Head and Neck Diseases by Alexandros G.Sfakianakis: 10/09/18

Τρίτη 9 Οκτωβρίου 2018

Phytohormone Abscisic Acid Protects Human Neuroblastoma SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity Through Its Antioxidant and Antiapoptotic Properties

Rejuvenation Research, Ahead of Print.

https://ift.tt/2yrJ7Wm

Full face ingenol mebutate for actinic keratosis: patient perspective

International Journal of Dermatology, EarlyView.

https://ift.tt/2CzrdFn

Transient dispersion of an initial point pollutant concentration in wetland flows

Abstract

Initial point pollutant transport in wetland flows acts as a typical form in various applications. Accurate determination of the basic characteristics for dispersion fundamentally supports the predication of pollutant transport especially in the transient stage. This work analytically studies the transient dispersion of an initial point pollutant concentration in wetland flows through the phase average technique and the method of concentration moments. The characteristics including the vertical mass distribution, longitudinal displacement, dispersivity, skewness, and kurtosis corresponding to the zeroth- to fourth-order concentration moments are accurately illustrated in their full-time dependance for the first time. Present results show to be distinctive from those of initial uniform concentration in the transient dispersion process. The temporal evolutions of the five characteristics are all dependent of the initial point release position. The results further demonstrate that the timescale 3.0 as measured by the skewness, rather than 0.5 as measured by the dispersivity, should be characterized as the transient period for the dispersion of initial point concentration in comparison with that of initial uniform. Furthermore, the longitudinally distributed mean concentration is as well analyzed through the Hermite polynomials. The results imply that strict criteria for environmental and ecological implications should be established by further accounting for the five characteristics.

https://ift.tt/2ysQbSz

Simulated reactive zone with emulsified vegetable oil for the long-term remediation of Cr(VI)-contaminated aquifer: dynamic evolution of geological parameters and groundwater microbial community

Abstract

Cr(VI), which is highly toxic and soluble, is one of the most challenging groundwater contaminants. Previous work has indicated that emulsified vegetable oil (EVO) is an effective in situ amendment for removing Cr(VI) from groundwater. However, the spatial and temporal changes in geological parameters and microbial community structures throughout the remediation period are poorly understood. In this study, a large laboratory-scale sand-packed chamber (reactive zone of 100 × 50 × 30 cm) was used to simulate the bioremediation of Cr(VI)-contaminated aquifer by EVO over a 512-day period. Various geological parameters and microbial communities were monitored during both the establishment and remediation stages. The results indicate that several biogeochemical reactions occurred in a specific sequence following the injection of EVO, creating an acidic and reducing environment. A shift in the community structure and a decrease in the community diversity were observed. The abundance of microbes involved in the degradation of EVO and reduction of electron acceptors significantly increased. Then, the EVO reactive zone was flushed with Cr(VI)-contaminated groundwater. Biogeochemical reactions were inhibited after the inflow of Cr(VI) and subsequently recovered a month later. The pH of the aquifer returned to the initial neutral condition (approximately 7.2). The EVO reactive zone could remediate Cr(VI)-contaminated groundwater at an efficiency exceeding 97% over 480 days. Biogeochemistry played a major role in the early period (0~75 days). In the later period (240~480 days), the remediation of Cr(VI) in the reactive zone depended mostly on bio-reduction by Cr(VI)-reducing bacteria.

https://ift.tt/2OdW1BY

Stage-specific testicular protein levels of the oestrogen receptors (ERα and ERβ) and Cyp19 and association with oestrogenic contamination in the lambari Astyanax rivularis (Pisces: Characidae)

Abstract

Oestrogens participate in various biological processes such as oogenesis, vitellogenesis and testicular development, but studies regarding the distribution and protein levels of oestrogen receptors (ERα and ERβ) and aromatase (Cyp19) in testis are rarely investigated in fish species. The aim of the present study was to analyse the expression pattern of ERα, ERβ and Cyp19 in testis of Astyanax rivularis and, in addition, to verify if oestrogenic contamination interferes in the expression levels of these proteins. Quarterly, field samplings were carried out during a reproductive cycle in a stream of the Upper Velhas River with a good conservation status (site S1). In the gonadal maturation peak (June), when ripe stage was most abundant, fish collection was made in three streams: S1, reference site, and S2 and S3, sites contaminated by untreated sewage. The results of immunohistochemistry demonstrated labelling of Cyp19 in Leydig cells and acidophilic granulocytes, but spermatogonia, Sertoli cells, spermatids and spermatozoa were also labelled. ERα was more widely distributed than ERβ being found in all developmental germ cell phases. On the other hand, ERβ was found only in spermatogonia and spermatocytes. During testicular maturation, ELISA levels for Cyp19, ERα and ERβ followed the gonadosomatic index (GSI) with significant higher values in the ripe stage. Regarding to endocrine disruption, the males exposed to domestic sewage presented significant higher expression of Cyp19 and ERα when compared to the non-exposed fish. Together, our results demonstrate expression patterns of Cyp19, ERα and ERβ in the testis of A. rivularis. In addition, we indicate ERα and Cyp19 as sensitive biomarkers for monitoring of oestrogenic contamination in freshwater environments.

