http://sfaki.blogspot.gr/2017/04/nasal-ala-reconstruction-surgical.html
Skin tumours of the nasal ala are common and surgery is the treatment
of choice. Nasal ala reconstruction is challenging due to the reduced
mobility and unique features of its thick and sebaceous skin. The
natural arc of the ala and its boundary with the cheek are difficult
features to reproduce. One should bear in mind the functional and
cosmetic risks of nasal ala reconstruction. A distorted nasal contour
may impair the nasal valve; the alar rim may notch or elevate; facial
symmetry may be disrupted by blunting of the alar crease, trapdooring,
bridging of the nasofacial sulcus and poor colour and texture match.
Our aim is to review and compare the functional and cosmetic results
of different local flaps used to correct intermediate-thickness
defects on the nasal ala after surgical excision of cutaneous tumours.
We present representative patients who were treated at our
Dermatological Surgery Unit from June 2015 to September 2016.
The choice of the flap was adapted to the patients' physiognomy and
the defects' size: tunnelled island pedicle melolabial flap [Figure
1]; jigsaw puzzle advancement flap [Figure 2]; spiral flap [Figure 3];
dog-ear island pedicle flap [Figure 4] and banner melolabial
transposition flap [Figure 5]. Surgery was performed under
loco-regional anaesthesia, in an outpatient basis, followed by
prophylactic antibiotic therapy. There were neither immediate
complications nor subsequent flap necrosis. The tumours were
completely excised.
Figure 1: Female, 86-year-old, nodular ulcerated basal cell carcinoma
in the nasal ala: tunnelled island pedicle melolabial flap. (a)
Surgical plan, (b) primary defect, (c) secondary defect after
tunnelling of the flap, (d) immediate post-operative, (e and f) result
after healing (10 months after surgery).
Click here to view
Figure 2: Male, 76-year-old, nodular basal cell carcinoma on the nasal
ala: jigsaw puzzle advancement flap. (a) surgical plan, (b) primary
and secondary defects, (c) anchoring sutures secure the flap in place;
(d) immediate post-operative, (e) result after healing (3 months after
surgery).
Click here to view
Figure 3: Female, 76-year-old, nodular basal cell carcinoma on the
nasal ala: spiral flap, a combination of advancement and rotation. (a)
Surgical plan, (b) immediate post-operative, (c) result after healing
(2 months after surgery).
Click here to view
Figure 4: Female, 76-year-old, basal cell carcinoma on the nasal ala:
dog-ear island flap, combining two flaps: cheek advancement and
rotated island pedicle. (a) Surgical plan, (b) primary defect, (c)
immediate post-operative, (d) day 7 post-operative, (e) result after
healing (1 month after surgery).
Click here to view
Figure 5: Male, 83-year-old, two nodular basal cell carcinomas on the
nasal ala and dorsum: Banner's melolabial transposition flap. (a)
Surgical plan, (b) primary defect, (c) immediate post-operative, (d)
result after healing (7 months after surgery)
Click here to view
Facial symmetry was well preserved by the spiral and jigsaw puzzle
flaps [Figure 2] and [Figure 3]. The nasal sulcus was left intact by
the spiral flap as well as the tunnelled melolabial island flap
[Figure 1] and [Figure 3]. The melolabial flaps and the dog-ear island
flap allowed for the correction of larger defects on the nasal ala
[Figure 1], [Figure 4] and [Figure 5]. The dog-ear island flap [Figure
4] obtained a good result despite the large size of the primary
defect. Banner's melolabial transposition flap [Figure 5] was used to
correct a complex defect involving not only the nasal ala but also the
nasal dorsum and resulted in facial asymmetry due to trapdooring.
The small size of the defects that can be addressed by the spiral and
puzzle flaps may explain their superior cosmetic results.[1],[2] The
tunnelled melolabial island flap, although technically demanding, may
produce excellent results; compared to the cheek-to-nose interpolation
flap, the tunnelling technique offers the advantage of being one-stage
procedure. The dog-ear island flap is an adaptation of the cheek
advancement flap; despite its apparent complexity, it offers a viable
alternative to the melolabial flaps,[3] with a lower risk of trapdoor
effect and with proper preservation of the alar contour. The discussed
flaps are useful alternatives to the bilobed transposition flap and
the skin graft for the surgical reconstruction of the nasal ala.
When planning the surgery, it is important to assess the primary
defect on the nasal ala: size and location (medial or lateral), depth,
involvement of other cosmetic units/subunits and extension to the alar
rim, nasal tip or adjacent cheek. Several techniques have been
developed that are useful for the reconstruction of defects of the
nasal ala. Based on our experience and a review of the literature, we
present an algorithm [Table 1] to optimise the choices in the
reconstruction of intermediate-thickness defects in nasal ala. In
[Table 2], we review the main advantages and caveats of some of the
most useful surgical techniques for nasal ala
reconstruction.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]
Table 1: Nasal ala reconstruction: What is the optimal approach
according to the defects' size and location?
Click here to view
Table 2: Nasal ala reconstruction: major advantages and potential
caveats of different surgical techniques
Click here to view
In the nasal ala, given the paucity of surrounding skin and the
importance of minimising nasal ala distortion, flaps that recruit skin
from a distant site should be considered. Mastering different
techniques is essential for a surgeon to optimise treatment for each
patient. At the end of the day, the best choice depends on many
factors and should be adapted on a case-by-case basis and to the
surgeon's expertise.
--
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
alsfakia@gmail.com
Δευτέρα 17 Απριλίου 2017
Paediatric traumatic pneumomediastinum: the spinnaker sail sign
Description
A 20-month-old female infant was admitted to the emergency room after being run over by a car. She presented with pallor and signs of impaired peripheral perfusion, despite being conscious and alert. Signs of respiratory distress were recognised. There was a bilateral decrease of respiratory murmurs at pulmonary auscultation and her heart sounds were also diminished. Her peripheral oxygen saturation was 94% and her respiratory rate was 54 breaths per minute. A cervical and thoracic crepitus were present. There were no alterations at abdominal examination. Her blood pressure was 142/58 mmHg.
She presented with a Glasgow Coma Scale score of 15 and had normal reactive pupils. Facial oedema was observed and an epicranial haematoma was also detected. Haematological workup revealed a haemoglobin value of 12.9 g/dL.
