Autophony of eyelid movement is not independent of eyeball movement

https://ift.tt/2Lmhxyl

Improvement in minimal cross-sectional area and nasal-cavity volume occurs in different areas after septoplasty and radiofrequency therapy of inferior turbinates

Abstract

Purpose

Septoplasty and radiofrequency therapy for inferior turbinate hypertrophy (RFIT) are common techniques used to improve nasal patency. Our aim was to compare nasal geometry and function using acoustic rhinometry and peak nasal inspiratory flow (PNIF) in three patients groups undergoing surgery for nasal obstruction, and to investigate if the improvement in minimal cross-sectional area (MCA) and nasal-cavity volume (NCV) occurred in different cavity areas in the groups. Finally, we evaluated the correlation between the objective measurements and the patients' assessment of nasal obstruction (SNO).

Methods

This prospective, observational study investigated 148 patients pre-operatively and 6 months post-operatively. Fifty patients underwent septoplasty (group 1), 51 underwent septoplasty combined with RFIT (group 2), and 47 underwent RFIT alone (group 3). The MCA and NCV were measured at two distances (MCA/NCV_0–3.0 and MCA/NCV_3–5.2), in addition to measuring PNIF and SNO.

Results

Pre-operatively, groups 1 and 2 had narrower MCA_0–3.0 on one side than group 3 (0.31 ± 0.14 and 0.31 ± 0.14) versus (0.40 ± 0.16) cm². Post-operatively, total MCA_0–3.0 and MCA/NCV_3–5.2 increased in group 1. In group 2, MCA/NCV_0–3.0 at the narrow side and total MCA/NCV_3–5.2 increased, while total MCA/NCV_3–5.2 increased in group 3. PNIF improved from 106 ± 49 to 150 ± 57 l/min post-operatively. We found a correlation between increased MCA and NCV and less SNO in the septoplasty group (p < 0.01).

Conclusion

Surgery produced an improvement in MCA and NCV in all groups. The improvement occurred in different areas of the nasal cavity in the patient groups. Both anterior and posterior areas increased in the septoplasty groups, while only the posterior area increased in the RFIT group. PNIF improved in all three patient groups, indicating that surgery produced an improvement in nasal patency.

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Oncological and functional outcomes of transoral laser surgery for laryngeal carcinoma

Abstract

Introduction

Transoral laser microsurgery (TLM) has become the standard approach for treatment of early-stage laryngeal carcinoma in most institutions due to their good oncological and functional results with few local complications. The purpose of this study was to analyze the oncological and functional results of TLM in the treatment of laryngeal tumors at our Hospital.

Materials and methods

Patients with laryngeal squamous cell carcinoma (LSCC) treated from 1998 to 2013 with TLM with curative intention, and with a minimum follow-up of 24 months, were reviewed.

Results

203 patients with LSCC were included. 195 patients were men (96%) and 8 women (4%), with a mean age of 63 years. The series includes 134 (66%) T1, 40 (20%) T2, and 29 (14%) T3-classified tumors. 116 tumors (57%) were in the glottis, 79 (39%) in the supraglottis and 8 (4%) in the anterior commissure. 16 patients (8%) received adjuvant radiotherapy. Initial local control was obtained in 75.5% of patients. The 5-year overall survival rate was 84% and the 5-year disease-specific survival was 90%. The presence of nodal metastasis (p < 0.001) and the involvement of the surgical margins (p = 0.004) were associated with a lower disease-specific survival in the multivariate analysis. All but three patients with local control of the disease reassumed oral diet, and none were tracheostomy-dependent. The 5-year laryngeal preservation rate was 85%.

Conclusions

TLM is a minimally invasive treatment for early and moderately-advanced laryngeal carcinomas, with good oncologic and functional outcomes, and few complications as well.

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The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): P. Praest, R.D. Luteijn, I.G.J. Brak-Boer, J. Lanfermeijer, H. Hoelen, L. Ijgosse, A.I. Costa, R.D. Gorham, R.J. Lebbink, E.J.H.J. Wiertz
Herpesviruses encode numerous immune evasion molecules that interfere with the immune system, particularly with certain stages in the MHC class I antigen presentation pathway. In this pathway, the transporter associated with antigen processing (TAP) is a frequent target of viral immune evasion strategies. This ER-resident transporter is composed of the proteins TAP1 and TAP2, and plays a crucial role in the loading of viral peptides onto MHC class I molecules. Several variants of TAP1 and TAP2 occur in the human population, some of which are linked to autoimmune disorders and susceptibility to infections. Here, we assessed the influence of naturally occurring TAP variants on peptide transport and MHC class I expression. In addition, we tested the inhibitory capacity of three viral immune evasion proteins, the TAP inhibitors US6 from human cytomegalovirus, ICP47 from herpes simplex virus type 1 and BNLF2a from Epstein-Barr virus, for a series of TAP1 and TAP2 variants. Our results suggest that these TAP polymorphisms have no or limited effect on peptide transport or MHC class I expression. Furthermore, our study indicates that the herpesvirus-encoded TAP inhibitors target a broad spectrum of TAP variants; inhibition of TAP is not affected by the naturally occurring polymorphisms of TAP tested in this study. Our findings suggest that the long-term coevolution of herpesviruses and their host did not result in selection of inhibitor-resistant TAP variants in the human population.



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Deleterious single nucleotide polymorphisms of protein kinase R identified by the computational approach

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Anna Maria Melzer, Navaneethan Palanisamy
The human protein kinase R (PKR) recognizes invading RNA viruses and mediates the antiviral immune response by phosphorylating the eukaryotic translation initiation factor 2α (eIF-2α), thus blocking protein translation in infected cells and thus preventing viral replication. The observation that individuals show different degrees of susceptibility to viral infections gives rise to the hypothesis that single nucleotide polymorphisms (SNPs) in the protein kinase R may alter the response to an infection. Using different available servers (e.g. SIFT, PROVEAN, Polyphen2, SNAP2, SNP&GOs, SNP-PhD, I-Mutant Suite), 14 SNPs were identified that were predicted to have deleterious effects on the protein kinase R. Five SNPs, namely D266Y, Y323D, I398 K, Y465C and Y472C, were selected for homology modeling and the generated models were investigated with regard to their secondary structure, residue fluctuations and eIF-2α binding. Analysis with computational tools POLYVIEW-MM, SAAPdap, SRIDE, CMView, elNémo, NMsim and PatchDock revealed structural changes in all mutants yielding a more stable structure at the cost of reduced flexibility (except Y465C) and less conformational freedom compared to the native protein. The conformational changes in the mutant protein structures and the displacement of functional residues from their strategic positions are predicted to affect the functionality of PKR, and consequently will affect the efficiency of the individual's antiviral immune response negatively. This study will aid the physicians in precision medicine field to tailor optimal treatment for the patients.



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Microbiota and Type 2 immune responses

Kathy D McCoy | Aline Ignacio | Markus B Geuking

https://ift.tt/2JjRyap

All along the watchtower: group 2 innate lymphoid cells in allergic responses

Madelene W Dahlgren | Ari B Molofsky

https://ift.tt/2Jgccbf

Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?

Juliane Liepe | Huib Ovaa | Michele Mishto

https://ift.tt/2Hmvvhl

Influence of Backscatter Radiation on Cranial Bone Fixation Devices

Postoperative radiation can cause ulcer formation, leading to the denudation of skin over alloplastic materials. The influence of backscatter radiation from fixation devices has not been investigated. The aim of this study is to evaluate backscatter dose variations for different cranial bone fixation devices in an experimental model designed to simulate postoperative radiotherapy. The authors assessed the radiation backscatter doses associated with resorbable (PLLA-PGA) and titanium plates. The samples were irradiated with 6 and 10 MV photon beams from a linear accelerator. Measurements were obtained using an ionization chamber and radiochromic films cut from the same batch. As a result, the backscatter radiation of water and PLLA-PGA proportionally decreased as the depth increased. However, the backscatter radiation of the titanium plate increased just above the plate. This depth lies in the region of the scalp. Each material showed a dose of radioactivity that was higher at 10 MV than that at 6 MV. These devices showed a significant difference, which suggested that these materials amplified the dose compared with water at 6 MV. In conclusion, it is supposed that PLLA-PGA should be used to fix the cranium to decrease the potential for radiation ulcers.

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Perception of Composite Face Allotransplantation From Science Fiction to Reality

No abstract available

https://ift.tt/2Jxgkr3

Simple Technique for Reducing the Buccal Fat Pad During Mandibular Orthognathic Surgery

Sagittal split ramus osteotomy and intraoral vertical ramus osteotomy are commonly performed for the correction of jaw deformities. However, during mandibular orthognathic surgeries such as sagittal split ramus osteotomy and intraoral vertical ramus osteotomy , the authors sometimes encounter exposure of the buccal fat pad (BFP), which decreases the surgical field. The exposed BFP makes it difficult to perform these operations, may result in unexpected complications, and may increase the operation time. Therefore, the authors herein describe a simple, safe, and convenient technique for reducing the volume of the exposed BFP during mandibular orthognathic surgery using an electric knife in the coagulation mode.

https://ift.tt/2LjOcEO

Allotransplantation: From Dream to Reality

No abstract available

https://ift.tt/2JxggHP

Early Tarsorrhaphy in Conjunctival Chemosis After Orbit Bone Reconstruction

Objective: Chemosis is a common occurrence after orbital reconstruction surgery by the transconjunctival approach. The authors propose an early tarsorrhaphy approach for treating severe conjunctival chemosis following orbital fracture repair. Methods: All severe conjunctival chemosis patients following orbital fracture repair were divided into 2 groups: tarsorrhaphy performed immediately when the eyelids could not close completely due to prominent conjunctival edema (early tarsorrhaphy, n = 10); and tarsorrhaphy performed 3 days after the appearance of severe chemosis (delayed tarsorrhaphy, n = 10). Once the conjunctiva subsided, the sutures were immediately removed. The duration of conjunctival edema was recorded. Results: The average time to resolution of severe chemosis was significantly shorter in the early versus delayed tarsorrhaphy group (3.5 ± 0.5 versus 7.2 ± 1.73 days, P 