https://ift.tt/2yp8uIg

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.

https://ift.tt/2yaypnU

Intralesional pentoxifylline injection in localized alopecia areata

Journal of Cosmetic Dermatology, EarlyView.

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Intralesional pentoxifylline injection in localized alopecia areata

Journal of Cosmetic Dermatology, EarlyView.

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Editorial Board w/barcode

https://ift.tt/2NvBbsp

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Hypertensive Waist and Lipid Accumulation Product as Predictors of Metabolic Syndrome

Metabolic Syndrome and Related Disorders, Ahead of Print.

https://ift.tt/2ysCP8P

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.

https://ift.tt/2OhVf6M

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.

https://ift.tt/2A1WxdD

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.

https://ift.tt/2Nzfxn4

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.

https://ift.tt/2Nzfxn4

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

Effect of sucralfate against hydrochloric acid-induced dental erosion

Abstract

Objective

Devising effective measures for the prevention of hydrochloric acid (HCl)-induced erosion is of great significance. This is even more important in dentine, in which products have limited diffusion. Therefore, agents that can bind to proteins forming an acid-resistant gel-like coat, such as sucralfate, may stand out as a promising alternative. This study investigated the protective effect of sucralfate suspensions against HCl-induced dental erosion.

Materials and methods

In the first experiment, hydroxyapatite (HAp) crystals were pre-treated with a commercial sucralfate suspension (CoSS, pH 5.9), a stannous-containing sodium fluoride solution (NaF/SnCl₂ pH 4.5), two prepared sucralfate suspensions (PrSS, pH 5.9 and 4.5), or deionized water (DI, control). HAp dissolution was measured using a pH-stat system. In a subsequent experiment, embedded/polished enamel and root dentine slabs were allocated into five groups to be treated with one of the tested substances prior to and during erosion-remineralization cycles (HCl-2 min + artificial saliva 60 min, two times per day, 5 days). Surface loss was assessed profilometrically. Data were analyzed by ANOVA and Tukey's tests.

Results

HAp dissolution was as follows: NaF/SnCl₂ < CoSS < PrSS/pH 4.5, while PrSS/pH 5.9 = DI and both did not differ from CoSS and PrSS/pH 4.5. In enamel, surface loss did not differ between CoSS and PrSS/pH 4.5, with both having lower surface loss than PrSS/pH 5.9 and DI and NaF/SnCl₂ differing only from DI. In root dentine, surface loss was as follows: CoSS < PrSS/pH 5.9 < (NaF/SnCl₂ = DI), while PrSS/pH 4.5 = CoSS = PrSS/pH 5.9.

Conclusion

Sucralfate suspension provided anti-erosive protection to HCl-induced erosion.

Clinical relevance

Sucralfate may protect teeth against erosion caused by gastric acid.

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Bone repair in craniofacial defects treated with different doses of alendronate: a histological, histomorphometric, and immunohistochemical study

Abstract

Objective

The objective of the study is to evaluate bone repair in rats treated with different alendronate doses.

Matherials and methods

Sixty female rats ovariectomized were randomly divided in three groups: group C (control group), group A1 (ALN/1 mg/kg), and A2 (ALN/ 3 mg/kg). Each animal received subcutaneous applications of sodium alendronate at a dose correspondent to group A1 or A2 three times a week, while the control group received 0.9% saline solution. After 4 weeks of application, a critical defect was created in the calvaria of animals of all groups. The defect was filled by particulate autogenous bone. The applications were maintained until euthanasia, which occurred 15 and 60 days after the surgical procedure. The pieces were sent for histological, histomorphometric and immunohistochemical analysis. The data were submitted to statistical analysis with significance level of 0.05.

Results

The descriptive histological analysis demonstrated an increase in bone neoformation in both groups treated with alendronate when compared to the control group. The histomorphometric analysis showed an increase in the amount of neoformed bone in A1 and A2 groups when compared to group C, both at 15 days (p = 0.0002) and at 60 days (p = 0.001). In the immunohistochemical analysis, it was possible to observe a difference in immunolabeling just for Mmp2 at the time of 60 days in A1 (p = 0.001) and A2 (p = 0.023) when compared to the control group.