A supine chest radiograph showed left hydropneumothorax, right pneumothorax and pulmonary contusion. This exam also showed significant pneumomediastinum revealing the spinnaker sail sign,...
http://ift.tt/2oH22ao
Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg-Negative Chronic Viral Hepatitis B
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2ooc3qU
Detection of the Canine Parvovirus 2c Subtype in Australian Dogs
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2pbZZOH
Development and Validation of Monoclonal Antibody-Based Antigen Capture ELISA for Detection of Group A Porcine Rotavirus
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2oohs1g
Metabolic reprograming of anti-tumor immunity
Madhusudhanan Sukumar | Rigel J Kishton | Nicholas P Restifo
http://ift.tt/2oQlELl
How Should Physicians Respond to Latest Alopecia Research?
Dr Lipper discusses evidence and strategy for treating patients with alopecia areata.
Medscape Dermatology
http://ift.tt/2nWZisk
Movie Villains With Scars May Haunt Those With Skin Conditions
The scars and facial features of some of cinema's most terrifying villains may end up haunting people who share those traits, suggests a new study.
Reuters Health Information
http://ift.tt/2nNhDb5
Genetic alterations in mesiodens as revealed by targeted NGS and gene co-occurrence network analysis
Abstract
Objective
Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes.
Materials and Methods
We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects were diagnosed on the basis of panoramic radiograph. 101 candidate genes which were captured custom gene were sequenced on the Illumina HiSeq2500. Multistep bioinformatics processing was performed including variant identification, base calling, and in silico analysis of putative disease-causing variants.
Results
Targeted capture identified 88 non-synonymous, rare, exonic variants involving 42 of the 101 candidate genes. Moreover, we investigated gene co-occurrence relationships between the genomic alterations and identified 88 significant relationships among 18 most recurrent driver alterations.
Conclusion
Our search for co-occurring genetic alterations revealed that such alterations interact cooperatively to drive mesiodens. We discovered a gene co-occurrence network in mesiodens patients with functionally enriched gene groups in the sonic hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT) signaling pathways.
This article is protected by copyright. All rights reserved.
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Oral Candida Colonization and Oral Lichen Planus
Abstract
In a well-designed clinical trial, Marable et al. has reported on the incidence of oral candidiasis in patients treated with topical steroids for oral lichen planus (OLP). (Marable et al, 2016) It has been observed that "There was no significant difference in the incidence of oral fungal infection between OLP patients treated with a preventive antimycotic therapy and those not treated prophylactically". (Marable et al, 2016)
This article is protected by copyright. All rights reserved.
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Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1)
HNSCC is the fifth most common malignancy worldwide and the eighth most common cause of cancer-related mortality [1,2]. Tobacco and alcohol abuse are the main risk factors, but in the past few years HPV infection has emerged as a new risk factor for a substantial percentage of HNSCC-especially in oropharyngeal cancer (OPC) [3]. Only one third of the patients present with early stage disease, while most of them will have locally advanced (LA) disease by the time of diagnosis [4]. In these patients, 5-year survival has remained invariable in the last decades [5].
http://ift.tt/2oQ3uJC
Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2)
Introduction and Methodology has been described in the first part of this article.
http://ift.tt/2oiM4lF
The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis
Intracranial lesions, trauma or surgery-related damage activate immune inflammation and neuroendocrine responses, causing ischemic brain injury. Studies have shown that inflammatory cascade mediated by neuroendocrine hormones and proinflammatory mediators is implicated in the pathophysiology of ischemic brain injury. Alpha2-adrenoceptor agonists, dexmedetomidine, is widely used as neuroprotectants in anesthesia practice. However, it is still lack of a comprehensive meta-analysis to evaluate the neuroprotection of dexmedetomidine against ischemic brain injury via suppressing these two physiological responses.
http://ift.tt/2psee1f
The effect of handedness and laterality in a microlaryngeal surgery simulator
There are no controlled prospective studies evaluating the effect of dominant handedness in left- and right-sided surgery in otolaryngology. Endoscopic microlaryngeal phonosurgery is an ideal procedure to assess technical aspects of handedness and laterality, due to anatomic symmetry. In this study, we analyzed (1) choice of surgical approach and (2) outcomes based on handedness and laterality in a microlaryngeal simulator.
http://ift.tt/2pscOUD
Prevalence and Descriptive Epidemiology of Atopic Dermatitis and Its Impact on Quality of Life in Singapore
Abstract
Atopic dermatitis (AD) is a common, chronic, pruritic skin condition that is known to negatively impact the quality of life (QOL) of patients1,2. Due to its increasing prevalence, AD can impose a substantial economic burden on a country's healthcare system.3 A study in 2002 found a prevalence of 20.8% of AD in Singapore schoolchildren aged between 7 and 12 years4.
This article is protected by copyright. All rights reserved.
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Healing of extraction socket following local application of simvastatin: A split mouth prospective study
Publication date: Available online 17 April 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Aamir Malick Saifi, Girish B. Giraddi, Nausheer Ahmed
BackgroundThe role of simvastatin in lowering serum cholesterol level is well described. However, recent findings suggest they have a role in bone formation as well.Aim and objectivesThe present prospective study was conducted to evaluate the efficacy of simvastatin on bone formation in extraction sockets.Materials and methods15 patients undergoing all four first premolar extraction were selected based on inclusion and exclusion criteria. Extraction sockets of left premolars (24 and 34) were considered as cases and right premolars (14 and 44) as controls. Overall 30 extraction sites were assigned to each group. Atraumatic extraction was done in all cases following which simvastatin mixed with gelatin sponge was placed in extraction socket of 24 and 34 while only gelatin sponge was placed in 14 and 44. All sockets were then closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. Intra oral peri apical radiographs were taken immediately after extraction and at 2nd month and 4th month to record changes in the density of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed.ResultPercent increase in bone density at the end of 8th week and 16th week was significantly high in case as compared to the control group.ConclusionLocal application of simvastatin induces bone formation in extraction sockets. Application is very simple and provides a very cost effective way of faster bone regeneration following tooth extraction.