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Face of the Future: Lessons Learned and Opportunities in Composite Allotransplantation

No abstract available

https://ift.tt/2Jxgbnv

Location of the Septoaponeurosis Junction Relative to the Tarsal Plate in Upper Eyelids

The aim of this study was to measure the location of the septoaponeurosis junction relative to the tarsal plate in the upper eyelids of Koreans through a histologic study. Thirty-four upper eyelids from 34 Korean adult cadavers (mean age, 77.8 years) were used. Sagittal sections on the midpupillary line were made, and 10-μm-thick sections were prepared and stained with hematoxylin-eosin and Masson trichrome. Under a magnifying loupe with a scale, the height of the tarsal plate (HTP), thickness of the tarsal plate (TTP), distance from the lid margin to the septoaponeurosis junction (MJD), and distance from the upper border of the tarsal plate to the septoaponeurosis junction (TJD) were measured. The mean HTP was 8.09 ± 1.68 mm (range: 4.0–0.8 mm). The mean TTP was 1.52 ± 1.56 mm (range: 0.8–3.0 mm). The mean MJD was 9.18 ± 2.69 mm (range: 2.5–13.0 mm). The mean TJD was 1.1 ± 2.6 mm (range: −5.5–7.0 mm). In 25 (73.5%) of the 34 eyelids, the SAJ (1.1 ± 2.6 mm) was above the upper border of the tarsal plate (UTP); however, in 9 (26.5%) of the 34 eyelids, below the UTP. The greater the HTP, the greater the MJD was (y=0.620x+4.166, P = 0.024 [linear regression analysis]). However, there was no significant correlation between the HTP and TJD (P = 0.155 [correlation analysis]). The results of this study provide a useful guide for performing operations involving the orbital septum and levator aponeurosis.

https://ift.tt/2LnbwBE

Face Transplant: Status of Current Supporting Technology to Plan and Perform the Operation and Monitor the Graft in the Postoperative Period

Face transplant has rapidly advanced since the first operation in 2005, and to date, 40 partial or full-face transplants have been performed. The safety and efficacy of this operation are aided at all phases by supporting technologies. These include advanced imaging techniques to plan the operation, devices to monitor the flap in the immediate perioperative period, and noninvasive imaging and serum markers to monitor for acute and chronic rejection. Some of the technologies, such as those used in the immediate perioperative period, have extensive evidence supporting their use, whereas those to detect acute or chronic rejection remain investigational. The technologies of today will continue to evolve and make the operation safer with improved outcomes; however, the most significant barrier for face transplant continues to be immunologic rejection.

https://ift.tt/2Jxg6Ad

Contour Restoration of Over-Resected Mandibular Angle and Lower Border by Reduction Mandibuloplasty Using Three-Dimensional Planning and Computer-Aided Design and Manufacturing Custom-Made Titanium Implants

Objective: The purpose of this clinical report was to introduce a new methodology for contour restoration of the over-resected mandible by reduction mandibuloplasty using 3-dimensional (3D) planning and computer-assisted design and manufacturing (CAD-CAM) custom-made titanium implants. Patient and method: A 20-year-old male patient had undergone reduction of the zygoma and mandibular angle and lower border for esthetic reason 1 year ago at a private clinic. However, he was not satisfied with surgical outcome and wanted to restore his original facial volume and contour. To assess the volume and dimension of resected bone, 3D-computed tomography (3D-CT) data at the original stage was superimposed with postsurgical CT. For restoration of the malar prominence, porous polyethylene malar implants with extensions into the lateral malar region (Medpor) were placed and fixed with microscrews. Custom-made titanium implants were fabricated for contour restoration of the mandibular angle and lower border using CAD-CAM technology (iDDA, Daegu, South Korea). Two-piece design per each titanium implant was adopted for easy placement and avoidance of tissue damage during placement. Thin buccal extension was incorporated for placement of screw holes. Location, direction, and length of bicortical screws were planned to avoid damage of the inferior alveolar nerve. Result: With the help of 3D planning and CAD-CAM technology, rigid fixation of the custom-made titanium implants into the mandibular angle and lower border successfully restored the contour of over-resected mandible to the original state. Conclusion: When over-resection by reduction mandibuloplasty becomes an issue, this method may be an effective treatment option for contour restoration of over-resected mandibular angle and lower border.

https://ift.tt/2LmwHnw

Organ-on-a-Chip: New Tool for Personalized Medicine

No abstract available

https://ift.tt/2Jxg23r

Does Pediatric Obstructive Sleep Apnea Syndrome Cause Systemic Microvascular Dysfunction?

The aim of this study was to evaluate whether pediatric obstructive sleep apnea syndrome (OSAS) secondary to adenoid hypertrophy causes systemic microvascular dysfunction. This is a prospective single-blinded case–control study. As the patient group, 81 patients diagnosed to have OSAS secondary to adenoid hypertrophy at our hospital between January 2016 and May 2016; as the control group, 26 healthy pediatric volunteers who presented to the hospital for health screening were included in this study. Three groups of OSAS patients were defined as mild, moderate, and severe respectively, according to the lateral nasopharynx x-ray. Patients with comorbid diseases were excluded from the study. For microvascular dysfunction, videocapillaroscopic evaluation was performed at the nailfold and capillary density (CD) and postocclusive reactive hyperemia (PORH) values were measured and statistical analysis between the groups was performed. The duration of complaints in all patients with OSAS was at least 6 months and 0.05). PORH measurement in the control group and mild, moderate, and severe OSAS group was 95.6 ± 8.6, 97.9 ± 10.1, 96 ± 8.7, and 93.9 ± 9.3, respectively, with no significant difference between the groups (P > 0.05). OSAS secondary to adenoid hypertrophy in pediatric patients was demonstrated to cause no dysfunction in microvascular circulation and carried no cardiovascular risk in the early period.

https://ift.tt/2LoGqtA

An Oculist and a Musician in Leipzig

No abstract available

https://ift.tt/2Jrd8wZ

Antral Wall Approach for Reconstruction of Orbital Floor Fractures Using Anterior Maxillary Sinus Bone Grafts

Isolated orbital wall fractures account for 4% to 16% of all facial fractures. Even a modest change in the position of the bony walls can have a significant impact on orbital volume and globe position. Alloplastic materials or autogenous bone grafts such as the antral maxillary wall can be used to reconstruct small- to medium-size orbital fractures. The main advantage of an antral wall graft is the intraoral approach with minimal morbidity. Nine patients underwent repair of orbital floor fractures using the extraoral and the intraoral antral wall approach. The patients underwent preoperative computed tomography imaging and a minimum of 1 year follow-up. The size of the defects ranged from 0.5 to 1.4 cm. Two patients experienced minor immediate postoperative complications; infraorbital hypoesthesia. On follow-ups, none of our patients suffered from ocular movement restrictions or complications regarding the maxillary antral wall approach. The use of harvested bone grafts from the anterolateral wall of the maxillary sinus is a promising approach for the reconstruction of small- to mid-size orbital floor defects with minimal complications and excellent cosmetic and functional results.

https://ift.tt/2LmhGSB

Facing a New Face: An Interpretative Phenomenological Analysis of the Experiences of a Blind Face Transplant Patient and His Partner

Increasing evidence points to good functional, aesthetic, and psychosocial outcomes after face transplantation. However, research investigating how patients and their families subjectively experience the transplantation process is lacking thus far. This study aims to investigate the personal experiences of a blind face transplant patient and his partner. In-depth interviews exploring different experiences were conducted with both partners separately 20 months after face transplantation. The interviews were analyzed using interpretative phenomenological analysis. Seven themes were identified in both interviews: coping with the facial trauma, motivation for the face transplantation, outcomes of the face transplantation, acceptance of the new face, gratitude toward the donor family, relation to the medical team, and dealing with the media. Two further themes were only mentioned by the patient (coping with complications and coping with blindness) and one theme only by the partner (loss of choices). The results of this study increase our understanding of the transplantation process as experienced by a face transplant recipient and his partner. They may help to better inform professionals to optimize transplantation procedures or supportive interventions.

https://ift.tt/2Jrd5kN

Anatomical Examination of Mandibular Condyle Protrusion Into the Middle Cranial Fossa

Trauma to the mandible can occasionally be a life-threatening event. Although extremely rare with only 56 reported patients in the English language, fracture of the floor of the middle cranial fossa with protrusion of the mandibular condyle into the middle cranial fossa was first reported in 1963 by Dingman. The authors review the anatomy of the temporomandibular joint in relation to the middle cranial fossa and demonstrate the possible complications due to condylar intrusion with anatomical dissection.

