Nasal Septal Spur Associated with Rhinogenic Contact Point Otalgia and Tinnitus

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0038-1660440

Rhinogenic contact point otalgia is a new term in medicine and it represents earache as a form of facial pain that is caused by intranasal mucosal contact points between the nasal septal spur or septal deviation and lateral nasal wall. It is a referred otalgia without any signs of inflammation. The author reports an unusual case of a 19-year-old male who complained of a 5-year history of right-sided otalgia and tinnitus. On physical exam, a big, right-sided nasal septal spur was seen in contact with the right lateral nasal wall. Other findings are unremarkable. Placement of anesthetic and vasoconstrictor solution provided relief of symptoms. After the exclusion of other causes of otalgia, and after surgical removal of septal spur, the patient experienced a significant relief of symptoms.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2uj1oD2

Dog Bite Injuries in the Head and Neck Region: A 20-Year Review

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0038-1660441

Dog bite–related wounds seem to have become a common problem, especially when they relate to the head and neck region. According to Overall and Love, up to 18 per 1,000 people sustain a dog bite every year, of whom 3 need medical attention. Approximately 1 to 2% of bite injuries require hospitalization of the victims. Most of the lacerations are found in the upper lip and the nose regions and they are classified according to severity and concomitant damage to other organs. Bite wounds are considered "dirty" wounds and are prone to infection. When dealing with bite wounds, there is always an indication for antibiotic treatment. Broad-spectrum antibiotics like amoxicillin-clavulanate and/or moxifloxacin cover most of the pathogenic flora and should be administered in every bite wound case at risk of infection. This article would like to present a medical record review: a retrospective analysis of all bite wounds sustained in the head and neck region, treated at the University Hospital of Leuven over the past 20 years. Furthermore, it provides an overview of the current literature and its standings on the treatment of dog bite injuries in the maxillofacial region. We assessed both surgical and medical treatment options, as well as primary management, which includes infection prevention strategies, closure management, and additional vaccination requirements. Secondary management or scar revision methods will be mentioned. After conducting a UZ Leuven database search using keywords such as "dog," "dog bite," "face," "head," "lip," and others, 223 patients were included. Age at the time of injury, location of the injury, treatment method used, and whether secondary infection was present or not were documented. All patients have been divided in age groups. We concluded that 21.52% was 5 years old or younger. Almost half of our patients (49.33%) were 18 years old or younger. Of all patients, 79 were hospitalized (35.43%). Primary closure was the treatment of choice. In 141 patients, the wounds were closed primarily (63.23%), resulting in only 2.24% reported secondary infections. Only one fatality was reported in our center over the course of 20 years (0.45%), a 6-year-old girl who had been attacked by her father's Rottweilers. Most patients who sustained dog bite injuries in the head and neck region seem to be children, specifically toddlers. Due to their height, it is possible they are more prone to dog bite injuries in the head and neck region. It is essential to optimize management of these injuries due to the impact they have on patients. This article provides the epidemiological data and clinical outcome of the approach at our center.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2m2LGbs

Outpatient Surgical Management of Orbital Blowout Fractures

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0038-1661355

There is ample investigation into the optimal timing and approach to orbital blowout fracture (OBF) repair; however, less attention has been directed toward postoperative care. This is a multicenter IRB-approved retrospective review of patients with OBF presenting to our study sites between November 2008 and August 2016. Those with isolated OBF, over 18 years of age, and who had not suffered additional facial injuries or globe trauma were included. A total of 126 surgical cases of isolated OBF repair were identified that met our inclusion and exclusion criteria; 42.1% were outpatient repairs while the remaining 57.9% were admitted for overnight monitoring. Time elapsed prior to repair differed between the two groups at a mean of 8.4 days versus 5.2 days for the outpatient and inpatient cohorts, respectively (p = 0.001). A majority of inpatient cases underwent immediate repair, while a majority of outpatient cases were delayed. There were two cases of RBH in the outpatient cohort resulting in an overall incidence of 1.6%. In both instances, a significant change in clinical exam including decreased visual acuity, diplopia, and eye pain prompted repeat evaluation and immediate intervention for hematoma evacuation. Estimated hospital charges to the patient's insurance for key components of an inpatient versus outpatient isolated OBF repair amounted to a total cost of $9,598.22 for inpatient management and $7,265.02 for outpatient management without reflexive postoperative imaging. Reflexive postoperative CT scans were obtained in 76.7% of inpatient cases and only two led to a reoperation. No outpatient repairs included reflexive postoperative imaging. Outpatient OBF repair is an attractive alternative to inpatient management.The potential cost savings of outpatient management of OBF, which do not detract from quality or safety of patient care, should not be ignored. Our results will hopefully contribute to updated shared practice patterns for all subspecialties that participate in the surgical management of OBF.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2zm048h

Craniomaxillofacial Trauma Experience in Otolaryngology Residency: A National Survey of Program Directors

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0038-1660442

This article aimed to assess the depth and volume of craniomaxillofacial (CMF) trauma exposure and education in otolaryngology residency training in the United States. This is a cross-sectional survey. A 15-question web-based survey was distributed to program directors of 106 Accreditation Council for Graduate Medical Education (ACGME)-approved otolaryngology residency programs to inquire about program size and demographics, trauma coverage, case volume, and education. Responses were collected anonymously. A total of 77 responses were received, representing 73% of residency programs. Seventy-five programs (97%) reported that their residents rotated at a level 1 trauma center, and 72 (94%) covered CMF trauma. Sixty-one programs (79%) included pediatric CMF trauma. The majority of programs (76%) allocated less than 10% of residency-dedicated didactic lecture time to CMF trauma. Residents in all programs typically logged at least 11 to 20 cases before graduation with 24% of programs averaging more than 50 cases per resident. Ninety percent of respondents described the training as "somewhat" to "very adequate." CMF coverage by the otolaryngology department, number of cases, and dedicated didactic lecture time to CMF trauma were significant factors on the perception of adequate training. The majority of program directors felt that the training in CMF trauma was adequate. Reasons for this may include that most residents rotate at level 1 trauma centers, have exposure to pediatric trauma, encounter an adequate volume of cases, and have dedicated didactic time to CMF education.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2m8bu6e

Jaw pain secondary to atypical maxillary torus near the incisive canal: A cone beam computed tomography study

Anthony Albert, Mel Mupparapu

Journal of Orofacial Sciences 2018 10(1):50-52

Pain in the anterior maxilla can be odontogenic or nonodontogenic. If it is not related to the teeth, then the differential diagnosis is based on a clinical exam, radiographic exam, and often, on advanced imaging. This case report is based on a 58-year-old male with a chief complaint of chronic pain with acute exacerbations in the region of the rugae of the maxillary central incisors. Clinical examination and planar radiography led to the suspicion of a cyst in the region of the incisive foramen. The patient was referred for advanced imaging. Cone beam computed tomography imaging confirmed the presence of an unusual tori in the region of the incisive foramen that led to periodic inflammation in the region. A differential diagnosis of the pain included pain secondary to a localized inflammation of the incisive canal and nasopalatine duct, and an inflammation of the soft tissue interdental col in the region of the central incisors as well as the benign and malignant minor salivary gland tumors. Because the rugae is attached to the palate, any expansion of the soft tissues in this region causes pain that must be diagnosed accurately to treat the cause.

https://ift.tt/2zrjqc6

In vitro visual and visible light transillumination methods for detection of natural non-cavitated approximal caries

Abstract

Objectives

The objective was to evaluate a visible-light-transillumination (using Digital Imaging Fiber-Optic Transillumination machine: DIFOTI) method using occlusal view (DIFOTI-occl), axial view (buccal and lingual: DIFOTI-axial), and combination of all views (DIFOTI-all) for detecting non-cavitated approximal caries and to compare its performance to visual examination (International Caries Detection and Assessment System: ICDAS).

Materials and methods

Thirty extracted human premolars were selected (sound to lesions into the outer one-third of the dentine) based on micro-computed tomography (μ-CT). Teeth were mounted in a custom-made device to simulate approximal contact. DIFOTI (Electro-Optical Sciences Inc., Irvington, NY, USA) images were obtained from the occlusal, buccal, and lingual views. DIFOTI image and ICDAS examinations were performed and repeated by three trained/calibrated examiners. Sensitivity, specificity, area under receiver operating characteristics curve (A_z), inter- and intra-class correlation coefficients (ICCs), and correlation were determined.

Results

Sensitivity/specificity was for DIFOTI-occl: 0.42/0.75, DIFOTI-axial: 0.86/0.93, DIFOTI-all: 0.91/0.69, and for ICDAS: 0.89/0.83. A_z for DIFOTI-occl was significantly lower than that of DIFOTI-axial (p < 0.001), DIFOTI-all (p = 0.002), and ICDAS (p = 0.005). Spearman correlation coefficients with μ-CT for DIFOTI-occl (r = 0.39) showed weak association, while DIFOTI-axial (r = 0.80), DIFOTI-all (r = 0.91), and ICDAS (r = 0.90) showed moderate association. ICCs for intra-examiner repeatability/inter-examiner agreement were for DIFOTI-occl (0.64/0.58), DIFOTI-axial (0.92/0.89), DIFOTI-all (0.85/0.83), and ICDAS (0.79/0.72).

Conclusions

The results of the current in vitro study suggest that, for detection of non-cavitated approximal caries lesions, DIFOTI performs better using axial than occlusal view.

