-d-manno-heptose 1,7-biphosphate (β-HBP) is a novel microbial-associated molecular pattern that triggers inflammation and thus has the potential to act as an immune modulator in many therapeutic contexts. To better understand the structure–activity relationship of this molecule, we chemically synthesized analogs of β-HBP and tested their ability to induce canonical TIFA-dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic epithelial cells (HCT 116). Of the analogs tested, only d-glycero-β-d-manno-heptose 1-phosphate (β-HMP) induced TIFA-dependent NF-B activation and cytokine production in a manner similar to β-HBP. This finding expands the spectrum of metabolites from the Gram-negative ADP–heptose biosynthesis pathway that can function as innate immune agonists and provides a more readily available agonist of the TIFA-dependent inflammatory pathway that can be easily produced by synthetic methods.

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What to know about age spots (liver spots)

Age spots, or liver spots, are common and harmless. They do not require treatment, but people can get rid of them with creams and cosmetic procedures. Age spots can resemble certain forms of skin cancer, and anyone concerned about an age spot should speak with a doctor.

https://ift.tt/2ILFa3f

Siglec-7 engagement by GBS {beta}-protein suppresses pyroptotic cell death of natural killer cells [Immunology and Inflammation]

Natural killer (NK) cells are innate immune lymphocytes that recognize and destroy abnormal host cells, such as tumor cells or those infected by viral pathogens. To safely accomplish these functions, NK cells display activating receptors that detect stress molecules or viral ligands displayed at the cell surface, balanced by inhibitory...

https://ift.tt/2Ogo9EC

PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice [Cell Biology]

PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a...

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Accurate timetrees require accurate calibrations [Biological Sciences]

Morris et al. (1) estimate divergence times for land plants (embryophytes), concluding that they originated in the early Phanerozoic (515 to 473 Ma; midpoint, 494 Ma). In contrast, other molecular clock studies have placed that event 40% earlier, in the Precambrian (707 to 670 Ma) (2–4). Knowing the correct time...

https://ift.tt/2NvNvJi

Functionally specific optogenetic modulation in primate visual cortex [Neuroscience]

In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection...

https://ift.tt/2yq2yP3

Reply to Hedges et al.: Accurate timetrees do indeed require accurate calibrations [Biological Sciences]

We (1) attempted to establish an evolutionary timescale for land plant evolution utilizing available genome-scale data and a new set of calibrations constraining the age of clades based on critical analysis of paleontologic, phylogenetic (2), and geologic evidence. We explored many factors, such as the inclusion or exclusion of a...

https://ift.tt/2OQ5NJO

Corepressor SMRT is required to maintain Hox transcriptional memory during somitogenesis [Developmental Biology]

Nuclear hormone receptors (NRs), such as retinoic acid receptors (RARs), play critical roles in vertebrate development and homeostasis by regulating target gene transcription. Their activity is controlled by ligand-dependent release of corepressors and subsequent recruitment of coactivators, but how these individual receptor modes contribute to development are unknown. Here, we...

https://ift.tt/2Oc80zX

Profile of Jonathan D. G. Jones [Profiles]

Plant molecular geneticist Jonathan D. G. Jones has made seminal contributions to understanding mechanisms underlying resistance to plant disease. A group leader at The Sainsbury Laboratory in Norwich, United Kingdom, Jones was among the first to isolate and characterize disease resistance genes. His discovery of receptor-like proteins (RLPs) preceded discovery...

https://ift.tt/2NzqPIl

A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice [Neuroscience]

Sleep is an evolutionally conserved behavior from vertebrates to invertebrates. The molecular mechanisms that determine daily sleep amounts and the neuronal substrates for homeostatic sleep need remain unknown. Through a large-scale forward genetic screen of sleep behaviors in mice, we previously demonstrated that the Sleepy mutant allele of the Sik3...

https://ift.tt/2yuSC6W

Ryanodine receptor cluster size sets the tone in cerebral smooth muscle [Physiology]

Ryanodine receptors (RyRs) are large intracellular Ca2+ channels that provide the molecular basis of the process termed Ca2+-induced Ca2+ release (1). Ca2+ signaling through RyRs has been shown to be critical for skeletal, cardiac, and smooth muscle physiology (2) as well as for neurons (3) and secretory cells like pancreatic...

https://ift.tt/2OQ5Jty

Correction for Mittal et al., Codon usage influences fitness through RNA toxicity [Corrections]

SYSTEMS BIOLOGY Correction for "Codon usage influences fitness through RNA toxicity," by Pragya Mittal, James Brindle, Julie Stephen, Joshua B. Plotkin, and Grzegorz Kudla, which was first published August 6, 2018; 10.1073/pnas.1810022115 (Proc Natl Acad Sci USA 115:8639–8644). The authors note that the following statement should be added as a...

https://ift.tt/2ObFDlk

Direct visualization of ion-channel gating in a native environment [Biophysics and Computational Biology]

Pentameric ligand-gated ion channels (pLGICs), also known as Cys-loop receptors, are localized primarily in the postsynaptic membranes, and mediate fast chemical transmission in the central and peripheral nervous systems. Binding of neurotransmitter activates these receptors, causing changes in postsynaptic membrane potential and consequently modulation of neuronal or muscle activity. pLGIC...

https://ift.tt/2NyrRE8

Revised M06 density functional for main-group and transition-metal chemistry [Chemistry]

We present a hybrid metageneralized-gradient-approximation functional, revM06, which is based on adding Hartree–Fock exchange to the revM06-L functional form. Compared with the original M06 suite of density functionals, the resulting revM06 functional has significantly improved across-the-board accuracy for both main-group and transition-metal chemistry. The revM06 functional improves on the M06-2X...

https://ift.tt/2yA3CQP

Collusion between neutralizing antibodies and other immune factions in the destruction of adenoviral vectors [Microbiology]

Adenoviral vectors hold great promise for gene therapy, the induction of antitumor immunity, and vaccination against viral infections (1, 2). But sometimes, preexisting antibodies elicited by natural infection with particular types of adenovirus prevent the desired expression of the transgene carried by the vector, such as a replication-defective adenovirus 5....

https://ift.tt/2Ea8Etc

Sediment starvation destroys New York City marshes’ resistance to sea level rise [Ecology]

New York City (NYC) is representative of many vulnerable coastal urban populations, infrastructures, and economies threatened by global sea level rise. The steady loss of marshes in NYC's Jamaica Bay is typical of many urban estuaries worldwide. Essential to the restoration and preservation of these key wetlands is an understanding...

https://ift.tt/2OdP2sS

Phevamine A, a small molecule that suppresses plant immune responses [Chemistry]

Bacterial plant pathogens cause significant crop damage worldwide. They invade plant cells by producing a variety of virulence factors, including small-molecule toxins and phytohormone mimics. Virulence of the model pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) is regulated in part by the sigma factor HrpL. Our study of the HrpL...

https://ift.tt/2EbUeZE

Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia [Microbiology]

Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for...

https://ift.tt/2REk7DP

Energy-dependent quenching adjusts the excitation diffusion length to regulate photosynthetic light harvesting [Chemistry]

An important determinant of crop yields is the regulation of photosystem II (PSII) light harvesting by energy-dependent quenching (qE). However, the molecular details of excitation quenching have not been quantitatively connected to the fraction of excitations converted to chemical energy by PSII reaction centers (PSII yield), which determines flux to...

https://ift.tt/2OQ5GOo

Small molecule inhibits {alpha}-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons [Neuroscience]

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of intracellular protein inclusions, known as Lewy bodies and Lewy neurites, which are mainly composed of α-synuclein. Here, we exploited a...

https://ift.tt/2ypRTE9

Use of scenario ensembles for deriving seismic risk [Earth, Atmospheric, and Planetary Sciences]

High death tolls from recent earthquakes show that seismic risk remains high globally. While there has been much focus on seismic hazard, large uncertainties associated with exposure and vulnerability have led to more limited analyses of the potential impacts of future earthquakes. We argue that as both exposure and vulnerability...

https://ift.tt/2NuYvqt

Dawn and photoperiod sensing by phytochrome A [Plant Biology]

In plants, light receptors play a pivotal role in photoperiod sensing, enabling them to track seasonal progression. Photoperiod sensing arises from an interaction between the plant's endogenous circadian oscillator and external light cues. Here, we characterize the role of phytochrome A (phyA) in photoperiod sensing. Our metaanalysis of functional genomic...

https://ift.tt/2OcndB7

Efficacy of an Intervention for the Children With Severe Speech Sounds Disorders

Conditions:   Speech Sound Disorder;   Apraxia of Speech;   Developmental Verbal Dyspraxia
Intervention:   Behavioral: Treatment for Children with Severe Speech Sound Disorders
Sponsor:   Chinese University of Hong Kong
Not yet recruiting

https://ift.tt/2OiFYmB

Application of Ultrasonic Gray-scale Ratio in Differentiating Benign From Malignant Thyroid Nodules.