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Face Transplantation: An Update for the United States Trauma System

Face transplantation has evolved over the last 12 years into a safe and feasible reconstructive solution, with good aesthetic and functional outcomes for patients with severe facial defects who are not amenable to reconstruction through conventional and autologous approaches. Among patients who underwent face transplantation to date, a significant proportion did so following trauma, mostly ballistic and thermal injuries. It is therefore important for trauma surgeons who deal with these injuries regularly to be familiar with the literature on face transplantation following traumatic injuries. In this study, we provide a focused review on this topic, with an emphasis on highlighting the limitations of conventional craniomaxillofacial reconstruction, while emphasizing data available on the risks, benefits, surgical indications, contraindications, as well as aesthetic and functional outcomes of face transplantation. The authors also provide an update on all face transplants performed to date including traumatic mechanisms of injury, and extent of defects. They finally describe 2 cases performed by the senior author for patients presenting with devastating facial ballistic and thermal injuries. The authors hope that this work serves as an update for the trauma surgery community regarding the current role and limitations of face transplantation as a craniomaxillofacial reconstructive option for their patient population. This can potentially expedite the reconstructive process for patients who may benefit from face transplantation.

https://ift.tt/2sDgDWF

Review of “Overlapping Surgeries Are Not Associated With Worse Patient Outcomes: Retrospective Multivariate Analysis of 14,872 Neurosurgical Cases Performed at a Single Institution” by Bohl MA in Neurosurg [published online September 27, 2017] doi: 10.1093/neuros/nyx472

No abstract available

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Single-Piece Titanium Plate Cranioplasty Reconstruction of Complex Defects

Background: Different methods have been described for the reconstruction of cranial defects and orbital defects. The complex contouring between the orbital roof and frontal bone creates significant design challenges for prefabricated cranio-orbital reconstructions. In describing the first reported patient of combined skull and orbital roof reconstruction with a single-piece titanium plate cranioplasty, the authors present a new method of combined complex cranio-orbital reconstruction. Methods: A 63-year-old lady presented with a large, right-sided frontal en–plaque meningioma involving the right orbit and sphenoid wing. Complete resection would require reconstruction of both the skull and the orbital roof. Surgical preplanning involved marking resection margins on a three-dimensional (3D) printed acrylonitrile-butadiene-styrene model. This margin was used to virtually resect the tumor and generate a repaired surface. A titanium plate was then fabricated using hydrostatic pressing into a 3D-printed mold and the orbital roof portion (a reentrant surface) was hand-finished. Lateral canthus and temporalis muscle suspension holes were prefabricated into the cranioplasty plate. Results: The patient underwent hemicraniectomy and tumor resection guided by a custom-made 3D-printed cutting guide. The surgical defect was reconstructed with the prefabricated titanium plate achieving a good functional and cosmetic result. Conclusion: Single-piece titanium plate cranioplasty is an effective novel reconstruction method for complex cranio-orbital defects.

https://ift.tt/2HmfesL

Long-Term Skeletal Changes After Maxillary Distraction Osteogenesis in Growing Children With Cleft Lip/Palate

Purpose: To systematically evaluate the skeletal changes after maxillary distraction osteogenesis (DO) in growing patients with cleft lip with or without cleft palate (CL/P). Materials and methods: Electronic databases, gray literature, and reference list searches were conducted. Articles reporting prospective and retrospective studies that included patients 1 year were reviewed. The original articles were evaluated by 2 investigators to ensure that they met the selection criteria. A methodologic quality assessment tool was used to evaluate the quality of selected studies. Twenty-six studies met the initial search criteria, and 9 articles included 101 growing patients with maxillary hypoplasia due to CL/P who received DO surgery were finally selected and analyzed. Results: The results showed that long term after maxillary advancement with DO, the horizontal relapse in A-point was 40% in 1 study. Totally, the range of horizontal relapse in A-point was 11.9% to 45.9%. Similarly, the relapse in SNA angle was 40% in 2 studies. Totally, the range of relapse in SNA was 25.7% to 77%. Two studies showed that the vertical relapse in A-point were 137% and 208%, and in the PNS point were 65% and 62.7%. Conclusion: Although findings demonstrated that DO is an effective treatment method for severe maxillary hypoplasia in growing patients with CL/P, there is a relatively high amount of skeletal relapse both in horizontal and vertical dimension. Thus, the first proposed alternative for CL/P patients would be to select the correct primary procedure to decrease damage and avoid unnecessary scars. Then appropriate preoperative and postoperative care is necessary to prevent postoperative relapse. In addition, overcorrection also may be a possible alternative for compensation of postoperative relapse.

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Trismus in Face Transplantation Following Ballistic Trauma

Background: Trismus can be a challenging consequence of ballistic trauma to the face, and has rarely been described in the setting of face transplantation. Almost half of all current face transplant recipients in the world received transplantation to restore form and function after a ballistic injury. Here we report our experience and challenges with long standing trismus after face transplantation. Methods: We reviewed the medical records of our face transplant recipients whose indication was ballistic injury. We focused our review on trismus and assessed the pre-, peri- and postoperative planning, surgery and functional outcomes. Results: Two patients received partial face transplantation, including the midface for ballistic trauma. Both patients suffered from impaired mouth opening, speech intelligibility, and oral competence. Severe scarring of the temporomandibular joint (TMJ) required intraoperative release in both patients, and additional total condylectomy on the left side 6 months posttransplant for 1 patient. Posttransplant, both patients achieved an improvement in mouth opening; however, there was persistent trismus. One year after transplantation, range of motion of the jaw had improved for both patients. Independent oral food intake was possible 1 year after surgery, although spillage of liquids and mixed consistency solids persisted. Speech intelligibility testing showed impairments in the immediate postoperative period, with improvement to over 85% for both patients at 1 year posttransplant. Conclusions: Ballistic trauma to the face and subsequent reconstructive measures can cause significant scarring and covert injuries to structures such as the TMJ, resulting in long standing trismus. Meticulous individual planning prior to interventions such as face transplantation must take these into account. We encourage intraoperative evaluation of these structures as well as peri- and postoperative treatment when necessary. Due to the nature of the primary injury, functional outcomes after face transplantation in these patients may differ substantially from those of other indications.

https://ift.tt/2HkqwxI

Correlation between gonial angle and dynamic tongue collapse in children with snoring/sleep disordered breathing – an exploratory pilot study

Drug induced sleep endoscopy (DISE) is hoped to identify reasons of failure of adenotonsillectomy (AT) in treating pediatric sleep disordered breathing (SDB). Maxillomandibular disproportion has been studied a...

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Cross-sectional study on sensitization to mite and cockroach allergen components in allergy patients in the Central European region

The major sources of allergens in the indoor air include house dust mites, dander derived from domestic animals and rodents, cockroach, and several fungi. Mites are the main cause of allergies in some countrie...

https://ift.tt/2sGWAXg

Immune checkpoint-mediated myositis and myasthenia gravis: A case report and review of evaluation and management

We present a case of myositis and possible overlapping neuromuscular junction disorder following treatment with nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

https://ift.tt/2LnAlgD

Outcomes in microvascular head and neck reconstruction in the setting of restricted residency hours

Resident duty hour restrictions can limit the frequency of resident flap checks at smaller institutions with "home" call. Institutions are compensating with adjuvant nursing flap checks as well as incorporating technology; however, this management remains controversial.

https://ift.tt/2JvxfKn

Comparison of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for the salvage treatment of refractory high-frequency sudden sensorineural hearing loss

This study aimed to compare the efficacy of intratympanic dexamethasone (ITD) therapy and hyperbaric oxygen(HBO) therapy for the salvage treatment of patients with high-frequency sudden sensorineural hearing loss (SSNHL) after the failure of conventional therapy.

https://ift.tt/2LmD620

A computed tomographic analysis of frontal recess cells in association with the development of frontal sinusitis

This study was done to determine frontal recess anatomy cell variations and its association with frontal sinusitis. The incidence of frontal recess cells in the population, the presence of frontal recess cell variations in chronic rhinosinusitis and non-chronic rhinosinusitis and the association of frontal recess cell variation in the development of frontal sinusitis were also assessed.

https://ift.tt/2LicA9V

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy [INNATE IMMUNITY AND INFLAMMATION]

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease.

https://ift.tt/2LZTV3F

eIF4E-Binding Proteins 1 and 2 Limit Macrophage Anti-Inflammatory Responses through Translational Repression of IL-10 and Cyclooxygenase-2 [INNATE IMMUNITY AND INFLAMMATION]

Macrophages represent one of the first lines of defense during infections and are essential for resolution of inflammation following pathogen clearance. Rapid activation or suppression of protein synthesis via changes in translational efficiency allows cells of the immune system, including macrophages, to quickly respond to external triggers or cues without de novo mRNA synthesis. The translational repressors eIF4E-binding proteins 4E-BP1 and 4E-BP2 (4E-BP1/2) are central regulators of proinflammatory cytokine synthesis during viral and parasitic infections. However, it remains to be established whether 4E-BP1/2 play a role in translational control of anti-inflammatory responses. By comparing translational efficiencies of immune-related transcripts in macrophages from wild-type and 4E-BP1/2 double-knockout mice, we found that translation of mRNAs encoding two major regulators of inflammation, IL-10 and PG-endoperoxide synthase 2/cyclooxygenase-2, is controlled by 4E-BP1/2. Genetic deletion of 4E-BP1/2 in macrophages increased endogenous IL-10 and PGE₂ protein synthesis in response to TLR4 stimulation and reduced their bactericidal capacity. The molecular mechanism involves enhanced anti-inflammatory gene expression (sIl1ra, Nfil3, Arg1, Serpinb2) owing to upregulation of IL-10–STAT3 and PGE₂–C/EBPβ signaling. These data provide evidence that 4E-BP1/2 limit anti-inflammatory responses in macrophages and suggest that dysregulated activity of 4E-BP1/2 might be involved in reprogramming of the translational and downstream transcriptional landscape of macrophages during pathological conditions, such as infections and cancer.

https://ift.tt/2JgLcIJ

RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death [INNATE IMMUNITY AND INFLAMMATION]

Linear ubiquitin chain assembly complex plays an important role in regulating TNF-α signaling activation by modifying target proteins with linear (M1-linked) ubiquitin chains. In this study, we report that the epidermis-specific knockout (KO) of RNF31, the catalytic subunit of linear ubiquitin chain assembly complex, results in an early postnatal lethality in mice due to severe skin inflammation. The inflammation was mainly triggered by TNF-α–induced apoptosis in RNF31 KO keratinocytes. Mechanistically, the deficiency of RNF31 not only impaired TNF-α–induced NF-B activation, but also significantly increased apoptosis. Consistently, deleting TNF receptor 1 could rescue the lethality of RNF31 epidermis-specific KO mice and also the skin inflammation. Collectively, our study provides an in vivo insight that linear ubiquitination is critical for maintaining the homeostasis of keratinocytes, which will shed light on designing therapeutic compounds to treat skin inflammation.