Clinical relevance

Approximal non-cavitated caries detection is challenging. DIFOTI can observe images from occlusal-, buccal-, and lingual views. DIFOTI and visual (ICDAS) examinations of buccal- and lingual- and all-views are more suitable than those of occlusal view for a detection of non-cavitated approximal caries.

https://ift.tt/2zoSppH

The effect of incomplete crown ferrules on fracture resistance and the failure modes of endodontically treated maxillary incisors restored with cast posts, cores, and crowns

Krai Kaewtip, Boonlert Kukiattrakoon, Boonrat Sattapan, Kewalin Thammasitboon, Robert R White

Journal of Orofacial Sciences 2018 10(1):37-41

Introduction: The purpose of this study was to investigate fracture resistance and the fracture modes of endodontically treated teeth restored with cast posts and cores in the presence of various configurations of incomplete ferrules. Materials and Methods: Fifty maxillary anterior teeth were endodontically treated and divided into five groups (n = 10) according to ferrule design: group complete ferrule (CF) had a 2-mm circumferential ferrule; group buccal-mesial-palatal (BMP) had a 2-mm ferrule on the buccal, mesial, and palatal sides; group P had a 2-mm ferrule only on the palatal side; group B had a 2-mm ferrule only on the buccal side of the tooth; and group no ferrule (NF) had no ferrule. Each tooth was restored with a cast post, core, and a Ni–Cr crown. All specimens were lingually loaded at 135° to their long axis in a universal testing machine until fractured. Fracture patterns were recorded. Data were analyzed using one-way analysis of variance and Tukey's honestly significant difference (Tukeyï?½s HSD) test (α = 0.05). Results: The highest load to fracture was CF (534.33 ± 100.30 N), followed by BMP (467.71 ± 54.54 N), P (462.71 ± 54.92 N), B (330.48 ± 54.86 N), and NF (275.93 ± 28.35 N), respectively. There was no statistically significant difference in load to fracture among CF, BMP, and P and between B and NF (P > 0.05). Conclusion: A tooth with incomplete ferrule had lower fracture resistance than one with complete ferrule, but it was still higher than one with no ferrule. The presence of a palatal ferrule was more effective than a buccal ferrule in providing fracture resistance to palatal occlusal loads.

https://ift.tt/2uhgSrl

Importance of depth of invasion in patients with oral squamous cell carcinoma: A review article

Narges Ghazi, Ala Ghazi, Shahrzad Shafiee, Mahsa Fayyazi

Journal of Orofacial Sciences 2018 10(1):3-6

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Despite several diagnostic and therapeutic advances over the last decades, the rate of mortality and 5-year survival of patients with OSCC has not been improved markedly. The unpredictable behavior of squamous cell carcinoma in digestive and respiratory system has led to search the reliable parameters as prognostic predictors. Histomorphological parameters including the depth of invasion (DOI) may be used as a prognosticate factor in patients with OSCC. It is determined microscopically by detecting the deepest invasive cells in the underlying tissues. Given that planned treatment after histological examination may be changed, measuring the DOI should be considered as a part of routine histological evaluation. In this study, we attempted to review the importance of DOI in the prognosis of cancers as well as its determination in the patients with OSCC lesions.

https://ift.tt/2u8EBdR

Endodontic microsurgery − A technique for the 21st century

Frank C Setzer

Journal of Orofacial Sciences 2018 10(1):1-2



https://ift.tt/2ul7V09

Correlations between tomographic findings related to degenerative changes, condylar excursions and position, and pain symptomatology in temporomandibular disorders

Esdras F de Carvalho, Israel Chilvarquer, João Gualberto Cerqueira Luz

Journal of Orofacial Sciences 2018 10(1):7-13

Aim: This study analyzed possible correlations between tomographic findings related to degenerative changes and condylar excursions and position with pain symptomatology in temporomandibular disorders (TMD). Materials and Methods: Sixty patients (40 women and 20 men; mean age: 37.9 years) with a diagnosis of TMD, according to the Diagnostic Criteria for Temporomandibular Disorders, were evaluated. The data of their tomographic examinations were retrieved in relation to their degenerative changes, estimations of condylar excursion, and condylar position. Associations between the variables were analyzed using the chi-square test (P ≤ 0.050). Results: There was a predominance of myopain (M) (35% left side), which was followed by arthralgia plus disc displacement (ADD) (23% left side) and latter myopain plus arthralgia and disc displacement (MADD) (18% left side). Regarding the degenerative changes, there was the predominance of flattening (100%), which was followed by sclerosis (85%). The estimation of condylar excursion was more frequent in the hyperexcursion form, followed by the normoexcursion form, and the hypoexcursion form, all on both sides. The position of the condyle was predominantly posterior and less frequently anterior, and there were few cases in the equidistant position. Considering the sides independently, hyperexcursion and MADD were correlated to the left side. For the total sample, condylar hyperexcursion and ADD, and also sclerosis and MADD, were correlated. There was no correlation between condylar position and symptomatology. Conclusion: There was a correlation between hyperexcursion and symptomatology, especially articular, few correlations between degenerative changes and symptomatology, and no correlation between condylar position and symptomatology.

https://ift.tt/2u5edSm

Assessment of gingival zenith position and distance from vertical bisecting midline in the maxillary anterior dentition − An observational study

Devapriya Appukuttan, Priyanka K Cholan, Canungo Ragothaman Ashwini, Sreenivasagan Swapna

Journal of Orofacial Sciences 2018 10(1):14-18

Background: Esthetics in the maxillary anterior segment is determined by both the hard and soft tissues. Gingival contour plays a vital role in pink esthetics. The most common apical position of the marginal gingiva is referred to as gingival zenith (GZ). This study aimed to assess the position and distance of the GZ from the vertical bisecting midline (VBM) in the anterior maxillary dentition in a sample of South Indian population. Materials and Methods: A total of 105 participants were recruited based on specific inclusion and exclusion criteria. Following recruitment, alginate impressions were made, and dental cast were poured. A total of 630 anterior teeth were evaluated on the cast. The position of the GZ was marked, and a vertical line was drawn through the point. The VBM was drawn on the cast based on the crown width. Using magnification loupes (2.5×) and calibrated digital vernier caliper, the distance between the GZ and VBM was measured twice for each tooth, and the average reading was recorded. The position of GZ was recorded as mesial, distal, or coinciding with the VBM. Results: Majority of the right and left maxillary central incisors and lateral incisors were placed distal to the VBM measuring a mean distance of 0.7 ± 0.4 and 0.76 ± 0.36 mm, respectively, for centrals and 0.59 ± 0.3 and 0.62 ± 0.31 mm, respectively, for laterals. The GZ of both the right and left canines were mesial to the VBM at a mean distance of 0.59 ± 0.4 and 0.61 ± 0.3 mm, respectively. Conclusion: Familiarity with the position and distance of the GZ enables the dentist to plan an appropriate esthetic rehabilitation for the patients based on the population in question.

https://ift.tt/2u3zSdx

Assessment of the marginal fit, ceramo-metal shear bond strength and the fractographic analysis of sinter cast gold: An In-vitro study

Hetal Turakhia, Sabita M Ram, Aruna Mehta, Abhishek S Nayyar

Journal of Orofacial Sciences 2018 10(1):31-36

Introduction: The fractographic analysis is performed by observing, measuring, and interpreting the fracture surface topography that can determine many features of the microstructure of materials and the mechanics of the fracture. The aim of this study was to assess the marginal fit and the ceramo-metal shear bond strength of sinter cast gold, and to analyze the debonded sample by fractography. Materials and Methods: A total of five sinter cast gold copings were prepared on a stainless master die resembling a maxillary 1st pre-molar to receive a ceramo-metal restoration. Each of the copings was then assessed for the marginal fit before and after ceramic firing. In addition, a total of five ceramo-metal discs were fabricated for testing shear bond strength at the metal-ceramic interface. The samples were subjected to increasing shear load on a universal testing machine with crosshead speed of 0.002 mm/s. The load at which the samples debonded completely was noted, and the fractographic analysis of the samples was performed. Results: The mean marginal fit found in this study for sinter cast gold before ceramic firing was found to be 11.5 μm with a standard deviation of ±4.64 μm, and after ceramic firing, it was found to be 9.38 μm with a standard deviation of ±3.57 μm. The average shear bond strength at the sinter cast gold ceramic interface was 18.216 MPa. The fractographic analysis showed the globular microstructure of sinter cast gold on sintering, adhesive, and mix-mode type of fracture with the presence of both gold and ceramic. Conclusion: The marginal fit observed before and after ceramic firing was within clinically acceptable range, whereas the ceramo-metal shear bond strength between sinter cast gold and ceramic was found to be inadequate.

https://ift.tt/2zrjpVA

Severity and clinical consequences of untreated dental caries using PUFA index among schoolchildren in Udupi Taluk, India

Deepak K Singhal, Nishu Singla

Journal of Orofacial Sciences 2018 10(1):19-23

Background: Data on dental decay using the Decayed, Missing, Filled teeth (DMFT/dmft) index provides information on caries and treatment experiences only, but fails to give information on clinical consequences of untreated dental caries. Aim: The aim of the study was to determine the prevalence and clinical consequences of untreated dental caries using Pulp, Ulceration, Fistula, Abscess (PUFA) index among schoolchildren. Materials and Methods: A cross-sectional survey of 957 schoolchildren, aged 6–15 years in Udupi taluk was conducted. Caries experience was evaluated according to World Health Organization (WHO) criteria, 1997 (DMFT/dmft index) and clinical consequences of untreated dental caries by PUFA/pufa index. Results: The results showed that 77.3% of 6–10 years old children had caries (mean dmft score: 3.30 ± 2.9, mean DMFT score: 0.26 ± 0.7), 47.3% showed clinical consequences of untreated caries (mean pufa score: 1.30 ± 1.9, mean PUFA score: 0.03 ± 0.2) and 26.8% reported pain. In 11–15 years old children, 55.6% had caries (mean dmft score: 0.36 ± 0.9, mean DMFT score: 1.04 ± 1.4), 18% showed prevalence of pulpal involvement (mean pufa score: 0.15 ± 0.5, mean PUFA score: 0.14 ± 0.4) and 11.6% reported pain. Statistical analysis revealed a strong relation between DMFT/dmft and PUFA/pufa in both age groups. Conclusion: The present study revealed negligence in the dental treatment of children resulting in pulpal involvement. This index is a valuable measurement tool to record clinical consequences of untreated dental caries.