Condition:   Thyroid Nodule
Intervention:   Diagnostic Test: ultrasound gray-scale ratio
Sponsor:   First People's Hospital of Hangzhou
Not yet recruiting

https://ift.tt/2yr1zy9

Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy

Condition:   Head and Neck Cancer
Interventions:   Procedure: Surgical resection of primary tumor;   Radiation: Adjuvant radio(-chemo)therapy;   Drug: Neoadjuvant Nivolumab;   Drug: Adjuvant Nivolumab;   Drug: Adjuvant Nivolumab and Ipilimumab
Sponsors:   Universitätsklinikum Hamburg-Eppendorf;   University Hospital, Essen;   Westpfalz-Clinical Center GmbH;   Charite University, Berlin, Germany
Recruiting

https://ift.tt/2OcPfwi

Neoadjuvant and Concurrent PD-1 Blockade Combined With Definitive Chemoradiation in Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Neoplasms
Interventions:   Drug: Sintilimab;   Drug: Gemcitabine;   Drug: Cisplatin;   Radiation: intensity-modulated radiotherapy
Sponsors:   Sun Yat-sen University;   Innovent Biologics (Suzhou) Co. Ltd.
Not yet recruiting

https://ift.tt/2ytZ9PA

Early Detection of Head and Neck Superficial Squamous Cell Carcinoma in Patients With Esophagus Squamous Cell Carcinoma

Condition:   Optical Enhancement Endoscopy
Interventions:   Device: first OE;   Device: first WLI
Sponsor:   Shandong University
Recruiting

https://ift.tt/2Og8KEf

Horse Riding and the Shape of the Acetabulum: Insights from the Bioarchaeological Analysis of Early Hungarian Mounted Archers (10th Century)

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2A0qn28

Beyond white‐tailed deer hunting in Aguazuque: Archaeofaunal data from an Archaic site at Sabana de Bogotá‐Colombia

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QAMVfh

Strontium and nitrogen isotopic evidence of food import to Tell Ashara – Terqa, a Bronze Age city on the Euphrates, Syria

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2A00dwf

HUMAN BIOGEOGRAPHY AND FAUNAL EXPLOITATION IN DIAMANTE RIVER BASIN, CENTRAL WESTERN ARGENTINA

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QCbeJH

Therapie des kutanen malignen Melanoms im Kopf-Hals-Bereich

Zusammenfassung

In den letzten Jahren hat es erhebliche Entwicklungen in der Behandlung des malignen Melanoms gegeben. Diese betreffen einerseits die durch Ergebnisse randomisierter Studien in ihrer Evidenz vergleichsweise gut abgesicherten Empfehlungen zur chirurgischen Resektion und zum Lymphknotenmanagement. Andererseits haben medikamentöse Neuentwicklungen wie die zielgerichteten Therapien zu umwälzenden Fortschritten in der Behandlung der metastasierten Stadien geführt. Die Kenntnis der Behandlungsalgorithmen und ihrer Aktualisierungen ist für den MKG-Chirurgen unabdingbar. Die S3-Leitlinie „Diagnostik, Behandlung und Nachsorge des malignen Melanoms" wurde im Jahr 2013 veröffentlicht und inzwischen zweimal, 2016 und 2018 aktualisiert. Der vorliegende Beitrag informiert über diese Entwicklungen und deren aktuellen Stand und geht auf die für die Therapie des Melanoms im Kopf-Hals-Bereich relevanten Punkte ein.

https://ift.tt/2PlmNF6

Use of Noninvasive Ventilation with Volume-Assured Pressure Support to Avoid Tracheostomy in Severe Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder in children but can occasionally present with life-threatening hypoxemia. Obesity is a significant risk factor for poor outcomes of OSA treatment. Continuous positive airway pressure (CPAP) is indicated in children who are not candidates for or have an unsatisfactory response to adenotonsillectomy. Children acutely at risk for significant morbidity with other therapies are candidates for a tracheostomy. An eight-year-old patient with morbid obesity and severe OSA refractory to CPAP therapy was treated successfully with a novel noninvasive ventilation (NIV) mode with volume-assured pressure support (VAPS) and avoided tracheostomy.

https://ift.tt/2y621Ta

Update on sinus disease in children with cystic fibrosis: advances in treatment modalities, microbiology, and health-related quality-of-life instruments

Purpose of review There is a lack of consensus with regards to the diagnosis and treatment of sinus disease in children with cystic fibrosis. Here, we review literature from the past 18 months in order to highlight the way forward in this contentious field. Recent findings Most of the literature (from the past 18 months) on sinus disease in pediatric cystic fibrosis focused on treatment approaches, bacteriology and immunology, and health-related quality-of-life (HRQOL) instruments. Quality studies have demonstrated that functional endoscopic sinus surgery (FESS) is as safe in children with or without cystic fibrosis; that the microbiology of the paranasal sinus in children with cystic fibrosis is different than that of their lungs; and, that HRQOL instruments may prove useful in determining sinonasal disease severity in children with cystic fibrosis. Summary Medical and surgical approaches appear to be viable in the treatment of sinonasal disease in pediatric cystic fibrosis; the microbiology and immunology of pediatric cystic fibrosis is proving more complex and nuanced than initially believed; and, HRQOL instruments show promise in reconciling differences between observable and clinically relevant sinus disease in pediatric cystic fibrosis patients. Correspondence to Frank W. Virgin, MD, Assistant Professor of Pediatric Otolaryngology, Monroe Carell Jr. Children's Hospital at Vanderbilt, 2200 Children's Way, 7224 Doctors' Office Tower, Nashville, TN 37232, USA. Tel: +1 615 936 8176; fax: +1 615 875 0101; e-mail: frank.w.virgin@vumc.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QGLlZt

Velopharyngeal incompetence: role in paediatric swallowing deficits

Purpose of review The purpose of this manuscript is to highlight the latest advances in diagnosis and management of velopharyngeal incompetence (VPI) as it pertains to swallowing deficits in children. This is timely and relevant as otolaryngologists are often amongst the first to diagnose and treat VPI. Although nasal regurgitation of a bolus is frequently transient, persistent problems can be associated with other swallowing problems and other significant medical problems. Furthermore, velopharyngeal incompetence has implications for speech production. Recent findings Persistent VPI associated with a swallowing deficit can be an isolated anomaly with or without a cleft palate or submucous cleft palate. VPI may be secondary to a cranial neuropathy, esophageal abnormality or associated with another airway anomaly, any of which may further contribute to dysphagia. Findings of additional anomalies may be suggestive of a syndrome. Workup should explore these potential causes. When velopharyngeal incompetence is associated with dysphagia, fiberoptic endoscopic evaluation of swallow (FEES) and videofluoroscopic swallow study (VFSS) can be helpful in diagnosis and management. The advantages and disadvantages of FEES and VFSS have been well delineated over the past few years. Similarly, nasopharyngoscopy and fluoroscopy are increasingly used in diagnosis and management of VPI that is associated with hypernasal resonance disorders. Summary Concurrent medical diagnoses or syndrome manifestations are often associated with or contribute significantly to the cause of dysphagia in children with VPI. As VPI can be a sign of brainstem vagal neuropathy, the clinician should investigate by imaging the CNS if other correlative symptoms of dysphagia and examination findings are present. Endoscopy is advocated for evaluation of vocal fold function. Fluoroscopy is best for further assessment of airway protection or safety of swallow. And, whenever indicated, additional workup is recommended to determine an underlying cause of the swallowing disorder. Correspondence to Laura H. Swibel Rosenthal, MD, 225 E. Chicago Avenue, Box 25, Chicago, IL 60611, USA. Tel: +1 312 227 6230; fax: +1 312 227 9414; e-mail: lrosenthal@luriechildrens.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2A0qFWT