https://ift.tt/2LXvyUt

Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance [IMMUNE REGULATION]

Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact–mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function. Treg cell–specific loss of talin, a β integrin–binding protein, or expression of talin(L325R), a mutant that selectively abrogates integrin activation, resulted in lethal systemic autoimmunity. This dysfunction could be attributed, in part, to a global dysregulation of the Treg cell transcriptome. Activation of integrin α₄β₁ led to increased suppressive capacity of the Treg cell pool, suggesting that modulating integrin activation on Treg cells may be a useful therapeutic strategy for autoimmune and inflammatory disorders. Taken together, these results reveal a critical role for integrin-mediated signals in controlling peripheral tolerance by virtue of maintaining Treg cell function.

https://ift.tt/2LWQQlf

MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function [TRANSPLANTATION]

MicroRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155–deficient (miR155^–/–) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated. We identify that miR-155 expression in both donor CD8⁺ T cells and conventional CD4⁺ CD25^– T cells is pivotal for aGVHD pathogenesis. Using murine aGVHD transplant experiments, we show that miR-155 strongly impacts alloreactive T cell expansion through multiple distinct mechanisms, modulating proliferation in CD8⁺ donor T cells and promoting exhaustion in donor CD4⁺ T cells in both the spleen and colon. Additionally, miR-155 drives a proinflammatory Th1 phenotype in donor T cells in these two sites, and miR-155^–/– donor T cells are polarized toward an IL-4–producing Th2 phenotype. We further demonstrate that miR-155 expression in donor T cells regulates CCR5 and CXCR4 chemokine-dependent migration. Notably, we show that miR-155 expression is crucial for donor T cell infiltration into multiple target organs. These findings provide further understanding of the role of miR-155 in modulating aGVHD through T cell expansion, effector cytokine production, and migration.

https://ift.tt/2xGHEOK

SOCS1 and SOCS3 Target IRF7 Degradation To Suppress TLR7-Mediated Type I IFN Production of Human Plasmacytoid Dendritic Cells [IMMUNE REGULATION]

Type I IFN production of plasmacytoid dendritic cells (pDCs) triggered by TLR-signaling is an essential part of antiviral responses and autoimmune reactions. Although it was well-documented that members of the cytokine signaling (SOCS) family regulate TLR-signaling, the mechanism of how SOCS proteins regulate TLR7-mediated type I IFN production has not been elucidated yet. In this article, we show that TLR7 activation in human pDCs induced the expression of SOCS1 and SOCS3. SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production. Furthermore, we demonstrated that SOCS1- and SOCS3-bound IFN regulatory factor 7, a pivotal transcription factor of the TLR7 pathway, through the SH2 domain to promote its proteasomal degradation by lysine 48-linked polyubiquitination. Together, our results demonstrate that SOCS1/3-mediated degradation of IFN regulatory factor 7 directly regulates TLR7 signaling and type I IFN production in pDCs. This mechanism might be targeted by therapeutic approaches to either enhance type I IFN production in antiviral treatment or decrease type I IFN production in the treatment of autoimmune diseases.

https://ift.tt/2JgIhQm

Regulation of the DNA Repair Complex during Somatic Hypermutation and Class-Switch Recombination [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

B lymphocytes optimize Ab responses by somatic hypermutation (SH), which introduces point mutations in the variable regions of the Ab genes and by class-switch recombination (CSR), which changes the expressed C region exon of the IgH. These Ab diversification processes are initiated by the deaminating enzyme activation-induced cytidine deaminase followed by many DNA repair enzymes, ultimately leading to deletions and a high mutation rate in the Ab genes, whereas DNA lesions made by activation-induced cytidine deaminase are repaired with low error rate on most other genes. This indicates an advanced regulation of DNA repair. In this study, we show that initiation of Ab diversification in B lymphocytes of mouse spleen leads to formation of a complex between many proteins in DNA repair. We show also that BCR activation, which signals the end of successful SH, reduces interactions between some proteins in the complex and increases other interactions in the complex with varying kinetics. Furthermore, we show increased localization of SH- and CSR-coupled proteins on switch regions of the Igh locus upon initiation of SH/CSR and differential changes in the localization upon BCR signaling, which terminates SH. These findings provide early evidence for a DNA repair complex or complexes that may be of functional significance for carrying out essential roles in SH and/or CSR in B cells.

https://ift.tt/2JjP1x2

Previously Hidden Dynamics at the TCR-Peptide-MHC Interface Revealed [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

A structural characterization of the interaction between αβ TCRs and cognate peptide–MHC (pMHC) is central to understanding adaptive T cell–mediated immunity. X-ray crystallography, although the source of much structural data, traditionally provides only a static snapshot of the protein. Given the emerging evidence for the important role of conformational dynamics in protein function, we interrogated 309 crystallographic structures of pMHC complexes using ensemble refinement, a technique that can extract dynamic information from the x-ray data. Focusing on a subset of human pMHC class I systems, we found that in many cases, ensemble methods were able to uncover previously hidden evidence of significant conformational plasticity, thereby revealing additional information that can build upon and significantly enhance functional interpretations that are based on a single static structure. Notable examples include the interpretation of differences in the disease association of HLA subtypes, the relationship between peptide prominence and TCR recognition, the role of conformational flexibility in vaccine design, and the discrimination between induced fit and conformational selection models of TCR binding. We show that the currently widespread practice of analyzing pMHC interactions via the study of a single crystallographic structure does not make use of pertinent and easily accessible information from x-ray data concerning alternative protein conformations. This new analysis therefore not only highlights the capacity for ensemble methods to significantly enrich the interpretation of decades of structural data but also provides previously missing information concerning the dynamics of existing characterized TCR–pMHC interactions.

https://ift.tt/2LVbj9P

Comparative Transcriptomic Response of Primary and Immortalized Macrophages to Murine Norovirus Infection [SYSTEMS IMMUNOLOGY]

Murine norovirus (NoV) is genetically similar to human NoV and offers both an efficient in vitro cell culture system and an animal model by which to investigate the molecular basis of replication. In this study, we present a detailed global view of host alterations to cellular pathways that occur during the progression of a NoV infection. This was accomplished for both Mus musculus BALB/c–derived RAW264.7 (RAW) cells, an immortalized cell line widely used in in vitro replication studies, and primary bone marrow–derived macrophages (BMDM), representing a permissive in vivo target cell in the host. Murine NoV replicated in both cell types, although detected genome copies were approximately one log lower in BMDM compared with RAW cells. RAW and BMDM cells shared an IRF3/7-based IFN response that occurred early in infection. In RAW cells, transcriptional upregulation and INF-β expression were not coupled in that a significant delay in the detection of secreted INF-β was observed. In contrast, primary BMDM showed an early upregulation of transcripts and immediate release of INF-β that might account for lower virus yield. Differences in the transcriptional pathway responses included a marked decrease in expression of key genes in the cell cycle and lipid pathways in RAW cells compared with that of BMDM. Our comparative analysis indicates the existence of varying host responses to virus infection in populations of permissive cells. Awareness of these differences at the gene level will be important in the application of a given permissive culture system to the study of NoV immunity, pathogenesis, and drug development.

https://ift.tt/2LZTPsP

Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms [IMMUNE REGULATION]

Platelet-activating factor (PAF) stimulates numerous cell types via activation of the G protein–coupled PAF receptor (PAFR). PAFR activation not only induces acute proinflammatory responses, but it also induces delayed systemic immunosuppressive effects by modulating host immunity. Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE₂ release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase– or cyclooxygenase-2–deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE₂-dependent mechanisms.

https://ift.tt/2xR3KOL

Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity [TUMOR IMMUNOLOGY]

Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Eμ–T cell leukemia oncogene-1 (TCL1) mouse CLL model to study the role of IL-10 in CLL associated immunosuppression. Eμ-TCL mice spontaneously develop CLL because of a B cell–specific expression of the oncogene, TCL1. Eμ-TCL1 mouse CLL cells constitutively produce IL-10, which is further enhanced by BCR cross-linking, CLL-derived IL-10 did not directly affect survival of murine or human CLL cells in vitro. We tested the hypothesis that the CLL-derived IL-10 has a critical role in CLL disease in part by suppressing the host immune response to the CLL cells. In IL-10R^–/– mice, wherein the host immune cells are unresponsive to IL-10–mediated suppressive effects, there was a significant reduction in CLL cell growth compared with wild type mice. IL-10 reduced the generation of effector CD4 and CD8 T cells. We also found that activation of BCR signaling regulated the production of IL-10 by both murine and human CLL cells. We identified the transcription factor, Sp1, as a novel regulator of IL-10 production by CLL cells and that it is regulated by BCR signaling via the Syk/MAPK pathway. Our results suggest that incorporation of IL-10 blocking agents may enhance current therapeutic regimens for CLL by potentiating host antitumor immune response.

https://ift.tt/2LXvzI1

The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions [INNATE IMMUNITY AND INFLAMMATION]

Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain–bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae–induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration. We show that overactivation of the neutrophil β₂ integrins Mac-1 and LFA-1 is responsible for increased adhesion and reduced neutrophil transmigration, resulting in a strongly impaired immune defense against pulmonary infection. Structure function analysis in vitro and in vivo demonstrated that different domains of Ly49Q are important for its function. In summary, Ly49Q regulates integrin activation and neutrophil recruitment and is required for an adequate immune response in pulmonary infection.

https://ift.tt/2xIch6t

Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging [IMMUNE SYSTEM DEVELOPMENT]

Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5–10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 x 10⁹ cells/l/d), basophils (1.78 ± 0.30 d, 5.89 x 10⁶ cells/l/d), and CD14⁺CD16^– classical monocytes (1.01 ± 0.15 d, 3.09 x 10⁸ cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4–5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

https://ift.tt/2LZ9qZH

Antibodies Encoded by FCRL4-Bearing Memory B Cells Preferentially Recognize Commensal Microbial Antigens [CLINICAL AND HUMAN IMMUNOLOGY]

FCRL4, a low-affinity IgA Ab receptor with strong immunoregulatory potential, is an identifying feature of a tissue-based population of memory B cells (Bmem). We used two independent approaches to perform a comparative analysis of the Ag receptor repertoires of FCRL4⁺ and FCRL4^– Bmem in human tonsils. We determined that FCRL4⁺ Bmem displayed lower levels of somatic mutations in their Ag receptors compared with FCRL4^– Bmem but had similar frequencies of variable gene family usage. Importantly, Abs with reactivity to commensal microbiota were enriched in FCRL4⁺ cells, a phenotype not due to polyreactive binding characteristics. Our study links expression of the immunoregulatory FCRL4 molecule with increased recognition of commensal microbial Ags.

https://ift.tt/2JejWuh

Small Molecule Mimetics of {alpha}-Helical Domain of IRAK2 Attenuate the Proinflammatory Effects of IL-33 in Asthma-like Mouse Models [IMMUNE REGULATION]

IL-33 and its receptor ST2 play important roles in airway inflammation and contribute to asthma onset and exacerbation. The IL-33/ST2 signaling pathway recruits adapter protein myeloid differentiation primary response 88 (MyD88) to transduce intracellular signaling. MyD88 forms a complex with IL-R–associated kinases (IRAKs), IRAK4 and IRAK2, called the Myddosome (MyD88–IRAK4–IRAK2). The myddosome subsequently activates downstream NF-B and MAPKs p38 and JNK. We established an asthma-like mouse model by intratracheal administration of IL-33. The IL-33 model has a very similar phenotype compared with the OVA-induced mouse asthma model. The importance of MyD88 in the IL-33/ST2 signaling transduction was demonstrated by the MyD88 knockout mice, which were protected from the IL-33–induced asthma. We synthesized small molecule mimetics of the α-helical domain of IRAK2 with drug-like characteristics based on the recent advances in the designing of α-helix compounds. The mimetics can competitively interfere in the protein–protein interaction between IRAK2 and IRAK4, leading to disruption of Myddosome formation. A series of small molecules were screened using an NF-B promoter assay in vitro. The lead compound, 7004, was further studied in the IL-33–induced and OVA-induced asthma mouse models in vivo. Compound 7004 can inhibit the IL-33–induced NF-B activity, disrupt Myddosome formation, and attenuate the proinflammatory effects in asthma-like models. Our data indicate that the Myddosome may represent a novel intracellular therapeutic target for diseases in which IL-33/ST2 plays important roles, such as asthma and other inflammatory diseases.

https://ift.tt/2LZTZAr

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life [CLINICAL AND HUMAN IMMUNOLOGY]

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin⁺ Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA⁺) Treg cells later in life. β7 integrin⁺ Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2–induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development.

https://ift.tt/2LVbjGR

An Unmutated IgM Response to the Vi Polysaccharide of Salmonella Typhi Contributes to Protective Immunity in a Murine Model of Typhoid [INFECTIOUS DISEASE AND HOST RESPONSE]

T cell–dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID^–/– mice with either heat-killed Salmonella enterica serovar Typhi (S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID^–/– mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID^–/– mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID^–/– mice, the ViPS-specific IgM levels and S. Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID^–/– mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to S. Typhi.

https://ift.tt/2LZTW7J

Simultaneous Presence of Non- and Highly Mutated Keyhole Limpet Hemocyanin (KLH)-Specific Plasmablasts Early after Primary KLH Immunization Suggests Cross-Reactive Memory B Cell Activation [CLINICAL AND HUMAN IMMUNOLOGY]

There are currently limited insights into the progression of human primary humoral immunity despite numerous studies in experimental models. In this study, we analyzed a primary and related secondary parenteral keyhole limpet hemocyanin (KLH) immunization in five human adults. The primary challenge elicited discordant KLH-specific serum and blood effector B cell responses (i.e., dominant serum KLH-specific IgG and IgM levels versus dominant KLH-specific IgA plasmablast frequencies). Single-cell IgH sequencing revealed early appearance of highly (>15 mutations) mutated circulating KLH-specific plasmablasts 2 wk after primary KLH immunization, with simultaneous KLH-specific plasmablasts carrying non- and low-mutated IgH sequences. The data suggest that the highly mutated cells might originate from cross-reactive memory B cells (mBCs) rather than from the naive B cell repertoire, consistent with previous reported mutation rates and the presence of KLH-reactive mBCs in naive vaccinees prior to immunization. Whereas upon secondary immunization, serum Ab response kinetics and plasmablast mutation loads suggested the exclusive reactivation of KLH-specific mBCs, we, however, detected only little clonal overlap between the peripheral KLH-specific secondary plasmablast IgH repertoire and the primary plasmablast and mBC repertoire, respectively. Our data provide novel mechanistic insights into human humoral immune responses and suggest that primary KLH immunization recruits both naive B cells and cross-reactive mBCs, whereas secondary challenge exclusively recruits from a memory repertoire, with little clonal overlap with the primary response.

https://ift.tt/2Jhky2k

Extracellular Histones Inhibit Complement Activation through Interacting with Complement Component 4 [INNATE IMMUNITY AND INFLAMMATION]

Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with K_D around 1 nM. The interaction did not affect C4 cleavage to C4a and C4b. Because histones bind to C4b, a component of C3 and C5 convertases, their activities were significantly inhibited in the presence of histones. Although it is not clear whether the inhibition was achieved through blocking C3 and C5 convertase assembly or just through reducing their activity, the outcome was that both classical and mannose-binding lectin pathways were dramatically inhibited. Using a high concentration of C4 protein, histone-suppressed complement activity could not be fully restored, indicating C4 is not the only target of histones in those pathways. In contrast, the alternative pathway was almost spared, but the overall complement activity activated by zymosan was inhibited by histones. Therefore, we believe that histones inhibiting complement activation is a natural feedback mechanism to prevent the excessive injury of host cells.

https://ift.tt/2JicBKy

Inability To Detect Cross-Reactive Memory T Cells Challenges the Frequency of Heterologous Immunity among Common Viruses [CLINICAL AND HUMAN IMMUNOLOGY]

Human memory T cells that cross-react with epitopes from unrelated viruses can potentially modulate immune responses to subsequent infections by a phenomenon termed heterologous immunity. However, it is unclear whether similarities in structure rather than sequence underpin heterologous T cell cross-reactivity. In this study, we aimed to explore the mechanism of heterologous immunity involving immunodominant epitopes derived from common viruses restricted to high-frequency HLA allotypes (HLA-A*02:01, -B*07:02, and -B*08:01). We examined EBV-specific memory T cells for their ability to cross-react with CMV or influenza A virus–derived epitopes. Following T cell immunoassays to determine phenotype and function, complemented with biophysical and structural investigations of peptide/HLA complexes, we did not detect cross-reactivity of EBV-specific memory T cells toward either CMV or influenza A virus epitopes presented by any of the selected HLA allomorphs. Thus, despite the ubiquitous nature of these human viruses and the dominant immune response directed toward the selected epitopes, heterologous virus-specific T cell cross-reactivity was not detected. This suggests that either heterologous immunity is not as common as previously reported, or that it requires a very specific biological context to develop and be clinically relevant.

https://ift.tt/2LShKdX

CD71+ Erythroid Suppressor Cells Promote Fetomaternal Tolerance through Arginase-2 and PDL-1 [IMMUNE REGULATION]

Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71⁺ erythroid cells are expanded at the fetomaternal interface and in the periphery during pregnancy in both humans and mice. These cells exhibit immunosuppressive properties, and their abundance is associated with a Th2 skewed immune response, as their depletion results in a proinflammatory immune response at the fetomaternal interface. In addition to their function in suppressing proinflammatory responses in vitro, maternal CD71⁺ erythroid cells inhibit an aggressive allogeneic response directed against the fetus such as reduction in TNF-α and IFN- production through arginase-2 activity and PD-1/programmed death ligand-1 (PDL-1) interactions. Their depletion leads to the failure of gestation due to the immunological rejection of the fetus. Similarly, fetal liver CD71⁺ erythroid cells exhibit immunosuppressive activity. Therefore, immunosuppression mediated by CD71⁺ erythroid cells on both sides (mother/fetus) is crucial for fetomaternal tolerance. Thus, our results reveal a previously unappreciated role for CD71⁺ erythroid cells in pregnancy and indicate that these cells mediate homeostatic immunosuppressive/immunoregulatory responses during pregnancy.

https://ift.tt/2xIcjeB

Case report presenting the diagnostic challenges in a patient with recurrent acquired angioedema, antiphospholipid antibodies and undetectable C2 levels

Angioedema secondary to acquired C1 inhibitor deficiency (AAE) is a rare disease. It usually is associated with lymphoproliferative disorders. We present a case of AAE in a patient with antiphospholipid syndro...

https://ift.tt/2JcjFw4

A computed tomographic analysis of frontal recess cells in association with the development of frontal sinusitis