https://ift.tt/2u898bC

A study on the expression of CD44 adhesion molecule in oral squamous cell carcinoma and its correlation with tumor histological grading

Srilalitha Kaza, Lalith P.C Kantheti, Chandrasekhar Poosarla, Sridhar R Gontu, Kiran K Kattappagari, Venkat R.R Baddam

Journal of Orofacial Sciences 2018 10(1):42-49

Background: The increasing incidence of oral squamous cell carcinoma (OSCC) combined with its poor and unchanged prognosis motivates a need for research into the aspects of tumor biology such as the expression of adhesion molecules. Alterations in the properties of adhesion molecules could play a pivotal role in the development and progression of invasive cancer and distant metastasis. Aim: This study aims to quantify the expression of cluster of differentiation 44 (CD44) in the different grades of OSCC. Materials and Methods: Immunohistochemical staining for CD44 was performed in 10 tissue sections each of normal mucosa, well-differentiated OSCC, moderately differentiated OSCC, and poorly differentiated OSCC. CD44 positivity was analyzed quantitatively in 10 representative fields of each section under 20× magnification. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for Social Sciences software, version 20.0 (SPSS Inc., Chicago, IL, United States). Results: The mean value of the number of positive cells in controls was 745 ± 68.17, in well-differentiated OSCC was 694.2 ± 145.47, in moderately differentiated OSCC was 349 ± 78.40, and in poorly differentiated OSCC was 108.8 ± 34.39. Conclusion: The results of this study suggest an altered expression of CD44 in OSCC with weak immunostaining in poorly differentiated squamous cell carcinoma. Thus, it can be inferred that the loss of cell adhesion, correlated to the decrease of CD44 expression, might be of value in determining the progression of OSCC.

https://ift.tt/2zrlvF4

Radiation safety protocol in dentistry: A neglected practice

T. P Kumar, Rizwana Azmi, Anu Premkumar, S. Sujatha, B. K. Y Devi, N. Rakesh, V. Shwetha

Journal of Orofacial Sciences 2018 10(1):24-30

Aim: The ready availability of radiodiagnostic aids has led to its overuse in dental practice. In addition, failure to reinforce the radiation safety procedures has unknowingly resulted in the negligence of the as low as reasonably achievable (ALARA) principles among many dentists. Apart from patients, the dentists and dental assistants are being exposed to radiation in the clinics during regular practice. The current survey was designed to assess the awareness, concern, and practice of radiation protection in general dental practice. Materials and Methods: The survey consisted of 86 dentists in Bangalore city. A cross-sectional self-administered questionnaire consisting of a total of 31 items was used. The obtained data were compiled and analyzed using the Statistical Package for the Social Sciences version 20.0 software (IBM Corporation, New York, United States). Results: All the dentists responded in the study (100%); the participants had limited knowledge regarding the radiation equipment. Majority of the participants were using rounded collimator (96.5%) and short cone (61.6%). E-speed film was used by most of the dentists (90.7%). Bisecting angle technique was preferred by most of the practitioners (69.8%) for making periapical radiographs. Only 20.9% of the dentists made their patients wear lead apron during X-ray exposure. None of them were using thyroid collar. Most of the dentists practiced at a safe distance of 6 ft from the X-ray tube, whereas 10.5% of the dentists assisted holding the radiographic receptor beside the patient. Radiation monitoring was performed by only 20% of the practitioners. Conclusion: The knowledge and practice of radiation protection were not satisfactory. Repeated reinforcement in the form of continued dental education program is necessary, and, most importantly, change in the attitude of the dentist to follow ALARA should be advocated.

https://ift.tt/2u5egO2

Osteomyelitis of the mandible exhibiting features of medication-related osteonecrosis in a patient with history of tocilizumab treatment

Mohammed A Bindakhil, Muralidhar Mupparapu

Journal of Orofacial Sciences 2018 10(1):53-55

Osteomyelitis of the jaw of microbial origin manifests in bone with specific radiographic features that are key to the diagnosis. On occasion, other types of bone diseases like medication-related osteonecrosis of the jaw (MRONJ) need to be differentiated from either acute or chronic osteomyelitis. This is especially important if the medical history and physical examination are inconsistent. Apart from a thorough clinical examination, radiographic features hold an important role in the disease process which could ultimately lead to appropriate intervention. Clinician needs to be well-versed with the differential diagnosis of the bone lesions that might mimic osteomyelitis radiographically. Different medications can be attributed to osteonecrosis of the jaw (ONJ). Some monoclonal antibody medications have been attributed in the development of ONJ. Tocilizumab is a monoclonal antibody therapy used for rheumatoid arthritis. Tocilizumab-related osteonecrosis without history of bisphosphonate use has not been reported in the literature. We present a case of osteomyelitis that demonstrated similar radiographic and histological features of MRONJ in a patient treated with tocilizumab for rheumatoid arthritis without history of bisphosphonate use. Further studies are needed to assess relation between tocilizumab and ONJ.

https://ift.tt/2zp1L4M

Eighteen-year-old man with autism, obsessive compulsive disorder and a SHANK2 variant presents with severe anorexia that responds to high-dose fluoxetine

The SHANK2 gene codes for a protein involved in organising the postsynaptic density and disruptions have been associated with autism spectrum disorders (ASDs). ASDs are frequently comorbid with intellectual disability and anxiety disorders and emerging evidence suggests potentially common aetiologies. Here, we report the case of an 18-year-old man with ASD who presented with severe anorexia due to fear of food contamination, food avoidance and stereotypies attributable to underlying obsessive compulsive disorder (OCD). The patient was found to be heterozygous for c.2518C>T (p.Pro840Ser), a likely damaging coding variant in the proline rich region of SHANK2. Interestingly, the patient's disordered eating behaviour began to improve only after high-dose fluoxetine was initiated to target OCD symptoms. Overall, this case highlights the utility of molecular genetic testing in clinical psychiatry and provides an example of how genetic information can inform clinicians in the treatment of complex neuropsychiatric syndromes.

https://ift.tt/2KWIzA4

Extremely common radiographic finding of cochlear nerve deficiency among infants with prelingual single-sided deafness and its clinical implications

Publication date: Available online 10 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Woongsang Sunwoo, Won-Wook Lee, Byung Yoon Choi

Abstract

Objectives

To clarify the common radiographic findings of audiologically documented prelingual single-sided deafness (SSD) and identify the prevalence of cochlear nerve deficiency (CND) in SSD infants referred from the newborn hearing screening program.

Methods

Between March 2012 and March 2017, the records of all infants referred to our otology clinic after undergoing newborn hearing screening program were retrospectively reviewed. Twenty-four consecutive well infants without risk factors who had a confirmed diagnosis of prelingual SSD under the age of 1 year and who underwent internal auditory canal (IAC) magnetic resonance imaging (MRI) were included. The sizes of cochlear nerve (CN), IAC, and cochlear nerve canal (CNC) were measured on MRI. The presence of CND was visually determined by comparing the CN size to the ipsilateral facial nerve (FN) in the affected side via an oblique sagittal view of IAC MRI and defined when CN was absent or smaller than FN.

Results

CND was seen in all 24 deaf ears (100%) on MRI. There was one with incomplete partition type I, and another with combined cochleovestibular nerve absence. Twenty-four subjects demonstrated either an absent (20/24, 83.3%) or small (4/24, 16.7%) CN. When the absent and small CN groups were compared, the former group had a higher prevalence of narrow CNC and narrow IAC. Of the 20 infants without identifiable CN on the affected side, 17 (85%) had narrow IAC and 17 (85%) had narrow CNC. In the 20 ears with absent CN, only one had both normal-sized IAC and CNC.

Conclusion

The contribution of CND to prelingual SSD in Korean infants reached 100%, according to IAC MRI alone.

https://ift.tt/2Ja1IJL

Pediatric vestibular testing: Tolerability of test components in children

Publication date: Available online 10 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Peter J. Ciolek, Elise Kang, Julie A. Honaker, Erika A. Woodson, Brandon S. Hopkins, Samantha Anne

Abstract

Introduction

Objective of the study is to define rates of successful completion of components of pediatric vestibular testing (VT).

Methods

Retrospective review of VT performed on patients less than 18 years of age from 2004 to 2015.

Results

188 pediatric patients (mean age: 13.9 ± 3.56 years old, range 2–17 years) underwent testing. Thirty-five (18.6%) had abnormal test results. Pediatric patients unable to complete all aspects of VT could still complete an average of 7.9 ± 4.0 of 12 test components. The optokinetic tracking test was the most commonly omitted component of the vestibular tests. In a multivariate analysis, failure to perform Nylen-Barany positional testing (χ² 27.5, p < 0.0001) or Dix-Hallpike (5.66, p = 0.0174) testing was associated with inability to obtain final diagnosis on VT.

Conclusions

Interpretable VT may be obtained in most children, even in those that do not tolerate the full testing protocol. Spontaneous and gaze-evoked nystagmus testing maybe considered as part of initial testing protocol before attempting less well-tolerated components such as bithermal calorics or components that require VNG goggles.

https://ift.tt/2NCKCYt

Two novel homozygous missense mutations identified in the BSND gene in Moroccan patients with Bartter's syndrome

Publication date: Available online 10 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Soukaina Elrharchi, Zied Riahi, Sara Salime, Halima Nahili, Hassan Rouba, Mostafa Kabine, Crystel Bonnet, Christine Petit, Abdelhamid Barakat

Abstract

Objectives

Hearing loss (HL) is one of the most common sensorineural disorders. In the present study, we identified two novel missense mutations in BSND gene causing Bartter syndrome type IV which is a genetic disease with an autosomal recessive transmission, characterized by hypokalaemia, metabolic alkalosis, an elevation in plasma renin activity and hyperaldosteronism as well as sensorineural deafness.