Recurrent respiratory papillomatosis: update 2018

Purpose of review Recurrent respiratory papillomatosis (RRP) is the most common as well as the costliest benign airway neoplasm in the United States [Ivancic et al. (2018). Laryngoscope Investig Otolaryngol 3:22; Derkay (1995). Arch Otolaryngol Head Neck Surg 121:1386]. In addition, it is potentially deadly, with risk of airway obstruction as well as a 3–7% risk of malignant conversion [Schraff et al. (2004). Arch Otolaryngol Head Neck Surg 130:1039]. This review highlights exciting advancements over the past 1–2 years in scientific understanding of the pathophysiology, epidemiology, natural history, prevention, and treatment of this difficult disease. Recent findings Recent studies have yielded the following findings: The primary quality of life reduction that patients perceive is voice-related; the membranous vocal folds are the most frequently involved anatomic subsite in adult-onset RRP; there may be a correlation between laryngopharyngeal reflux, herpes simplex virus type 2, and adult-onset RRP; there has been a decline in RRP incidence in Australia following the implementation of a national vaccination program; addition of educational audiovisual aids assists in vaccine acceptance rates; preventive vaccination can be used as treatment for pediatric as well as adult RRP patients with demonstrable effects on antibody titers and reoperation rates; calreticulin-linked DNA vaccines show promise in reducing the growth rate of human papilloma virus (HPV)11 E6/E7-expressing tumors in mice; injection of bevacizumab is associated with no adverse tissue affects; systemic bevacizumab is effective as a treatment for severe uncontrolled disease; pegylated interferon treatment is effective in select severe pediatric RRP disease; and finally, increased rates of programed death 1 T-lymphocyte infiltration and programed death-ligand 1 expression are seen on both papilloma and infiltrating immune cells. Summary RRP is declining in incidence but remains a challenging disease to treat with great costs to patients, families, and the healthcare system. As the disease continues to be better understood, new frontiers are opening in treatment, particularly for severe or poorly controlled disease. Until the disease can be eradicated, it remains a vital area of research to help prevent new cases and treat afflicted patients. Correspondence to Craig S. Derkay, MD, Professor and Vice-Chairman, Department of Otolaryngology – Head and Neck Surgery; Director, Pediatric Otolaryngology, Eastern Virginia Medical School, Children's Hospital of the King's Daughters, 601 Children's Lane, 2nd Floor, Norfolk, VA 23507, USA. Tel: +1 757 668 9853; fax: +1 757 668 9838; e-mail: craig.derkay@chkd.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QGLb4j

Vocal fold nodules in children

Purpose of review Vocal nodules are a common presentation in children, representing the most common cause of dysphonia. Recent findings Children with siblings, ADHD, and of male sex are most likely to be affected. Female children, however, tend to have more likely progression into adolescence. Quality-of-life indices can aid in screening for vocal nodules whereas stroboscopy, and possibly, ultrasound are required for definitive diagnosis. Summary Management has not significantly changed over time and should begin with conservative behavioral and environmental modifications along with voice therapy in those more severely impacted. Though immediate outcomes vary somewhat depending on management direction, the overall prognosis seems to be good even with lack of intervention. It is most critical to ensure a definitive diagnosis, and offer management therapies that are appropriate for the level of impact the vocal nodules have on communication and voice production in the child. Correspondence to Pamela Mudd, MD, MBA, 111 Michigan Avenue, NW, Washington, DC 20010, USA. Tel: +1 202 476 4852; e-mail: pmudd@cnmc.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2A0qvPh

Recurrent laryngeal nerve reinnervation: is this the standard of care for pediatric unilateral vocal cord paralysis?

Purpose of review Ansa to recurrent laryngeal nerve reinnervation, otherwise known as a nonselective laryngeal reinnervation (NSLR), is growing in popularity for the management of pediatric unilateral neuronal vocal fold movement impairment (VFMI). In this chapter, we will review the current treatment options for neuronal VFMI and role that NSLR plays in the treatment algorithm. Recent findings In 2018, Bouhabel and Hartnick published a survey of fellowship trained pediatric otolaryngologists and found an increasing comfort level with NSLR. Respondents felt that NSLR resulted in favorable subjective and objective postsurgical voice outcomes. Furthermore, NSLR may decrease the risk of aspiration in children with neuronal VFMI. Although NSLR appears to work, the voice results are not perfect for all children. Further work is being done to understand which preoperative variables, such as age, time from injury, and preop laryngeal electromyography, may predict a better voice outcome. Summary A variety of treatment options exist for unilateral neuronal VFMI. Recent data and developments demonstrate the effectiveness of reinnervation as a potential first-line surgical intervention in children with unilateral neuronal VFMI. Correspondence to Julina Ongkasuwan, MD, FAAP, FACS, Pediatric Otolaryngology, Texas Children's Hospital, 6701 Fannin Street, Mark Wallace Tower, Suite 640, Houston, TX 77030, USA. Tel: +1 832 822 3250; fax: +1 832 825 9070; e-mail: julinao@bcm.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QFKaJQ

The long and winding road

No abstract available

https://ift.tt/2A2sWAR

Treatment of mycosis fungoides and Sezary syndrome with romidepsin: a series of 32 cases of the French Study Group for Cutaneous Lymphoma

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OQ0hHe

Case Series showing efficacy of ALA‐Photodynamic therapy for Epidermal Growth factor Receptor Inhibitors‐induced paronychia and pyogenic granuloma like lesions

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NxsEoW

Improved patient adherence to subcutaneous allergen immunotherapy using a modified rush immunotherapy protocol

Publication date: Available online 9 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): J. Teachout, S. Vandegrift, C. Schafer, S. Uekert, K. Gell

https://ift.tt/2EaZ5dr

Anaphylaxis After Anal Intercourse With Tolerance By Vaginal Route

Publication date: Available online 9 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): J. Martí Garrido, R. López Salgueiro, B. Bartolomé Zavala, C. Perales Chordá, D. Hernández Fernández de Rojas

https://ift.tt/2RALA9z

The impact of dynamic roughness elements on marginally separated boundary layers

Servini, P; Smith, FT; Rothmayer, A; (2018) The impact of dynamic roughness elements on marginally separated boundary layers. Journal of Fluid Mechanics , 855 pp. 351-370. 10.1017/jfm.2018.589 .

https://ift.tt/2RD5sc3

Conceptual approaches to wellbeing in buildings: a scoping review

Hanc, M; McAndrew, C; Ucci, M; (2018) Conceptual approaches to wellbeing in buildings: a scoping review. Building Research and Information 10.1080/09613218.2018.1513695 . (In press).

https://ift.tt/2E93Kg7

Adaptation to milking agropastoralism in Chilean goat herders and nutritional benefit of lactase persistence

Montalva, N; Adhikari, K; Liebert, A; Mendoza-Revilla, J; Flores, SV; Mace, R; Swallow, DM; (2018) Adaptation to milking agropastoralism in Chilean goat herders and nutritional benefit of lactase persistence. Annals of Human Genetics 10.1111/ahg.12277 . (In press). Green open access

https://ift.tt/2Rwuvh7

Statins for children with familial hypercholesterolemia

Vuorio, A; Kuoppala, J; Kovanen, PT; Humphries, SE; Tonstad, S; Wiegman, A; Drogari, E; Vuorio, A; Kuoppala, J; Kovanen, PT; Humphries, SE; Tonstad, S; Wiegman, A; Drogari, E; Ramaswami, U; - view fewer (2017) Statins for children with familial hypercholesterolemia. Cochrane Database of Systematic Reviews , 7 , Article CD006401. 10.1002/14651858.CD006401.pub4 . Green open access

https://ift.tt/2EhFjx8

Valproate and childbearing potential: new regulations

Sisodiya, SM; (2018) Valproate and childbearing potential: new regulations. [Editorial comment]. Practical Neurology , 18 (3) pp. 176-178. 10.1136/practneurol-2018-001955 . Green open access

https://ift.tt/2RAqh81

Association Between Lifestyle Factors and the Incidence of Multimorbidity in an Older English Population

Dhalwani, NN; Zaccardi, F; O'Donovan, G; Carter, P; Hamer, M; Yates, T; Davies, M; Dhalwani, NN; Zaccardi, F; O'Donovan, G; Carter, P; Hamer, M; Yates, T; Davies, M; Khunti, K; - view fewer (2017) Association Between Lifestyle Factors and the Incidence of Multimorbidity in an Older English Population. The Journals of Gerontology: Series A , 72 (4) pp. 528-534. 10.1093/gerona/glw146 . Green open access

https://ift.tt/2EhEHrk

Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics

Kamleh, MA; McLeod, O; Checa, A; Baldassarre, D; Veglia, F; Gertow, K; Humphries, SE; ... Wheelock, CE; + view all Kamleh, MA; McLeod, O; Checa, A; Baldassarre, D; Veglia, F; Gertow, K; Humphries, SE; Rauramaa, R; de Faire, U; Smit, AJ; Giral, P; Kurl, S; Mannarino, E; Tremoli, E; Silveira, A; Orvik, J; Hamsten, A; Wheelock, CE; - view fewer (2017) Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics. Journal of Proteome Research , 17 (2) pp. 870-878. 10.1021/acs.jproteome.7b00671 .

https://ift.tt/2RwtMfT

Bioethics after Brexit: Brexit an opportunity to rationalize bioethics governance in the United Kingdom