Publication date: Available online 4 June 2018
Source:Auris Nasus Larynx
Author(s): Hafizah Husna Johari, Irfan Mohamad, Ida Sadja'ah Sachlin, Mohd Ezane Aziz, Teoh Yuen Mey, Ramiza Ramza Ramli
ObjectiveThis study was done to determine frontal recess anatomy cell variations and its association with frontal sinusitis. The incidence of frontal recess cells in the population, the presence of frontal recess cell variations in chronic rhinosinusitis and non-chronic rhinosinusitis and the association of frontal recess cell variation in the development of frontal sinusitis were also assessed.MethodsThis was an observational, retrospective cross-sectional study of computed tomography (CT) scan of paranasal sinus that had been performed on patients in Hospital Universiti Sains Malaysia and Hospital Sultanah Bahiyah done from January 2009 until December 2016. The presence of frontal recess cells variation was compared with other populations.ResultsA total of 312 sides from 156 patients' CT scan images were analyzed. Left and right sinuses were considered individually. A total of 63 sides showed evidence of frontal sinusitis, 37 were male and 26 were female, whereas 249 sides were clear from frontal sinus disease. It was not much difference in mean age for frontal sinusitis patient (46.51±14.00) and patients without frontal sinusitis (48.73±16.44). The percentage was almost equal for CRS and non-CRS groups regardless of side and gender. In our study, the frontal recess cell such as agger nasi cell was found in almost all patients 98.1%, frontal ethmoidal cell type 1, type 2, type 3 and type 4 comprised of 28.8%, 31.1%, 14.4% and 0% respectively. Whereas, suprabullar cell can be seen in 40.3%, supraorbital ethmoid cells 16.7%, frontal bullar cell 33.0% and inter-frontal sinus septal cells 10.8%. There was a statistically significant association between the presence of frontal bullar cell and the development of frontal sinusitis (p value<0.001).ConclusionThe frontal recess cells variation in Malaysian subjects were almost similar to those reported in other Asian populations such as Japanese, Taiwanese, Chinese and Korean. Our study found that frontal bullar cells had a significant association with the development of frontal sinusitis than other frontal recess cells. The understanding of the frontal recess anatomical structures was very important as this would lead to a successful treatment of CRS and at the same time it helped the surgeon to have a better plan of endoscopic sinus surgery to prevent the disease recurrence and surgical complication.



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Internal biliary drainage for isolated posterior segmental biliary obstruction: a case report

Biliary system anatomical abnormalities can be preoperatively detected on magnetic resonance imaging; therefore, some presume that the number of bile duct injuries should decline. However, once a bile duct inj...

https://ift.tt/2kMgvR6

Platelet-Derived Growth Factor Subunit B Signaling Promotes Pericyte Migration in Response to Loud Sound in the Cochlear Stria Vascularis

Abstract

Normal blood supply to the cochlea is critical for hearing. Noise damages auditory sensory cells and has a marked effect on the microvasculature in the cochlear lateral wall. Pericytes in the stria vascularis (strial pericytes) are particularly vulnerable and sensitive to acoustic trauma. Exposure of NG2DsRedBAC transgenic mice (6–8 weeks old) to wide-band noise at a level of 120 dB for 3 h per day for 2 consecutive days produced a significant hearing threshold shift and caused pericytes to protrude and migrate from their normal endothelial attachment sites. The pericyte migration was associated with increased expression of platelet-derived growth factor beta (PDGF-BB). Blockade of PDGF-BB signaling with either imatinib, a potent PDGF-BB receptor (PDGFR) inhibitor, or APB5, a specific PDGFRβ blocker, significantly attenuated the pericyte migration from strial vessel walls. The PDGF-BB-mediated strial pericyte migration was further confirmed in an in vitro cell migration assay, as well as in an in vivo live animal model used in conjunction with confocal fluorescence microscopy. Pericyte migration took one of two different forms, here denoted protrusion and detachment. The protrusion is characterized by pericytes with a prominent triangular shape, or pericytes extending fine strands to neighboring capillaries. The detachment is characterized by pericyte detachment and movement away from vessels. We also found the sites of pericyte migration highly associated with regions of vascular leakage. In particular, under transmission electron microscopy (TEM), multiple vesicles at the sites of endothelial cells with loosely attached pericytes were observed. These data show that cochlear pericytes are markedly affected by acoustic trauma, causing them to display abnormal morphology. The effect of loud sound on pericytes is mediated by upregulation of PDGF-BB. Normal functioning pericytes are required for vascular stability.

https://ift.tt/2J9DvYL

Psychophysical Tuning Curves as a Correlate of Electrode Position in Cochlear Implant Listeners

ABSTRACT

Speech understanding abilities vary widely among cochlear implant (CI) listeners. A potential source of this variability is the electrode-neuron interface (ENI), which includes peripheral factors such as electrode position and integrity of remaining spiral ganglion neurons. Suboptimal positioning of the electrode array has been associated with poorer speech outcomes; however, postoperative computerized tomography (CT) scans are often not available to clinicians. CT-estimated electrode-to-modiolus distance (distance from the inner wall of the cochlea) has been shown to account for some variability in behavioral thresholds. However, psychophysical tuning curves (PTCs) may provide additional insight into site-specific variation in channel interaction. Thirteen unilaterally implanted adults with the Advanced Bionics HiRes90K device participated. Behavioral thresholds and PTCs were collected for all available electrodes with steered quadrupolar (sQP) configuration, using a modified threshold sweep procedure, used in Bierer et al. (Trends Hear 19:1–12, 2015). PTC bandwidths were quantified to characterize channel interaction across the electrode array, and tip shifts were assessed to identify possible contributions of neural dead regions. Broader PTC bandwidths were correlated with electrodes farther from the modiolus, but not correlated with sQP threshold, though a trend was observed. Both measures were affected by scalar location, and PTC tip shifts were observed for electrodes farther from the modiolus. sQP threshold was the only variable correlated with word recognition. These results suggest PTCs may be used as a site-specific measure of channel interaction that correlates with electrode position in some CI listeners.

https://ift.tt/2sCqKuR

Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines

Abstract

Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26^tdTomato reporter line and tamoxifen induction at 6 weeks of age. This characterization included Calbindin2^CreERT2 , Fgfr3-iCreER^T2 , GFAP-A-CreER™, GFAP-B-CreER™, GLAST-CreER^T2 , Id2^CreERT2 , Otoferlin^CreERT2 , Parvalbumin^CreERT2 , Prox1^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 . Otoferlin^CreERT2 mice had inducible Cre activity specific to hair cells. GLAST-CreER^T2 , Id2^CreERT2 , and Sox9-CreER^T2 had inducible Cre activity specific to supporting cells. Sox2^CreERT2 had inducible Cre activity in supporting cells and most type II hair cells. Parvalbumin^CreERT2 mice had small numbers of labeled vestibular nerve afferents. Calbindin2^CreERT2 mice had labeling of most type II hair cells and some type I hair cells and supporting cells. Only rare (or no) tdTomato-positive cells were detected in utricles of Fgfr3-iCreER^T2 , GFAP-A-CreER™, GFAP-B-CreER™, and Prox1^CreERT2 mice. No Cre leakiness (tdTomato expression in the absence of tamoxifen) was observed in Otoferlin^CreERT2 mice. A small degree of leakiness was seen in GLAST-CreER^T2 , Id2^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 lines. Calbindin2^CreERT2 mice had similar tdTomato expression with or without tamoxifen, indicating lack of inducible control under the conditions tested. In conclusion, 5 lines—GLAST-CreER^T2 , Id2^CreERT2 , Otoferlin^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 —showed cell-selective, inducible Cre activity with little leakiness, providing new genetic tools for researchers studying the vestibular periphery.

https://ift.tt/2kOrgCg

Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines

Abstract

Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26^tdTomato reporter line and tamoxifen induction at 6 weeks of age. This characterization included Calbindin2^CreERT2 , Fgfr3-iCreER^T2 , GFAP-A-CreER™, GFAP-B-CreER™, GLAST-CreER^T2 , Id2^CreERT2 , Otoferlin^CreERT2 , Parvalbumin^CreERT2 , Prox1^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 . Otoferlin^CreERT2 mice had inducible Cre activity specific to hair cells. GLAST-CreER^T2 , Id2^CreERT2 , and Sox9-CreER^T2 had inducible Cre activity specific to supporting cells. Sox2^CreERT2 had inducible Cre activity in supporting cells and most type II hair cells. Parvalbumin^CreERT2 mice had small numbers of labeled vestibular nerve afferents. Calbindin2^CreERT2 mice had labeling of most type II hair cells and some type I hair cells and supporting cells. Only rare (or no) tdTomato-positive cells were detected in utricles of Fgfr3-iCreER^T2 , GFAP-A-CreER™, GFAP-B-CreER™, and Prox1^CreERT2 mice. No Cre leakiness (tdTomato expression in the absence of tamoxifen) was observed in Otoferlin^CreERT2 mice. A small degree of leakiness was seen in GLAST-CreER^T2 , Id2^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 lines. Calbindin2^CreERT2 mice had similar tdTomato expression with or without tamoxifen, indicating lack of inducible control under the conditions tested. In conclusion, 5 lines—GLAST-CreER^T2 , Id2^CreERT2 , Otoferlin^CreERT2 , Sox2^CreERT2 , and Sox9-CreER^T2 —showed cell-selective, inducible Cre activity with little leakiness, providing new genetic tools for researchers studying the vestibular periphery.

https://ift.tt/2kOrgCg

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies

Abstract

The recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach's translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisting of an EGFR-specific single-domain V_HH antibody fused to a CD3-specific scFv. We generated two LiTEs with the anti-EGFR V_HH and the anti-CD3 scFv arranged in both possible orders. Both constructs were well expressed in mammalian cells as highly homogenous monomers in solution with molecular weights of 43 and 41 kDa, respectively. In situ secreted LiTEs bound the cognate antigens of both parental antibodies and triggered the specific cytolysis of EGFR-expressing cancer cells without inducing T-cell activation and cytotoxicity spontaneously or against EGFR-negative cells. Light T-cell engagers are, therefore, suitable for future applications in gene-based immunotherapy approaches.