http://ift.tt/2oiSvVO
Role of Chemiluminescence examination as non-invasive diagnostic tool in early detection of Leukoplakia
Publication date: Available online 17 April 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Nidhi Jain, Anil Kumar Nagarajappa, Meenakshi Bhasin, Divya Pandya, Kaushal Pati Tripathi
ObjectivesTo assess the efficacy of Chemiluminescent light (Vizilite plus) in enhancing visualization and its ability to highlight Leukoplakia lesion.Material and methodsThis was a cross-sectional study done on 40 study subjects. Subjects were inducted into the study irrespective of age and sex based on the specific inclusion and exclusion criteria. The lesion parameters like the location of the lesion, the shape of lesion, the size, the extent, borders and the presence or absence of any adjacent satellite lesions were assessed under Incandescent light followed by Toluidine blue and Vizilite plus examinations. Histopathological examination results were considered as the gold standard and TBLU and CHEM outcomes were compared to them.ResultsVizilite plus examination method was most effective in assessing the size, borders and shape of the lesions followed by Toluidine blue and Incandescent light examinations. Toluidine blue and Vizilite plus examination methods demonstrated the sensitivity of 100% and specificity of 97.3%. They also demonstrated PPV of 100% and NPV of 75% with reliable accuracy of 97.5%.ConclusionChemiluminescent light is a stepping stone and has the potential to revolutionize the diagnostic protocol for patients with potentially premalignant lesions. The device can be used as a general oral mucosal examination system and may in particular improve the visualization of potentially premalignant lesions.
http://ift.tt/2pbiRNt
Serum Endocan Levels in Children with Community-Acquired Pneumonia
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2oFrywr
Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo [TRANSPLANTATION]
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4+CD25+FOXP3+) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4+CD25–FOXP3–) and the direct antiproliferative effects of AzaC on allogeneic T cells. Using B6.Foxp3DTR/GFP mice in which Tregs can be specifically ablated through administration of diphtheria toxin, we demonstrate that natural Tregs are required in the donor graft for AzaC to optimally protect against GvHD and that nTregs, unlike Teffs (CD3+FOXP3–), are resistant to the antiproliferative effects of AzaC. Gene expression analysis identified the potent cell cycle inhibitor, p21, was significantly upregulated in Teffs but not nTregs after treatment with AzaC. Furthermore, we demonstrate that Teffs deficient in p21 are less sensitive to the antiproliferative effects of AzaC. These results demonstrate that nTregs are essential for AzaC to fully protect against GvHD and have important clinical implications for future clinical trials testing AzaC as a novel method of GvHD prophylaxis in man.
http://ift.tt/2onyCMC
Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis [SYSTEMS IMMUNOLOGY]
The transcription factor STAT6 plays a key role in mediating signaling downstream of the receptors for IL-4 and IL-13. In B cells, STAT6 is required for class switch recombination to IgE and for germinal center formation during type 2 immune responses directed against allergens or helminths. In this study, we compared the transcriptomes and proteomes of primary mouse B cells from wild-type and STAT6-deficient mice cultured for 4 d in the presence or absence of IL-4. Microarray analysis revealed that 214 mRNAs were upregulated and 149 were downregulated >3-fold by IL-4 in a STAT6-dependent manner. Across all samples, ~5000 proteins were identified by label-free quantitative liquid chromatography/mass spectrometry. A total of 149 proteins was found to be differentially expressed >3-fold between IL-4–stimulated wild-type and STAT6–/– B cells (75 upregulated and 74 downregulated). Comparative analysis of the proteome and transcriptome revealed that expression of these proteins was mainly regulated at the transcriptional level, which argues against a major role for posttranscriptional mechanisms that modulate the STAT6-dependent proteome. Nine proteins were selected for confirmation by flow cytometry or Western blot. We show that CD30, CD79b, SLP-76, DEC205, IL-5Rα, STAT5, and Thy1 are induced by IL-4 in a STAT6-dependent manner. In contrast, Syk and Fc receptor–like 1 were downregulated. This dataset provides a framework for further functional analysis of newly identified IL-4–regulated proteins in B cells that may contribute to germinal center formation and IgE switching in type 2 immunity.
http://ift.tt/2oGqASA
Rip2 Is Required for Nod2-Mediated Lysozyme Sorting in Paneth Cells [MUCOSAL IMMUNOLOGY]
Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2–LRRK2–Rip2–Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.
http://ift.tt/2oGxZBf
Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma [MUCOSAL IMMUNOLOGY]
The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.
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Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex [INNATE IMMUNITY AND INFLAMMATION]
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum–associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-B signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-β–activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IB kinase complex and NF-B inhibitor α (IBα) as well as NF-B nuclear translocation. Our findings collectively suggest that TAP1 plays a novel role in the negative regulation of virus-triggered NF-B signaling and the innate immune response by targeting the TAK1 complex.
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Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration [INNATE IMMUNITY AND INFLAMMATION]
H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.
http://ift.tt/2oGuN8G
Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small-molecule inhibitors, small-molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study, we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies, we identified 45 small molecules that putatively bind C3b near ligand-guided functional hot spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand that guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed cmp-5, and mechanistic studies of the cmp-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small-molecule complement inhibitors and, to our knowledge, provides the first demonstration of cheminformatics-based, complement-directed drug discovery.
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Vigilin Regulates the Expression of the Stress-Induced Ligand MICB by Interacting with Its 5' Untranslated Region [INNATE IMMUNITY AND INFLAMMATION]
NK cells are part of the innate immune system, and are able to identify and kill hazardous cells. The discrimination between normal and hazardous cells is possible due to an array of inhibitory and activating receptors. NKG2D is one of the prominent activating receptors expressed by all human NK cells. This receptor binds stress-induced ligands, including human MICA, MICB, and UL16-binding proteins 1-6. The interaction between NKG2D and its ligands facilitates the elimination of cells under cellular stress, such as tumor transformation. However, the mechanisms regulating the expression of these ligands are still not well understood. Under normal conditions, the NKG2D ligands were shown to be posttranscriptionally regulated by cellular microRNAs and RNA-binding proteins (RBPs). Thus far, only the 3' untranslated regions (UTRs) of MICA, MICB, and UL16-binding protein 2 were shown to be regulated by RBPs and microRNAs, usually resulting in their downregulation. In this study we investigated whether MICB expression is controlled by RBPs through its 5'UTR. We used an RNA pull-down assay followed by mass spectrometry and identified vigilin, a ubiquitously expressed multifunctional RNA-binding protein. We demonstrated that vigilin binds and negatively regulates MICB expression through its 5'UTR. Additionally, vigilin downregulation in target cells led to a significant increase in NK cell activation against said target cells. Taken together, we have discovered a novel mode of MICB regulation.