Montgomery, J; (2018) Bioethics after Brexit: Brexit an opportunity to rationalize bioethics governance in the United Kingdom. Medical Law International (In press). Green open access

https://ift.tt/2EhEq7M

Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI

Oya, H; Howard, MA; Magnotta, VA; Kruger, A; Griffiths, TD; Lemieux, L; Carmichael, DW; ... Adolphs, R; + view all Oya, H; Howard, MA; Magnotta, VA; Kruger, A; Griffiths, TD; Lemieux, L; Carmichael, DW; Petkov, CI; Kawasaki, H; Kovach, CK; Sutterer, MJ; Adolphs, R; - view fewer (2017) Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI. Journal of Neuroscience Methods , 277 pp. 101-112. 10.1016/j.jneumeth.2016.12.014 . Green open access

https://ift.tt/2RCSECG

Probing Endocytosis During the Cell Cycle with Minimal Experimental Perturbation

Santos, AJM; Boucrot, E; (2018) Probing Endocytosis During the Cell Cycle with Minimal Experimental Perturbation. Methods in Molecular Biology , 1847 pp. 23-35. 10.1007/978-1-4939-8719-1_3 .

https://ift.tt/2E6NMTy

Personalised medicine in general practice: the example of raised cholesterol

Qureshi, N; Humphries, SE; Gray, H; (2018) Personalised medicine in general practice: the example of raised cholesterol. British Journal of General Practice , 68 (667) pp. 68-69. 10.3399/bjgp18X694481 .

https://ift.tt/2RDeB4A

Euro-China Green Economy theme: SINCERE (Sino-European Circular Economy and Resource Efficiency) - ESRC

Bleischwitz, R; Yong, G; Walz, R; Welfens, P; Kemp, R; (2018) Euro-China Green Economy theme: SINCERE (Sino-European Circular Economy and Resource Efficiency) - ESRC. Impact , 2018 (4) pp. 6-7. 10.21820/23987073.2018.4.6 .

https://ift.tt/2El7jQv

Brugada syndrome is associated with scar and endocardial involvement: Insights from high-density mapping with the Rhythmia™ mapping system

Providência, R; Carmo, P; Moscoso Costa, F; Cavaco, D; Morgado, F; Scanavacca, M; Adragão, P; (2017) Brugada syndrome is associated with scar and endocardial involvement: Insights from high-density mapping with the Rhythmia™ mapping system. Revista Portuguesa de Cardiologia , 36 (10) 773.e1-773.e4. 10.1016/j.repc.2017.08.004 . Green open access

https://ift.tt/2RDesy4

Panoramic atrial mapping with basket catheters: A quantitative analysis to optimize practice, patient selection, and catheter choice

Honarbakhsh, S; Schilling, RJ; Providência, R; Dhillon, G; Sawhney, V; Martin, CA; Keating, E; ... Hunter, RJ; + view all Honarbakhsh, S; Schilling, RJ; Providência, R; Dhillon, G; Sawhney, V; Martin, CA; Keating, E; Finlay, M; Ahsan, S; Chow, A; Earley, MJ; Hunter, RJ; - view fewer (2017) Panoramic atrial mapping with basket catheters: A quantitative analysis to optimize practice, patient selection, and catheter choice. Journal of Cardiovascular Electrophysiology , 28 (12) pp. 1423-1432. 10.1111/jce.13331 . Green open access

https://ift.tt/2E6Odgw

Cerebrospinal fluid β-amyloid₄₂ and neurofilament light relate to white matter hyperintensities

Osborn, KE; Liu, D; Samuels, LR; Moore, EE; Cambronero, FE; Acosta, LMY; Bell, SP; ... Jefferson, AL; + view all Osborn, KE; Liu, D; Samuels, LR; Moore, EE; Cambronero, FE; Acosta, LMY; Bell, SP; Babicz, MA; Gordon, EA; Pechman, KR; Davis, LT; Gifford, KA; Hohman, TJ; Blennow, K; Zetterberg, H; Jefferson, AL; - view fewer (2018) Cerebrospinal fluid β-amyloid₄₂ and neurofilament light relate to white matter hyperintensities. Neurobiology of Aging , 68 pp. 18-25. 10.1016/j.neurobiolaging.2018.03.028 .

https://ift.tt/2RF2NyT

In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis

Howells, J; Matamala, JM; Park, SB; Garg, N; Vucic, S; Bostock, H; Burke, D; Howells, J; Matamala, JM; Park, SB; Garg, N; Vucic, S; Bostock, H; Burke, D; Kiernan, MC; - view fewer (2018) In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis. The Journal of Physiology 10.1113/JP276624 . (In press).

https://ift.tt/2E89cjh

Review of the development of China's Eco-industrial Park standard system

Huang, B; Yong, G; Zhao, J; Domenech, T; Liu, Z; Chiu, SF; McDowall, W; ... Yao, Y; + view all Huang, B; Yong, G; Zhao, J; Domenech, T; Liu, Z; Chiu, SF; McDowall, W; Bleischwitz, R; Liu, J; Yao, Y; - view fewer (2018) Review of the development of China's Eco-industrial Park standard system. Resources, Conservation and Recycling , 140 pp. 137-144. 10.1016/j.resconrec.2018.09.013 .

https://ift.tt/2RCfWbR

Rewilding in the English Uplands: Policy and Practice

Sandom, CJ; Dempsey, B; Bullock, D; Ely, A; Jepson, P; Jimenez-Wisler, S; Newton, A; ... Senior, RA; + view all Sandom, CJ; Dempsey, B; Bullock, D; Ely, A; Jepson, P; Jimenez-Wisler, S; Newton, A; Pettorelli, N; Senior, RA; - view fewer (2019) Rewilding in the English Uplands: Policy and Practice. Journal of Applied Ecology (In press).

https://ift.tt/2EaH4w1

The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer's disease

Kvartsberg, H; Lashley, T; Murray, CE; Brinkmalm, G; Cullen, NC; Höglund, K; Zetterberg, H; ... Portelius, E; + view all Kvartsberg, H; Lashley, T; Murray, CE; Brinkmalm, G; Cullen, NC; Höglund, K; Zetterberg, H; Blennow, K; Portelius, E; - view fewer (2018) The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer's disease. Acta Neuropathologica 10.1007/s00401-018-1910-3 . Green open access

https://ift.tt/2RB5rp0

Evolution of China's water footprint and virtual water trade: A global trade assessment

Tian, X; Sarkis, J; Geng, Y; Qian, Y; Gao, C; Bleischwitz, R; Xu, Y; (2018) Evolution of China's water footprint and virtual water trade: A global trade assessment. Environment International , 121 (Pt 1) pp. 178-188. 10.1016/j.envint.2018.09.011 .

https://ift.tt/2El7hrR

Periodontal ligament fibroblasts migration injury via ROS/TXNIP/Nlrp3 inflammasome pathway with Porphyromonas gingivalis lipopolysaccharide

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Dawei Lian, Linfeng Dai, Zhaoyu Xie, Xing Zhou, Xiaohong Liu, Yang Zhang, Yi Huang, Yang Chen

Abstract

Inflammasomes serve as an intracellular machinery to initiate inflammatory response to various danger signals. However, the chronic periodontitis pathological relevance of this inflammasome activation, particularly in periodontal ligament fibroblasts, remains largely unknown. The present study demonstrated that Nlrp3 inflammasome components abundantly expressed in cultured mouse periodontal ligament fibroblasts (mPDLFs). In addition, our data demonstrated that P.g-LPS (Porphyromonas gingivalis Lipopolysaccharide), a major injurious factor during chronic periodontitis, could induce the mPDLFs migration dysfunction and the inhibition of Nlrp3 inflammasome by Isoliquiritigenin (ISO) markedly recovered the migration dysfunction in mPDLFs. And Nlrp3 inflammasome components could be aggregated to form an inflammasome complex on stimulation of P.g-LPS, as shown by fluorescence confocal microscopy. Correspondingly, P.g-LPS induced Nlrp3 inflammasome activation, caspase-1 activation, IL-1β and HMGB1 release, which were blocked by Nlrp3 inflammasome inhibitor (ISO). Interestingly, reactive oxygen species, TXNIP protein and TXNIP binding to Nlrp3 were markedly increased in mPDLFs with P.g-LPS. Furthermore, ROS generation inhibitor (Apocynin; APO) significantly reduced Nlrp3 inflammasome formation and IL-1β production in mPDLFs with P.g-LPS. And APO attenuated P.g-LPS-induced TXNIP protein expression and mPDLFs injury. In conclusion, our results demonstrate that ROS/TXNIP/Nlrp3 Inflammasome pathway is a key initiating mechanism necessary for P.g-LPS-induced subsequent mPDLFs inflammatory response leading to chronic periodontitis.

https://ift.tt/2y9jKZM

Potential advantages of CD1-restricted T cell immunotherapy in cancer

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Michela Consonni, Paolo Dellabona, Giulia Casorati

