Dural recurrence among esthesioneuroblastoma patients presenting with intracranial extension

Objective

To quantify the rate of late intracranial recurrences among esthesioneuroblastoma patients treated with surgical resection and postoperative radiation.

Study Design

Retrospective review.

Methods

All patients receiving definitive-intent therapy for esthesioneuroblastoma between March 1995 and September 2015 were reviewed. Presenting disease extent was categorized based on radiologic, operative, and pathologic findings. Between-group survival differences were assessed using Kaplan-Meier method and log-rank test. Multivariate analyses were performed using Cox proportional hazards model.

Results

Of 38 patients initially treated at our institution, 53% (20 of 38) presented with intracranial extension. At a median follow-up of 90 months (range, 6–199), 37% (14 of 38) recurred; 5- and 8-year disease-free survival rates were 69% and 54%; and overall survival rates were 81% and 72%, respectively.

Among these patients, the dura was the most commonly involved site of relapse (8), followed by local (6), regional (5), and distant extracranial (3) sites; and five patients had ≥ two categories of failure. Eight-year dural disease-free survival was 57% versus 90% (P = 0.017) and 0% versus 87% (P < 0.0001), with and without intracranial extension and subtotal resection, respectively.

Of six patients treated at recurrence, five (83%) experienced dural-based failure such that, among all 44 patients, 13 (65%) of 20 recurrences involved the dura. After dural recurrence, the median survival time was 42 months (range, 12–125); salvage treatments were effective in rare cases of isolated low-volume recurrence.

Conclusion

Esthesioneuroblastoma patients presenting with intracranial extension are at substantial and unique risk for long-term dural-based relapse.

Level of Evidence

4. Laryngoscope, 2018

http://ift.tt/2BkBunv

Reviewing smokeless tobacco epidemiology, carcinogenesis, and cessation strategy for otolaryngologists

Objectives/Objectives

We aimed to provide an otolaryngologist-targeted summary regarding the epidemiology, carcinogenesis, and cessation strategies for smokeless tobacco usage.

Study Design

Evidence-based literature review.

Methods

We reviewed the current evidence-based literature concerning trends in smokeless tobacco use, associations with neoplastic change, and therapeutic interventions to assist with sustained abstinence. In complement, we present an actual case of laryngeal squamous cell carcinoma in the setting of chronic tobacco-dentifrice usage in a lifelong nonsmoker.

Results

This report provides a synopsis of epidemiological data and evidence-based recommendations for general, pharmaceutical, and behavioral cessation strategies.

Conclusions

Smokeless tobacco use continues to be prevalent among patients seen by otolaryngologists, particularly of various Indian and Southeast Asian descent. The data presented in this article will aid in the identification of at risk patients. The provided recommended cessation strategies will tool otolaryngologists for patient counseling and management, ultimately aimed at improving health outcomes. Laryngoscope, 2018

http://ift.tt/2BOFWvP

Risk factors for complications in cochlear implant surgery

Abstract

Purpose

The objective of this study was to achieve uniform reporting of complications and failures in cochlear implantation, to analyze complications and failures and to identify risk factors for complications in a series of over 1300 cochlear implantations.

Methods

In a retrospective chart review and observational study, data from all cochlear implantations from 1987 to 2015 were entered in a custom-made database. Complications were classified using the contracted form of the Clavien–Dindo system and risk factors were identified by statistical analysis.

Results

A complication rate of 18.4% and a device failure rate of 2.9% were found. There was a higher rate of hematoma in patients with a clotting disorder and when a subtotal petrosectomy was performed, a higher rate of wound infections in patients who were not vaccinated against Streptococcus pneumoniae and a higher rate of meningitis in patients with an inner ear malformation.

Conclusions

The use of a strict definition of a medical complication and device failure—in combination with the Clavien–Dindo classification system—enables uniform and objective registration of adverse events and prevents any tendency to downgrade complications. Complication and failure rates in this series are comparable to those reported in the literature. These results stress the need for pneumococcal vaccination, which may prevent general wound infections, but is especially important for patients with inner ear malformation, who have an increased risk of (postoperative) meningitis.

http://ift.tt/2smwdcg

Middle ear microvascularization: an “in vivo” endoscopic anatomical study

Abstract

Purpose

To describe the in vivo vascularization of middle ear by an endoscopic point of view, particularly focusing on the medial wall of tympanic cavity and incudostapedial region (ISR).

Study design

Case series with surgical videos review and anatomical description.

Methods

48 videos from exclusive endoscopic middle ear surgery performed at the University Hospital of Modena from November 2015 to July 2017 were reviewed. Data about anatomy of vessels, and blood flow direction (BFD) were collected in an appropriate database for further analyses.

Results

48 cases were included in the present study. In 18/48 patients (37,5%), a clearly identifiable inferior tympanic artery (ITA) was present, running just anteriorly to the round window (RW), with a superior BFD (65% of cases) from the hypotympanic region toward the epitympanum. Some promontorial variants were described in 67% of cases and the most common finding was a mucosal vascular network with a multidirectional BFD. On the ISR, an incudostapedial artery (ISA) was detected in 65% of cases with BFD going from the long process of the incus (LPI) toward the pyramidal eminence in the majority of cases.

Conclusion

The vascular anatomy and BFD of the medial wall of the tympanic cavity can be easily studied in transcanal endoscopy. ITA (with a superior BFD in most cases) and ISA (with a main BFD from the incus to the stapes) are the most constant identifiable vessels.

http://ift.tt/2EuugPL

Systemic juvenile xanthogranuloma: a case report and brief review

http://ift.tt/2EhnYng

First report of COL7A1 mutations in two patients with recessive dystrophic epidermolysis bullosa from Peru

http://ift.tt/2C8LFsi

High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of a Cross-Sectional Study

Thyroid , Vol. 0, No. 0.


http://ift.tt/2Eft5k2

Fehlerhafte Daten in randomisierten Studien: Statistik kann sie aufdecken

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 82-82
DOI: 10.1055/s-0043-123125

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nMyZTC

Macitentan senkt Lungengefäßwiderstand bei CTEPH

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 84-85
DOI: 10.1055/s-0044-101345

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nRXHBK

Respiratorisches Versagen: State of the Art – Diagnose und Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 90-101
DOI: 10.1055/s-0043-107167

Die respiratorische Insuffizienz beschreibt die Unfähigkeit des Körpers, einen adäquaten Gasaustausch aufrechtzuerhalten. Sie stellt – insbesondere, wenn sie akut auftritt – einen lebensbedrohlichen Zustand dar, der umgehend therapiert werden muss. Dieser Artikel zeigt, welche Diagnostik erforderlich ist, um den Patienten schnell und korrekt behandeln zu können, und welche Therapieverfahren zur Verfügung stehen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nUTigI

ARDS – Ein Update – Teil 1: Epidemiologie, Pathophysiologie und Diagnostik

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 102-111
DOI: 10.1055/s-0043-107166

Das akute Lungenversagen (Acute respiratory Distress Syndrome, ARDS) ist inzwischen seit mehr als 50 Jahren als schwerwiegende Komplikation unterschiedlicher Grunderkrankungen gefürchtet [1]. Häufig leiden ARDS-Patienten langfristig unter schwerwiegenden Beeinträchtigungen – auch nach primär erfolgreicher Therapie. Der erste Teil dieses Updates gibt einen aktualisierten Überblick zu Definition, Epidemiologie und Pathophysiologie des ARDS.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nWbx5y

Schlafmangel – Einfluss auf Kommunikation und Interaktion im Team?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 81-82
DOI: 10.1055/s-0044-101343

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nWD6f7

Senkt die zusätzliche kontinuierliche Infusion von Tranexamsäure Blutverluste?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 82-83
DOI: 10.1055/s-0044-101342

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nOGadQ

Respiratorisches Versagen: Innovationen zur Diagnostik und Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 126-140
DOI: 10.1055/s-0043-108216

Die akute oder chronische respiratorische Insuffizienz hat eine große Bedeutung sowohl in der präklinischen als auch innerklinischen Versorgung. Sie zählt zu den häufigsten Gründen für stationäre Aufnahmen. Dieser Beitrag fasst aktuelle Entwicklungen in der Diagnostik und Therapie des Krankheitsbildes zusammen. Darüber hinaus gibt er einen Ausblick, wie sich die Behandlung in den kommenden Jahren weiterentwickeln könnte.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nWD5YB

Langzeitüberleben nach venovenöser ECMO

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 85-85
DOI: 10.1055/s-0044-101344