Methods

Whole-exome sequencing was performed to study the genetic causes of Hearing loss in two unrelated patients from two Moroccan families.

Results

The two novel homozygous mutations p.Arg8Gly (c.22C > G), p.Thr36Asn (c.107C > A) in exon 1 of BSND gene which encodes barttin were identified in 7 patients belonging to two unrelated families originated from central region of Morocco.

Conclusion

We identified two novel missense mutations p.Arg8Gly and p.Thr36Asn in exon 1 of BSND gene; both mutations were described for the first time in Moroccan patients with Bartter syndrome type IV.

https://ift.tt/2J9K4pH

Decreased disulphide/thiol ratio in patients with autosomal recessive non-syndromic hearing loss

Publication date: Available online 10 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Burhan Balta, Ramazan Gundogdu, Murat Erdogan, Murat Alisik, Aslihan Kiraz, Ibrahim Ozcan, Ozcan Erel

Abstract

Introduction

Oxidative stress plays a key role in the formation of age-related, noise-induced and drug-induced hearing loss. Thiols are organic compounds which can react with free radicals to protect against tissue and cell damage caused by reactive oxygen. There are no studies in literature on the association between autosomal recessive non-syndromic hearing loss(ARNSHL) including GJB2 and non-GJB2 mutations and thiol-disulphide balance. In this study, we aim to assess whether thiol-disulphide balance is disrupted in patients with ARNSHL.

Methods

Thirty-one ARNSHL patients and thirty-one healthy controls were included in this study. Patients whose parents were first degree cousins and who had at least two congenital hearing loss in the same family were included in the study. Audiological tests included air - bone pure tone audiometry and auditory brain stem response. GJB2 gene analysis was performed using sanger sequence method. Tests of thiol/disulphide homeostasis were conducted using the automated spectrophotometric method. We first investigated whether there was a significant difference between ARNSHL patients and healthy controls. Then, in order to determine the differential effect of the GJB2 gene mutations and non-GJB2 gene mutations on the thiol-disulphide balance, subjects were divided into three groups: Group 1 included patients with GJB2 mutations; Group 2 included patients with non-GJB2 mutations; Group 3 included healthy subjects.

Results

Patients with ARNSHL had significantly higher native thiol (411.6 ± 54.3 μmol/l vs. 368.0 ± 64.3 μmol/l, p = 0.006), total thiol levels (440.3 ± 56.2 μmol/l vs. 402.4 ± 65.9 μmol/l, p = 0.018), and lower disulphide levels (14.3 ± 5.7 μmol/l) vs. (17.1 ± 4.9 μmol/l), (p = 0.043) compared to the control group. Moreover, disulphide /native thiol (p < 0.001) and disulphide/total thiol (p < 0.001) were also detected lower in the ARNSHL group compared to the control group. Thiol-disulphide hemostasis parameters between all three groups showed that the native thiol and total thiol were increased in the Group 1 and Group 2. The disulphide levels decreased in Group 1 and 2, although not statistically significant.

Conclusion

It was shown that thiol levels increased and disulphide levels decreased in patients with autosomal recessive non-syndromic hearing loss. It also may suggest that there is a reverse association between ARNSHL and oxidative stress. Further studies are needed on whether or not ARNSHL cause oxidative stress limited to the inner ear and cochlea.

https://ift.tt/2NB7IP0

Hydroxychloroquine as a novel therapeutic approach in mast cell activation diseases

Publication date: Available online 10 July 2018

Source: Clinical Immunology

Author(s): Eric Espinosa, Salvatore Valitutti, Michel Laroche, Camille Laurent, Pol André Apoil, Olivier Hermine, Michel Lavit, Carle Paul, Cristina Bulai Livideanu

Abstract

There is no therapeutic agent approved in cutaneous mastocytosis and mast cell activation syndrome. We report the efficacy of hydroxychloroquine in four patients with cutaneous mastocytosis (n = 2) and mast cell activation syndrome (n = 2).

We show that this molecule reduces the long-term survival of primary human mast cells, interferes with lysosome function and leads to the accumulation of non-functional tryptase in the mast cell granules. Furthermore, hydroxychloroquine decreases the production of pro-inflammatory mediators.

https://ift.tt/2KML9sQ

Nasenseptumplastik und Nasenmuschelbehandlung – ambulant oder stationär?

Laryngo-Rhino-Otol 2018; 97: 450-452
DOI: 10.1055/a-0621-2108

Menezes AS et al. Septal and turbinate surgery: is overnight essential? Eur Arch Otorhinolaryngol 2018; 275: 131–138 Die ambulante Operation von Nasenscheidewand und Nasenmuschel ist zunehmende Praxis. Allerdings wird dieses Thema kontrovers diskutiert. Portugiesische Kopf- und Halschirurgen überprüften anhand eigener Daten, mit welchen unerwarteten Krankenhauswiederaufnahmen und Komplikationen zu rechnen ist.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2unDUNk

Welche Behandlung wirkt beim Hörsturz am besten?

Laryngo-Rhino-Otol 2018; 97: 448-449
DOI: 10.1055/a-0621-2081

Ashtiani MK at al. Efficacy of systemic and intratympanic corticosteroid combination therapy versus intratympanic or systemic therapy in patients with idiopathic sudden sensorineural hearing loss: a randomized controlled trial. Eur Arch Otorhinolaryngol 2018; 275: 89–7 Iranische HNO-Ärzte verglichen die Heilungsraten einer Behandlung des idiopathischen Hörsturzes mit oralen und intratympanalen Kortikosteroidgaben in Mono- und Kombinationstherapien.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2m7Hsj0

Prävention von Stimmstörungen

Laryngo-Rhino-Otol 2018; 97: 453-454
DOI: 10.1055/a-0626-8754

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2ulKiV0

Schonende Operationstechnik beim Attikcholesteatom vielversprechend

Laryngo-Rhino-Otol 2018; 97: 449-450
DOI: 10.1055/a-0588-9272

Presutti L et al. The Impact of the Transcanal Endoscopic Approach and Mastoid Preservation on Recurrence of Primary Acquired Attic Cholesteatoma. Otol Neurotol 2018; 39: 445–450 Die chirurgische Behandlung eines Attikcholesteatoms ist anspruchsvoll und über eine optimale Strategie wird aktuell immer noch diskutiert. Wissenschaftler haben nun untersucht, welche Faktoren einen Einfluss auf postoperative Erkrankungen eines primär erworbenen Attikcholesteatoms haben. Die Autoren nahmen an, dass minimalinvasiv, schleimhautschonende Operationstechniken einen positiven Effekt auf die Ergebnisse in Bezug auf Rezidive haben.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2m6KPqa

„Plastische Gesichtschirurgie – Hautdefekte und Wundversorgung“

Laryngo-Rhino-Otol 2018; 97: 453-453
DOI: 10.1055/a-0625-8508

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2zqh25l

Akute Kehlkopfentzündung

Laryngo-Rhino-Otol 2018; 97: 455-456
DOI: 10.1055/a-0589-3229

Durch die akute Laryngitis wird die Stimme heiser und ist in ihrer Leistungsfähigkeit herabgesetzt. Stimmruhe ist die sicherste Methode, Folgeschäden durch weitere Belastung zu vermeiden.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2m6Xtp2

Aus der Gutachtenpraxis: Objektive Diagnostik mithilfe von Chirp-Stimuli bei stationären auditorischen Potenzialen (ASSR) in der Begutachtung von Hörstörungen

Laryngo-Rhino-Otol 2018; 97: 493-496
DOI: 10.1055/a-0589-3251

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2zqgWL1

Update Schwangerschaftsrhinitis

Laryngo-Rhino-Otol 2018; 97: 457-464
DOI: 10.1055/a-0589-3218

Als sog. Schwangerschaftsrhinitis (SSR) wird eine mehrwöchige, schwangerschaftsbegleitende nasale Obstruktion bezeichnet, die sich durch eine Schwellung der Mukosa sowie vermehrte Sekretion ohne Hinweis auf eine Entzündung, Infektion, Allergie oder Raumforderung auszeichnet und deren Symptome nach der Geburt rasch wieder verschwinden. Die SSR zählt zu den endokrinen nasalen Hyperreaktivitäten. Etwa ein Viertel aller Schwangeren ist von diesem Krankheitsbild betroffen, das zu jedem Zeitpunkt der Schwangerschaft auftreten kann. Pathophysiologisch werden vor allem hormonelle Einflüsse diskutiert, Rauchen sowie eine vorbestehende Hausstaubmilbenallergie gelten als Risikofaktoren. Nachfolgend stellen wir ein stufentherapeutisches Konzept für die Behandlung der SSR vor und diskutieren die aktuelle Literatur.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2m3aKiq

Otitis media – Definition, Pathogenese, Klinik, Diagnose und Therapie

Laryngo-Rhino-Otol 2018; 97: 497-508
DOI: 10.1055/s-0044-101327

Unter dem Begriff Otitis media werden die akute Otitis media, die rezidivierende akute Otitis media, die Otitis media mit Erguss, die chronische Otitis media mesotympanalis und die chronische Otitis media epitympanalis, das Cholesteatom, zusammengefasst. Es handelt sich um vielfältige Krankheitsbilder, die teils ineinander übergehen können und eine individuell angepasste, zielgerichtete Therapie erfordern.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2zqgP23

Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2018; 97: 509-510
DOI: 10.1055/a-0589-3262