Conclusion

Systemic delivery of alendronate, regardless of the dose, increased the amount of bone neoformation.

Clinical relevance

Prescription of sodium alendronate at 1 mg/kg for improvement of bone neoformation in bone graft procedures.

https://ift.tt/2ycPPjE

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).

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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

Dissipation of polycyclic aromatic hydrocarbons (PAHs) in soil amended with sewage sludge and sludge compost

Abstract

In this study, greenhouse experiments were conducted under the condition of different amendment ratios and planting tall fescue (Festuca arundinacea). The amendment ratios of sewage sludge or sludge compost to soil were of 0, 10, 25, and 50% (w/w). The removal rates of PAH, catalase, and dehydrogenase activities of amended soil and accumulation of PAHs by vegetation were detected to investigate the differences of PAH dissipation in sludge-amended and compost-amended soils. The initial PAH concentrations in three amended soils increased with the more addition of sludge or compost. After 126-day experiment, maximum PAH removal rates were observed in sludge-amended and compost-amended soils with PAH concentration of about 200 μg kg⁻¹. And the removal of PAHs showed better efficiencies in compost soil rather than in sludge soil. The more catalase activity and dehydrogenase activity of soil were obtained, respectively, in sludge soil and compost soil. The results indicated that the mechanism of PAH dissipation in two types of amended soils were different. The abundant amount of microorganism dominated PAH dissipation in sludge soils, and PAHs dissipated mainly caused of intense activity of microorganism in compost soils. In addition, PAH accumulation in tall fescue suggested that the transference approach of PAHs was from soil to the roots, and then accumulated in the shoots of tall fescue. It was prone to store up more PAHs in vegetation in the condition of high molar weight of PAHs, more biomass of vegetation, and heavy PAH concentration in soil.

https://ift.tt/2RDObj6

The trade-environment nexus in light of governance: a global potential

Abstract

The theme of paper is to explore the trade-environment relationship and the role of institutions for 117 countries from global standpoint and five regions: Sub Saharan, European, Middle East and North Africa, Asia and Pacific, and Latin America and Caribbean, using the panel data span 2002–2014. By considering the endogeneity problem, to validate the nature of trade-environment nexuses, we applied the GMM first difference model in two steps. Likewise, Dumitrescu-Hurlin panel causality analysis is employed to affirm the causal relationship among the concern variables. The empirical findings of this study validate that the overall trade is significantly good to environment for sample countries (117) of the entire World, Europe, Asia, and Pacific regions. In further assessment, we incorporate interactive terms of institutions with trade, scale effect, and scale-technique effect. The estimated results confirm that institution is the persistent instrument for resolving the environmental problems. Furthermore, we find the evidence of inverted u shape EKC in overall selected sample of the World, Sub-Saharan, Europe, Asia, and Pacific regions. In contrast, there is no confirmation of inverted u shape EKC hypothesis in Middle East and North Africa regions. Similarly, no strong evidence of inverted u-shaped EKC hypothesis is observed in Latin-America and Caribbean region.

https://ift.tt/2EbUbwO

Low-frequency electromagnetic treatment of oilfield produced water for reuse in agriculture: effect on water quality, germination, and plant growth

Abstract

Competing demand for high-quality fresh water for agricultural, industrial, and municipal uses has placed tremendous stress on water resources; irrigating crops with fresh water is expensive and unsustainable. Using unconventional water sources such as oilfield produced water (PW) and treating PW with physical treatment methods such as electromagnetic treatment may overcome water-limitation challenges. A germination experiment was conducted using treated and untreated PW to examine the effect on the germination of iron and clay cowpeas (ICCs) since germination is the stage at which plants are most sensitive to external factors and stresses. The results from the study showed that ICCs germinated when irrigated with higher salinity water that was treated using the electromagnetic technology. A plant growth study was also conducted to assess the effect of electromagnetic treatment of high-salinity PW on the growing ability and crop health of ICCs. A reduction in leaf area expansion rate, the first indicator of salt stress on plants, was observed. After 14 days, plants showed early signs of salt stress such as wilting, lightening in color, and reduction in leaf area. After 28 days, plants watered with higher salinity PW (21,475–42,950 mg/L total dissolved solids) died and plants watered with lower salinity PW (< 21,475 mg/L total dissolved solids) survived but grew smaller than plants irrigated using fresh water. Results from both experiments suggested a potential total dissolved solids limit of ICCs or electromagnetic technology (or both) between 4000 and 10,000 mg/L. The results further suggested that while the electromagnetic technology did not have a strong effect on plant growth, high-salinity water might be treated for reuse in agriculture.

https://ift.tt/2RBLEFY

Dysregulation of Sqstm1, mitophagy, and apoptotic genes in chronic exposure to arsenic and high-fat diet (HFD)