http://ift.tt/2oGpSVf
IL-26 Confers Proinflammatory Properties to Extracellular DNA [INNATE IMMUNITY AND INFLAMMATION]
In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors. IL-26 is a member of the IL-10 cytokine family, overexpressed in numerous chronic inflammatory diseases, in which biological activity remains unclear. We demonstrate in this study that IL-26 binds to genomic DNA, mitochondrial DNA, and neutrophil extracellular traps, and shuttles them in the cytosol of human myeloid cells. As a consequence, IL-26 allows extracellular DNA to trigger proinflammatory cytokine secretion by monocytes, in a STING- and inflammasome-dependent manner. Supporting these biological properties, IL-10–based modeling predicts two DNA-binding domains, two amphipathic helices, and an in-plane membrane anchor in IL-26, which are structural features of cationic amphipathic cell-penetrating peptides. In line with these properties, patients with active autoantibody-associated vasculitis, a chronic relapsing autoimmune inflammatory disease associated with extensive cell death, exhibit high levels of both circulating IL-26 and IL-26–DNA complexes. Moreover, in patients with crescentic glomerulonephritis, IL-26 is expressed by renal arterial smooth muscle cells and deposits in necrotizing lesions. Accordingly, human primary smooth cells secrete IL-26 in response to proinflammatory cytokines. In conclusion, IL-26 is a unique cationic protein more similar to a soluble pattern recognition receptor than to conventional cytokines. IL-26 expressed in inflammatory lesions confers proinflammatory properties to DNA released by dying cells, setting up a positive amplification loop between extensive cell death and unabated inflammation.
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Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation [INNATE IMMUNITY AND INFLAMMATION]
Psoriasis is a chronic inflammatory disease resulting from dysregulated immune activation associated with a large local secretion of cytokines. Among them, IL-22 largely contributes to epithelial remodeling and inflammation through inhibiting the terminal differentiation of keratinocytes and inducing antimicrobial peptides and selected chemokines. The activity of IL-22 is regulated by IL-22 binding protein (IL-22BP); however, the expression and role of IL-22BP in psoriatic skin has remained unknown so far. Here we showed that nonaffected skin of psoriasis patients displayed lower expression of IL-22BP than skin of healthy controls. Furthermore, the strong IL-22 increase in lesional psoriatic skin was accompanied by a moderate induction of IL-22BP. To investigate the role of IL-22BP in controlling IL-22 during skin inflammation, we used imiquimod-induced skin disease in rodents and showed that rats with genetic IL-22BP deficiency (Il22ra2–/–) displayed exacerbated disease that associated with enhanced expression of IL-22–inducible antimicrobial peptides. We further recapitulated these findings in mice injected with an anti–IL-22BP neutralizing Ab. Hypothesizing that the IL-22/IL-22BP expression ratio reflects the level of bioactive IL-22 in psoriasis skin, we found positive correlations with the expression of IL-22–inducible molecules (IL-20, IL-24, IL-36, CXCL1, and BD2) in keratinocytes. Finally, we observed that serum IL-22/IL-22BP protein ratio strongly correlated with psoriasis severity. In conclusion, we propose that although IL-22BP can control deleterious actions of IL-22 in the skin, its limited production prevents a sufficient neutralization of IL-22 and contributes to the development and maintenance of epidermal alterations in psoriasis.
http://ift.tt/2oGonX0
Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation [INNATE IMMUNITY AND INFLAMMATION]
The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders. Upon nonspecific binding of cytosolic B–form DNA, cGAS synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent signaling to produce type I IFNs. The cGAS comprises less-conserved N-terminal residues and highly conserved nucleotidyltransferase/Mab21 domains. The function and structure of the well-conserved domains have been extensively studied, whereas the physiological function of the N-terminal domain of cGAS is largely uncharacterized. In this study we used a single-molecule technique combined with traditional biochemical and cellular assays to demonstrate that binding of nonspecific dsDNA by the N-terminal domain of cGAS promotes its activation. We have observed that the N terminus of human cGAS (hcGAS-N160) undergoes secondary structural change upon dsDNA binding in solution. Furthermore, we showed that the hcGAS-N160 helps full length hcGAS to expand the binding range on DNA and facilitates its binding efficiency to dsDNA compared with hcGAS without the 160 N-terminal residues (hcGAS-d160). More importantly, hcGAS-N160 endows full length hcGAS relatively higher enzyme activity and stronger activation of STING/IRF3-mediated cytosolic DNA signaling. These findings strongly indicate that the N-terminal domain of cGAS plays an important role in enhancing its function.
http://ift.tt/2onEMfB
Activation of Myeloid TLR4 Mediates T Lymphocyte Polarization after Traumatic Brain Injury [INNATE IMMUNITY AND INFLAMMATION]
Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tissue was attenuated by myeloid cell depletion after TBI. Functionally, C3H/HeJ (TLR4 mutant) mice reversed M1 macrophage and TH1/TH17 polarization after TBI compared with C3H/OuJ (wild-type) mice. Moreover, brain monocytes isolated from C3H/HeJ mice were less potent stimulators of T lymphocyte proliferation and TH1/TH17 polarization compared with C3H/OuJ monocytes. Taken together, our data implicate TLR4-dependent, M1 macrophage trafficking/polarization into the CNS as a key mechanistic link between acute TBI and long-term, adaptive immune responses.
http://ift.tt/2oGOInZ
IFN Regulatory Factor 3 Potentiates Emphysematous Aggravation by Lipopolysaccharide [INNATE IMMUNITY AND INFLAMMATION]
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is often induced by infection and often has a poor prognosis. Bacterial LPS activates innate immune receptor TLR4 followed by activation of a transcriptional factor IFN regulatory factor-3 (IRF3) as well as NF-B, resulting in upregulation of various inflammatory mediators. To clarify the role of IRF3 in the pathogenesis of LPS-triggered COPD exacerbation, porcine pancreatic elastase (PPE) followed by LPS was administered intranasally to wild-type (WT) or IRF3–/– male mice. Sequential quantitative changes in emphysema were evaluated by microcomputed tomography, and lung histology was evaluated at the sixth week. WT mice treated with PPE and LPS exhibited enlarged alveolar spaces, whereas this feature was attenuated in similarly treated IRF3–/– mice. Moreover, LPS-induced emphysema aggravation was detected only in WT mice. Analysis of acute inflammation induced by PPE plus LPS revealed that the lungs of treated IRF3–/– mice had decreased mRNA transcripts for MCP-1, MIP-1α, TNF-α, and IFN-–inducible protein-10 but had increased neutrophils. IRF3 was involved in the production of mediators from macrophages, alveolar epithelial cells, and neutrophils. Furthermore, compared with isolated WT neutrophils from inflamed lung, those of IRF3–/– neutrophils exhibited impaired autophagic activation, phagocytosis, and apoptosis. These results suggest that IRF3 accelerated emphysema formation based on distinct profiles of mediators involved in LPS-induced COPD exacerbation. Regulation of the IRF3 pathway can affect multiple cell types and contribute to ameliorate pathogenesis of infection-triggered exacerbation of COPD.
http://ift.tt/2ony3m0
The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages [INNATE IMMUNITY AND INFLAMMATION]
Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-B and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun–deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways. Mice deficient for c-Jun in macrophages show an amelioration of inflammation and bone destruction in the serum-induced arthritis model. In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels.
http://ift.tt/2oGvDSM
Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery [INNATE IMMUNITY AND INFLAMMATION]
Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics.
http://ift.tt/2onjIWQ
Serum Endocan Levels in Children with Community-Acquired Pneumonia
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2oPT4JZ
Folic Acid – Who does what with Methotrexate?