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nRXCxW

ARDS – Ein Update – Teil 2: Therapie und Outcome

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 112-125
DOI: 10.1055/s-0043-122136

Das Acute respiratory Distress Syndrome (ARDS) ist nunmehr seit über 50 Jahren als gravierende Komplikation verschiedener Grunderkrankungen bekannt [1]. Trotz intensiver Forschung in all dieser Zeit gibt es hinsichtlich der bestmöglichen Therapie des ARDS auch heute noch viele offene Fragen – insbesondere zur maschinellen Beatmung. Der zweite Teil des Update ARDS gibt einen aktualisierten Überblick zu Therapie und Outcome des ARDS.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nWD5I5

50 Jahre ARD-Forschung und -Therapie: Resümee und Ausblick

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 87-89
DOI: 10.1055/s-0043-124225

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2nPAf8u

Behandlung der Sepsis und des septischen Schocks – die neuen Leitlinien

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 142-148
DOI: 10.1055/s-0043-114639

Die neue Leitlinie der Surviving Sepsis Campaign wurde im Jahr 2016 überarbeitet und im Jahr 2017 veröffentlicht. Darüber hinaus änderte sich durch „Sepsis-3" die Definition der Sepsis im Jahr 2016 grundlegend, von einer Inflammation mit Infektion hin zu einer „lebensbedrohlichen Organ-Dysfunktion, die durch eine fehlregulierte Wirtsreaktion" verursacht wird. Um die große Herausforderung zu bewältigen, die neuen Erkenntnisse zur Sepsisbehandlung mit der neuen Definition zu vereinen, wurden die Leitlinien vollständig neu strukturiert und umfassend überarbeitet. Die Leitlinie diskutiert die sepsisspezifische Behandlung und gibt Empfehlungen für allgemeine intensivmedizinische Maßnahmen. Der Artikel fasst die wichtigsten Empfehlungen zusammen und diskutiert zusätzlich einige entscheidende Änderungen. Dies soll den Leser ermutigen, die neue Leitlinie in den klinischen Alltag zu übernehmen und somit die Prognose der Patienten, die an einer Sepsis oder einem septischem Schock leiden, zu verbessern.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nVqJQr

Nierenersatzverfahren bei akuter Nierenschädigung – Indikation und Durchführung

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 150-157
DOI: 10.1055/s-0043-110038

Die akute Nierenschädigung ist eine häufige Komplikation kritisch kranker Patienten auf Intensivstationen, die mit einer hohen Morbidität und Letalität einhergeht [1]. Sie ist ein unabhängiger Risikofaktor für ein verschlechtertes Outcome kritisch kranker Patienten [2]. Diese Übersichtsarbeit fasst die verfügbare Evidenz für die Indikation und den Einsatz von Nierenersatzverfahren bei akuter Nierenschädigung anhand aktueller Literatur zusammen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2nQSfiC

Bowman Birk Inhibitors (BBI) in interception of inflammation and malignant transformation of OPMDs

Publication date: Available online 9 February 2018
Source:Oral Oncology
Author(s): Dr. Samapika Routray




http://ift.tt/2C8vj2M

Latent human papillomavirus type 16 infection is widespread in patients with oropharyngeal cancers

Publication date: Available online 9 February 2018
Source:Oral Oncology
Author(s): Rong Wu, Francesca Paolini, Douglas Frank, Dev Kamdar, Gianfranca Curzio, Barbara Pichi, Raul Pellini, Giuseppe Spriano, Vincent R. Bonagura, Aldo Venuti, Bettie M. Steinberg




http://ift.tt/2Eemk5S

Time-course change in temporomandibular joint space after advancement and setback mandibular osteotomy with Le Fort I osteotomy

The purpose of this study was to compare time-course changes in temporomandibular joint (TMJ) space between mandibular advancement surgery and setback surgery after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy.

http://ift.tt/2nRk1vv

Study of surgical treatment for elderly patients with head and neck cancer

Publication date: Available online 9 February 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): Y. Wu, B. Zhang, Z. Huang, Y. Ruan, Z. Huang
The aim of this study was to evaluate the clinical results of surgery for head and neck cancer (HNC) in elderly patients and to determine whether surgery for elderly HNC patients is safe and what types of surgery result in the most favourable outcomes for this age group. The cases of 637 elderly patients who were diagnosed with HNC and underwent surgical treatment were studied retrospectively. Patient demographic characteristics and treatment data were extracted from the appropriate patient records and analysed. Age did not significantly predict postoperative complications or death rates. Flap reconstruction surgery had no significant association with necrosis, haemorrhage, infection, need for rescue treatment, or length of intensive care unit stay. Age was not a risk factor for surgical treatment of HNC in the elderly patients. Flap reconstruction should not be considered riskier for elderly patients. The treatment choice for elderly patients with HNC should be based on medical assessments but not on age.



http://ift.tt/2H4V0VJ

Root migration pattern after third molar coronectomy: a long-term analysis

Publication date: Available online 9 February 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): Y.Y. Leung, K.Y. Cheung
Coronectomy was introduced as a treatment for impacted lower third molars at high risk of inferior alveolar nerve damage. Root migration is considered one of the common surgical complications of this procedure. This study aimed to investigate the long-term behaviour of retained root(s) after coronectomy. This was a prospective study, with 3–5 years of follow-up, of patients who underwent lower third molar coronectomy. Panoramic radiographs were taken preoperatively and at 1 week, 6, 12, 24, 36, and 60 months postoperative. Root migration patterns were recorded. Factors including age, sex, type and pattern of impaction, and root form were analyzed with respect to the root migration rate. A total of 356 coronectomies were performed in 254 patients. Most root migration was found to occur within 6 months (91.1%) and 12 months (61.4%) postoperative. From 24 months onwards, less than 5% migrated further. Age was found to be a factor affecting root migration: migration decreased with increasing age (by 0.203mm less per year increase in age). Other factors investigated were found to be unrelated. Therefore, adequate preoperative warning should be given to young patients considering coronectomy as treatment for impacted lower third molars. However, it should also be noted that the incidence of root exposure leading to re-operation is low.



http://ift.tt/2G4q3Q1

Age-related prevalence of chronic rhinosinusitis and nasal polyps and their relationships with asthma onset

Chronic rhinosinusitis (CRS) is a major disease condition with high morbidity, and may influence lower airway disease status in adults. However, its associations with adult asthma onset and activity have not been examined in detail in a general adult population.

http://ift.tt/2Echxls

Repeatability of nasal allergen challenge results – further validation of the allergic rhinitis clinical investigator collaborative (AR-CIC) protocols

Nasal Allergen Challenge(NAC) models have been used to study allergic rhinitis and new therapies. Symptoms and biological samples can be evaluated at time points following allergen exposure.

http://ift.tt/2CauBSG

Learnings from a pragmatic pilot trial of text messaging for high risk adolescents with asthma

Clinical research with high risk patient populations is complex due to economic burdens, lack of transportation, etc.1, 2; therefore, it is critical to conduct pilot studies prior to entering into a full scale study. Pilot studies can confirm the design and operational processes for a study3 and increase the likelihood of a successful clinical trial by identifying problems that may occur in the methods.4, 5 Thus, we conducted a pilot study to identify issues in a research trial with low-income, publically insured, minority adolescents.

http://ift.tt/2EfgYrc

Rapid oral desensitization protocol to abiraterone acetate

Abiraterone acetate (AA) is a potent selective inhibitor of cytochrome P450 (CYP) 17, a key enzyme involved in testosterone synthesis. Due to this inhibition, the production of androgens by endocrine tissues decreases. Therefore, this oral hormone therapy is used in castration-resistant prostate cancer combined with prednisone/prednisolone, with a significant increase in overall survival. Common side effects of AA include hypertension, hypokalaemia, peripheral oedema and urinary tract infections.

http://ift.tt/2CauJl8

Lack of effect of Grastek® on birch pollen-induced allergic rhinoconjunctivitis in the Environmental Exposure Unit

Grastek® is a standardized sublingual immunotherapy tablet(SLIT-T) approved for the treatment of grass pollen-induced allergic rhinitis(AR) and conjunctivitis. Many grass-allergic patients are also co-sensitized to birch pollen. Whether Grastek® can confer symptomatic benefits for birch pollen-induced AR symptoms is unknown.