Abstract

Arsenic (As) is a toxic and hazardous metalloid. Unfortunately, its presence in drinking water together with wrong nutritional patterns is associated with an increase in the occurrence of metabolic disorders in young people. Degradation of mitochondria is presented by a specific form of autophagy called mitophagy which is an important landmark leading to apoptosis during lipotoxicity. Lipotoxicity and cellular toxicity due to arsenic intake can lead to changes in mitophagy and apoptosis. The protein derived from SQSTM1 gene, also called p62, plays an important role in energy homeostasis in the liver, and it can contribute to the regulation of autophagic responses given its effect on signaling of mTOR, MAPK, and NF-KB. Consequently, changes in Sqstm1, mitophagy (BNIP3), and apoptotic (caspase 3) genes in the livers of NMRI mice were examined with the use of real-time RT-PCR Array followed by exposure to an environmentally relevant and negligible cytotoxic concentration of arsenite (50 ppm) in drinking water while being fed with a high-fat diet (HFD) or low-fat diet (LFD) for 20 weeks (LFD-As and HFD-As groups). While LFD-As and HFD groups showed a decrease in BNIP3 expression, a significant increase was observed in the HFD-As group. P62 gene showed downregulation in LFD-As and HFD groups, and upregeneration was observed in the HFD-As group. Caspase 3 showed increased expression as the key factor associated with apoptotic liver cell death in the three groups, with the highest value in HFD-As group. Overall, the changes observed in the expression of Sqstm1, BNIP3, and caspase 3 in this study can be related to the level of liver damage caused by exposure to arsenic and HFD and probably, BNIP3 pro-apoptotic protein is associated with an increased cell death due to HFD and As.

https://ift.tt/2Ebsgxb

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.

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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.

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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.

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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.

https://ift.tt/2yraAYa

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.

https://ift.tt/2OjJKMw

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.

https://ift.tt/2OhPbLG

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.

https://ift.tt/2yuEzi2

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]

https://ift.tt/2OhOG4g

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.

https://ift.tt/2yrDsiR

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.

https://ift.tt/2yoRj9L

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.

https://ift.tt/2yrI0G3

Yes-associated protein (YAP) molecule expression in odontogenic epithelium of ameloblastoma

Abstract

Objectives

YAP (Yes-associated protein molecule) augments multiple processes known to be important for tumor progression and metastasis. Hence, the application of YAP as a targeted therapy for several malignancies has been documented in the literature. Ameloblastoma being a locally invasive odontogenic lesion causes tissue destruction and presents with a great chance of recurrence. Based on these qualities, we hypothesized that YAP could exhibit increased expression in the odontogenic epithelium of ameloblastoma. Therefore, the objective of the present study was to evaluate the immunohistochemical expression of YAP in ameloblastoma and compare the immunoreactivity of YAP in ameloblastoma and dental follicle.

Materials and methods

Twenty-four paraffin-embedded tissue blocks of ameloblastoma and dental follicle each were retrieved from the departmental archives. Immunohistochemical (IHC) staining was performed employing YAP antibody on 5-μm thick sections. The expression of YAP was reviewed on the peripheral lining of ameloblast-like cells and centrally placed stellate reticulum–like cells and was further graded as negative, weak, or strong. For data analysis, Chi-square test and Fisher's exact test were applied.

Results

In ameloblastoma, peripheral/basal cells exhibited strong expression for YAP in 12/24 cases and weak expression in the other 12 cases. Whereas, 20 cases of dental follicle presented negative expression and only four cases exhibited weak expression (p < 0.001). On statistical analysis, the differences in expression of YAP in stellate cells of ameloblastoma and dental follicle were found to be significant (p < 0.001).

Conclusion

YAP expression was strongly seen in ameloblastoma as compared to the epithelial islands of dental follicle. The neoplastic nature of ameloblastoma could be attributed to YAP molecule and it may play a possible role in tumor invasiveness.

Clinical relevance

Positive YAP expression in ameloblastoma and negative expression in the odontogenic epithelial islands of dental follicle insinuate that YAP could be responsible for the aggressiveness and local tissue invasion commonly encountered with ameloblastoma.

https://ift.tt/2Ebh7wl

Presentation of gaps around endodontic access cavity restoration by phase contrast-enhanced micro-CT

Abstract

Objective

To evaluate the feasibility of synchrotron-based phase-contrast (PC) μCT for visualization of the gaps and differentiation between the gaps, restorative, and endodontic materials at the tooth-restoration interface.