Abstract

Adoptive cell therapy (ACT) using tumor-specific "conventional" MHC-restricted T cells obtained from tumor-infiltrating lymphocytes, or derived ex vivo by either antigen-specific expansion or genetic engineering of polyclonal T cell populations, shows great promise for cancer treatment. However, the wide applicability of this therapy finds limits in the high polymorphism of MHC molecules that restricts the use in the autologous context. CD1 antigen presenting molecules are nonpolymorphic and specialized for lipid antigen presentation to T cells. They are often expressed on malignant cells and, therefore, may represent an attractive target for ACT. We provide a brief overview of the CD1-resticted T cell response in tumor immunity and we discuss the pros and cons of ACT approaches based on unconventional CD1-restricted T cells.

https://ift.tt/2PsbkDP

Reply to “Letter to the Editor in response to the article, ‘The epidemiology of oral human papillomavirus infection in healthy populations: A systematic review and meta-analysis’”

Publication date: Available online 9 October 2018

Source: Oral Oncology

Author(s): Samantha Tam, Shuangshuang Fu, Li Xu, Kate Krause, David R. Lairson, Hongyu Miao, Erich M. Sturgis, Kristina R. Dahlstrom

https://ift.tt/2A0efyf

Accuracy of objective tests for diagnosing adult asthma in symptomatic patients: A systematic literature review and hierarchical Bayesian latent-class meta-analysis

Publication date: Available online 8 October 2018

Source: Allergology International

Author(s): Hiroyuki Sano, Katsuyuki Tomita, Akiko Sano, Shou Saeki, Yusaku Nishikawa, Osamu Nishiyama, Takashi Iwanaga, Yuji Tohda

Abstract

Background

We obtain summary estimates of the accuracy of additional objective tests for the diagnosis of adult asthma using systematic review and meta-analysis of diagnostic test accuracy studies.

Methods

Medline, Embase, and other relevant electronic databases were searched for papers published between January 1989 and December 2016. Studies were included if they evaluated the diagnostic accuracy of objective tests, including airway reversibility (AR), airway hyperresponsiveness (AHR), and fractionated exhaled nitric oxide (FeNO) for the diagnosis of adult asthma in patients with symptoms suggestive of asthma. If papers were assessed appropriate using the adapted QUADAS-2 tool, meta-analysis was conducted using the hierarchical bivariate model. This hierarchical model accounts for both within and between study variability.

Results

Sixteen studies reported the performance of the evaluated objective tests at presentation. For diagnosis of adult asthma, overall sensitivity and specificity for AR were 0.39 (95% confidence interval [CI] 0.18 to 0.66) and 0.95 (95% CI 0.86 to 1.00); for AHR, 0.86 (95% CI 0.61 to 1.00) and 0.95 (95% CI 0.77 to 1.00); for FeNO, 0.65 (95% CI 0.53 to 0.77) and 0.83 (95% CI 0.75 to 0.90). Comprehensive comparison of three diagnostic tools for adult asthma using the back-calculated likelihood rate (LR) showed that AR and AHR corresponded to a higher LR+, and AHR gave a lower LR-.

Conclusions

In the current situation of no gold standard for diagnosis of adult asthma, AR and AHR are appropriate for ruling-in the true diagnosis, and AHR is superior for ruling-out a diagnosis. Since each objective test had a specific characteristic, it should be chosen depending on the situation, such as the capacity of the institution and the conditions of patients.

https://ift.tt/2y92VOO

Chalazodermie amyloïde multifocale. Le concept d’élastopathie immunoglobulinémique

Publication date: Available online 9 October 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): G. Hazemann, L. Gusdorf, M. Mitcov, C. Lenormand, D. Lipsker

Résumé

Introduction

Des altérations du tissu élastique dermique surviennent au cours de différentes entités, associées à une synthèse anormale d'immunoglobulines par un clone plasmocytaire, comme dans l'élastose amyloïde, l'amylose cutanée nodulaire anétodermique ou la cutis laxa associée à une gammapathie monoclonale. Nous rapportons le cas d'une amylose cutanée immunoglobulinémique révélée par une présentation chalazodermique inhabituelle et revisitons le spectre anatomoclinique des altérations du tissu élastique au cours des maladies impliquant une synthèse anormale d'immunoglobulines.

Observation

Une femme de 67 ans consultait pour des lésions non infiltrées anétodermiques du flanc gauche évoluant depuis une dizaine d'années. Elle avait aussi une plaque molle chalazodermique axillaire droite. Des biopsies révélaient des dépôts amyloïdes dermo-hypodermiques marqués par les anticorps anti-chaînes légères lambda en immunohistochimie, tandis que la coloration par l'orcéine et la microscopie électronique montraient une disparition quasi-complète des fibres élastiques. Il n'y avait pas d'argument en faveur d'une amylose systémique, mais une gammapathie monoclonale IgG lambda à l'état de traces est apparue au cours du suivi.

Discussion

Il s'agit d'une présentation clinique chalazodermique tout à fait inhabituelle d'une amylose immunoglobulinémique, ne s'intégrant dans aucun cadre nosologique clairement défini. Cela met en évidence les interactions complexes entre les protéines dérivées des immunoglobulines, incluant les chaînes légères et lourdes, et les composants du tissu élastique, conduisant à différents types d'altérations de ce dernier. Nous proposons donc le concept unificateur d'élastopathie immunoglobulinémique, soulignant la nécessité de rechercher une gammapathie monoclonale chez les patients atteints d'altérations du tissu élastique.

Summary

Introduction

Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies.

Observation

A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGλ gammopathy was detected during follow-up.

Discussion

This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments.

https://ift.tt/2Pm1Byz

Anatomical study of jugular foramen in the neck

Publication date: Available online 9 October 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Carlos Alberto Ferreira de Freitas, Luiz Roberto Medina dos Santos, Andreza Negreli Santos, Augusto Barreto do Amaral Neto, Lenine Garcia Brandão

Abstract

Introduction

The anatomical complexity of the jugular foramen makes surgical procedures in this region delicate and difficult. Due to the advances in surgical techniques, approaches to the jugular foramen became more frequent, requiring improvement of the knowledge of this region anatomy.

Objective

To study the anatomy of the jugular foramen, internal jugular vein and glossopharyngeal, vagus and accessory nerves, and to identify the anatomical relationships among these structures in the jugular foramen region and lateral-pharyngeal space.

Methods

A total of 60 sides of 30 non-embalmed cadavers were examined few hours after death. The diameters of the jugular foramen and its anatomical relationships were analyzed.

Results

The diameters of the jugular foramen and internal jugular vein were greater on the right side in most studied specimens. The inferior petrosal sinus ended in the internal jugular vein up to 40 mm below the jugular foramen; in 5% of cases. The glossopharyngeal nerve exhibited an intimate anatomical relationship with the styloglossus muscle after exiting the skull, and the vagal nerve had a similar relationship with the hypoglossal nerve. The accessory nerve passed around the internal jugular vein via its anterior wall in 71.7% of cadavers.

Conclusion

Anatomical variations were found in the dimensions of the jugular foramen and the internal jugular vein, which were larger in size on the right side of most studied bodies; variations also occurred in the trajectory and anatomical relationships of the nerves. The petrosal sinus can join the internal jugular vein below the foramen.

Resumo

Introdução

A complexidade anatômica do forame jugular torna a realização de procedimentos cirúrgicos nessa região delicada e difícil. Devido aos avanços obtidos nas técnicas cirúrgicas, as abordagens do forame jugular estão sendo realizadas com maior frequência, o que requer uma melhora correspondente no conhecimento de sua anatomia.

Objetivo

Estudar a anatomia do forame jugular, da veia jugular interna e dos nervos glossofaríngeo, vago e acessório, assim como as relações anatômicas entre estas estruturas na região do forame jugular e no espaço parafaríngeo.

Método

Um total de 60 lados de 30 cadáveres frescos foram examinados algumas horas após a morte. Os diâmetros e suas relações anatômicas foram analisados.

Resultados

Os diâmetros do forame jugular e da veia jugular interna foram maiores no lado direito na maioria dos espécimes estudados. O seio petroso inferior terminava na veia jugular interna até 40 mm abaixo do forame jugular, em 5% dos casos. O nervo glossofaríngeo exibiu uma relação íntima anatômica com o músculo estiloglosso após a sua saída do crânio, e o nervo vago exibiu uma relação semelhante com o nervo hipoglosso. O nervo acessório passou em torno da veia jugular interna via sua parede anterior em 71,7% dos cadáveres.