http://ift.tt/2EfgTDU

Root migration pattern after third molar coronectomy: a long-term analysis

Coronectomy was introduced as a treatment for impacted lower third molars at high risk of inferior alveolar nerve damage. Root migration is considered one of the common surgical complications of this procedure. This study aimed to investigate the long-term behaviour of retained root(s) after coronectomy. This was a prospective study, with 3–5 years of follow-up, of patients who underwent lower third molar coronectomy. Panoramic radiographs were taken preoperatively and at 1 week, 6, 12, 24, 36, and 60 months postoperative.

http://ift.tt/2nWP1tk

Alloplastic temporomandibular joint replacement systems: a systematic review of their history

This systematic review provides an overview of the historical evolution of the prosthetic temporomandibular joint and addresses the challenges and complications faced by engineers and surgeons, in an effort to shed light on why only a few systems remain available. A better understanding of the history of temporomandibular joint prostheses might also provide insights into the origin of the negative public opinion of the prosthesis, which is based on outdated information. A computerized search using the PubMed Central, ScienceDirect, Wiley Online, Ovid, and Cochrane Library databases was performed following the PRISMA guidelines.

http://ift.tt/2nPhqCm

Latent human papillomavirus type 16 infection is widespread in patients with oropharyngeal cancers

Most oropharyngeal squamous cell cancers (OSCC) are caused by human papillomaviruses (HPVs), primarily HPV16 [1]. HPVs also establish latent infections that can be activated to cause disease [2,3]. The immune system plays a key role in controlling or eliminating viral infections. However, HPVs can circumvent immune control, especially in susceptible patients [4] and patients with HPV-induced recurrent respiratory papillomatosis have a systemic immunologic failure to control latent reactivation [5].

http://ift.tt/2C8EgJm

PRAC Seeks New Pregnancy Prevention Measures For Retinoids

The EMA committee calls for updating pregnancy prevention measures and including a warning with retinoid products on the possible risk for neuropsychiatric disorders.
News Alerts

http://ift.tt/2H49QMe

Larval Therapy for Chronic Cutaneous Ulcers

Larval debridement has been historically used in the management of chronic ulcers, but does it still have a place in modern wound healing?
Wounds

http://ift.tt/2EcU3c4

A Holistic Care Approach to Malignant Melanoma

In this editorial, the author underscores the need for a multidisciplinary, collaborative approach to treatment of malignant melanoma, uniting dermatologists, oncologists and researchers.
The British Journal of Dermatology

http://ift.tt/2ESaMCD

Seasonal variation in circulating group 2 innate lymphoid cells in mugwort-allergic asthmatics during and outside pollen season

Group 2 innate lymphoid cells (ILC2s) are a newly identified cell population with the potent capability to produce Th2-type cytokines in a non-antigen specific manner. Previous study demonstrated that enhanced...

http://ift.tt/2C9HA6R

Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection

Conditions:   Barrett Esophagus;   Barrett Adenocarcinoma;   Esophagus Neoplasm
Interventions:   Procedure: Endoscopic mucosal resection;   Procedure: Endoscopic submucosal dissection
Sponsor:   Universitätsklinikum Hamburg-Eppendorf
Recruiting

http://ift.tt/2nNSqer

Adjuvant PD-1 Antibody in Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Neoplasms
Intervention:   Drug: PD-1 antibody
Sponsor:   Sun Yat-sen University
Not yet recruiting

http://ift.tt/2nVWtF3

Phase II Trial of M7824 in Subjects With HPV Positive Malignancies

Conditions:   Human Papilloma Virus;   Cervical Cancer;   Oropharyngeal Cancer;   Anal Cancer;   Vaginal or Penile Cancer
Intervention:   Drug: M7824
Sponsor:   National Cancer Institute (NCI)
Not yet recruiting

http://ift.tt/2nOnyL4

A Observational Study to Compare Effectiveness and Safety of the Surgeries in Patients With Esophageal Cancer

Condition:   Esophageal Cancer
Intervention:   Procedure: Minimally invasive surgery of Ivor-Lewis
Sponsors:   Chinese PLA General Hospital;   LinkDoc Technology (Beijing) Co. Ltd.
Recruiting

http://ift.tt/2nVWjgV

PSTPIP1 controls immune synapse stability in human T-cells

Publication date: Available online 9 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): W.J.M. Janssen, V. Grobarova, J. Leleux, C.H. Jongeneel, M. van Gijn, J.M. van Montfrans, M. Boes
BackgroundPSTPIP1 is a cytosolic adaptor protein involved with T-cell activation, differentiation, and migration. Upon cognate T-cell contact, PSTPIP1 is recruited to surface-expressed CD2, where it regulates f-actin remodeling. An immune synapse (IS) is thereby rapidly formed, consisting of TCR clusters surrounded by a ring of adhesion molecules including CD2.ObjectiveFrom genetic screening of primary immunodeficiency patients, we identified two mutations in PSTPIP1, R228C and T274M which we further characterized in primary patient T-cells.MethodsF-actin dynamics were assessed in patient and healthy control primary T-cells by use of FACS. HEK293T and Jurkat cells were transfected with R228C, T274M and WT PSTPIP1 in order to visualize f-actin in immune synapse formation. CD2-PSTPIP1 association was quantified through immunoprecipitation assays.ResultsThe patients presented with immunodeficiency without signs of auto-inflammation. The R228C patient had expansion of mostly naive phenotype T-cells and few memory T-cells; the T274M patient had 75% reduction in CD4 T-cells that were predominantly of memory subset.We observed f-actin polymerization defects in both PSTPIP1 patient T-cells, most notably T274M. Capping of CD2-containing membrane microdomains was disrupted. Analysis of IS formation using Jurkat T-cell transfectants revealed a reduction in f-actin accumulation at the IS, again especially in T274M PSTPIP1 cells. Patient T274M T-cells migrated spontaneously at increased speed as assessed in a 3D collagen matrix, while TCR crosslinking induced a significantly diminished calcium flux.ConclusionsWe propose that PSTPIP1 T-cell differentiation defects are caused by defective control of f-actin polymerization. A pre-activated polymerized f-actin status, as seen in PSTPIP1-T274M T-cells, appears particularly damaging. PSTPIP1 controls IS formation and cell adhesion, through its function as orchestrator of the f-actin cytoskeleton.



http://ift.tt/2Bnbesy

Evolution of IgE responses to multiple allergen components throughout childhood

Publication date: Available online 9 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Rebecca Howard, Danielle Belgrave, Panagiotis Papastamoulis, Angela Simpson, Magnus Rattray, Adnan Custovic
BackgroundThere is a paucity of information about longitudinal patterns of IgE responses to allergenic proteins (components) from multiple sources.ObjectiveTo investigate temporal patterns of component-specific IgE responses from infancy to adolescence, and their relationship with allergic diseases.MethodsIn a population-based birth cohort, we measured IgE to 112 components at 6 follow-ups during childhood. We used a Bayesian method to discover cross-sectional sensitization patterns and their longitudinal trajectories, and related these patterns to asthma and rhinitis in adolescence.ResultsWe identified one sensitization cluster at age one, 3 at age three, 4 at ages five and eight, 5 at age 11, and six at age 16 years. "Broad" cluster was the only cluster present at every follow-up, comprising of components from multiple sources. "Dust mite" cluster formed at age three and remained unchanged to adolescence. At age three, a single-component "Grass" cluster emerged, which at age five absorbed additional grass components and Fel d 1 to form the "Grass/cat" cluster. Two new clusters formed at age 11: "Cat" cluster and "PR-10/profilin" (which divided at age 16 into "PR-10" and "Profilin"). The strongest contemporaneous associate of asthma at age 16 years was sensitization to "Dust mite" cluster (OR [95% CI]: 2.6 [1.2-6.1], P<0.05), but the strongest early-life predictor of subsequent asthma was sensitization to "Grass/cat" cluster (3.5 [1.6–7.4], P<0.01).ConclusionsWe describe the architecture of the evolution of IgE responses to multiple allergen components throughout childhood, which may facilitate development of better diagnostic and prognostic biomarkers for allergic diseases.



http://ift.tt/2BNC6mF

Table of Contents

Publication date: March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 3





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Society Page

Publication date: March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 3





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Information for Readers

Publication date: March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 3





http://ift.tt/2EccoWt

Editorial Board

Publication date: March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 3





http://ift.tt/2ESQ4Cr

mDixon-based texture analysis of an intraosseous lipoma: a case report and current review for the dental clinician