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2maIcUB

Rhinoplastik

Laryngo-Rhino-Otol 2018; 97: 511-513
DOI: 10.1055/a-0589-3316

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2zoJep5

Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2018; 97: 444-445
DOI: 10.1055/a-0589-3196

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2m8TAzX

Contributors

SUJANA S. CHANDRASEKHAR, MD

https://ift.tt/2NF2WAe

Contents

Sujana S. Chandrasekhar

https://ift.tt/2L6ELJ5

Forthcoming Issues

Nasal Obstruction

https://ift.tt/2NF2O3I

CME Accreditation Page

https://ift.tt/2J9AliP

Age-Related Deficits in Taste and Smell

Disturbances in both the ability to smell and to taste are common in older persons. Such disturbances influence nutrition, safety, quality of life, and psychological and physical health. The anatomic and physiologic causes of age-related disturbances are multiple and interacting, and depend on genetic and environmental factors. Frank losses of function, distortions, and hallucinations are common. Most distortions resolve over time, although this can take months or even years. Olfactory dysfunction occurs during the earliest stages of several neurologic disorders, most notably Alzheimer's disease and Parkinson's disease, likely heralding the onset of the underlying pathologies.

https://ift.tt/2NCMvEt

Copyright

ELSEVIER

https://ift.tt/2L6EK7Z

Geriatric Otolaryngology

According to the US census publications, the US population is expected to grow by 27% between 2012 and 2050, which would be an increase from 314 million to 400 million. About 80 million in the US are expected to be over 65 years old. The projection of increased elderly population is due to several factors: increase in life expectancy, decrease in mortality, and decrease in fertility. As such, the recognition of the geriatric patient with otolaryngologic problems will present some unique challenges.

https://ift.tt/2NBCCah

Geriatric Otolaryngology

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

https://ift.tt/2J7YGpv

Ability of two single-step restorative materials to avoid crown darkening caused by intracanal minocycline paste

Abstract

Objectives

This study aimed to quantitatively assess the ability of two single-step restorative materials to avoid crown darkening caused by the use of minocycline as an intracanal medicament.

Materials and methods

After coronal access and instrumentation, 120 maxillary incisors were divided into four groups (n = 30). Two experimental groups according to the restorative material applied to the inner walls of the access cavity: OB, OptiBond All-In-One + minocycline intracanal paste; U200, RelyX U200 + minocycline intracanal paste. Two control groups without restorative materials: MIN, minocycline intracanal paste and SL, saline intracanal. Color determination was performed using a spectrophotometer at five time points, immediately after materials were applied (baseline), and at 7, 14, 21, and 28 days from the baseline.

Results

Decrease in the mean values of L* (luminosity) was observed after insertion of minocycline paste in all groups at all time points. Statistically significant differences were absent between the time points (P > .05). After 28 days, MIN showed significantly more darkening (ΔL*) (− 10.6 ± 7.3) than OB (− 5.4 ± 6.2), U200 (− 5.8 ± 3.9) and SL (− 2.3 ± 1.2) (P < .05).

Conclusions

Crown darkening can be minimized by the previous application of RelyX U200 or OptiBond All-In-One to the inner walls of the access cavity before a minocycline-containing paste is applied as an intracanal medication.

Clinical relevance

The American Association of Endodontists Clinical Considerations for Regenerative Procedures in necrotic immature teeth suggests the triple antibiotic paste as an intracanal medication (2018). However, discoloration and crown darkening are common unfavorable outcomes. The clinical protocol suggested in this paper has shown to be able to minimize crown darkening, predictably leading to a better patient-centered clinical success.

https://ift.tt/2L4tf11

Management of deep carious lesions and pulps exposed during carious tissue removal in adults: a questionnaire study among dentists in Finland

Abstract

Objectives

To find out which management methods are preferred by dentists in Finland for a deep carious lesion or a pulp exposed during carious tissue removal in adult patients.

Materials and methods

An electronic questionnaire consisting of 25 questions was sent to 1000 randomly sampled dentists in Finland. The response rate was 32%.

Results

Less invasive excavation strategies (stepwise or selective removal) were preferred by 64% for an asymptomatic deep lesion, while 34% chose nonselective removal to hard dentine. In the presence of an asymptomatic pulpal exposure, vital pulp therapy was preferred, as 71% of the respondents chose direct pulp capping (DPC) or partial pulpotomy, compared to root canal treatment (26%). Mineral trioxide aggregate (MTA) and calcium hydroxide-based materials were both chosen by 40% for vital pulp therapy. In the management of a deep carious lesion, less invasive excavation strategies were significantly associated with having clinical guidelines vs. no guidelines at the practice [odds ratio (OR) 3.5, confidence interval (CI) 1.4–9.0]. MTA was favored over other DPC materials significantly more often by those who had attended continuing education courses during the last 3 years (OR 2.8, CI 1.2–6.5).

Conclusions

Less invasive management strategies have been adopted into clinical practice by the majority of dentists in Finland. There is a need to encourage the use of MTA in the case of a pulpal exposure.

Clinical relevance

The results of this study can be utilized in continuing education, to raise awareness of management strategies supported by present scientific evidence.

https://ift.tt/2NCBymc

Severity strata for POEM, PO-SCORAD and DLQI in US adults with atopic dermatitis

Patient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms, yet severity strata are not established.

https://ift.tt/2L01Jlc

Effect of chitosan nanoparticles on the inhibition of Candida spp. biofilm on denture base surface

Publication date: Available online 9 July 2018

Source: Archives of Oral Biology

Author(s): Brenna Louise Cavalcanti Gondim, Lúcio Roberto Cançado Castellano, Ricardo Dias de Castro, Giovanna Machado, Hugo Lemes Carlo, Ana Maria Gondim Valença, Fabíola Galbiatti de Carvalho

Abstract

Objectives

Chitosan nanoparticles (ChNPs) have antifungal effects, however there is a lack of information about the effects of ChNPs against Candida biofilm on denture base surface. This study investigated the ChNPs effect against C. albicans biofilm adhesion and formation, and against Candida spp. biofilm on heat-cured acrylic resin.

Design

The ChNPs were synthetized (3,800 µg/mL) and characterized by infra-red spectrophotometry and transmission electron microscopy. The minimum inhibitory/fungicidal concentrations (MIC/MFC) against Candida spp. were determined. The time-kill assay and changes on C. albicans micromorphology were evaluated. The % inhibition of ChNPs on C. albicans biofilm formation and reduction were investigated using 1 min and 8 h exposure. Candida biofilm was developed on resin surfaces and ChNPs were applied every 8 h for 5 days. After, fungal cells were counted (CFU/mL) and the surface roughness (Ra) and vickers microhardness (HV) of resin were analysed. For all experiments, sodium hypochlorite (NaOCl) was used as control. Data were analyzed by ANOVA, Tukey and paired t-tests (α = 0.05).

Results

The MIC_80% of ChNPs was 30.1 µg/mL. ChNPs at 4 MIC showed complete inhibition in the time-kill assays. Blastoconidia cells were predominant after ChNPs application. The % inhibition ChNPs on C. albicans was proportional to its concentration, regardless of the exposure time. ChNPs decreased the CFU/mL of Candida spp. and showed lower alteration of HV and Ra values of resin surface compared to NaOCl.

Conclusions

The ChNPs inhibited C. albicans biofilm, reduced Candida biofilm on resin and caused small changes in roughness and hardness of acrylic resin surface.

Graphical abstract

https://ift.tt/2N0Y1Z6

Severity strata for POEM, PO-SCORAD and DLQI in US adults with atopic dermatitis

Publication date: Available online 9 July 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): JI Silverberg, JM Gelfand, D Margolis, L Fonacier, M Boguniewicz, LB Schwartz, EL Simpson, M Grayson, PY Ong, ZC Chiesa Fuxench

Abstract

Background

Patient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms, yet severity strata are not established.

Objective

We sought to confirm previously developed strata for POEM and DLQI, and develop strata for the PO-SCORAD in a population-based cohort of adults with AD.

Methods

A cross-sectional, population-based study of 8,217 adults was performed using a structured questionnaire. A diagnosis of AD was determined using modified UK Diagnostic Criteria for AD (N=602). AD severity was assessed using self-reported global AD severity (anchoring question), POEM, PO-SCORAD, and DLQI. Strata were selected using an anchoring approach based on patient-reported disease severity.

Results

We confirmed the existing strata for DLQI (mild=0-5, moderate=6-10, severe=11-30) (kappa=0.446). However, the preferred strata for POEM was mild=0-7, moderate=8-19 and severe=20-28 (kappa=0.409) and PO-SCORAD was mild=1-27, moderate=28-56, severe=57-104 (kappa=0.444).

Conclusion

Existing strata for DLQI performed well in a population-based cohort of adult AD. The optimal severity strata for the POEM in our AD population varies slightly from those previously published for AD. This may suggest that different strata may be optimal in different study settings and cohorts. Finally, we proposed new strata for PO-SCORAD in adult AD.

https://ift.tt/2zqQGA8

Effect of chitosan nanoparticles on the inhibition of Candida spp. biofilm on denture base surface

Publication date: Available online 9 July 2018

Source: Archives of Oral Biology

Author(s): Brenna Louise Cavalcanti Gondim, Lúcio Roberto Cançado Castellano, Ricardo Dias de Castro, Giovanna Machado, Hugo Lemes Carlo, Ana Maria Gondim Valença, Fabíola Galbiatti de Carvalho

Abstract

Objectives

Chitosan nanoparticles (ChNPs) have antifungal effects, however there is a lack of information about the effects of ChNPs against Candida biofilm on denture base surface. This study investigated the ChNPs effect against C. albicans biofilm adhesion and formation, and against Candida spp. biofilm on heat-cured acrylic resin.