Materials and methods

Standardized access cavities were prepared in human maxillary molars and subjected to materials, simulating endodontic treatment: (1) saline irrigation; (2) NaOCl and 17% EDTA irrigation; (3) same as group 2, followed by application of Ca(OH)₂; and (4) same as group 2, followed by application of root canal sealer. The access cavities were cleaned and restored using an etch-and-rinse adhesive and a composite material in multilayering technique. The samples were thermocycled (1000 cycles, 5–55 °C). Synchrotron-based μCT imaging was performed obtaining absorption and PC μCT images before and after the immersion of the samples into 50% AgNO₃. PC μCT images were compared to absorption μCT and conventional optical microscopy images.

Results

PC μCT of unstained samples enabled the best visualization of gaps and differentiation of restorative and endodontic materials, contaminating the cavity surface. PC μCT revealed that AgNO₃ staining leads to an overestimation of gap size due to anterograde and retrograde AgNO₃ infiltration into dentinal tubules and underestimation of large gaps due to lack of AgNO₃ penetration.

Conclusion

Synchrotron PC μCT imaging enables better visualization of gap and differentiation of materials at the tooth-restoration interface. μCT imaging with AgNO3 staining has shown certain over- and underestimations. Future research should be aimed at incorporating PC μCT imaging of unstained samples for the validation of results obtained with other methods.

Clinical significance

Contamination of cavity walls with an endodontic sealer or Ca(OH)₂ leads to increased gap formation at the tooth-restoration interface.

https://ift.tt/2RCirLd

Comparative evaluation of autofluorescence imaging and histopathological investigation for oral potentially malignant disorders in Taiwan

Abstract

Objectives

Autofluorescence imaging is gaining popularity as an adjunctive test for oral potentially malignant disorders (OPMD). This study evaluated the efficacy of autofluorescence imaging based on the current standard oral mucosal disorder checklist in Taiwan.

Materials and methods

In total, 126 patients suspected to have mucosal disorders at the Division of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan, were enrolled. Following a conventional oral examination by using the oral mucosal disorder checklist and an autofluorescence imaging examination, all participants underwent histopathological examination to access epithelial dysplasia.

Results

Among 126 patients, 68 patients were diagnosis as having an OPMD and 63 having epithelial dysplasia. Autofluorescence imaging exhibited a sensitivity, specificity, positivity predictive value (PPV), negative predictive value (NPV), and accuracy of 77.94%, 35.42%, 63.10%, 53.13%, and 60.34%, respectively, for OPMD and of 88.89%, 43.86%, 63.64%, 78.13%, and 67.50%, respectively, for epithelial dysplasia. After the exclusion of 48 non-OPMD cases according to the checklist, the sensitivity, specificity, PPV, NPV, and accuracy of autofluorescence imaging became 87.50%, 72.73%, 94.23%, 53.33%, and 85.07%, respectively, for epithelial dysplasia.

Conclusion

The efficacy of epithelial dysplasia identification and OPMD risk assessment can be increased after the exclusion of the non-OPMD cases through autofluorescence imaging.

Clinical relevance

Autofluorescence imaging is a useful adjunct that can assist specialists in assessing OPMD patients prone to dysplasia without compromising patient care.

https://ift.tt/2E7qe0V

Comparing the outcomes of gold-standard dental examinations with photographic screening by mid-level dental providers

Abstract

Objectives

To determine the detectability of the intra-oral photographic method in comparison to the baseline, comprehensive dental examination (CDE), in children when performed by different levels of dental practitioners.

Materials and methods

As part of a quality assurance program, intra-oral photographs were obtained from 77 patients (2–18 years) as part of a CDE before undertaking dental treatment under general anaesthesia. A DSLR camera was utilised to acquire images which were subsequently uploaded to a cloud-based server. The baseline for each participant was established during the CDE, utilising both visual and radiographic examination, which was then compared to the assessment made by a mid-level dental practitioners (MLDP). The evaluation was based on utilising an odontogram where the teeth were charted either as decayed or filled.

Results

Specificity (95%) was higher than sensitivity (61.5%) when comparing the photographic assessment with the benchmark CDE assessment. The inter-rater reliability between the two methods of assessment was substantial, with a kappa score of 0.62. The photographic assessment method underestimated the decayed and filled teeth, as observed by the caries experience (dft/DFT scores) (CDE = 7.01 vs. photographic assessment = 5.22). There were lower levels of diagnostic detection in the posterior teeth as compared to the anterior teeth assessments.

Conclusions

Although the CDE is still considered to be the gold-standard, this study found that the photographic caries assessment by MLDP produced an acceptable diagnostic level of detection particularly for the anterior teeth.