Publication date: March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 3
Author(s): Kyung Mi Lee, Hyug-Gi Kim, Yeon-Hee Lee, Eui Jong Kim
An intraosseous lipoma is a rare histologic variant of lipoma, accounting for only 0.1% of all primary bone tumors. This may not be the actual incidence because most of these lesions are frequently asymptomatic, but imaging modalities, such as computed tomography or magnetic resonance imaging (MRI) seem to have increased the detection rate. Lipoma occasionally undergoes osseous metaplasia and becomes an osseous lipoma. Although there are numerous papers discussing intraosseous lipoma and some authors have tried to differentiate lipomas from osseous lipomas, there is still a great deal of confusion with regard to characteristic radiologic features and the use of terms. Use of the mDixon sequence in MRI could be an effective, noninvasive method of lesion detection and differential diagnosis. Texture analysis is a useful technique for capturing intratumoral characteristics. We report what is possibly the first use of the mDixon MRI sequence in the measurement of tumoral texture in a case of the extremely rare inferior nasal turbinate intraosseous lipoma in a 58-year-old female. We conclude that mDixon and texture analysis are helpful methods for differentiating intraosseous lipomas from other masses and confirming the benign characteristics of lipoma. Our review of head and neck intraosseous lipoma could be of particular interest to head and neck surgeons and dental clinicians.



http://ift.tt/2Ehv5s1

Endoscopic Repair of Persistent Oroantral Communications Using the Caldwell-Luc Approach

In this article, a novel endoscopic technique used to close oro-antral fistulas will be described. In the technique described here, 24 cases were surgically treated between May 2011, and November 2014. Under endonasal endoscopic examination following partial inferior uncinectomy, the natural ostium of the maxillary sinus was identified; through this tract, a curved aspirator was advanced into the sinus. If present, we extracted endoscopically tissues causing obliteration of the ostium through the Caldwell-Luc antrostomy, taking care to preserve the integrity of the natural ostium. In the technique described here, endoscopic examination using the Caldwell-Luc approach, the inside of the maxillary sinus is explored fully, existing infection and polyps are eliminated locally, and natural patency of the maxillary sinus ostium can be achieved. The graft used to obliterate the oroantral fistula can be easily harvested from the bone of the anterior wall of the maxillary sinus by accessing the surgical entry tract. Address correspondence and reprint requests to Murat Songu, MD, Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey; E-mail: songumurat@yahoo.com Received 13 June, 2017 Accepted 19 October, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Current status of surgical incisions used in donors during living related liver transplantation – a nationwide survey in Japan

AbstractBackgroundSmaller surgical incisions have recently been introduced in living donor liver procurement. This study used national data from Japan to clarify the present status of surgical incisions in living donor liver procurement.MethodsA nationwide, questionnaire-based survey related to 3121 donors and recipients was used. Donors were divided into two groups: left lateral segment graft (LLSG) procurement (n=690) and other types (n=2431). Incisions were classified into six types: type I, upper midline and bilateral subcostal; type II, upper midline and right subcostal; type III: upper midline and right subcostal to the right lateral margin of the abdominal rectus muscle; type IV, upper midline without laparoscopy; type V, upper midline with laparoscopy; and type VI, lower abdominal using the full laparoscopic technique. Types I, II, and III were regarded as standard, and types IV, V, and VI as small incisions.ResultsIn LLSGs, blood transfusion and postoperative complication rates were significantly less frequent in the small incision group than in the standard group. In other graft types, there were no significant differences in blood transfusion, postoperative complication, and recipients' graft loss rates. The rates of wound extension during surgery were 2.8% and 2.1% in the small incision group in LLSGs and in other graft types, respectively. A small incision was adopted more frequently and postoperative complications were less common in high-volume centers.ConclusionsVarious incisions have been adopted in living donor liver procurement. Donor safety and graft integrity appear to have been retained for donors receiving small incisions. Background Smaller surgical incisions have recently been introduced in living donor liver procurement. This study used national data from Japan to clarify the present status of surgical incisions in living donor liver procurement. Methods A nationwide, questionnaire-based survey related to 3121 donors and recipients was used. Donors were divided into two groups: left lateral segment graft (LLSG) procurement (n=690) and other types (n=2431). Incisions were classified into six types: type I, upper midline and bilateral subcostal; type II, upper midline and right subcostal; type III: upper midline and right subcostal to the right lateral margin of the abdominal rectus muscle; type IV, upper midline without laparoscopy; type V, upper midline with laparoscopy; and type VI, lower abdominal using the full laparoscopic technique. Types I, II, and III were regarded as standard, and types IV, V, and VI as small incisions. Results In LLSGs, blood transfusion and postoperative complication rates were significantly less frequent in the small incision group than in the standard group. In other graft types, there were no significant differences in blood transfusion, postoperative complication, and recipients' graft loss rates. The rates of wound extension during surgery were 2.8% and 2.1% in the small incision group in LLSGs and in other graft types, respectively. A small incision was adopted more frequently and postoperative complications were less common in high-volume centers. Conclusions Various incisions have been adopted in living donor liver procurement. Donor safety and graft integrity appear to have been retained for donors receiving small incisions. Correspondence: Ken Shirabe, MD, PhD, Department of Hepatobiliary and Pancreatic Surgery, Gunma University, 3-39-22 Showa Machi, Maebashi, Gunma 371-8511, Japan. E-mail: kshirabe@gunma-u.ac.jp Authorship Ken Shirabe • Participated in research design • Participated in the writing of the paper • Participated in the performance of the research • Contributed new reagents or analytic tools • Participated in data analysis Susumu Eguchi • Participated in research design • Participated in the writing of the paper • Participated in the performance of the research • Participated in data analysis Hideaki Okajima • Participated in research design • Participated in the writing of the paper • Participated in the performance of the research Kiyoshi Hasegawa • Participated in research design • Participated in the writing of the paper • Participated in data analysis Shigeru Marubashi • Participated in research design • Participated in the writing of the paper • Participated in the performance of the research • Participated in data analysis Koji Umeshita • Participated in research design • Participated in the writing of the paper Seiji Kawasaki • Participated in research design Katsuhiko Yanaga • Participated in research design Mitsuo Shimada • Participated in research design • Participated in the writing of the paper Toshimi Kaido • Participated in research design • Participated in the writing of the paper Naoki Kawagishi • Participated in research design Akinobu Taketomi • Participated in research design • Participated in data analysis Koichi Mizuta • Participated in research design Norihiro Kokudo • Participated in research design • Participated in the writing of the paper Shinji Uemoto • Participated in research design • Participated in the writing of the paper Yoshihiko Maehara • Participated in research design • Participated in the writing of the paper Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Extracellular vesicles from human liver stem cells reduce injury in an ex vivo normothermic hypoxic rat liver perfusion model

ABSTRACTBackgroundThe gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV).MethodsWe established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused during 4 hours without (control group, n=10) or with HLSC-EV (treated group, n=9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, ALT, LDH). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by TUNEL assay, and tissue HIF-1α and TGF-β1 RNA expression by quantitative RT-PCR.ResultsDuring hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (p=0.018) and LDH (p=0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (p=0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes and EV treatment significantly reduced histological damage (p=0.030), apoptosis (p=0.049), and RNA over-expression of HIF-1α (p

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Oral health-related quality of life changes in children following dental treatment under general anaesthesia: a meta-analysis

Abstract

Objective

To conduct a meta-analysis of studies that have employed the Early Childhood Oral Health Impact Scale (ECOHIS) and Child Oral Health-Related Quality of Life (COHRQoL) instruments, to evaluate the oral health-related quality of life (OHRQoL) changes in children following dental treatment under general anaesthesia (DGA).

Method

A systematic search of 5 databases was conducted in accordance with the PRISMA guidelines. The inclusion criteria were use of ECOHIS and COHRQoL, pre-and post-operative assessments, patients aged between 0 and 16 years, no restrictions on the follow-up period and DGA. The primary outcome measure was changes in quality of life for both the children, which was based on mean difference (MD). Twenty-two articles were included in the meta-analysis.

Results

A favourable outcome in OHRQoL was identified in all studies. The combined MD for ECOHIS and COHRQoL were 1.62 [95% CI 1.52–1.71; P < 0.00001; I2 = 0%] and 0.86 [95% CI 0.74–0.99; P < 0.00001; I2 = 0%], respectively, both with no evidence of heterogeneity.

Conclusion

There is evidence to support that the OHRQoL of children was improved, with large effect size, in the short-term following DGA.

Clinical Relevance

Dental treatment under GA significantly improved the OHRQoL of children.