Abstract
Methotrexate is a folic acid derivative that inhibits dihydrofolate reductase which has effects on DNA synthesis and cellular replication. In Dermatology, it is licensed for use in recalcitrant psoriasis but is also used off-label in many other conditions.1
It is given either orally or by subcutaneous injection. Folic acid is usually prescribed alongside methotrexate but there is often variation in prescribing practice.
This article is protected by copyright. All rights reserved.
http://ift.tt/2puGTjA
Oral Lichenoid Reactions associated with anti-PD-1/PD-L1 therapies: clinicopathological findings
Abstract
Immune checkpoint inhibitors targeting the programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) show broad activity across different tumor types and currently represent one of the keystones of cancer management. Dermatologic toxicities are one of the most frequent immune-related adverse events (irAEs) induced by these new monoclonal antibodies. Maculopapular rash, pruritus, exacerbation of psoriasis or more specific autoimmune disorders (e.g. vitiligo, alopecia areata, and bullous pemphigoid) are amongst the most commonly reported AEs.1-4 In addition, cutaneous lichenoid reaction has also emerged as one of the most prevalent dermatological toxicities in treated patients.
This article is protected by copyright. All rights reserved.
http://ift.tt/2nWbeKW
Do outdoor workers know their risk of NMSC? Perceptions, beliefs and preventive behaviour among farmers, roofers and gardeners
Abstract
Background
Non-melanoma skin cancer (NMSC) was officially recognized in 2015 as an occupational disease for outdoor workers in Germany. Together with the enormous socioeconomic impact of NMSC, this has led to the continuous demand of evidence-based prevention. However, studies assessing the perceptions and beliefs along with risk behavior of outdoor workers as an essential prerequisite for prevention are rare.
Objective
To assess perceptions, beliefs, barriers, risk and preventive behavior towards non-melanoma skin cancer among different outdoor groups as a basis for the development of sustainable prevention programs.
Patients and Methods
Cross-sectional study among outdoor workers of three different occupational groups (farmer, gardener, roofer) using a 20-question online survey on NMSC awareness, risk and preventive behavior.
Results
Between March and April 2016, 353 outdoor workers participated in the study. Of these, 153 (43.4%) reported never to use sunscreen during work. Wearing headgear and long pants were the most common sun protection measures. Poor use of sunscreen was more likely in males and farmers. A low perceived skin cancer risk was significantly associated with poor use of sunscreen, long-sleeved shirts, sunglasses and headgear.
Conclusions
Despite great evidence on NMSC risk in outdoor professions throughout the literature, high risk groups in fact are not yet aware of the topic. Sustainable target group oriented awareness prevention programs are needed to lower the immense burden of NMSC.
This article is protected by copyright. All rights reserved.
http://ift.tt/2puPsLt
Prepubertal vulvar fibroma, a rare entity little-known to dermatologists: Report of two cases
Abstract
Prepubertal vulvar tumors are rare and may represent mesenchymal tumors, hamartomas, or vascular malformations. Their presentation may be similar but they do not have the same prognosis and management. We report 2 cases of labium majus hypertrophy corresponding to prepubertal vulvar fibromas.
This article is protected by copyright. All rights reserved.
http://ift.tt/2nWhtOO
Lava lake structure and cloud-like structureless area: new clues for diagnosing extramammary Paget disease
Abstract
Extramammary Paget disease (EMPD) is a rare malignant skin neoplasm mostly found in the genital area. Its clinical and histopathological features are similar to mammary Paget disease. The clinical differential diagnosis includes various skin diseases. The dermoscopic findings of EMPD have been described in the literature.
This article is protected by copyright. All rights reserved.
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Genome-wide differential expression profiling of long non-coding RNAs in androgenetic alopecia in a Chinese male population
Abstract
Background
Androgenetic alopecia (AGA), or male pattern baldness (MPB), is the most common form of hair loss in males. A combination of genetic and androgen causes have been suggested as factors that contribute to the development of AGA. However, the specific molecular mechanisms that underly AGA remain largely unknown. Long noncoding RNAs (lncRNAs), a new class of regulatory noncoding RNAs that are longer than 200 nucleotides, have been shown to play important roles in a number of cellular processes, including transcription, chromosome remodelling, and posttranscriptional processing. The dysregulation of lncRNAs is associated with many forms of diseases, but it remains unknown whether lncRNAs are associated with AGA.
Objective
The aim of this study was to identify AGA-associated lncRNAs and predict the potential roles of these lncRNAs in AGA.
Methods
A genome-wide microarray was used to identify lncRNAs that are differentially expressed between AGA and adjacent normal tissues. Real-time qRT-PCR was used to validate the microarray data.
Results
A large number of lncRNAs were differentially expressed (fold change >2.4) between AGA and adjacent normal tissues. Of these, 770 were up-regulated, and 1,373 were down-regulated. Moreover, pathway analysis revealed that 53 functional pathways were associated with the up-regulated transcripts, while 11 pathways were associated with the down-regulated transcripts.
Conclusion
To our knowledge, this is the first study to investigate AGA-associated lncRNAs. LncRNA profiles are altered in AGA, and these lncRNAs and their target genes may serve as novel candidates for preventing and treating AGA.
This article is protected by copyright. All rights reserved.
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Prognostic risk factors of first recurrence in patients with primary stage I-II cutaneous malignant melanoma -from the population-based Swedish melanoma register
Abstract
Background
Prognostic factors in patients with localised primary cutaneous malignant melanoma (CMM) are well described. However, prognostic factors for recurrence are less documented.
Objectives
The aim of this study was to identify prognostic risk factors for first recurrence in patients with localised stage I-II CMM using population-based data.
Methods
This study included 1 437 CMM patients registered in one region of Sweden during 1999-2012 followed-up through December 31, 2012. To identify first recurrence of CMM disease, data from a care data warehouse, the pathology and radiology department registries were used. Patients were also followed through a census register and the national Cause of Death Register.