Clinical relevance

The photographic method could offer a potential cost-saving and user-friendly screening.

https://ift.tt/2RFrESO

Melanocyte activation and skin barrier disruption induced in melasma patients after 1064 nm Nd:YAG laser treatment

Abstract

Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.

https://ift.tt/2ytOSTe

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

What to know about age spots (liver spots)

Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond 18 F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon

Abstract

Cardiovascular disease is the major cause of morbidity and mortality in developed countries and atherosclerosis is the major cause of cardiovascular disease. Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can rupture leading to the formation of occlusive thrombi. Conventional diagnostic tools are still of limited value for identifying the vulnerable arterial plaque and for predicting its risk of rupture and of releasing thromboembolic material. Knowledge of the molecular and biological processes implicated in the process of atherosclerosis will advance the development of imaging probes to differentiate the vulnerable plaque. The development of imaging probes with high sensitivity and specificity in identifying high-risk atherosclerotic vessel wall changes and plaques is crucial for improving knowledge-based decisions and tailored individual interventions. Arterial PET imaging with ¹⁸F-FDG has shown promising results in identifying inflammatory vessel wall changes in numerous studies and clinical trials. However, due to its limited specificity in general and its intense physiological uptake in the left ventricular myocardium that impair imaging of the coronary arteries, different PET tracers for the molecular imaging of atherosclerosis have been evaluated. This review describes biological, chemical and medical expertise supporting a translational approach that will enable the development of new or the evaluation of existing PET tracers for the identification of vulnerable atherosclerotic plaques for better risk prediction and benefit to patients.

https://ift.tt/2IKEJGt

Assessing the ratio of Bacillus spores and vegetative cells by shotgun proteomics

Abstract

Mass spectrometry for rapid identification of microorganisms is expanding over the last years because this approach is quick. This methodology provides a decisive interest to fight against bioterrorism as it is applicable whatever the pathogen to be considered and often allows subtyping which may be crucial for confirming a massive and widespread attack with biological agents. Here, we present a methodology based on next-generation proteomics and tandem mass spectrometry for discovering numerous protein biomarkers allowing the discrimination of spores and vegetative cells of Bacillus atrophaeus, a biowarfare simulant. We propose a global quantitative evaluation of the two groups of discriminant biomarkers based on their aggregated normalized spectral abundance factors.

https://ift.tt/2y6iEhy

Alveolar bone preservation by a hydroxyapatite/collagen composite material after tooth extraction

Abstract

Objective

The aim of this study was to assess the effectiveness of a hydroxyapatite/collagen composite material (HAp/Col) for preservation of alveolar bone after tooth extraction.

Materials and methods

HAp/Col was applied to the alveolus bone ridge preservation after tooth extraction, because of subsequent dental implant placement in 35 regions of 24 patients (mean age, 59.3 years; range, 25–81 years). Cone beam computed tomography was used to assess changes in alveolar bone at the extraction site before and at 3 months (mean, 13.7 weeks; range, 10–17 weeks) after tooth extraction. Changes in height and width of the alveolar bone were measured to evaluate bone reduction after surgery. Bone biopsy was performed at 11 regions of dental implant placement to observe bone regeneration and remaining material in the extraction socket.

Results

The alveolar bone height was decreased by 0.00 ± 2.44 mm at the buccal side and 0.35 ± 1.73 mm at the lingual side, while the width was decreased by 1.02 ± 1.64 mm at 3 months after surgery. The middle of the socket floor was elevated by 5.71 ± 3.45 mm at 3 months after surgery. Bone biopsy specimens revealed no remaining implanted material, and approximately 49.79 ± 14.41% of the specimens were occupied by bone tissue.

Conclusions

According to the result of this study, HAp/Col is a reliable material to presearve alveolar bone after tooth extraction.

Clinical relevance

HAp/Col contributes dental implant treatment due to maintain the alveolar bone after tooth extraction.