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Feasibility of Salvage Selective Neck Dissection after Primary Irradiation of Pharyngeal and Laryngeal Carcinoma

Introduction: The concept of neck dissection (ND) in the management armamentarium of head and neck squamous cell carcinoma has evolved throughout the years. Nowadays, ND becomes more functional. Methodology: A retrospective study of 865 patients was performed at Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital to investigate the feasibility of selective ND (SND). All patients with squamous cell carcinoma of the pharynx and larynx who received primary radiation and underwent salvage ND were included in the study. Result: A total of 29 NDs were analyzed. In 17 neck sides, viable metastases were found (58%), whereas in the other 12 specimens there were no viable metastases. In 16 of the 17 necks (94%), the metastases were located either in level II, III, or IV or in a combination of these 3 levels. Level V was involved in only 1 case (6%). Conclusion: It is well justified to perform a salvage SND (levels II, III, and IV) for pharyngeal and laryngeal carcinoma after primary radiation. In carefully selected cases of supraglottic and oropharyngeal carcinoma, a superselective ND also appears as an efficient option.
ORL 2018;80:10–18

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Multiple Levels of Control Determine How E4bp4/Nfil3 Regulates NK Cell Development [IMMUNE SYSTEM DEVELOPMENT]

The transcription factor E4bp4/Nfil3 has been shown to have a critical role in the development of all innate lymphoid cell types including NK cells. In this study, we show that posttranslational modifications of E4bp4 by either SUMOylation or phosphorylation have profound effects on both E4bp4 function and NK cell development. We examined the activity of E4bp4 mutants lacking posttranslational modifications and found that Notch1 was a novel E4bp4 target gene. We observed that abrogation of Notch signaling impeded NK cell production and the total lack of NK cell development from E4bp4^–/– progenitors was completely rescued by short exposure to Notch peptide ligands. This work reveals both novel mechanisms in NK cell development by a transcriptional network including E4bp4 with Notch, and that E4bp4 is a central hub to process extrinsic stimuli.

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Cellularity of Thymic Epithelial Cells in the Postnatal Mouse [IMMUNE SYSTEM DEVELOPMENT]

The molecular and cellular biology of thymic epithelial cells (TECs) often relies on the analysis of TECs isolated in enzymatically digested single-cell suspensions derived from mouse thymus. Many independent studies have reported that the estimated cellularity of total TECs isolated from one adult mouse is on the order of up to 10⁵. However, these numbers appear extremely small given that the cellularity of total thymocytes exceeds 10⁸ and that TECs play multiple roles in thymocyte development and repertoire formation. In the present study, we aimed to measure the numbers of β5t-expressing cortical TECs and Aire-expressing medullary TECs in postnatal mouse thymus in situ without enzymatic digestion. The numbers of these TECs were manually counted in individual thymic sections and were three-dimensionally summed throughout the entire thymic lobes. The results show that the cellularity of total TECs in one 5-wk-old female mouse exceeds 10⁶, containing ~9 x 10⁵ β5t⁺ cortical TECs and ~1.1 x 10⁶ Aire⁺ medullary TECs. These results suggest that the use of conventional enzymatic digestion methods for the isolation of TECs may have resulted in the underestimation of the cellularity, and possibly the biology, of TECs.

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Correction: A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic-like Event in Immunity against Respiratory Viruses [CORRECTIONS]

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An Immunotherapeutic CD137 Agonist Releases Eomesodermin from ThPOK Repression in CD4 T Cells [TUMOR IMMUNOLOGY]

Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8⁺ and CD4⁺ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8⁺ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8⁺ CTLs. Further, Eomes and Runx3 were indispensable for dual-costimulated CD4 T cells to mediate antitumor activity in an aggressive melanoma model. Runx3 is also known to be expressed in standard CD4 Th1 cells where it fosters IFN- expression; however, the CD4 T cell lineage commitment factor ThPOK represses transcription of Eomes and other CD8 lineage genes, such as Cd8a. Hence, CD4 T cells can differentiate into Eomes⁺ cytotoxic CD4⁺CD8⁺ double-positive T cells by terminating ThPOK expression. In contrast, dual-costimulated CD4 T cells express Eomes, despite the continued expression of ThPOK and the absence of CD8α, indicating that Eomes is selectively released from ThPOK repression. Finally, although Eomes was induced by CD137 agonist, but not CD134 agonist, administered individually, CD137 agonist failed to induce CD134^–/– CD4 T cells to express Eomes or Runx3, indicating that both costimulatory pathways are required for cytotoxic Th1 programming, even when only CD137 is intentionally engaged with a therapeutic agonist.

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Correction: Virtual Sorting Has a Distinctive Advantage in Identification of Anticorrelated Genes and Further Negative Regulators of Immune Cell Subpopulations [CORRECTIONS]

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Novel Transcriptional Activity and Extensive Allelic Imbalance in the Human MHC Region [SYSTEMS IMMUNOLOGY]

The MHC region encodes HLA genes and is the most complex region in the human genome. The extensively polymorphic nature of the HLA hinders accurate localization and functional assessment of disease risk loci within this region. Using targeted capture sequencing and constructing individualized genomes for transcriptome alignment, we identified 908 novel transcripts within the human MHC region. These include 593 novel isoforms of known genes, 137 antisense strand RNAs, 119 novel long intergenic noncoding RNAs, and 5 transcripts of 3 novel putative protein-coding human endogenous retrovirus genes. We revealed allele-dependent expression imbalance involving 88% of all heterozygous transcribed single nucleotide polymorphisms throughout the MHC transcriptome. Among these variants, the genetic variant associated with Behcet's disease in the HLA-B/MICA region, which tags HLA-B*51, is within novel long intergenic noncoding RNA transcripts that are exclusively expressed from the haplotype with the protective but not the disease risk allele. Further, the transcriptome within the MHC region can be defined by 14 distinct coexpression clusters, with evidence of coregulation by unique transcription factors in at least 9 of these clusters. Our data suggest a very complex regulatory map of the human MHC, and can help uncover functional consequences of disease risk loci in this region.

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IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection [INNATE IMMUNITY AND INFLAMMATION]

Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms, including the nucleotide and oligomerization domain, leucine-rich repeat–containing protein family, pyrin domain containing 3 (NLRP3) inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection. Both inflammasome-dependent responses and induction of apoptosis and necroptosis are reduced in cells lacking IRF1 infected with IAV. The observed reduction in inflammasome activation and cell death in IRF1-deficient cells during IAV infection correlates with reduced levels of Z-DNA binding protein 1 (ZBP1), a key molecule mediating IAV-induced inflammatory and cell death responses. We further demonstrate IRF1 as a transcriptional regulator of ZBP1. Overall, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.

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Simultaneous Recognition of Allogeneic MHC and Cognate Autoantigen by Autoreactive T Cells in Transplant Rejection [TRANSPLANTATION]

The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet cells. These results reveal the presence of autoreactive T cells that mediate cross-reactive alloreactivity, and indicate a requirement for regulating such dual-reactive T cells in tissue replacement therapies given to autoimmune individuals.

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Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells [INFECTIOUS DISEASE AND HOST RESPONSE]

Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein–coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA, pull-downs, and surface plasmon resonance) provided direct evidence of the interaction between staphylococcal enterotoxin E and LAMA2. Through its G4 domain, LAMA2 mediated the LCK-independent T cell activation by these toxins. Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor type because the selective antagonist NPS 2143 inhibited superantigen-induced T cell activation in vitro and delayed the effects of toxic shock syndrome in vivo. Collectively, our data identify LAMA2 as a target of antagonists of staphylococcal superantigens to treat toxic shock syndrome.

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IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis [INFECTIOUS DISEASE AND HOST RESPONSE]

T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4⁺ and CD8⁺ T cells leads to arthritis-promoting IFN-, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non–Borrelia epitopes confirmed that bystander T cell activation was responsible for disease development. The microbial pattern recognition receptor TLR2 was upregulated on T cells following infection, implicating it as marker of bystander T cell activation. In fact, T cell–intrinsic expression of TLR2 contributed to IFN- production and arthritis, providing a mechanism for microbial-induced bystander T cell activation during infection. The IL-10–deficient mouse reveals a novel TLR2-intrinsic role for T cells in Lyme arthritis, with potentially broad application to immune pathogenesis.