Conclusão

Foram encontradas variações anatômicas nas dimensões do forame jugular e da veia jugular interna, que apresentaram tamanhos maiores à direita na maioria dos espécimes estudados; variações também ocorreram na trajetória e nas relações anatômicas dos nervos. O seio petroso pode se unir à veia jugular interna abaixo do forame.

https://ift.tt/2QF85cm

Interoceptive inference: From computational neuroscience to clinic

Owens, AP; Allen, M; Ondobaka, S; Friston, KJ; (2018) Interoceptive inference: From computational neuroscience to clinic. [Review]. Neuroscience & Biobehavioral Reviews , 90 pp. 174-183. 10.1016/j.neubiorev.2018.04.017 .

https://ift.tt/2y9uaZt

Recommended Methods to Study Resistive Switching Devices

Lanza, M; Wong, HSP; Pop, E; Ielmini, D; Strukov, D; Regan, BC; Larcher, L; ... Shi, Y; + view all Lanza, M; Wong, HSP; Pop, E; Ielmini, D; Strukov, D; Regan, BC; Larcher, L; Villena, MA; Yang, JJ; Goux, L; Belmonte, A; Yang, Y; Puglisi, FM; Kang, J; Magyari-Köpe, B; Yalon, E; Kenyon, A; Buckwell, M; Mehonic, A; Shluger, A; Li, H; Hou, TH; Hudec, B; Akinwande, D; Ge, R; Ambrogio, S; Roldan, JB; Miranda, E; Suñe, J; Pey, KL; Wu, X; Raghavan, N; Wu, E; Lu, WD; Navarro, G; Zhang, W; Wu, H; Li, R; Holleitner, A; Wurstbauer, U; Lemme, MC; Liu, M; Long, S; Liu, Q; Lv, H; Padovani, A; Pavan, P; Valov, I; Jing, X; Han, T; Zhu, K; Chen, S; Hui, F; Shi, Y; - view fewer (2018) Recommended Methods to Study Resistive Switching Devices. Advanced Electronic Materials 10.1002/aelm.201800143 . (In press).

https://ift.tt/2PpwAKc

Sources, sinks and transport of energetic electrons near Saturn’s main rings

Roussos, E; Kollmann, P; Krupp, N; Paranicas, C; Dialynas, K; Jones, GH; Mitchell, DG; ... Cooper, JF; + view all Roussos, E; Kollmann, P; Krupp, N; Paranicas, C; Dialynas, K; Jones, GH; Mitchell, DG; Krimigis, SM; Cooper, JF; - view fewer (2018) Sources, sinks and transport of energetic electrons near Saturn's main rings. Geophysical Research Letters 10.1029/2018GL078097 . (In press). Green open access

https://ift.tt/2ycc7Ss

It Takes One to Tango: The Single UK Competition and Markets Authority

Mantzari, D; Korah, V; (2012) It Takes One to Tango: The Single UK Competition and Markets Authority. Competition Policy International, Antitrust Chronicle , 12 (1)

https://ift.tt/2PoZL07

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions

Phillips, JO; Butt, LE; Henderson, CA; Devonshire, M; Healy, J; Conway, SJ; Locker, N; ... Callaghan, AJ; + view all Phillips, JO; Butt, LE; Henderson, CA; Devonshire, M; Healy, J; Conway, SJ; Locker, N; Pickford, AR; Vincent, HA; Callaghan, AJ; - view fewer (2018) High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions. Nucleic Acids Research , 46 (14) , Article e86. 10.1093/nar/gky410 . Green open access

https://ift.tt/2y8P2Ag

Alzheimer's disease markers in the aged sheep (Ovis aries)

Reid, SJ; Mckean, NE; Henty, K; Portelius, E; Blennow, K; Rudiger, SR; Bawden, CS; ... Snell, RG; + view all Reid, SJ; Mckean, NE; Henty, K; Portelius, E; Blennow, K; Rudiger, SR; Bawden, CS; Handley, RR; Verma, PJ; Faull, RLM; Waldvogel, HJ; Zetterberg, H; Snell, RG; - view fewer (2017) Alzheimer's disease markers in the aged sheep (Ovis aries). Neurobiology of Aging , 58 pp. 112-119. 10.1016/j.neurobiolaging.2017.06.020 . Green open access

https://ift.tt/2Ppwhz2

On the thermal performance of a micro parallel channels heat exchanger

Fernandes de Sousa, I; Palma Naveira Cotta, C; Cordeiro Guerrieri, D; Tiwari, MK; (2018) On the thermal performance of a micro parallel channels heat exchanger. Journal of Thermal Science and Engineering Applications 10.1115/1.4041439 . (In press).

https://ift.tt/2yaWACv

Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelinating Neuropathy

Sophie, B; Ornaghi, F; Shackleford, G; Wang, J; Scapin, C; Lopez-Anido, C; Silvestri, N; ... Wrabetz, L; + view all Sophie, B; Ornaghi, F; Shackleford, G; Wang, J; Scapin, C; Lopez-Anido, C; Silvestri, N; Robertson, N; Williamson, C; Ishii, A; Taveggia, C; Svaren, J; Bansal, R; Schwab, M; Nave, K-A; Fratta, P; Poitelon, Y; D'Antonio, M; Feltri, ML; Wrabetz, L; - view fewer (2018) Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelinating Neuropathy. bioRxiv: Cold Spring Harbor Laboratory. Green open access

https://ift.tt/2PomPMq

Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review

Knorr, U; Simonsen, AH; Zetterberg, H; Blennow, K; Hasselbalch, SG; Kessing, LV; (2018) Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review. European Neuropsychopharmacology , 28 (7) pp. 783-794. 10.1016/j.euroneuro.2018.04.002 .

https://ift.tt/2y4VN67

Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants

Krishnan, ML; Van Steenwinckel, J; Schang, A-L; Yan, J; Arnadottir, J; Le Charpentier, T; Csaba, Z; ... Gressens, P; + view all Krishnan, ML; Van Steenwinckel, J; Schang, A-L; Yan, J; Arnadottir, J; Le Charpentier, T; Csaba, Z; Dournaud, P; Cipriani, S; Auvynet, C; Titomanlio, L; Pansiot, J; Ball, G; Boardman, JP; Walley, AJ; Saxena, A; Mirza, G; Fleiss, B; Edwards, AD; Petretto, E; Gressens, P; - view fewer (2017) Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants. Nature Communications , 8 , Article 428. 10.1038/s41467-017-00422-w . Green open access

https://ift.tt/2PpuTwe

Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia

Jansen, WJ; Ossenkoppele, R; Tijms, BM; Fagan, AM; Hansson, O; Klunk, WE; van der Flier, WM; ... Amyloid Biomarker Study Group, .; + view all Jansen, WJ; Ossenkoppele, R; Tijms, BM; Fagan, AM; Hansson, O; Klunk, WE; van der Flier, WM; Villemagne, VL; Frisoni, GB; Fleisher, AS; Lleo, A; Mintun, MA; Wallin, A; Engelborghs, S; Na, DL; Chetelat, G; Molinuevo, JL; Landau, SM; Mattsson, N; Kornhuber, J; Sabri, O; Rowe, CC; Parnetti, L; Popp, J; Fladby, T; Jagust, WJ; Aalten, P; Lee, DY; Vandenberghe, R; de Oliveira, CR; Kapaki, E; Froelich, L; Ivanoiu, A; Gabryelewicz, T; Verbeek, MM; Sanchez-Juan, P; Hildebrandt, H; Camus, V; Zboch, M; Brooks, DJ; Drzezga, A; Rinne, JO; Newberg, A; de Mendonca, A; Sarazin, M; Rabinovici, GD; Madsen, K; Kramberger, MG; Nordberg, A; Mok, V; Mroczko, B; Wolk, DA; Meyer, PT; Tsolaki, M; Scheltens, P; Verhey, FRJ; Visser, PJ; Amyloid Biomarker Study Group, .; - view fewer (2018) Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry , 75 (1) pp. 84-95. 10.1001/jamapsychiatry.2017.3391 .

https://ift.tt/2y9W8Vc

The "Habitus" of the Royal Officer: Ideal, Perception and Exercise of Office in the Spanish Monarchy (Xv-xviii Centuries)

Brendecke, A; Martín Romera, MÁ; (2017) The "Habitus" of the Royal Officer: Ideal, Perception and Exercise of Office in the Spanish Monarchy (Xv-xviii Centuries). [Review]. Studia Historica, Historia Moderna , 39 (1) pp. 23-51. 10.14201/shhmo20173912351 . Green open access

https://ift.tt/2Ppw0w0

Bottom-Up Evolution of Vesicles from Disks to High-Genus Polymersomes

Contini, C; Pearson, R; Wang, L; Messager, L; Gaitzsch, J; Rizzello, L; Ruiz-Perez, L; Contini, C; Pearson, R; Wang, L; Messager, L; Gaitzsch, J; Rizzello, L; Ruiz-Perez, L; Battaglia, G; - view fewer (2018) Bottom-Up Evolution of Vesicles from Disks to High-Genus Polymersomes. iScience , 7 pp. 132-144. 10.1016/j.isci.2018.08.018 . Green open access

https://ift.tt/2y8FWn7

LRID: A new metric of multi-class imbalance degree based on likelihood-ratio test