https://ift.tt/2LUUUCm

Completely Endoscopic Approach Using a Skeeter Drill to Treat Bilateral Congenital Choanal Atresia in a 33 Week Born Pre-term Baby

Abstract

Choanal atresia (CA) is a relatively rare condition manifesting with respiratory distress. Endoscopic approaches have superseded transnasal and transpalatal approaches. We present a case of a premature baby of 1.10 kg, who developed respiratory distress and was diagnosed with bilateral CA. A nasal airway was created endoscopically using a skeeter drill.

https://ift.tt/2JaOuBc

Voice Change Following Adenotonsillectomy in Pediatric Population: Myth or Reality?—A Pilot Study

Abstract

Modifications in the structure of pharynx following adenotonsillectomy are presumed to cause changes in the voice characteristics of patients. Data on effect of tonsillectomy/adenotonsillectomy on changes in voice among Indian children are sparse. This study was thus conducted to study the effect of adenotonsillectomy/tonsillectomy on childrens' voice. It was a prospective observational study of children aged 4–15 years undergoing tonsillectomy with or without adenoidectomy. Measures of voice were noted preoperatively, 1 and 3 months post-operatively. Subjective evaluation was done using Paediatric Voice Outcome Survey (PVOS) questionnaire administered to participants' parents. Objective evaluation was done by recording and analyzing using PRAAT voice analysis software which is an open-software tool. Statistical analysis was done using the statistical software SPSS 17.0 version. There were 31 children between 4 and 14 years of age 65% being male. Adenotonsillectomy was done in 83.5%. There was statistically significant difference in the subjective scores (PVOS) pre-operatively and 3 month postoperative score (p value = 0.001). However, there was no statistically significant difference between any other pre op and post op parameters. Though the only significant post tonsillectomy voice changes noted was subjective by parents 3 months later, it does raise concern whether this could be a reality and not a myth. Further studies with larger number of patients, including involving the subjective evaluation (PVOS) by another person in addition to patients' parent need to be undertaken to address this issue.

https://ift.tt/2HjZ57f

Management of Head and Neck Hemangiomas in Adults: Oral Propranolol Versus Oral Itraconazole in Conjugation with Injection Sodium Tetra Decyl Sulphate

Abstract

Management of head and neck hemangiomas with oral propranolol versus oral itraconazole in conjugation with injection sodium tetra decyl sulphate. This prospective parallel clinical trial was done to check for the effectiveness of oral propranolol and oral itraconazole when used in conjugation with inj. sodium tetra decyl sulphate in treatment of head and neck haemangiomas in adult patients visiting department of ENT and head and neck surgery, VIMSAR, Burla. All the patients visiting the department with hemangioma (diagnosed clinically and by FNAC) were considered and only those who gave written informed consent and were according to our inclusion and exclusion criteria were included into the study as subjects. Dimension (length, width and hemi-circumference) of the haemangiomas were measured using disposable paper taper measures. Depth of the hemangioma was calculated based on formula and using that volume was calculated both at baseline and after 8 weeks of drug administration. Data so collected was entered into Microsoft Office Excel 2013 and statistical analysis was performed using SPSS Version 20.0. Descriptive statistics was calculated and student's t test (paired and unpaired) was used to compare within the group (before and after) and between the groups respectively. Statistical significance was set at p ≤ 0.05. Both the groups showed statistically significant volume reduction in the lesions [p < 0.018 (propranolo + sodium tetra decyl sulphate), p < 0.025 (itraconazole + sodium tetra decyl sulphate)]. The mean decrease in volume in propranolol group was 91.92% and that in itraconazole group was 88.97%. There was no statistical difference between the final outcome of both the groups (p < 0.766) but 3 patients on propranolol had complete resolution while 1 patient on itraconazole had complete resolution of the lesion. Oral propranolol and itraconazole are both effective and safe in hemangioma in adults. The combination with inj. sodium tetra decyl sulphate has a (1) favorable impact on decreasing the overall duration of treatment. (2) Aiding in complete resolution of lesions (especially < 3 cm). Propranolol has an edge over itraconazole (more no of tumors had complete resolution).

https://ift.tt/2J8HEMK

Tumor-derived exosomes, microRNAs, and cancer immune suppression

Abstract

Originally considered to be part of a cellular waste pathway, expansive research into exosomes has shown that these vesicles possess a vast array of functional utilities. As vital transporters of materials for communications between cells, particular interest has been generated in the ability of cancer cells to use exosomes to induce immune suppression, and to establish a thriving microenvironment, ideal for disease progression. Exosomes carry and transfer many types of cargo, including microRNAs (miRNAs; miRs), which are important modulators of messenger RNA (mRNA) expression. These miRNAs have been shown to be noteworthy components of the mechanisms used by tumor-derived exosomes to carry out their functions. Alternatively, research has been expanding into using exosomes and miRNAs as both biomarkers for detecting cancer and disease progression, and as potential treatment tools. Here, we discuss some of the progress that researchers have made related to cancer exosomes, their suppression of the immune system and the importance of the miRNAs they shuttle, along with some of the shortcomings, obstacles, and challenges that lie ahead.

https://ift.tt/2sv3yPQ

Innate lymphoid cells—key immune integrators of overall body homeostasis

Abstract

The maintenance of the tissue barrier is essential to protect the host from external pathogens, thus ensuring the survival of the organism. This process requires the integration of various physiological signals originating from the digestive, immune, endocrine, and the nervous system as indicators of overall body fitness. Innate lymphoid cells (ILC) are a group of immune cells equipped for the guarding and maintenance of the tissue barrier against invading pathogens. Extensive research has focused on the regulation of ILC by cytokines derived from immune or non-immune cells, such as the epithelium. However, recent findings suggest that ILC may play an additional role in the monitoring of the overall health status of the host. This requires the combined sensing of cytokines, metabolites, hormones, and neuropeptides. ILC appear to be essential in this process functioning as hubs for the integration of different physiological signals to facilitate barrier immunity. Here, we discuss the emerging literature revealing dietary, metabolic, hormonal, and neuronal signals as important controllers and modulators of ILC function in health and disease.

https://ift.tt/2Hig3TD

Inhaled Isoflurane for Life-Threatening Bronchospasm in Children

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


https://ift.tt/2JcG8Jp

A Comparison of Ambu® AuraGain™ Laryngeal Mask Airway and I-gel in Adult

Conditions:   Laryngeal Mask;   Intubation; Difficult or Failed
Interventions:   Device: Ambu® AuraGain™;   Device: I-gel
Sponsor:   Seoul National University Hospital
Recruiting

https://ift.tt/2JfsQYB

Safety and Efficacy of Ad-p53 in Head and Neck Cancer

Condition:   Recurrent Head and Neck Cancer
Interventions:   Drug: Ad-P53;   Drug: Opdivo
Sponsor:   MultiVir, Inc.
Recruiting

https://ift.tt/2LVDENv

Early Enteral Nutritional Supplementation on Patients With Oral Cancer Undergoing Radio(Chemo)Therapy After Surgical

Condition:   Malnutrition
Intervention:   Other: Ensure
Sponsor:   Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Recruiting

https://ift.tt/2xHiqQm

Rehabilitation Outcomes of Shoulder Function in Oral Cancer Survivors Cancer Survivors

Condition:   Oral Cancer
Interventions:   Other: motor control therapy;   Other: regular physical therapy
Sponsor:   Chang Gung Memorial Hospital
Recruiting

https://ift.tt/2LW985O

Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC)

Condition:   Esophageal Cancer
Interventions:   Drug: Nivolumab;   Radiation: Radiotherapy;   Drug: Chemotherapy;   Procedure: Surgery
Sponsors:   Oslo University Hospital;   Bristol-Myers Squibb
Recruiting

https://ift.tt/2xMkAhk

Association of severe and therapy-refractory systemic lupus erythematosus and neuromyelitis optica: a management challenge

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder. Neuromyelitis optica (NMO) is an infrequent neuroinflammatory disorder, whose association with SLE remains rare. The authors report the case of an 18-year-old woman, with SLE refractory to multiple immunosuppressive therapies and novel biological agents. Under immunosuppressive therapy, the patient presented with transverse myelitis with contiguous spinal cord lesions and urinary incontinence, having been diagnosed with seropositive NMO, which was also proven to be refractory to common treatments. Partial recovery of the neurological deficits occurred with plasmapheresis, although not averting the brain involvement by NMO that ensued. The patient was listed nationally for allogeneic bone marrow transplant, but, unfortunately, no match was found and the patient died of severe cerebral NMO flare with coma due to brain swelling and consequent respiratory failure. Although the association of SLE and NMO is very rare, early diagnosis is crucial to facilitate initiation of immunosuppressive therapy.

https://ift.tt/2JhICSV

Early effects of irradiation on laryngeal mucosa in a gastroesophageal reflux model: an experimental study

Abstract

Objective

The aim of this study was to evaluate the early histopathological changes of gastroesophageal reflux and irradiation on laryngeal mucosa in rats.

Study design

Animal study.

Setting

Experimental animal laboratory, tertiary referral center.

Subject and method

Twenty-four adult female Wistar Albino rats were grouped as: control (n = 6), reflux and irradiation (n = 10), and irradiation (n = 8). Rats were operated to create a reflux model 30 days before irradiation. Ionizing radiation was administered in a single fraction of a 20 Gy to the larynx. Laryngeal tissue samples were taken at the 4th day of irradiation and all specimens underwent histopathological examination.

Results

Edema and vascular dilation in lamina propria were higher in the reflux and irradiation, and irradiation groups than control group. Inflammation was higher in the reflux and irradiation group than the control group. Inflammation in squamous epithelium was higher in the reflux and irradiation and irradiation groups compared to the control group. Inflammation in the squamous epithelium of the irradiation group was higher than the reflux and irradiation group. In the respiratory tract epithelium, inflammation was higher in the reflux and irradiation group; additionally, a significant loss of cilia was present in the reflux and irradiation and irradiation groups while pseudostratification was higher in the reflux and irradiation group.