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Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization [INNATE IMMUNITY AND INFLAMMATION]

Golgi phosphoprotein 2 (GOLPH2), a widely expressed Golgi type II transmembrane protein, has been implicated in several important physiological and pathological processes, including virus infections, cancer cell proliferation, and metastasis. However, its biological functions and mechanisms, particularly in the immune system, remain highly obscure. In this study, we report the biochemical identification of GOLPH2 from B cell lymphoma culture supernatant and show that the secreted protein could inhibit IL-12 production by dendritic cells (DCs) and IL-12–induced IFN- production by activated T cells. Further molecular analysis revealed that GOLPH2's IL-12–inhibiting activity was mediated through a proximal IL12p35 promoter element involving a previously identified transcriptional repressor named GC-binding protein that is induced during phagocytosis of apoptotic cells by macrophages. We subsequently generated global golph2 knockout mice, which exhibited little developmental abnormality but were more susceptible to LPS-induced endotoxic shock than were wild-type mice with elevated serum IL-12 levels. Furthermore, we found that GOLPH2 played a regulatory role in macrophage polarization toward the M2 type. A comprehensive analysis of gene expression profiles of activated wild-type and GOLPH2-deficient DCs by RNA sequencing uncovered mechanistic insights into the way GOLPH2 potentially modulates DC function during inflammatory insults. Our functional study of GOLPH2 helps advance the scientific understanding of the biological and pathogenic roles of this novel and intriguing molecule with great potential as a diagnostic and prognostic marker as well as a therapeutic target in many acute and chronic inflammatory disorders.

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ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis [INFECTIOUS DISEASE AND HOST RESPONSE]

IFN-stimulated gene 15 (ISG15) deficiency in humans leads to severe IFNopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. In this study, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. A balanced ISG15-induced monocyte/IL-10 versus lymphoid/IFN- expression, correlating with p38 MAPK and PI3K signaling, was found using targeted in vitro and ex vivo systems analysis of human transcriptomic datasets. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmed in vitro using CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, this ISG15/IL-10 axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB, suggesting its potential use as a biomarker, awaiting clinical validation. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB.

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IL-1 Signaling Prevents Alveolar Macrophage Depletion during Influenza and Streptococcus pneumoniae Coinfection [INFECTIOUS DISEASE AND HOST RESPONSE]

Influenza and bacterial coinfection is a significant cause of hospitalization and death in humans during influenza epidemics and pandemics. However, the fundamental protective and pathogenic mechanisms involved in this complex virus–host–bacterium interaction remain incompletely understood. In this study, we have developed mild to lethal influenza and Streptococcus pneumoniae coinfection models for comparative analyses of disease pathogenesis. Specifically, wild-type and IL-1R type 1–deficient (Il1r1^–/–) mice were infected with influenza virus and then superchallenged with noninvasive S. pneumoniae serotype 14 (Spn14) or S. pneumoniae serotype 19A (Spn19A). The coinfections were followed by comparative analyses of inflammatory responses and animal protection. We found that resident alveolar macrophages are efficient in the clearance of both pneumococcal serotypes in the absence of influenza infection; in contrast, they are essential for airway control of Spn14 infection but not Spn19A infection. In agreement, TNF-α and neutrophils play a compensatory protective role in secondary bacterial infection associated with Spn19A; however, the essential requirement for alveolar macrophage–mediated clearance significantly enhances the virulence of Spn14 during postinfluenza pneumococcal infection. Furthermore, we show that, although IL-1 signaling is not required for host defense against pneumococcal infection alone, it is essential for sustaining antibacterial immunity during postinfluenza pneumococcal infection, as evidenced by significantly aggravated bacterial burden and animal mortality in Il1r1^–/– mice. Mechanistically, we show that through preventing alveolar macrophage depletion, inflammatory cytokine IL-1 signaling is critically involved in host resistance to influenza and pneumococcal coinfection.

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Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive Immune Cells [IMMUNE REGULATION]

TNF superfamily cytokines play major roles in the regulation of adaptive and innate immunity. The TNF superfamily cytokine TL1A (TNFSF15), through its cognate receptor DR3 (TNFRSF25), promotes T cell immunity to pathogens and directly costimulates group 2 and 3 innate lymphoid cells. Polymorphisms in the TNFSF15 gene are associated with the risk for various human diseases, including inflammatory bowel disease. Like other cytokines in the TNF superfamily, TL1A is synthesized as a type II transmembrane protein and cleaved from the plasma membrane by metalloproteinases. Membrane cleavage has been shown to alter or abrogate certain activities of other TNF family cytokines; however, the functional capabilities of membrane-bound and soluble forms TL1A are not known. Constitutive expression of TL1A in transgenic mice results in expansion of activated T cells and promotes intestinal hyperplasia and inflammation through stimulation of group 2 innate lymphoid cells. Through the generation of membrane-restricted TL1A-transgenic mice, we demonstrate that membrane TL1A promotes expression of inflammatory cytokines in the lung, dependent upon DR3 expression on T cells. Soluble TL1A alone was unable to produce this phenotype but was still able to induce intestinal type 2 inflammation independently of T cells. These data suggest differential roles for membrane and soluble TL1A on adaptive and innate immune cells and have implications for the consequences of blocking these two forms of TL1A.

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IFN Regulatory Factor 3 Balances Th1 and T Follicular Helper Immunity during Nonlethal Blood-Stage Plasmodium Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

Differentiation of CD4⁺ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4⁺ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion. In contrast, IFN regulatory factor 3 (IRF3) was important for supporting PbTII expansion, promoting Th1 over T follicular helper (Tfh) differentiation, and controlling parasites during the first week of infection. IRF3 was not required for early priming by conventional dendritic cells, but was essential for promoting CXCL9 and MHC class II expression by inflammatory monocytes that supported PbTII responses in the spleen. Thereafter, IRF3-deficiency boosted Tfh responses, germinal center B cell and memory B cell development, parasite-specific Ab production, and resolution of infection. We also noted a B cell–intrinsic role for IRF3 in regulating humoral immune responses. Thus, we revealed roles for IRF3 in balancing Th1- and Tfh-dependent immunity during nonlethal infection with blood-stage Plasmodium parasites.

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Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade [IMMUNE SYSTEM DEVELOPMENT]

Despite the well-documented effect of castration in thymic regeneration, the singular contribution of the bone marrow (BM) versus the thymus to this process remains unclear. The chief role of IL-7 in pre- and intrathymic stages of T lymphopoiesis led us to investigate the impact of disrupting this cytokine during thymic rebound induced by androgen blockade. We found that castration promoted thymopoiesis in young and aged wild-type mice. In contrast, only young germline IL-7–deficient (Il7^–/–) mice consistently augmented thymopoiesis after castration. The increase in T cell production was accompanied by the expansion of the sparse medullary thymic epithelial cell and the peripheral T cell compartment in young Il7^–/– mice. In contrast to young Il7^–/– and wild-type mice, the poor thymic response of aged Il7^–/– mice after castration was associated with a defect in the expansion of BM hematopoietic progenitors. These findings suggest that BM-derived T cell precursors contribute to thymic rebound driven by androgen blockade. To assess the role of IL-7 within the thymus, we generated mice with conditional deletion of IL-7 (Il7 conditional knockout [cKO]) in thymic epithelial cells. As expected, Il7cKO mice presented a profound defect in T cell development while maintaining an intact BM hematopoietic compartment across life. Unlike Il7^–/– mice, castration promoted the expansion of BM precursors and enhanced thymic activity in Il7cKO mice independently of age. Our findings suggest that the mobilization of BM precursors acts as a prime catalyst of castration-driven thymopoiesis.

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CD40 Mediates Maturation of Thymic Dendritic Cells Driven by Self-Reactive CD4+ Thymocytes and Supports Development of Natural Regulatory T Cells [IMMUNE SYSTEM DEVELOPMENT]

Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4⁺ thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs. In addition, CD40-deficient DCs failed to fully mature upon cognate interaction with CD4⁺ thymocytes in vitro and failed to differentiate them into Treg cells to a sufficient number. These findings suggest that tDCs mature and potentiate Treg cell development in feedback response to self-reactive CD4⁺ thymocytes.