Zhu, R; Wang, Z; Ma, Z; Wang, G; Xue, JH; (2018) LRID: A new metric of multi-class imbalance degree based on likelihood-ratio test. Pattern Recognition Letters , 116 pp. 36-42. 10.1016/j.patrec.2018.09.012 .

https://ift.tt/2PkQtlD

A systematic approach to mapping longitudinal data usage: Reflections on tracking Millennium Cohort Study activity

Kneale, D; Patalay, P; Thomas, J; Khatwa, M; Stansfield, C; Fitzsimons, E; (2018) A systematic approach to mapping longitudinal data usage: Reflections on tracking Millennium Cohort Study activity. F1000Research , 7 (1559) 10.12688/f1000research.15990.1 . Green open access

https://ift.tt/2y4VAjl

Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases

Bekers, EM; Groenen, PJTA; Verdijk, MAJ; Raaijmakers-van Geloof, WL; Roepman, P; Vink, R; Gilhuijs, NDB; ... Flucke, U; + view all Bekers, EM; Groenen, PJTA; Verdijk, MAJ; Raaijmakers-van Geloof, WL; Roepman, P; Vink, R; Gilhuijs, NDB; van Gorp, JM; Bovee, JVMG; Creytens, DH; Flanagan, AM; Suurmeijer, AJH; Mentzel, T; Arbajian, E; Flucke, U; - view fewer (2017) Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases. Genes Chromosomes & Cancer , 56 (10) pp. 750-757. 10.1002/gcc.22478 . Green open access

https://ift.tt/2Ppw132

A systematic approach to normalization in probabilistic models

Lipani, A; Roelleke, T; Lupu, M; Hanbury, A; (2018) A systematic approach to normalization in probabilistic models. Information Retrieval Journal 10.1007/s10791-018-9334-1 . (In press). Green open access

https://ift.tt/2ycbPek

Climate adaptability construction technology of historic conservation areas: The case study of the Chinese-Baroque historic conservation area in Harbin

Jin, H; Zhao, J; Liu, S; Kang, J; (2018) Climate adaptability construction technology of historic conservation areas: The case study of the Chinese-Baroque historic conservation area in Harbin. Sustainability , 10 (10) , Article 3374. 10.3390/su10103374 . Green open access

https://ift.tt/2PoZBG3

Functionalized MoS2-nanosheets for targeted drug delivery and chemo-photothermal therapy

Zhang, X; Wu, J; Williams, GR; Niu, S; Qian, Q; Zhu, L-M; (2018) Functionalized MoS2-nanosheets for targeted drug delivery and chemo-photothermal therapy. Colloids Surf B Biointerfaces , 173 pp. 101-108. 10.1016/j.colsurfb.2018.09.048 . (In press).

https://ift.tt/2ycbE2E

The design dimension of planning: making planning proactive again

Carmona, MP; (2018) The design dimension of planning: making planning proactive again. In: Tomaney, J and Ferm, J, (eds.) Planning Practice: Critical Perspectives from the UK. Routledge: New York, NY, USA.

https://ift.tt/2PoZfzd

Genotyping of Candida albicans and Candida dubliniensis by 25S rDNA analysis shows association with virulence attributes in oral candidiasis

Publication date: Available online 9 October 2018

Source: Archives of Oral Biology

Author(s): Pornpen Tantivitayakul, Naruemon Panpradit, Thaniya Maudcheingka, Arthit Klaophimai, Jinthana Lapirattanakul

ABSTRACT

Objectives

This study genotyped oral isolates of Candida albicans and C. dubliniensis by analyzing 25S rDNA transposable intron and evaluated their virulence attributes in oral candidiasis.

Design

C. albicans and C. dubliniensis were isolated from oral cavity of normal carriers (n = 100) and oral candidiasis patients (n = 100), genotyped by PCR, and virulence properties, namely, secreted phospholipase and proteinase activities (using an agar plate method) and binding to buccal epithelial cells, were determined. In addition, antifungal sensitivity was assayed for all Candida isolates.

Results

C. albicans genotypes A, B, C and D (C. dubliniensis) were identified. Genotype B was the most prevalent in both healthy and candidiasis groups and had highest buccal epithelial cell binding ability but lowest secreted phospholipase activity. Genotype C was the third most prevalent, with higher frequency in patients than normal carriers. Genotype A, the second most prevalent, was equally found in both groups. There were no significant differences in secreted proteinase activity among the three C. albicans genotypes. C. dubliniensis, the least prevalent, was more frequent in healthy carriers and demonstrated minimal levels of the virulence properties. When all Candida isolates were compared based on groups of subjects, only secreted phospholipase activity was significantly higher in isolates from candidiasis patients. All Candida isolates were susceptible to clotrimazole, fluconazole, miconazole and nystatin.

Conclusions

Genotyping based on the 25S rDNA transposable intron region provided a simple method allowing studies of the pathogenicity of each genotype.

https://ift.tt/2yp2qPU

Asymmetrical proliferative pattern loss linked to cyclin D1 overexpression in adjacent non-tumour epithelium in oral squamous cell carcinoma

Publication date: Available online 9 October 2018

Source: Archives of Oral Biology

Author(s): Pablo Ramos-García, Miguel Ángel González-Moles, Ángela Ayén, Lucía González-Ruiz, Isabel Ruiz-Ávila, Daniel Lenouvel, José Antonio Gil-Montoya, Manuel Bravo

Abstract

Objective

To evaluate cyclin D1 overexpression in oral squamous cell carcinomas and adjacent non-tumour epithelium as a biomarker of premalignant fields and a risk factor for multiple tumour development.

Design

We studied cyclin D1 expression in 54 patients with 68 oral squamous cell carcinomas plus adjacent non-tumour epithelia characterized as close (n = 58) or distant (n = 41) from the invasion point. Randomized 40x fields were evaluated (4 in tumour tissue and 1 each in close and distant non-tumour epithelium). Expression in non-tumour epithelium was evaluated in basal, parabasal, middle-third and upper-third compartments.

Results

Cyclin D1 overexpression was found in both carcinomas and non-tumour epithelia. Nuclear expression in basal and parabasal layers of distant epithelium was significantly increased in patients with multiple tumours (p < 0.001). A significant association between cyclin D1 overexpression in different epithelial layers was found in both close and distant epithelia. A significant association was found between nuclear expressions of cyclin D1 and Ki-67 in the basal layer of distant epithelium (p = 0.02).

Conclusions

Cyclin D1 overexpression is an early event in oral carcinogenesis linked to loss of the physiological asymmetrical proliferation pattern. Cyclin D1 overexpression in basal and parabasal layers of epithelia distant from the invasion point may act as a potential marker of premalignant fields and multiple tumour development.

https://ift.tt/2OgVFKX

Effects of articular disc or condylar cartilage resection on mandibular growth in young rats

Publication date: Available online 9 October 2018

Source: Archives of Oral Biology

Author(s): Shuo Chen, Lin-hai He, Lu Zhao, E. Xiao, Yang He, Yi Zhang

Abstract

Objective

This study was aimed to compare the effects of articular disc and condylar cartilage resection on mandibular growth in Sprague Dawley rats.

Design

Eighty-four male Sprague Dawley rats (age = 4 weeks) were grouped according to the following procedures: group A (n = 21), exclusive surgical exposure of articular disc and condylar cartilage; group B (n = 21), exclusive surgical resection of articular disc; group C (n = 21), exclusive surgical resection of condylar cartilage; group D (n = 21), surgical resection of both articular disc and condylar cartilage. All surgery was performed in unilateral. One rat was killed in each group immediately after the surgery. Hematoxylin and eosin (H&E) staining was used to confirm the completely removal of the disc or cartilage. Five rats in the four groups were sacrificed in 1, 3, 6, and 9 weeks post-operation. The heights and lengths of the mandibles were measured and analyzed statistically.

Results

The mandibular height of group D (5.01 ± 0.25 mm) was statistically lower than group A (5.59 ± 0.17 mm) at 1 week post-operation. The height of group C (5.62 ± 0.26 mm) was significantly lower than group A (6.27 ± 0.31 mm) 3 weeks after surgery. The height of group B (6.38 ± 0.36 mm) was significantly lower than group A (6.95 ± 0.10 mm) 6 weeks after surgery. At 9 weeks post-operation, the mandibular heights in groups B, C, and D were lower than group A, group D was lower than group C, and group C was lower than group B. The lengths of the mandibles were not significantly decreased until 9 weeks post-operation in group D.