Conclusion

Ionizing radiation-induced inflammation may increase on previously inflammated area due to gastroesophageal reflux. Therefore, it may be helpful to investigate and treat the reflux in laryngeal cancer patients that will receive ionizing radiation.

https://ift.tt/2kKLrBd

Delayed Diagnosis of Acute Rheumatic Fever in a Patient with Multiple Emergency Department Visits

While the incidence of acute rheumatic fever (ARF) in the United States has declined over the past years, the disease remains one of the causes of severe cardiovascular morbidity in children. The index of suspicion for ARF in health care providers may be low due to decreasing incidence of the disease and clinical presentation that can mimic other conditions. We present the case of a 5-year-old boy with a history of intermittent fevers, fatigue, migratory joint pain, and weight loss following group A Streptococcus pharyngitis. The patient presented to the emergency department twice with the complaints described above. On his 3rd presentation, the workup for his symptoms revealed the diagnosis of acute rheumatic fever with severe mitral and aortic valve regurgitation. The patient was treated with penicillin G benzathine and was started on glucocorticoids for severe carditis. The patient was discharged with recommendations to continue secondary prophylaxis with penicillin G benzathine every 4 weeks for the next 10 years. This case illustrates importance of primary prevention of acute rheumatic fever with adequate antibiotic treatment of group A Streptococcus pharyngitis. Parents should also receive information and education that a child with a previous attack of ARF has higher risk for a recurrent attack of rheumatic fever. This can lead to development of severe rheumatic heart disease. Prevention of recurrent ARF requires continuous antimicrobial prophylaxis. Follow-up with a cardiologist every 1-2 years is essential to assess the heart for valve damage.

https://ift.tt/2supxq6

Atypical mandibular metastasis as the first presentation of a colorectal cancer

We describe a case of a 70-year-old man presenting with a mandibular metastasis as the first sign of a mucinous adenocarcinoma of the rectum. After 6 months of a protracted toothache, the patient presented with a palpable mandibular mass and trismus, precluding adequate clinical evaluation. A CT scan was performed, and imaging findings suggested an aggressive primary jawbone tumour, most likely an osteosarcoma. However, biopsy and further patient's management proved to be a metastasis. Metastasis to the oral cavity account for only 1%–3% of all malignant oral tumours, and the mandible is the most frequent site. Clinical presentation can be quite variable, and most often a primary malignancy is already known. Jawbone metastases are a sign of disseminated malignant neoplasms, with poor prognosis and usually an indication for palliative therapy.

https://ift.tt/2J8oYwr

Micro-fragmented adipose tissue for treatment of knee osteoarthritis with Bakers cyst: a case study

Adipose-derived therapies have increased in popularity for treatment of painful orthopaedic conditions, such as osteoarthritis. We report the passage of fat into a Baker's cyst after injection of micro-fragmented adipose tissue in a patient with bilateral knee arthritis. Following fat grafting, the patient required drainage of fatty fluid from within the Baker's cyst on multiple occasions. Approximately 3 months postprocedure, she began to notice an improvement in her knee pain with no further recurrence of pain or swelling from her Baker's cyst.

https://ift.tt/2sFg5iX

Testicular plasmacytoma misdiagnosed as orchitis

Testicular plasmacytomas are rare, accounting for only 1.3% of all extramedullary plasmacytomas. The infrequency in which it is encountered, coupled with its non-specific clinical and sonographic presentation, makes its diagnosis a challenge. We present a case of a 70-year-old man with multiple myeloma, which was systemically responding to chemotherapy, who developed testicular swelling, erythema and pain. Ultrasound findings were concerning for infection, although urine and serum testing were unremarkable. The patient did not improve after several rounds of antibiotics prompting further evaluation. The patient underwent radical orchiectomy which revealed testicular plasmacytoma. Fluorescent in situ hybridisation (FISH) of the testicular tissue noted mutations which had not been present in the FISH analysis of bone marrow. Positron emission tomography scan later revealed new retroperitoneal plasmacytomas involving the new clone and his chemotherapy regimen needed to be adjusted for treatment.

https://ift.tt/2J551GS

Management of cervical root fracture by reattachment using fibre post

Description

Tooth fractures are commonly reported emergencies in dental practise. They can vary in severity from a simple enamel fracture to complete avulsion of tooth. Among these injuries, crown-root fractures are considered to be the most common cause of tooth loss.1 They are clinically challenging cases to treat as management of such cases requires a multidisciplinary approach for complete rehabilitation. Reattachment of the tooth fragment is the most conservative and biological treatment available in case of crown-root fractures if the fractured tooth fragments are available and reported early in a clean and hydrated state.2 Reattachment can be done with the help of fibre-reinforced posts which provides increased retention of fractured crown segment and is less subjected to root fracture due to adhesive and elastic properties.3 In cases of fractures extending subgingivally, an envelope flap helps to achieve the desired isolation and visibility....

https://ift.tt/2sBzQbl

Rare paratesticular aggressive angiomyxoma with negative oestrogen and progesterone receptors in a male patient

Aggressive angiomyxoma (AAM) is a rare mesenchymal myxoid tumour localised to the pelvis and/or perineum in adult females in reproductive age group. AAM is very rare in males, with <50 cases described in literature, and involves scrotum, spermatic cord and perineum. It is slow growing, with a marked tendency for local recurrence after excision, but without metastatic potential. We present a rare case of a paratesticular AAM in a man aged 53 years. Tumour cells were immunoreactive for desmin, smooth muscle actin (SMA), vimentin, CD34 and were negative for S100. Unlike AAMs in females which express oestrogen receptor (ER) and/or progesterone receptor (PR) in >90% cases, the tumour cells in our case were negative for ER and PR, suggesting that the hypothesis that these markers play a role in tumour development and pathogenesis, does not apply in males. Androgen receptor positivity was noted in 2%–5% tumour cells.

https://ift.tt/2kLSpWv

Ciprofloxacin-induced generalised non-bullous fixed drug eruption

Ciprofloxacin, a very common antibiotic used in our day-to-day practice can cause adverse cutaneous reactions in 1–2% of patients. Photosensitivity, urticaria and maculopapular rash are the usual skin reactions. Fixed drug eruption (FDE) is an uncommon side effect of ciprofloxacin. Ciprofloxacin-induced generalised bullous FDEs have been very rarely reported in the literature. We report one such case of a young man who developed generalised non-bullous FDEs after treatment with ciprofloxacin.

https://ift.tt/2sBzO3d

Unusual presentation of primary cutaneous melanoma of the forearm with epitrochlear and axillary lymphadenopathy

In patients with primary cutaneous melanomas of the distal upper limb, metastatic involvement of the epitrochlear lymph nodes is uncommon. It belongs to a particular category of nodal metastasis termed as interval or in-transit lymphadenopathies often encountered by tumour cells as they spread from the primary sites. We describe the case of a 41-year-old woman who presented with a right forearm melanoma that was metastatic to both the epitrochlear and axillary lymph nodes. She underwent wide excision of the primary lesion as well as epitrochlear and axillary nodal clearances in the same sitting. Although uncommon, It is prudent to search for the presence of sentinel lymph nodes in the epitrochlear region although uncommon, and where positive, a completion axillary clearance should be undertaken at the same time as the epitrochlear clearance. Failure to detect the presence of interval lymph nodes along the melanoma spread pathways may be a cause of tumour recurrence.

https://ift.tt/2kKmdmz

Primary cardiac angiosarcoma: a rare cause of diffuse alveolar haemorrhage

Primary cardiac angiosarcoma is a rare disease with a dismal prognosis. We report a case of a 50-year-old man who presented with haemoptysis, cough and worsening dyspnoea. An intracardiac mass was visualised on echocardiogram. He was treated for diffuse alveolar haemorrhage and acute respiratory distress syndrome but died from refractory hypoxaemic respiratory failure leading to cardiac arrest. The diagnosis of primary cardiac angiosarcoma with haemorrhagic pulmonary metastases leading to diffuse alveolar damage was confirmed on autopsy.

https://ift.tt/2sFfU7h

Management of acute lower extremity deep venous thrombosis in a patient with duplicated inferior vena cava and contraindication to anticoagulation: case and review of the literature

Duplication of the inferior vena cava (DIVC) is an uncommon embryological anatomic phenomenon.

We report a 63-year-old woman with extensive right leg deep vein thrombosis who required an IVC filter due to contraindications for anticoagulation, but was found to have DIVC which required the placement of two IVC filters with good result. This report will review and summarise past reports of DIVC management to provide a guide for future clinicians, and review the embryological development, diagnosis and IVC filter placement options as they are based on the type of anatomic malformation encountered.

https://ift.tt/2kKzbkb

Unusual cause of pneumomediastinum

Description 

A 25-year-old man presented to the emergency department reporting a 6-hour history of progressive neck swelling associated with a single episode of chest pain. He had no significant medical history. He initially denied any illicit drug use.

On examination, the neck was visibly distended with palpable crepitus that extended to the upper torso. Cardiorespiratory examination was otherwise unremarkable. He was systemically well and routine observations were normal. The ECG showed widespread concave ST elevation suggestive of pericarditis. The chest radiograph demonstrated pneumomediastinum. A CT scan of the neck and thorax revealed widespread surgical emphysema along the thoracic wall, extending through the mediastinum, upwards into the neck involving both superficial and deep compartments (figure 1) up to the skull base (figure 2). No pneumothorax was seen. The white blood cell count was mildly raised at 17.7x10⁹/L, C reactive protein was 24 mg/L and troponin was...

https://ift.tt/2Hifzg0