Design

The ChNPs were synthetized (3,800 µg/mL) and characterized by infra-red spectrophotometry and transmission electron microscopy. The minimum inhibitory/fungicidal concentrations (MIC/MFC) against Candida spp. were determined. The time-kill assay and changes on C. albicans micromorphology were evaluated. The % inhibition of ChNPs on C. albicans biofilm formation and reduction were investigated using 1 min and 8 h exposure. Candida biofilm was developed on resin surfaces and ChNPs were applied every 8 h for 5 days. After, fungal cells were counted (CFU/mL) and the surface roughness (Ra) and vickers microhardness (HV) of resin were analysed. For all experiments, sodium hypochlorite (NaOCl) was used as control. Data were analyzed by ANOVA, Tukey and paired t-tests (α = 0.05).

Results

The MIC_80% of ChNPs was 30.1 µg/mL. ChNPs at 4 MIC showed complete inhibition in the time-kill assays. Blastoconidia cells were predominant after ChNPs application. The % inhibition ChNPs on C. albicans was proportional to its concentration, regardless of the exposure time. ChNPs decreased the CFU/mL of Candida spp. and showed lower alteration of HV and Ra values of resin surface compared to NaOCl.

Conclusions

The ChNPs inhibited C. albicans biofilm, reduced Candida biofilm on resin and caused small changes in roughness and hardness of acrylic resin surface.

Graphical abstract

https://ift.tt/2N0Y1Z6

Antiandrogen therapy with spironolactone for the treatment of hidradenitis suppurativa

Antiandrogen therapy has been reported as an effective treatment for hidradenitis suppurativa. This study evaluated both physician and patient reported hidradenitis suppurativa severity outcomes for patients treated with spironolactone. Antiandrogen therapy with spironolactone may be a useful treatment option for reducing inflammatory lesions and pain for female patients with HS.

https://ift.tt/2m8AhXI

Surgical Pearl: A Granny Sliding Knot for High Tension Closures

https://ift.tt/2zvqkgG

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 Phase 3 Randomized Controlled Trials

Current treatment options for hyperhidrosis are limited. The topical anticholinergic, glycopyrronium tosylate, results in significant reductions in sweating severity/production and favorable tolerability in two phase 3, randomized, vehicle-controlled trials in primary axillary hyperhidrosis. These results suggest glycopyrronium tosylate may provide a non-invasive, once-daily, topical treatment option for primary axillary hyperhidrosis.

https://ift.tt/2m4G0xC

Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta-Analysis

Sonic hedgehog inhibitors are systemic treatments for locally advanced and metastatic basal cell carcinomas. In locally advanced disease, overall response rate is similarly significant for sonidegib and vismodegib; complete response rate is significant for vismodegib only. Rates of major side effects do not differ between vismodegib and sonidegib. Patients should expect partial responses in locally advanced disease.

https://ift.tt/2uikclN

Ustekinumab treatment for neutrophilic dermatoses associated with Crohn’s disease: a multicenter-retrospective study

https://ift.tt/2m8A86C

Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-analysis

Although intralesional immunotherapy is commonly used for wart treatment, selection among existing immunotherapeutic modalities remains challenging. PPD and MMR are the most effective modalities for lesion clearance at primary and distant sites (along with autoinoculation), and also reduce recurrence. PPD and MMR may be considered as first-line treatments for warts.

https://ift.tt/2zvpXCO

Methotrexate for alopecia areata: a systematic review and meta-analysis

There is lack of synthesised data regarding methotrexate in AA, Good response was observed in 63% of patients and complete response in 36% of patients, Initial regrowth is observed after 3 months of treatment and takes 6-12 months to achieve complete regrowth, The pooled recurrence rate of AA was 47.7%

https://ift.tt/2m7BFda

The ALT-70 Predictive Model Outperforms Thermal Imaging for the Diagnosis of Lower Extremity Cellulitis: A Prospective Evaluation

Point-of-care diagnostic tools may decrease misdiagnosis rates and unnecessary care associated with lower extremity cellulitis. In our prospective study, the ALT-70 predictive model for lower extremity cellulitis outperformed thermal imaging in diagnostic accuracy. The high negative predictive value of ALT-70 effectively allows clinicians to rule out lower extremity cellulitis.

https://ift.tt/2zvpS1Y

Pigmentation of basal cell carcinoma is inversely associated with tumor aggressiveness in Asian patients

https://ift.tt/2m8zOoq

Drug-Induced Phototoxicity: A Systematic Review

Numerous oral drugs are implicated in phototoxicity; however, the level of evidence for most has not been assessed. Vemurafenib, NSAIDs, and antibiotics (fluoroquinolones, tetracyclines) have strongest evidence for phototoxicity. Most associations are not supported by robust evidence. Improved documentation of phototoxicity testing is required before labelling oral drugs as phototoxic.

https://ift.tt/2uj4K9g

“Comparing the eighth and the seventh editions of the ajcc staging system and the brigham and women’s hospital alternative staging system for cutaneous squamous cell carcinoma: implications for clinical practice”

The new 8th edition of the American Joint Committee on Cancer (AJCC) staging system incorporates changes regarding cutaneous squamous cell carcinoma (CSCC).

https://ift.tt/2m8zIgy

Mohs micrographic surgery (MMS) with MART-1 immunostaining for atypical intraepidermal melanocytic proliferation (AIMP)

Surgical outcomes for AIMP are unknown. Upstaging to unequivocal melanoma was identified in 18.8% of AIMP. No local recurrences occurred with a mean follow-up of 2.7 years. 23.8% of AIMP required greater than one stage of MMS. MMS may be an effective treatment option for AIMP.

https://ift.tt/2uihNrm

Beyond JAAD - October 2018

https://ift.tt/2m3BL5n

Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis [TUMOR IMMUNOLOGY]

Naive T cells are thought to be functionally quiescent. In this study, we studied and compared the phenotype, cytokine profile, and potential function of human naive CD4⁺ T cells in umbilical cord and peripheral blood. We found that naive CD4⁺ T cells, but not memory T cells, expressed high levels of chemokine CXCL8. CXCL8⁺ naive T cells were preferentially enriched CD31⁺ T cells and did not express T cell activation markers or typical Th effector cytokines, including IFN-, IL-4, IL-17, and IL-22. In addition, upon activation, naive T cells retained high levels of CXCL8 expression. Furthermore, we showed that naive T cell–derived CXCL8 mediated neutrophil migration in the in vitro migration assay, supported tumor sphere formation, and promoted tumor growth in an in vivo human xenograft model. Thus, human naive T cells are phenotypically and functionally heterogeneous and can carry out active functions in immune responses.

https://ift.tt/2uhLsAV

Early Generated B-1-Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma-like Neoplasia in Aged Mice [TUMOR IMMUNOLOGY]

In mice, fetal/neonatal B-1 cell development generates murine CD5⁺ B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a V_H11/D/J_H knock-in mouse line (V_H11t) that generates an autoreactive antiphosphatidylcholine BCR. Our study revealed that antiphosphatidylcholine B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN), and body cavity as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel, and blood. The body cavity–deposited B1a cells also remigrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an antithymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Eμ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgM^hiIgD^loCD5⁺CD23^–CD43⁺ cells, resembling aggressive human mantle cell lymphoma. Thus, our findings reveal that early generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and mantle cell lymphoma–like neoplasia in aged mice.

https://ift.tt/2m2NEZg

PD-1 Blockade Unleashes Effector Potential of Both High- and Low-Affinity Tumor-Infiltrating T Cells [TUMOR IMMUNOLOGY]

Antitumor T cell responses involve CD8⁺ T cells with high affinity for mutated self-antigen and low affinity for nonmutated tumor-associated Ag. Because of the highly individual nature of nonsynonymous somatic mutations in tumors, however, immunotherapy relies often on an effective engagement of low-affinity T cells. In this study, we studied the role of T cell affinity during peripheral priming with single-peptide vaccines and during the effector phase in the tumor. To that end, we compared the antitumor responses after OVA_257–264 (N4) peptide vaccination of CD8⁺ T cells carrying TCRs with high (OT-1) and low (OT-3) avidity for the N4 peptide in B16.N4 tumor-bearing C57BL/6 mice. Additionally, we assessed the response of OT-1 cells to either high-affinity (B16.N4) or low-affinity (B16.T4) Ag-expressing tumors after high-affinity (N4) or low-affinity (T4) peptide vaccination. We noticed that although low-affinity tumor-specific T cells expand less than high-affinity T cells, they express lower levels of inhibitory receptors and produce more cytokines. Interestingly, tumor-infiltrating CD8⁺ T cells show similar in vivo re-expansion capacity to their counterparts in secondary lymphoid organs when transferred to tumor-free hosts, suggesting that T cells in tumors may be rekindled upon relief of tumor immunosuppression. Moreover, our results show that αPD-1 treatment enhances tumor control of high- and low-affinity ligand-expressing tumors, suggesting that combination of high-affinity peripheral priming by altered peptide ligands and checkpoint blockade may enable tumor control upon low-affinity Ag recognition in the tumor.

https://ift.tt/2uhLt7X

A2A Adenosine Receptor Gene Deletion or Synthetic A2A Antagonist Liberate Tumor-Reactive CD8+ T Cells from Tumor-Induced Immunosuppression [TUMOR IMMUNOLOGY]