Results
The 5- and 10-year RFS were 85.7% and 81.2%, respectively. The most common site of first recurrence was regional lymph node metastasis closely followed by distant metastasis. After adjusting for all prognostic factors, women had 50% lower risk of recurrence than men (HR = 0.5, 95% CI 0.4 - 0.7) and patients ≥75 had higher risk compared to patients 55-69 years (HR = 1.7, 95% CI 1.2 - 2.5). Other significant prognostic factors for risk of recurrence were tumour thickness, presence of ulceration, Clark's level of invasion and histogenetic type.
Conclusion
Tumour thickness was found to be the predominant risk factor for recurrence. The prognostic factors for recurrence coincided with prognostic factors for CMM-death. The most common site of first recurrence in stage I-II CMM is regional lymph node (42.8%) closely followed by distant metastases (37.6%), a fact which has to be taken into consideration when choosing follow-up strategies.
This article is protected by copyright. All rights reserved.
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Reformulations of well-known active ingredients in the topical treatment of psoriasis vulgaris can improve clinical outcomes for patients
Abstract
Background
Although the majority of patients with psoriasis vulgaris are treated exclusively with topical therapies, research to develop more effective topical therapies that are associated with higher patient satisfaction has lagged behind the development of systemic agents.
Objective
The aim of this literature review was to determine whether there is documented evidence that applying an innovative approach to improving the formulation of active ingredients commonly used in the topical treatment of psoriasis can have a positive effect on clinical outcomes and patient-reported outcomes (PROs).
Methods
The Embase and PubMed databases were searched for articles published between 2001 and 2016 that made direct head-to-head comparisons of different formulations of an active pharmaceutical ingredient (API), focusing on clinical outcomes and PROs.
Results
In total, 22 publications on APIs or API combinations met the eligibility criteria (19 head-to-head clinical trials, one pooled analysis, one health-economic modelling study, and one systematic review). Significant clinical benefit associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of calcipotriol, three trials of betamethasone, and five trials/pooled analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD) formulations. Significantly improved PRO associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of betamethasone valerate, and two trials of Cal/BD formulations.
Conclusion
These results demonstrate that the innovative reformulation of APIs used in the treatment of psoriasis can produce therapies that attain significantly improved clinical outcomes and PROs. This suggests that improvement in topical therapy for psoriasis need not only to be achieved by the identification of new targets and the development of new APIs, but that improvement in the vehicle used to deliver existing APIs has the potential to result in significant clinical and patient benefits.
This article is protected by copyright. All rights reserved.
http://ift.tt/2nW6zZi
Regulation of Th2 responses by different cell types expressing the interleukin-31 receptor
Interleukin-31 (IL-31) is a recently identified cytokine produced by Th2 cells that is involved in the development of atopic dermatitis-induced skin inflammation and pruritus. Its receptor, IL-31RA, is express...
http://ift.tt/2oEGw5W
Preconception allergen sensitization can induce B10 cells in offspring: a potential main role for maternal IgG
The mechanisms through which allergies can be inhibited after preconception immunization with allergens are not fully understood. We aimed to evaluate whether maternal immunization can induce a regulatory B (B...
http://ift.tt/2oEKPhL
Factors associated with lingual tonsil hypertrophy in Canadian adults
Hypertrophy of the lingual tonsil tissue in the adult patient is thought to contribute to the pathophysiology of obstructive sleep apnea. The underlying etiology of lingual tonsil hypertrophy (LTH) in the adul...
http://ift.tt/2omU6cx
Factors associated with lingual tonsil hypertrophy in Canadian adults
Abstract
Background
Hypertrophy of the lingual tonsil tissue in the adult patient is thought to contribute to the pathophysiology of obstructive sleep apnea. The underlying etiology of lingual tonsil hypertrophy (LTH) in the adult patient is unclear and likely multifactorial. Previous studies have suggested that the lingual tonsils may undergo compensatory hyperplasia post-tonsillectomy in children, although it is unknown if this occurs or persists into adulthood. The purpose of this study was to determine what factors are associated with LTH in a population of Canadian adults.
Methods
Adult patients presenting for consultation to an academic Rhinology/General Otolaryngology practice were eligible for enrollment. Demographic data including age, body mass index (BMI), Reflux Symptom Index (RSI), history of allergy, and history of tonsillectomy was collected via questionnaire. Endoscopic photographs of the base of tongue and larynx were captured. These were graded for LTH and Reflux Finding Scale (RFS) by blinded examiners. Statistical analysis was performed by comparing the mean LTH value to the variables of interest using two-tailed T-test. P < .05 was considered significant.
Results
One hundred two subjects were enrolled. Age ranged from 18 to 78. 28 patients had previous tonsillectomy. This was not associated with a significant increase in lingual tonsil tissue (r = −0.05, p = 0.61). RFS >7 or RSI >13 was considered positive for laryngopharyngeal reflux. There was no difference in LTH based on RSI positivity (p = 0.44). RFS positivity correlated with increased lingual tonsil tissue (p < 0.05). BMI >30 was associated with increased lingual tonsil hypertrophy (p < 0.05).
Conclusions
An elevated body mass index and positive Reflux Finding Score are associated with lingual tonsil hypertrophy in adults. Reflux symptom index, history of allergy and history of childhood tonsillectomy are not associated with LTH.
http://ift.tt/2oPeUx8
The Blood Brain Barrier and Neuropsychiatric Lupus: New perspectives in light of advances in understanding the neuroimmune interface
Source:Autoimmunity Reviews
Author(s): Ariel D. Stock, Sivan Gelb, Ofer Pasternak, Ayal Ben-Zvi, Chaim Putterman
Experts have previously postulated a linkage between lupus associated vascular pathology and abnormal brain barriers in the immunopathogenesis of neuropsychiatric lupus. Nevertheless, there are some discrepancies between the experimental evidence, or its interpretation, and the working hypotheses prevalent in this field; specifically, that a primary contributor to neuropsychiatric disease in lupus is permeabilization of the blood brain barrier. In this commonly held view, any contribution of the other known brain barriers, including the blood-cerebrospinal fluid and meningeal barriers, is mostly excluded from the discussion. In this review we will shed light on some of the blood brain barrier hypotheses and try to trace their roots. In addition, we will suggest new research directions to allow for confirmation of alternative interpretations of the experimental evidence linking the pathology of intra-cerebral vasculature to the pathogenesis of neuropsychiatric lupus.