https://ift.tt/2OM9DDP

“Green” UV‐LED Gel Nail Polishes from Bio‐Based Materials

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

https://ift.tt/2NumiGY

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

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

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

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

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

Obstructive Sleep Apnea in Neuro-Ophthalmology

Background: Obstructive sleep apnea (OSA) is a common pulmonary disorder with many systemic sequelae. Its association with diseases seen in neuro-ophthalmology is being increasingly recognized. Treatment of OSA with continuous positive airway pressure (CPAP) may reverse the pathology in some eye diseases. Evidence Acquisition: We conducted a search of the literature using the Ovid Medline database and Google Scholar, focusing on articles that explored the association between OSA and ophthalmic conditions. These included hypertensive retinopathy, diabetic retinopathy, central serous retinopathy (CSR), retinal vein occlusion (RVO), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, idiopathic intracranial hypertension (IIH), papilledema, and stroke. Results: There is evidence of an independent association between OSA, and both hypertension and Type 2 diabetes mellitus, as well as the retinopathy associated with each disease. Evidence also suggests a link between OSA and CSR, NAION, and stroke. The evidence remains controversial or insufficient for convincing causative association with RVO, glaucoma, and IIH. However, in patients presenting with CSR, and IIH, underlying OSA is a common finding. CPAP reverses some pathological changes, but the evidence is limited. Conclusions: OSA is associated with many diseases seen in neuro-ophthalmology clinics. More studies are required to assess the real ability of CPAP to reverse pathological changes. Ophthalmologists can screen for undiagnosed OSA in patients presenting with certain eye diseases. Address correspondence to Clare L. Fraser, MMed, FRANZCO, Save Sight Institute, University of Sydney, 8 Macquarie Street, Sydney, NSW 2000, Australia; Email: manuscript@clarefraser.com The authors report no conflicts of interest. © 2018 by North American Neuro-Ophthalmology Society

https://ift.tt/2OiAIiR

Risk Factors for Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic Neuropathy

Background: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals older than 50 years. Demographic, ocular, and systemic risk factors for NAION have been identified, and we sought to determine which, if any, of these factors also increase risk of NAION in the fellow eye. Methods: We performed a retrospective chart review of patients with "ischemic optic neuropathy" (based on International Classification of Disease [ICD] codes) seen at a single eye center between 2007 and 2017. Patients who met diagnostic criteria for unilateral NAION without fellow eye optic neuropathy at diagnosis were included. Demographic information, ocular comorbidities, and systemic diagnoses were recorded, in addition to whether the fellow eye developed NAION during the follow-up period. Univariate and multivariate Cox proportional hazard regression were used to calculate hazard ratios (HRs) for fellow eye involvement. Results: Three hundred eighteen patients were identified by ICD codes, and 119 were included in the study. Twenty-nine (24%) patients developed NAION in the fellow eye over the mean follow-up period of 3.6 years (range: 1 month–11 years). Significant risk factors for fellow eye NAION included the presence of bilateral optic disc drusen (ODD, HR 2.78, 95% confidence interval [CI] 1.12–6.90, P = 0.02) and noncompliance with continuous positive airway pressure (CPAP) in patients with moderate-to-severe obstructive sleep apnea (HR 4.50, 95% CI 1.79–11.3, P = 0.0015). Conclusions: Bilateral ODD and noncompliance with CPAP when indicated are associated with increased risk of NAION in the fellow eye. Patients with these risk factors should be counseled on the potentially devastating visual consequences of bilateral NAION, and compliance with CPAP should be stressed when appropriate. Address correspondence to Melinda Y. Chang, MD, Department of Ophthalmology and Vision Science, University of California, Davis, 4860 Y Street, Suite 2400, Sacramento, CA 95817; E-mail: Melinda.y.wu@gmail.com The authors report no conflicts of interest. 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 Web site (https://ift.tt/2BFTkP1). © 2018 by North American Neuro-Ophthalmology Society

https://ift.tt/2ypF0df

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

Issue Information

Journal of Cutaneous Pathology, Volume 45, Issue 11, November 2018.

https://ift.tt/2pRel5r

Nail clipping with onychomycosis and surprise clue to the diagnosis of nail unit melanoma

Journal of Cutaneous Pathology, Volume 45, Issue 11, Page 803-806, November 2018.

https://ift.tt/2yq06bA

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

ISSUE INFORMATION

Skin Research and Technology, Volume 24, Issue 4, Page i-iv, November 2018.

https://ift.tt/2Nyfxnk

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

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

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

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

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

Effects of boundary condition on shrinkage vectors of a flowable composite in experimental cavity models made of dental substrates

Abstract

Objectives

Bond strength to enamel and dentin depends on the bonding approach or condition. This study investigated the effects of the boundary conditions, in terms of the bonding substrate and the bonding condition, on the shrinkage vectors of a flowable composite.

Materials and methods

An experimental cylindrical cavity (diameter = 6 mm, depth = 3 mm) consisting of the enamel floor and the surrounding dentin cavity walls was prepared for the "enamel-floor" group. Cylindrical cavities of the same dimensions were prepared with access from the occlusal enamel into dentin and served as controls. Each cavity model group was divided and bonded with two bonding conditions (n = 9): a self-etch (Adper Easy Bond, 3M ESPE) and a total-etch approach (OptiBond FL, Kerr). The composite (Tetric EvoFlow, Ivoclar Vivadent) was mixed with glass beads, applied to the cavity, scanned twice by micro-CT (uncured and cured states). The scans were evaluated by rigid registration, sphere segmentation, and registration for computing shrinkage vectors.