Tumor hypoxia–driven accumulation of extracellular adenosine was shown to facilitate tumor evasion by engaging the immunosuppressive, intracellular cAMP-elevating A₂ adenosine receptors (A₂R) on tumor-reactive effector T cells, but there remains a need for careful evaluation of the limiting factors and properties of A₂R blockade–enabled antitumor immunity. In studies of A_2AR and/or A_2BR gene–deficient mice, we found that A_2AR deletion—but not A_2BR deletion—liberates endogenous CD8⁺ T cell antitumor immunity against weakly immunogenic MCA205 sarcomas. Studies of adoptively transferred A_2AR^–/–, A_2BR^–/–, or A_2AR^–/–/A_2BR^–/– tumor-reactive T cells confirmed that immunosuppression in the tumor microenvironment was mediated by A_2AR on CD8⁺ T cells. Treatment with A_2AR antagonist mimicked A_2AR gene deletion in adoptive T cell immunotherapy. This therapeutic benefit of targeting A_2AR was independent of the anatomical location of tumor growth. The enhanced antitumor reactivity also led to the eradication of established intracranial tumors, which was associated with mouse survival and the maintenance of long-lasting, tumor-specific immunological memory. The blockade of the A_2AR on adoptively transferred T cells by synthetic A_2AR antagonist led to higher levels of IFN- secretion by tumor-infiltrating CD8⁺ T cells. These data clarify the mechanism of hypoxia-driven immunosuppression in the tumor microenvironment by A_2AR on tumor-reactive CD8⁺ T cells and show that selective A_2AR antagonists can be effective in improving the outcomes of T cell–based immunotherapies. Demonstration of the T cell dose dependency of tumor rejection points to a major limitation of current cancer immunotherapies, in which the presence of sufficient numbers of tumor-reactive T cells in a patient is not known.

https://ift.tt/2m8ubGO

Leukocyte-Associated Ig-like Receptor 1 Inhibits Th1 Responses but Is Required for Natural and Induced Monocyte-Dependent Th17 Responses [TRANSPLANTATION]

Leukocyte-associated Ig-like receptor 1 (LAIR1) is an ITIM-bearing collagen receptor expressed by leukocytes and is implicated in immune suppression. However, using a divalent soluble LAIR1/Fc recombinant protein to block interaction of cell surface LAIR1 with matrix collagen, we found that whereas T_h1 responses were enhanced as predicted, T_h17 responses were strongly inhibited. Indeed, LAIR1 on both T cells and monocytes was required for optimal T_h17 responses to collagen type (Col)V. For pre-existing "natural" T_h17 response to ColV, the LAIR1 requirement was absolute, whereas adaptive T_h17 and T_h1/17 immune responses in both mice and humans were profoundly reduced in the absence of LAIR1. Furthermore, the addition of C1q, a natural LAIR1 ligand, decreased T_h1 responses in a dose-dependent manner, but it had no effect on T_h17 responses. In IL-17–dependent murine organ transplant models of chronic rejection, LAIR1^+/+ but not LAIR1^–/– littermates mounted strong fibroproliferative responses. Surface LAIR1 expression was higher on human T_h17 cells as compared with T_h1 cells, ruling out a receptor deficiency that could account for the differences. We conclude that LAIR1 ligation by its natural ligands favors T_h17 cell development, allowing for preferential activity of these cells in collagen-rich environments. The emergence of cryptic self-antigens such as the LAIR1 ligand ColV during ischemia/reperfusion injury and early acute rejection, as well as the tendency of macrophages/monocytes to accumulate in the allograft during chronic rejection, favors T_h17 over T_h1 development, posing a risk to long-term graft survival.

https://ift.tt/2ujzuH0

Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression [SYSTEMS IMMUNOLOGY]

Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. The transcription factor Ikaros has been shown to play a critical role in lymphoid cell development and differentiation; however, its function in myeloid cells and innate immune responses is less appreciated. Using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility, we describe unexpected dual repressor and activator functions for Ikaros in the LPS response of murine macrophages. Consistent with the described function of Ikaros as transcriptional repressor, Ikzf1^–/– macrophages showed enhanced induction for select responses. In contrast, we observed a dramatic defect in expression of many delayed LPS response genes, and chromatin immunoprecipitation sequencing analyses support a key role for Ikaros in sustained NF-B chromatin binding. Decreased Ikaros expression in Ikzf1^+/– mice and human cells dampens these Ikaros-enhanced inflammatory responses, highlighting the importance of quantitative control of Ikaros protein level for its activator function. In the absence of Ikaros, a constitutively open chromatin state was coincident with dysregulation of LPS-induced chromatin remodeling, gene expression, and cytokine responses. Together, our data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge.

https://ift.tt/2m7bdjW

Epithelial IL-15 Is a Critical Regulator of {gamma}{delta} Intraepithelial Lymphocyte Motility within the Intestinal Mucosa [MUCOSAL IMMUNOLOGY]

Intraepithelial lymphocytes (IELs) expressing the TCR ( IELs) provide continuous surveillance of the intestinal epithelium. However, the mechanisms regulating the basal motility of these cells within the epithelial compartment have not been well defined. We investigated whether IL-15 contributes to IEL localization and migratory behavior in addition to its role in IEL differentiation and survival. Using advanced live cell imaging techniques in mice, we find that compartmentalized overexpression of IL-15 in the lamina propria shifts the distribution of T cells from the epithelial compartment to the lamina propria. This mislocalization could be rescued by epithelial IL-15 overexpression, indicating that epithelial IL-15 is essential for IEL migration into the epithelium. Furthermore, in vitro analyses demonstrated that exogenous IL-15 stimulates IEL migration into cultured epithelial monolayers, and inhibition of IL-2Rβ significantly attenuates the basal motility of these cells. Intravital microscopy showed that impaired IL-2Rβ signaling induced IEL idling within the lateral intercellular space, which resulted in increased early pathogen invasion. Similarly, the redistribution of T cells to the lamina propria due to local IL-15 overproduction also enhanced bacterial translocation. These findings thus reveal a novel role for IL-15 in mediating T cell localization within the intestinal mucosa and regulating IEL motility and patrolling behavior as a critical component of host defense.

https://ift.tt/2uhLvg5

Mucosal Immunity in the Female Murine Mammary Gland [MUCOSAL IMMUNOLOGY]

The mammary gland is not classically considered a mucosal organ, although it exhibits some features common to mucosal tissues. Notably, the mammary epithelium is contiguous with the external environment, is exposed to bacteria during lactation, and displays antimicrobial features. Nonetheless, immunological hallmarks predictive of mucosal function have not been demonstrated in the mammary gland, including immune tolerance to foreign Ags under homeostasis. This inquiry is important, as mucosal immunity in the mammary gland may assure infant and women's health during lactation. Further, such mucosal immune programs may protect mammary function at the expense of breast cancer promotion via decreased immune surveillance. In this study, using murine models, we evaluated mammary specific mucosal attributes focusing on two reproductive states at increased risk for foreign and self-antigen exposure: lactation and weaning-induced involution. We find a baseline mucosal program of RORT⁺ CD4⁺ T cells that is elevated within lactating and involuting mammary glands and is extended during involution to include tolerogenic dendritic cell phenotypes, barrier-supportive antimicrobials, and immunosuppressive Foxp3⁺ CD4⁺ T cells. Further, we demonstrate suppression of Ag-dependent CD4⁺ T cell activation, data consistent with immune tolerance. We also find Ag-independent accumulation of memory RORT⁺ Foxp3⁺ CD4⁺ T cells specifically within the involution mammary gland consistent with an active immune process. Overall, these data elucidate strong mucosal immune programs within lactating and involuting mammary glands. Our findings support the classification of the mammary gland as a temporal mucosal organ and open new avenues for exploration into breast pathologic conditions, including compromised lactation and breast cancer.

https://ift.tt/2m4zvuI

Bcl2L12 Contributes to Th2-Biased Inflammation in the Intestinal Mucosa by Regulating CD4+ T Cell Activities [MUCOSAL IMMUNOLOGY]

The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4⁺ T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4⁺ T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4⁺ T cells from UC patients. Naive CD4⁺ T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the Il4 promoter to enhance the expression of IL-4 in CD4⁺ T cells. CD4⁺ T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation.

https://ift.tt/2zqsA8K

Evidence for the Existence of a CXCL17 Receptor Distinct from GPR35 [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

The chemokine CXCL17 is associated with the innate response in mucosal tissues but is poorly characterized. Similarly, the G protein–coupled receptor GPR35, expressed by monocytes and mast cells, has been implicated in the immune response, although its precise role is ill-defined. A recent manuscript reported that GPR35 was able to signal in response to CXCL17, which we set out to confirm in this study. GPR35 was readily expressed using transfection systems but failed to signal in response to CXCL17 in assays of β-arrestin recruitment, inositol phosphate production, calcium flux, and receptor endocytosis. Similarly, in chemotaxis assays, GPR35 did not confirm sensitivity to a range of CXCL17 concentrations above that observed in the parental cell line. We subsequently employed a real time chemotaxis assay (TAXIScan) to investigate the migratory responses of human monocytes and the monocytic cell line THP-1 to a gradient of CXCL17. Freshly isolated human monocytes displayed no obvious migration to CXCL17. Resting THP-1 cells showed a trend toward directional migration along a CXCL17 gradient, which was significantly enhanced by overnight incubation with PGE₂. However, pretreatment of PGE₂-treated THP-1 cells with the well-characterized GPR35 antagonist ML145 did not significantly impair their migratory responses to CXCL17 gradient. CXCL17 was susceptible to cleavage with chymase, although this had little effect its ability to recruit THP-1 cells. We therefore conclude that GPR35 is unlikely to be a bona fide receptor for CXCL17 and that THP-1 cells express an as yet unidentified receptor for CXCL17.

https://ift.tt/2m6OeW9

C2 Domains of Munc13-4 Are Crucial for Ca2+-Dependent Degranulation and Cytotoxicity in NK Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