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Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo [IMMUNOGENETICS]

The neonatal Fc receptor (FcRn) is involved in IgG metabolism and transport in placental mammals. However, whether FcRn is responsible for IgG transfer from maternal serum to colostrum/milk is controversial. Interestingly, large domestic animals, such as cows, pigs, sheep, and horses, in which passive IgG transfer is exclusively completed via colostrum/milk, all express an FcRn α-chain that is shorter in the cytoplasmic tail (CYT) than its counterparts in humans and rodents. To address whether the length variation has any functional significance, we performed in vitro experiments using the Transwell system with the MDCK cell line stably transfected with various FcRn constructs; these clearly suggested that truncation of the CYT tail caused a polar change in IgG transfer. However, we observed no evidence supporting functional changes in IgG in vivo using mice in which the FcRn CYT was precisely truncated. These data suggest that the length variation in FcRn is not functionally associated with passive IgG transfer routes in mammals.

http://ift.tt/2EQUM3E

Modulation of the IL-33/IL-13 Axis in Obesity by IL-13R{alpha}2 [IMMUNE REGULATION]

In obesity, IL-13 overcomes insulin resistance by promoting anti-inflammatory macrophage differentiation in adipose tissue. Endogenous IL-13 levels can be modulated by the IL-13 decoy receptor, IL-13Rα2, which inactivates and depletes the cytokine. In this study, we show that IL-13Rα2 is markedly elevated in adipose tissues of obese mice. Mice deficient in IL-13Rα2 had high expression of IL-13 response markers in adipose tissue, consistent with increased IL-13 activity at baseline. Moreover, exposure to the type 2 cytokine-inducing alarmin, IL-33, enhanced serum and tissue IL-13 concentrations and elevated tissue eosinophils, macrophages, and type 2 innate lymphoid cells. IL-33 also reduced body weight, fat mass, and fasting blood glucose levels. Strikingly, however, the IL-33–induced protection was greater in IL-13Rα2–deficient mice compared with wild-type littermates, and these changes were largely attenuated in mice lacking IL-13. Although IL-33 administration improved the metabolic profile in the context of a high fat diet, it also resulted in diarrhea and perianal irritation, which was enhanced in the IL-13Rα2–deficient mice. Weight loss in this group was associated with reduced food intake, which was likely related to the gastrointestinal effects. These findings outline both potentially advantageous and deleterious effects of a type 2–skewed immune response under conditions of metabolic stress, and identify IL-13Rα2 as a critical checkpoint in adipose tissues that limits the protective effects of the IL-33/IL-13 axis in obesity.

http://ift.tt/2ESANll

The Effects of Dendritic Cell Hypersensitivity on Persistent Viral Infection [IMMUNE REGULATION]

Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid–inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8^–/– mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4⁺ T cells. Such mice infected with chronic lymphocytic choriomeningitis virus, an RNA virus detected by RIG-I, mounted an enhanced lymphocytic choriomeningitis virus–specific immune response as measured by increased proportions of Ag-specific CD4⁺ T cells and multicytokine-producing CD4⁺ and CD8⁺ T cells. These results show that CASP8 subtly modulates DC maturation, which controls the spontaneous appearance of autoimmune T cells while simultaneously attenuating the acquired immune system and its potential to control a persistent viral infection.

http://ift.tt/2EdIeSX

Putting All the Pieces Together: Clinical, Macroscopic and Microscopic Characteristics of Subacute Thyroiditis

Abstract

Subacute thyroiditis (SAT) is a self-limiting inflammatory condition of the thyroid gland in which multinucleated giant cells constitute a key histological finding. SAT is generally a clinical diagnosis and consequently its histological features are rarely encountered by pathologist. Herein, we present a case that exemplifies the characteristic clinical and pathological features of this entity. In addition, we compare SAT to other thyroid disorders characterized by the presence of multinucleated giant cells.

http://ift.tt/2nTsP36

Sinonasal Neuroendocrine Neoplasms: Current Challenges and Advances in Diagnosis and Treatment, with a Focus on Olfactory Neuroblastoma

Abstract

Sinonasal tumors with neuroendocrine differentiation form a group of rare heterogeneous neoplasms of neuroectodermal and epithelial origin, consisting of olfactory neuroblastomas and neuroendocrine carcinomas. Because the natural history and biological behavior of this group of tumors vary, the morphological diagnosis coupled with grading/staging is important for prognostication, and the approach to treatment and rehabilitation is multidisciplinary. The identification of molecular abnormalities underlying these tumors is critical to the development of specific targeted therapies and the design of clinical trials.

http://ift.tt/2nPlLVY

A Retrospective 20-Year Analysis of Proliferative Verrucous Leukoplakia and Its Progression to Malignancy and Association with High-risk Human Papillomavirus

Abstract

Proliferative verrucous leukoplakia (PVL) is defined as an aggressive, relentless and recalcitrant form of leukoplakia that has a high propensity for malignant transformation. The aim of this study was to evaluate the malignant potential of PVL and determine its possible association with high-risk human papillomavirus (HPV). Twenty cases with a clinical and biopsy proven diagnosis of PVL were collected from the University of Florida Oral Medicine clinic database. Immunohistochemistry was performed to evaluate the expression of p16^INK4A and p53 genes in the PVL lesions. The lesions were also tested for high-risk HPV by DNA in-situ hybridization. The average age of the patients at the time of first biopsy was 62.7 years. Most patients had multiple sites of involvement, gingiva being the most common location. The lesions progressed to malignancy in approximately 50% of patients. The expression of p16^INK4A gene was considered negative, with at least a 50–65% immunoreactivity observed in only three cases that progressed to malignancy. No expression of high-risk HPV was detected, whereas p53 staining was positive in less than 25% of the cells demonstrating gene expression. No definite association between PVL and high-risk HPV infection could be established. Due to the high transformation potential of PVL, early recognition with aggressive treatment, including multiple biopsies, and continued close clinical follow-up, remain the mainstay of favorable management of this condition.

http://ift.tt/2nUPr3m

Unusual Multinucleated Giant Cell Reaction in a Tongue Squamous Cell Carcinoma: Histopathological and Immunohistochemical Features

Abstract

Multinucleated giant cell (MGC) reaction in oral squamous cell carcinoma (OSCC) usually represents a stromal foreign body reaction to keratin from neoplastic epithelial cells. We describe and illustrate by double immunohistochemistry a case of a tongue squamous cell carcinoma (SCC) in a 70-year-old female patient, with a copious MGC reaction not associated to keratin, showing a histopathological pattern not described before. The MGCs were directly associated with neoplastic cells, which are phagocytosed by the MGCs. Immunohistochemistry for CD68, AE1/AE3, CD163, CD11c, RANK, RANK-L, OPG were performed, as well as double staining for CD68 and AE1/AE3 to better illustrate the relationship between MGCs and neoplastic cells. The clinical and biological significance of this pattern of MGC reaction in OSCC needs to be better elucidated.

http://ift.tt/2nPlFO6

Can a postnasal drip can be aspirated into the lungs?

http://ift.tt/2nTsvBq

Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node

Abstract

A better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood. This technology could facilitate the discovery of antitumor antibody therapeutics and conceivably identify novel tumor antigens. Lastly, these findings highlight the unique and specialized niche the SN can fill in the advancement of cancer immunotherapy.

http://ift.tt/2snXyLo

Comparison of the Transient Evoked Otoacoustic Emissions (TEOAEs) and Distortion Products Otoacoustic Emissions (DPOAEs) in Normal Hearing Subjects With and Without Tinnitus

Abstract

The aim of this study was to investigate the possible role of cochlear outer hair cell function with TEOAE and DPOAE tests in patients with normal hearing and tinnitus. 25 tinnitus patients with normal hearing sensitivity selected as study group. Control group consist of 50 normal hearing subjects without tinnitus. All subjects had thresholds below 25 dBHL at frequencies 250–8,000 Hz, tympanogram type A and normal acoustic reflex thresholds. TEOAE were recorded with click stimulus at 80 dB SPL at 1,000, 2,000, 3,000 and 4000 Hz. DPOAE were measured at frequencies 1,000–8,000 Hz and intensity of L1 55 dB SPL and L2 65 dB SPL. Amplitude of DPOAE and TEOAE were decreased in all frequencies in study group. There was significant difference regarding prevalence abnormal TEOAE and DPOAE between study group and control group. There was relationship between dysfunction of outer hair cells and tinnitus in subjects with normal hearing.

http://ift.tt/2sj0mcz

Histopathological Analysis of the Effects of Corticosteroids on Vocal Cords: Experimental Study

Abstract

Local treatment with corticosteroids results in side effects involving the upper respiratory tract including candidiasis, sore throat, and dysphonia. Although these effects are well known, they have not been evaluated using a histopathological approach. This study investigated the histopathological aspects of steroid-induced dysphonia. A total of 16 female Wistar albino rats were divided into two groups. The eight rats in the experimental group were given an inhaled dose of mometasone furoate daily for 4 weeks. The control group was kept at room temperature for 4 weeks. The vocal cords were evaluated histopathologically using hematoxylin and eosin staining. Both groups had typical epithelial lining and basal membranes. Inflammation differed between the two groups (P = 0.024). There were no differences in squamous metaplasia and hyperplasia (P = 0.302 and 0.302, respectively). This study revealed that inhaled corticosteroids inhibit mucosal immunity, and may result in reversible mucosal changes.