http://ift.tt/2pqbdi8
Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A systematic review
Source:Autoimmunity Reviews
Author(s): Bernd Merkel, Helmut Butzkueven, Anthony L. Traboulsee, Eva Havrdova, Tomas Kalincik
BackgroundImmunotherapy initiated early after first presentation of relapsing-remitting multiple sclerosis is associated with improved long-term outcomes. One can therefore speculate that early initiation of highly effective immunotherapies, with an average efficacy that is superior to the typical first-line therapies, could further improve relapse and disability outcomes. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity. While this monitoring approach is logical, the current lack of effective regenerative or remyelinating therapies behoves us to consider high-efficacy treatment strategies from disease onset (including induction therapy) in order to prevent irreversible disability.ObjectiveIn this systematic review, we evaluate the effect of high-efficacy immunotherapies at different stages of MS.MethodsA systematic review of literature reporting outcomes of treatment with fingolimod, natalizumab or alemtuzumab at different stages of MS was carried out.Results and conclusionsTwelve publications reporting relevant information were included in the systematic review. The literature suggests that treatment with high-efficacy immunotherapies is more potent in suppressing relapse activity when initiated early vs. with a delay after the MS diagnosis. The evidence reported for disability and MRI outcomes is inconclusive.
http://ift.tt/2ppX3xG
Docetaxel and Loplatin Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced SCCHN
Condition: Locally Advanced Head and Neck Squamous Cell Carcinoma
Interventions: Drug: Lobaplatin; Drug: Cisplatin
Sponsor: Guiyang Medical University
Recruiting - verified April 2017
http://ift.tt/2omJLgR
Interventions: Drug: Lobaplatin; Drug: Cisplatin
Sponsor: Guiyang Medical University
Recruiting - verified April 2017
http://ift.tt/2omJLgR
A dramatic response to a single dose of infliximab in a patient with prolonged pustular psoriasis derived from inverse psoriasis
Abstract
We report a case of a 25-year-old Chinese man with an exceptionally prolonged history of pustular psoriasis derived from inverse psoriasis who was unsatisfied with conventional treatment and was successfully treated with a single dose of infliximab without noticeable adverse effects. No recurrence or flaring was observed after 3 months of follow-up. This case illustrates that infliximab may be an effective and safe therapeutic option for patients with refractory pustular psoriasis derived from inverse psoriasis.
http://ift.tt/2ppf1jS
Correction to: Atypical presentation of a spontaneous celiac artery dissection resulting in jejuna ischaemia
George J, Nathani H, Hu A et al. Atypical presentation of a spontaneous celiac artery dissection resulting in jejuna ischaemia. BMJ Case Reports 2017;doi:10.1136/bcr-2016-218182.
We would like to issue a correction to the acknowledgements of this paper. The published article misspelled the name of a collaborator. The authors would like to thank Dr Fred Lee, Consultant Radiologist for his help in gaining some of the images.
http://ift.tt/2oDhC6W
Anosmia with hypogonadism: but NOT Kallmann syndrome
Description
A girl aged 16 years presented with primary amenorrhoea and absent secondary sexual characteristics. She had arhinia at birth and had undergone reconstruction twice in her childhood. Family history was unremarkable. On examination, she had a partially reconstructed nose with patent left nare, absent nasal root, hypertelorism, midfacial hypoplasia and anosmia (figure 1A and B). Her height was 156 cm (50th percentile for ethnicity) with sexual maturity rating of Tanner stage 1. Investigations showed follicle-stimulating hormone, 0.02 (normal, 2.5–10.2 mIU/mL), luteinising hormone, 0.01 (normal, 1.9–12.5 mIU/mL)and 17-β estradiol, 8 (normal, 27–143 pg/mL) suggestive of hypogonadotrophic hypogonadism (HH). Her thyroid function and prolactin were normal. MRI of the brain showed normal-sized pituitary, absent olfactory bulbs with aplastic (yellow arrow) and hypoplastic olfactory sulci (red arrow head) on the right and left side, respectively (figure 1C). With the above findings, a diagnosis of HH with arhinia was made. She...
http://ift.tt/2psQRSm
Pneumatic dental extractions: an unusual cause of extensive cervical surgical emphysema
A 50-year-old fit and well man presented to the Accident and Emergency Department in a tertiary centre following lower molar extraction, complaining of voice hoarseness with neck and facial swelling. Clinical examination along with plain film radiography revealed pneumomediastinum and extensive cervical surgical emphysema. He was subsequently admitted for observation and managed conservatively under the ENT team with input from the maxillofacial and anaesthetic teams. With supportive treatment only, the emphysema resolved and he remained well up until discharge.
http://ift.tt/2oOujha
Pazopanib-associated posterior reversible encephalopathy syndrome with intracerebral haemorrhage
Pazopanib is a tyrosine kinase receptor antagonist used for renal cell carcinoma and soft tissue sarcoma that inhibits tumour growth and angiogenesis. A common side effect of pazopanib is hypertension. We report a case of a 69-year-old woman with clear cell renal cell carcinoma who developed a large right occipital intracerebral haemorrhage 3 weeks after initiating pazopanib. Although this was initially suspected to be a haemorrhagic metastasis, MRI revealed bi-occipital oedema, supporting a diagnosis of posterior reversible encephalopathy syndrome (PRES). A craniectomy was required. Immunohistochemical stains for renal cell carcinoma antigen, CA IX and PAX8 were negative. This case suggests that PRES and intracerebral haemorrhage may result from pazopanib use and are important complications to consider prior to initiating this agent.
http://ift.tt/2psVgoE
Multiple jaw cysts and ectopic calcification
Description
A 41-year-old woman presented with pus discharge from the gingival pocket and a 10-year history of intermittent buccal swelling on the left side. Physical examination revealed increased height, macrocephaly, hypertelorism, wide nasal bridge and sloping shoulders. Orthopantomography showed multiple jaw cysts (figure 1). Keratocystic odontogenic tumour (KCOT) was histologically suggested by the preoperative biopsy. CT revealed ectopic calcifications in the falx and tentorium (figure 2A). Subcutaneous radiopaque bodies that seemed like granules were diffusely scattered in the skull (figure 2B). Punch biopsy revealed foreign calcifications but no histological abnormalities in the hair follicle. Then all jaw cysts were extirpated under general anaesthesia. The histological analysis confirmed the diagnosis of KCOT. These clinical presentations were consistent with a diagnosis of nevoid basal cell carcinoma syndrome (NBCCS). On the other hand, palmar or plantar pits, basal cell carcinoma (BCC) and bifid ribs, which...