Conclusions

The increase in mandibular height was interfered after either articular disc or condylar cartilage was resected, and mandibular height deficiency likely occurred earlier and more severely when cartilage was resected. However, the increase in mandibular length was barely interfered when either articular disc or condylar cartilage was resected.

https://ift.tt/2yoPMAl

Gata3 hypermethylation and Foxp3 hypomethylation are associated with sustained protection and bystander effect following epicutaneous immunotherapy in peanut‐sensitized mice

Allergy, EarlyView.


https://ift.tt/2ysJ6kH

IL‐3–producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model

Allergy, EarlyView.


https://ift.tt/2OevHHR

An immunologically relevant rodent model demonstrates safety of therapy using a tumour‐specific IgE

Allergy, EarlyView.


https://ift.tt/2ynJPDN

Immunological and hematological effects of IL‐5(Rα)‐targeted therapy: An overview

Allergy, EarlyView.


https://ift.tt/2OhAj05

Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil‐associated RNases

Clinical &Experimental Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QAYOBP

Can alternative epitope mapping approaches increase the impact of B‐cell epitopes in food allergy diagnostics?

Clinical &Experimental Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2A0fZYl

Disseminated Trichosporon asahii infection in a patient with acute myeloid leukemia

The Journal of Dermatology, EarlyView.


https://ift.tt/2zZu0VT

Novel MBTPS2 mutation causes a mild phenotype of ichthyosis follicularis with atrichia and photophobia syndrome in a Chinese pedigree

The Journal of Dermatology, EarlyView.


https://ift.tt/2yqcXKQ

Demographic and clinical features of hidradenitis suppurativa in Korea

The Journal of Dermatology, EarlyView.


https://ift.tt/2A07w78

Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2CxsxZv

Epidermal barrier function in healthy black South African infants compared with adults

Pediatric Dermatology, EarlyView.


https://ift.tt/2pHwGS3

Opposing roles of eosinophils in cancer

Abstract

Eosinophils are a subset of granulocytes mostly known for their ability to combat parasites and induce allergy. Although they were described to be related to cancer more than 100 years ago, their role in tumors is still undefined. Recent observations revealed that they display regulatory functions towards other immune cell subsets in the tumor microenvironment or direct cytotoxic functions against tumor cells, leading to either antitumor or protumor effects. This paradoxical role of eosinophils was suggested to be dependent on the different factors in the TME. In addition, the clinical relevance of these cells has been recently addressed. In most cases, the accumulation of eosinophils both in the tumor tissue, called tumor-associated tissue eosinophilia, and in the peripheral blood were reported to be prognostic markers for a better outcome of cancer patients. In immunotherapy of cancer, particularly in therapy with immune checkpoint inhibitors, eosinophils were even shown to be a potential predictive marker for a beneficial clinical response. A better understanding of their role in cancer progression will help to establish them as prognostic and predictive markers and to design strategies for targeting eosinophils.

https://ift.tt/2OhCssn

BRAF Mutation in Papillary Thyroid cancer ‐ prevalence and clinical correlation in a Southeast Asian cohort

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2C2YR5w

Effect of adjuvant radiotherapy on the local recurrence of oral squamous cell carcinoma with perineural invasion: a systematic review

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Cyktrx

Log margin‐to‐thickness ratio improves disease‐specific survival prediction in oral cancer: A single cancer center database

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2C4kn9W

DRESS syndrome-associated acute necrotizing eosinophilic myocarditis with giant cells

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon drug hypersensitivity reaction caused by a wide variety of agents. It has a characteristic latent period between 2 and 8 weeks from the onset of drug ingestion followed by a slow resolution with the potential for relapse. Despite being a potentially fatal disease, little is understood about its variable clinical presentation and why it can present long after removal of the offending drug. Visceral organ involvement typically occurs, but rarely results in clinically manifested cardiac injury. In its most aggressive form, acute necrotizing eosinophilic myocarditis (ANEM) can present with DRESS. We present an unusual case of DRESS syndrome due to lamotrigine with confirmed ANEM showing both eosinophils and rare giant cell infiltrates on endomyocardial biopsy. Although lamotrigine has been reported to cause DRESS, it has not been previously implicated as a cause of ANEM.

https://ift.tt/2QEPLjv

Visual deficit possibly caused by lutetium-177 PSMA treatment

This report describes a case of a 54-year-old man who underwent lutetium-177-PSMA therapy in the setting of metastatic castration-resistant prostate cancer (mCRPC) in the University Medical Center Utrecht. Following administration of the second cycle, patient presented with a slowly impairing, bilateral visual loss. This clinical presentation was most likely the result of the high intracranial pressure due to impediment of cerebrospinal fluid circulation, possibly related to obstructive dural thickness, being either caused by dural and/or leptomeningeal metastases of advanced mCRPC or by local radiation effects following lutetium-177-PSMA therapy. Describing this case, we aim to add to the discussion on ¹⁷⁷Lu-PSMA safety, in which prospective research will ultimately offer definite answers.

https://ift.tt/2A0l8Q8

Lady with 'lobster claw feet

A 94-year-old woman admitted with confusion secondary to a urinary tract infection exhibited deformities in all four limbs that were present from birth. Her appearance was suggestive of split hand/split foot malformation a rare congenital condition that affects the central rays of the distal limb portion. She had no syndromic features and had lived without support or assistance of her daily activities. A keen knitter, she regularly knitted for her three grandchildren, all of which, along with her son, were unaffected by this condition.

https://ift.tt/2QDq3fb

Fluoxetine overdose in a teenager resulting in serotonin syndrome, seizure and delayed onset rhabdomyolysis

A 14-year-old young adult took an overdose of 1.2 g of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) that he had been prescribed for depression. He had a generalised tonic/clonic seizure at 6 hours postingestion.

After the seizure, he developed signs consistent with serotonin syndrome: fine tremor, agitation, sweating and hyperreflexia. This was followed by severe muscle pain and rhabdomyolysis with peak creatine kinase (CK) of 33 941 at 74 hours. He was managed with intravenous fluids and analgesia and discharged after 4 days, having avoided renal injury. The use of SSRI's such as fluoxetine in teenagers has increased in recent years. While it is generally considered benign in overdose, this report illustrates the severe consequences of overdose at high quantities and discusses appropriate management in these cases. We note that in this case, there was a delayed onset of rhabdomyolysis with peak CK at 74 hours postingestion.

https://ift.tt/2A09NQ5

Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy

Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the antitumour activity of the immune system and have produced durable tumour responses in several solid tumours including non-small cell lung cancer (NSCLC). However, PD-1 inhibitors can lead to immune-related adverse events , including pneumonitis, which is typically mild, but can be severe and potentially fatal. Pneumonitis often resolves with steroids, but some cases are steroid refractory, leading to a relapsing and remitting course in milder cases or the need for salvage therapies in more severe cases. Here, we present two patients with NSCLC who developed severe pneumonitis following therapy with nivolumab and pembrolizumab. While one patient improved with steroids and infliximab, the other patient failed to respond to steroids and subsequently died. These cases demonstrate the highly variable presentation and therapeutic responses seen in patients with pneumonitis following anti-PD-1 therapy and illustrate that severe cases can often present refractory to steroid therapy.

https://ift.tt/2QDq1E5

Two distinct histological Richters transformations 23 years apart in a patient with chronic lymphocytic leukaemia

A 53-year-old man with a 1-year history of chronic lymphocytic leukaemia (CLL) presented with a left bicep mass. Biopsy and staging workup revealed Richter's transformation (RT) Ann Arbor stage 1E diffuse large B-cell lymphoma in the bicep. The patient was treated with combination chemotherapy with cyclophosphamide, doxorubicin, Vincristine and prednisone followed by site radiation and did well thereafter. His CLL progressed and required treatment on two more occasions 11 and 18 years after his initial diagnosis with fludarabine, Cytoxan and Rituxan and then with bendamustine and rituximab. 23 years after initial presentation, he developed diffuse lymphadenopathy and B-symptoms. A biopsy of an enlarged cervical lymph node demonstrated only CLL for which he was started on ibrutinib. Treatment was shortly discontinued thereafter due to intolerance and worsening symptoms. A second biopsy was performed which revealed concurrent CLL and Hodgkin's lymphoma representing a second and histologically distinct RT.

https://ift.tt/2A04sb8

Ascites with hepatic extravasation of total parenteral nutrition (TPN) secondary to umbilical venous catheter (UVC) malposition in an extremely preterm baby

The ease of access and advantages of a secure central line makes use of umbilical venous catheter (UVC) and umbilical artery catheters a part of the standard of care in the extremely premature babies in the neonatal intensive care unit. However, there are complications associated with their use. One of the uncommon complications reported is total parenteral nutrition (TPN) ascites secondary to vessel perforation or hepatic erosion by the tip of the catheter due to malposition of a UVC. We present here a case of such catheter perforation causing ascites and right hepatic collection of TPN in a 28-week-old infant. Abdominal paracentesis was therapeutic by relieving the distension as well as confirming the presence of parenteral nutrition in the peritoneal cavity.

https://ift.tt/2QDpZfr