http://ift.tt/2G1Maqu

Increased Atherosclerosis Correlates with Subjective Tinnitus Severity

Abstract

The aim of the present study was to investigate whether increased intima media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. Data of the patients who came to Otorhinolaryngology Department of Isparta Government Hospital with subjective non-pulsatile tinnitus complaint, between January 2012 and June 2013, were evaluated retrospectively. A total of 215 patients were included in the present study. Hearing tests, biochemical analysis, tinnitus handicap inventory (THI), visual analogue scale (VAS) and doppler ultrasonography results of the patients were reviewed and recorded. The patients were classified into two groups as those having an increased intima media thickness and those having a normal intima media thickness. The said groups were compared with respect to age, gender, THI, VAS, hearing test findings and lipid values. Moreover, THI and VAS groups were compared with respect to intima-media thickness. In the group having increased intima-media thickness, THI and VAS average, frequency of hypertension, total cholesterol, low density lipoprotein and triglyceride averages and mean frequencies obtained by hearing test were significantly higher. Comparison of THI and VAS groups showed that intima-media thickness was significantly different between those having a mild tinnitus and those having a severe tinnitus. Increased intima-media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. For this reason, the carotid system should be examined in subjective non-pulsatile tinnitus patients.

http://ift.tt/2H2UXtq

A rare presentation of pheochromocytoma in pregnancy: a case report

Early diagnosis of pheochromocytoma and its proper management can lessen its mortality and morbidity. This case report describes a 24-year-old pregnant woman with an unusual presentation of pheochromocytoma.

http://ift.tt/2EQv27s

The host defense peptide LL-37 is detected in human parotid and submandibular/sublingual saliva and expressed in glandular neutrophils

The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL-37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL-37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL-37 in saliva were analyzed by dot blot, ELISA, and western blotting. Cellular expression of hCAP18/LL-37 in human parotid and submandibular glands was investigated by immunohistochemistry. Immunoreactivity for hCAP18/LL-37 was detected in both parotid and submandibular/sublingual saliva of all individuals. The concentration of hCAP18/LL-37 was similar in parotid and submandibular/sublingual saliva, and was determined by densitometric scanning of each dot and normalization to the total protein concentration of each sample, and by ELISA. Double immunohistochemistry revealed that intravascular neutrophils of both parotid and submandibular glands express hCAP18/LL-37. For the first time, we demonstrate hCAP18/LL-37 in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/LL-37 in glandular intravascular neutrophils, indicating that neutrophils of the major salivary glands contribute to the LL-37 content of whole saliva.

http://ift.tt/2skEy04

Cytokine gene polymorphism in denture stomatitis patients: A clinical study

Abstract

Objective

This clinical study investigated the association between cytokine gene polymorphism and Candida growth in DS patients.

Subjects and Methods

Saliva and blood samples of 160 complete denture wearers (80 healthy controls and 80 with DS) were collected for mycological and gene polymorphism testing, respectively. Salivary Candida growth and TNF-α, TGF-β, IL-6 and IL-10 genotypes were investigated. Data were analyzed using Student t-test, Mann-Whitney U, Chi-square analysis and Continuity (yates) correction tests (p<.05).

Results

C. albicans colony counts in saliva were significantly higher in the DS group and in the TNF-α GG genotype (p<.05). TGF-β TC GG and TGF-β CC GG haplotype was significantly higher in DS and control groups, respectively (p<.05). C. albicans colony counts were significantly higher in control group in the TGF-β TC GG haplotype (p<.05). C. glabrata colony counts were significantly higher in the DS group than the control group in IL-6 GG genotype (p<.05). The difference between DS types in IL-6 genotypes was significant with lower expression level in DS type 3 than DS type 1 and also type 2 (p≤ .01).

Conclusion

The significant differences in some genotypes of the TNF- α, TGF- β and IL-6 in DS patients are promising in understanding the host defense in DS.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nNksqq

Comparison of the Transient Evoked Otoacoustic Emissions (TEOAEs) and Distortion Products Otoacoustic Emissions (DPOAEs) in Normal Hearing Subjects With and Without Tinnitus

Abstract

The aim of this study was to investigate the possible role of cochlear outer hair cell function with TEOAE and DPOAE tests in patients with normal hearing and tinnitus. 25 tinnitus patients with normal hearing sensitivity selected as study group. Control group consist of 50 normal hearing subjects without tinnitus. All subjects had thresholds below 25 dBHL at frequencies 250–8,000 Hz, tympanogram type A and normal acoustic reflex thresholds. TEOAE were recorded with click stimulus at 80 dB SPL at 1,000, 2,000, 3,000 and 4000 Hz. DPOAE were measured at frequencies 1,000–8,000 Hz and intensity of L1 55 dB SPL and L2 65 dB SPL. Amplitude of DPOAE and TEOAE were decreased in all frequencies in study group. There was significant difference regarding prevalence abnormal TEOAE and DPOAE between study group and control group. There was relationship between dysfunction of outer hair cells and tinnitus in subjects with normal hearing.

http://ift.tt/2sj0mcz

A Rare Form of Corneal Opacity Associated with Spondyloepiphyseal Dysplasia Congenita

A 13-year-old Japanese female diagnosed with spondyloepiphyseal dysplasia congenita (SEDC) was referred for ophthalmologic evaluation. Examination with slit-lamp and optical coherence tomography revealed bilateral thin cornea with diffuse corneal opacity which was localised at the posterior stromal depth in the central cornea. Unlike the two previously reported cases of diffuse and nodular patterns of corneal opacity in SEDC, the current case exhibited a rare form of corneal opacity. SEDC is one of the type II collagenopathies, characterised by dwarfism because the mutations in COL2A1 prevent bone growth. Although the existence of type II collagen has not been reported in the human corneal stroma, the aetiology of the opacity in the corneal stroma in SEDC type II collagenopathy is of interest.
Case Rep Ophthalmol 2018;9:138–142

http://ift.tt/2ER37Ex

The Effects of a CCR3 Inhibitor, AXP1275, on Allergen-Induced Airway Responses in Adults with Mild-to-Moderate Atopic Asthma

Abstract

Background

CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity.

Objective

This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge.

Methods

Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind crossover study to compare early and late allergen-induced asthmatic responses, methacholine PC₂₀, blood and sputum eosinophils, and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo.

Results

There was a significant increase in methacholine PC₂₀ after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, p=0.01), but this protection was lost post-allergen challenge. There was no effect of AXP1275 on allergen-induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment-emergent adverse events while receiving AXP1275 was comparable placebo.

Conclusions & Clinical Relevance

AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity, or frequency of treatment-emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC₂₀ however the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes.

This article is protected by copyright. All rights reserved.

http://ift.tt/2Efqt5t

Ten-year retrospective clinicohistological study of cutaneous lupus erythematosus in Korea

Abstract

An understanding of the differences in clinical manifestations and laboratory abnormalities between subtypes of cutaneous lupus erythematosus (CLE) is still lacking. The purpose of this study was to analyze demographic, clinical and histological features of CLE according to three main presentation subsets: acute (ACLE), subacute (SCLE) and chronic (CCLE). A 10-year retrospective analysis was performed on data from patients who were diagnosed with CLE between March 2005 and September 2015 in a Korean tertiary referral dermatology clinic. We compared demographic data and clinical and histological findings between three different CLE groups. An overall sample of 220 patients with CLE consisted of 67 patients with ACLE, 25 patients with SCLE and 135 patients with CCLE. Patients with CCLE regardless of systemic lupus erythematosus (SLE) presence had lower prevalence of anemia, urinary abnormalities and elevated erythrocyte sedimentation rate. Furthermore, CCLE patients who only had skin lesions showed lower female predominance, lower extracutaneous manifestation, fewer laboratory and immunological abnormalities including low antinuclear antibody titers and the lowest positivity for C3, C4 and anti-dsDNA, anti-Ro, anti-Sm and anti-RNP antibodies, and more prominent perieccrine inflammation and dermal fibrosis in histological findings. Considering distinct cutaneous manifestations of LE, a comprehensive awareness of each CLE subtype is important for achieving a favorable prognosis through appropriate diagnosis and management. This study provides comparative clinical and histological profiles of patients with different CLE subtypes in Korea.

http://ift.tt/2BjxTWM