http://ift.tt/2oOwmBQ
Oesophageal cancer presenting as Lemierres syndrome caused by Streptococcus anginosus
A 59-year-old man presented to the emergency department with complaints of dysphagia, right-sided neck swelling, fever and chills. Physical examination was remarkable for fever and tender swelling over the right side of the neck. Laboratory investigations revealed leucocytosis with neutrophilia. CT of the neck showed right internal jugular vein thrombosis with an overlying abscess and a nodular opacity in the right lung apex with air locules. He underwent surgical drainage of the neck abscess. Aerobic cultures from the drainage and blood cultures grew Streptococcus anginosus. Given his initial complaint of dysphagia, upper endoscopy was performed which showed a mass in the upper oesophagus. Histopathology confirmed squamous cell carcinoma. The patient received 6 weeks of antibiotics therapy.
http://ift.tt/2psU1Wx
Olliers disease: features of the hands
Description
A 14-year-old boy attended our services for orthopaedic evaluation due to the development of multiple enchondromatous lesions. Clinical examination of the hands revealed painless swollen digits of asymmetric lengths (figure 1). Plain film radiographs demonstrated extensive bilateral expansile lytic lesions of metacarpals and phalanges with diffuse matrix calcification resulting in cortical thinning, which is in keeping with Ollier's disease (figure 2). With no features concerning for malignancy in the hands, this patient is being followed up annually and remained symptom free at his last review.
Figure 1
Topographical view of a patient's hands with Ollier's disease.
Figure 2
Plain radiography; anteroposterior of left and right hands depicting multiple radiolucent expansile lesions with cortical thinning of the metacarpal and phalanges.
Ollier's disease is defined as multiple enchondromas with asymmetric distribution that are...
http://ift.tt/2oOLNdk
Posterior reversible encephalopathy in an adult patient with poststreptococcal glomerulonephritis
Description
A previously healthy 32-year-old man presented to the hospital with cough, sore throat, facial swelling and intermittent fever for 1 week. Initial physical examination revealed blood pressure of 160/98 mm Hg, erythematous throat, bilateral periorbital swelling, right basilar crackles and no neurological abnormalities. Laboratory tests were remarkable for leucocytosis (13 320 cell/mm3), hyperkalaemia (5.2 mmoL/L), azotemia (Cr 2 mg/dL), haematuria (urine red blood cells of 50–100 cells/high power field) and proteinuria (urine protein/creatine ratio >7 g/gCr). Chest X-ray showed right lower lobe pneumonia with parapneumonic effusion. The patient was admitted for community-acquired pneumonia, non-oliguric acute kidney injury and nephritic syndrome. Later, antistreptolysin O was found to be elevated (1610 IU/mL) and the patient was diagnosed with poststreptococcal glomerulonephritis.
On day 2 of hospitalisation, he developed headache, blurred vision and confusion, followed by a tonic–clonic seizure. The blood pressure recorded before the seizure was 138/98 mm Hg. Brain CT showed decreased white matter attenuation of the bilateral parieto-occipital and...
http://ift.tt/2psXsMZ
Effects of Risk Factors on Periodontal Disease Defined by Calibrated Community Periodontal Index and Loss of Attachment Scores
Abstract
Objectives
We evaluated whether and how the effects of risk factors on periodontal disease (PD) were modified by measurement errors using community periodontal index (CPI) and loss attachment (LA) in the community{\hyphen}based survey.
Methods
A pilot validation study was performed to estimate the rates of false negative and false positive for both CPI and LA in 31 subjects from different regions using measurements from 12 well{\hyphen}trained dentists and a senior periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was conducted by enrolling 3860 participants to estimate the effect of each risk factor on PD calibrated with both sensitivity and specificity of two indices.
Results
The values obtained for the sensitivity to false positive ratio for CPI ranged widely from 1.12 to 7.71, indicating regional variation in both errors. The calibrated adjusted odds ratio for smoking versus non{\hyphen}smoking was higher than the uncalibrated odds ratio for PD defined by CPI (2.75(2.01, 3.77) versus 2.02(1.63, 2.52)) and LA (3.85(2.44, 6.13) versus 1.93(1.47, 2.54)) scores. Similar underestimation was noted for other risk factors.
Conclusion
The effects of risk factors on PD measured using CPI and LA in a large population{\hyphen}based survey were underestimated without correcting for measurement errors.
This article is protected by copyright. All rights reserved.
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HPV-related carcinomas of the head and neck: morphologic features, variants, and practical considerations for the surgical pathologist
Abstract
Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma is a distinct tumor entity with clinical, epidemiologic, genetic, histologic, prognostic, and treatment differences from smoking- and alcohol-related head and neck squamous cell carcinoma. This is now well known by the pathology and medical community. What is not yet widely known is that several emerging variants of HPV-related carcinoma of the head and neck exist apart from the prototypical non-keratinizing morphology. Further, there is currently considerable variation in methodologies used and clinical scenarios in which to test for HPV-related head and neck squamous cell carcinoma, and no standard approach has emerged. In this article, we will review the morphology of prototypical HPV-related squamous cell carcinoma of the oropharynx and other HPV-related variants of head and neck carcinoma with an emphasis on their differential diagnosis, grade, and prognosis, as well as outline the current best practices for testing for HPV in head and neck carcinomas.
http://ift.tt/2psZVXI
The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation
Abstract
Emerging evidence indicates that even subtle changes in the expression of key genes of signaling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtleness and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer, and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes, subsequently leading to aberrant proliferation, apoptosis and differentiation that result in altered hair growth, while loss of miR-31 leads to increased hair growth. Through in vitro and in vivo studies, we have defined a set of conserved miR-31 target genes, including LATS2 and STK40, which serve as new players in the regulation of keratinocyte growth and hair follicle biology. LATS2 can regulate growth of keratinocytes, while we have identified a function of STK40 in promoting the expression of key hair follicle program regulators such as HR, DLX3, and HOXC13.
This article is protected by copyright. All rights reserved.
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Noma as a complication of false teeth (Ebiino) extraction: a case report
Ebiino, also known as false tooth extraction, is a traditional practice done mainly in the remote areas of African countries, including Uganda. It involves the extraction of tooth buds in babies with common ch...
http://ift.tt/2poBbTl
Acute hepatitis B virus infection with delayed appearance of hepatitis B core antibody in an immunocompromised patient: a case report
Despite the introduction of universal hepatitis B immunization programs worldwide, outbreaks of acute infection still occur in unimmunized individuals. A timely diagnosis of hepatitis B is necessary to ensure ...
http://ift.tt/2pstl89
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