Results

The free surface of all restorations moved downward. The shrinkage vectors in the experimental cavity model pointed downward towards the enamel cavity floor, and the net axial movement was downward. In the control group, shrinkage vectors additionally moved upward, away from the cavity floor. The effect of the bonding substrate and the bonding condition was investigated for the shrinkage vectors and the axial movement (univariate ANOVA).

Conclusion

The bonding substrate, enamel, influenced the shrinkage vectors' direction, while the bonding condition caused only variations in the magnitude.

Clinical relevance

Bonding to enamel influences shrinkage vectors' direction, while the bonding condition plays only a minor role.

Graphical abstract

ᅟ

https://ift.tt/2E7WQrp

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

Capturing complexity of the diffusion-weighted MR signal decay

Publication date: Available online 9 October 2018

Source: Magnetic Resonance Imaging

Author(s): Richard L. Magin, M. Muge Karaman, Matt G. Hall, Wenzhen Zhu, Xiaohong Joe Zhou

Abstract

Diffusion-weighted MRI (dMRI) is a key component of clinical radiology. When analyzing diffusion-weighted images, radiologists often seek to infer microscopic tissue structure through measurements of the diffusion coefficient, D₀ (mm²/s). This multi-scale problem is framed by the creation of diffusion models of signal decay based on physical laws, histological structure, and biophysical constraints. The purpose of this paper is to simplify the model building process by focusing on the observed decay in the effective diffusion coefficient as a function of diffusion weighting (b-value), D(b), that is often observed in complex biological tissues. We call this approach the varying diffusion curvature (VDC) model. Since this is a heuristic model, the exact functional form of this decay is not important, so here we examine a simple exponential function, D(b) = D₀exp(−bD₁), where D₀ and D₁ capture aspects of hindered and restricted diffusion, respectively. As an example of the potential of the VDC model, we applied it to dMRI data collected from normal and diseased human brain tissue using Stejskal-Tanner diffusion gradient pulses. In order to illustrate the connection between D₀ and D₁ and the sub-voxel structure we also analyzed dMRI data from families of Sephadex beads selected with increasing tortuosity. Finally, we applied the VDC model to dMRI simulations of nested muscle fiber phantoms whose permeability, atrophy, and fiber size distribution could be changed. These results demonstrate that the VDC model is sensitive to sub-voxel tissue structure and composition (porosity, tortuosity, and permeability), hence can capture tissue complexity in a manner that could be easily applied in clinical dMRI.

https://ift.tt/2Ob8iXI

Responsibility of Neuropsychologists: The Case of the “Sonic Attack”

Publication date: Available online 9 October 2018

Source: Cortex

Author(s): Sergio Della Sala

https://ift.tt/2RERzKL

Announcing a Registered Reports special issue at Cortex for the ABCD study

Publication date: Available online 9 October 2018

Source: Cortex

Author(s): Chris Chambers

https://ift.tt/2E6DyCw

35. Jahrestagung der Österreichischen Gesellschaft für Radioonkologie, Radiobiologie und Medizinische Radiophysik

https://ift.tt/2E6Ah6k

Cosmetics, Vol. 5, Pages 59: Formulating O/W Emulsions with Plant-Based Actives: A Stability Challenge for an Effective Product

Cosmetics, Vol. 5, Pages 59: Formulating O/W Emulsions with Plant-Based Actives: A Stability Challenge for an Effective Product

Cosmetics doi: 10.3390/cosmetics5040059

Authors: Alessandra Semenzato Alessia Costantini Marisa Meloni Giada Maramaldi Martino Meneghin Gianni Baratto

Quality, safety, and efficacy concerns added to instability, poor absorption, and the dispersion of actives are common problems while formulating plant-based cosmetics. Furthermore, a correct balance between the stability of the emulsion, the sensory profile, and the high efficacy has to be considered to formulate an effective product. In this paper, we demonstrate that rheology is a methodological tool that can be used while designing a new product. In particular, we developed an O/W emulsion which is easy to spread on irritated skin, and that can soothe the redness and discomfort caused by the exposure to both physical and chemical irritating agents. The green active mixture consists of three natural raw materials: Bosexil®, Zanthalene®, and Xilogel®. Each ingredient has a well-demonstrated efficacy in terms of soothing, anti-itching, and moisturizing properties respectively. Starting from the selection of a new green emulsifying system, through the analysis of the rheological properties, we obtained a stable and easy-to-apply o/w emulsion. The efficacy of the optimized product was assessed in vitro on intact and injured skin using the SkinEthic™ Reconstituted Human Epidermis (RHE) as a biological model.

https://ift.tt/2yoUvCo

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

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 9 Οκτωβρίου 2018

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Materials and methods

Results

Conclusions

Clinical relevance

Zusammenfassung