In the immune system, degranulation/exocytosis from lymphocytes is crucial for life through facilitating eradication of infected and malignant cells. Dysfunction of the NK cell exocytosis process has been implicated with devastating immune diseases, such as familial hemophagocytic lymphohistiocytosis, yet the underlying molecular mechanisms of such processes have remained elusive. In particular, although the lytic granule exocytosis from NK cells is strictly Ca²⁺-dependent, the molecular identity of the Ca²⁺ sensor has yet to be identified. In this article, we show multiple lines of evidence in which point mutations in aspartic acid residues in both C2 domains of human Munc13-4, whose mutation underlies familial hemophagocytic lymphohistiocytosis type 3, diminished exocytosis with dramatically altered Ca²⁺ sensitivity in both mouse primary NK cells as well as rat mast cell lines. Furthermore, these mutations within the C2 domains severely impaired NK cell cytotoxicity against malignant cells. Total internal reflection fluorescence microscopy analysis revealed that the mutations strikingly altered Ca²⁺ dependence of fusion pore opening of each single granule and frequency of fusion events. Our results demonstrate that both C2 domains of Munc13-4 play critical roles in Ca²⁺-dependent exocytosis and cytotoxicity by regulating single-granule membrane fusion dynamics in immune cells.

https://ift.tt/2uhLvN7

Opposing Effects of IL-1Ra and IL-36Ra on Innate Immune Response to Pseudomonas aeruginosa Infection in C57BL/6 Mouse Corneas [INNATE IMMUNITY AND INFLAMMATION]

Pseudomonas aeruginosa keratitis is characterized by severe corneal ulceration and may lead to blindness if not treated properly in a timely manner. Although the roles of the IL-1 subfamily of cytokines are well established, as a newly discovered subfamily, IL-36 cytokine regulation, immunological relevance, and relation with IL-1 cytokines in host defense remain largely unknown. In this study, we showed that P. aeruginosa infection induces the expression of IL-36α and IL-36, as well as IL-1β and secreted IL-1Ra (sIL-1Ra), but not IL-36Ra. Downregulation of IL-1Ra increases, whereas downregulation of IL-36Ra decreases the severity of P. aeruginosa keratitis. IL-1R and IL-36Ra downregulation have opposing effects on the expression of IL-1β, sIL-1Ra, IL-36, S100A8, and CXCL10 and on the infiltration of innate immune cells. Administration of recombinant IL-1Ra improved, whereas IL-36Ra worsened the outcome of P. aeruginosa keratitis. Local application of IL-36 stimulated the expression of innate defense molecules S100A9, mouse β-defensin 3, but suppressed IL-1β expression in B6 mouse corneas. IL-36 diminished the severity of P. aeruginosa keratitis, and its protective effects were abolished in the presence of S100A9 neutralizing Ab and partially affected by CXCL10 and CXCR3 neutralizations. Thus, our data reveal that IL-1Ra and IL-36Ra have opposing effects on the outcome of P. aeruginosa keratitis and suggest that IL-36 agonists may be used as an alternative therapeutic to IL-1β–neutralizing reagents in controlling microbial keratitis and other mucosal infections.

https://ift.tt/2m6uDWc

ATXN3 Positively Regulates Type I IFN Antiviral Response by Deubiquitinating and Stabilizing HDAC3 [INNATE IMMUNITY AND INFLAMMATION]

Ataxin-3 (ATXN3) belongs to the Josephin family of deubiquitinases. So far, ATXN3 is majorly linked to the neurodegenerative disease, Machado–Joseph disease. The role of ATXN3 in the antiviral function has not been explored, and the in vivo deubiquitinating activity of ATXN3 remains largely unknown. In this study, we report that ATXN3 is an important positive regulator of type I IFN (IFN-I)–mediated antiviral activity in murine primary lung cells and human epithelial and fibroblast cell lines. We clarify that ATXN3 does not promote IFN-I production, but enhances the IFN-I–mediated signaling pathway. Furthermore, ATXN3 physically interacts with histone deacetylase 3 (HDAC3) and upregulates the level of HDAC3 protein. Moreover, ATXN3 deubiquitinates HDAC3, thereby enhancing HDAC3 protein stability. Interestingly, the interaction between ATXN3 and HDAC3 increases during viral infection, which promotes IFN-I–induced signaling in murine primary lung cells. Finally, we reveal the ATXN3/HDAC3 axis–mediated regulation of IFN-I antiviral response. These findings reveal a novel biological function of ATXN3 and an important antiviral mechanism by which the deubiquitinase ATXN3 positively regulates IFN-I antiviral response, and they may provide a novel strategy for enhancing IFN-based antiviral therapy.

https://ift.tt/2zvvOYq

Myeloid Cell-Restricted STAT3 Signaling Controls a Cell-Autonomous Antifibrotic Repair Program [INNATE IMMUNITY AND INFLAMMATION]

Myeloid cells can be beneficial as well as harmful in tissue regenerative responses. The molecular mechanisms by which myeloid cells control this critical decision of the immune system are not well understood. Using two different models of physiological acute or pathological chronic skin damage, in this study we identified myeloid cell–restricted STAT3 signaling as important and an injury context–dependent regulator of skin fibrosis. Targeted disruption of STAT3 signaling in myeloid cells significantly accelerated development of pathological skin fibrosis in a model of chronic bleomycin-induced tissue injury, whereas the impact on wound closure dynamics and quality of healing after acute excision skin injury was minor. Chronic bleomycin-mediated tissue damage in control mice provoked an antifibrotic gene signature in macrophages that was characterized by upregulated expression of IL-10, SOCS3, and decorin. In contrast, in STAT3-deficient macrophages this antifibrotic repair program was abolished whereas TGF-β1 expression was increased. Notably, TGF-β1 synthesis in cultured control bone marrow–derived macrophages (BMDMs) was suppressed after IL-10 exposure, and this suppressive effect was alleviated by STAT3 deficiency. Accordingly, coculture of IL-10–stimulated control BMDMs with fibroblasts suppressed expression of the TGF-β1 downstream target connective tissue growth factor in fibroblasts, whereas this suppressive effect was lost by STAT3 deficiency in BMDMs. Our findings highlight a previously unrecognized protective role of myeloid cell–specific STAT3 signaling in immune cell–mediated skin fibrosis, and its regulatory pathway could be a potential target for therapy.

https://ift.tt/2m8ubXk

Down Syndrome as an Indicator for Pediatric Otolaryngologic Procedures

Publication date: Available online 9 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Terral A. Patel, Shaun A. Nguyen, David R. White

Abstract

Objective

Down Syndrome (DS) is the most common chromosome abnormality in humans. Due to the phenotype associated with DS, there are many disease states that require otolaryngologic procedures. Our goal is to use national data to study otolaryngologic procedures, their association with DS, and the degree of difference in risk profiles encountered with DS.

Methods

Data was obtained from the 2012-2015 American College of Surgeons' National Surgical Quality Improvement Program-Pediatric public use files. ENT procedure CPT codes were used to query the database and DS patients were identified using ICD-9 code 758.0. The ENT procedures were grouped into 18 categories and their frequency in DS patients as well as outcomes were analyzed. Postoperative outcomes were measured by complication rates, readmission rates, operation time, anesthesia time, and total length of stay.

Results

Results showed that DS patients are significantly (p<0.05) over-represented in the following categories: Tracheostomy, Endoscopy, Laryngoscopy, Tracheoplasty, Myringoplasty, Tympanoplasty with Mastoidectomy, and Tympanoplasty without Mastoidectomy. DS patients are under-represented in the following categories: Abscess, Palatoplasty, Excision of Congenital Neck Cyst, and Cochlear Implantation. Logistic regression analysis showed that DS patients were significantly (p<0.05) more likely to undergo procedures in the over-represented categories and were significantly (p<0.05) less likely to undergo procedures in the under-represented categories as listed above. Outcomes analysis yielded no pattern of significance.

Conclusion

Our data showed that DS may predispose patients to require certain procedures over others.

https://ift.tt/2una77s

SLC15A2 and SLC15A4 Mediate the Transport of Bacterially Derived Di/Tripeptides To Enhance the Nucleotide-Binding Oligomerization Domain-Dependent Immune Response in Mouse Bone Marrow-Derived Macrophages [INNATE IMMUNITY AND INFLAMMATION]

There is increasing evidence that proton-coupled oligopeptide transporters (POTs) can transport bacterially derived chemotactic peptides and therefore reside at the critical interface of innate immune responses and regulation. However, there is substantial contention regarding how these bacterial peptides access the cytosol to exert their effects and which POTs are involved in facilitating this process. Thus, the current study proposed to determine the (sub)cellular expression and functional activity of POTs in macrophages derived from mouse bone marrow and to evaluate the effect of specific POT deletion on the production of inflammatory cytokines in wild-type, Pept2 knockout and Pht1 knockout mice. We found that PEPT2 and PHT1 were highly expressed and functionally active in mouse macrophages, but PEPT1 was absent. The fluorescent imaging of muramyl dipeptide–rhodamine clearly demonstrated that PEPT2 was expressed on the plasma membrane of macrophages, whereas PHT1 was expressed on endosomal membranes. Moreover, both transporters could significantly influence the effect of bacterially derived peptide ligands on cytokine stimulation, as shown by the reduced responses in Pept2 knockout and Pht1 knockout mice as compared with wild-type animals. Taken as a whole, our results point to PEPT2 (at plasma membranes) and PHT1 (at endosomal membranes) working in concert to optimize the uptake of bacterial ligands into the cytosol of macrophages, thereby enhancing the production of proinflammatory cytokines. This new paradigm offers significant insight into potential drug development strategies along with transporter-targeted therapies for endocrine, inflammatory, and autoimmune diseases.

https://ift.tt/2zqEm34

Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation [INNATE IMMUNITY AND INFLAMMATION]

Macrophages manifest distinct phenotype according to the organs in which they reside. In addition, they flexibly switch their character in adaptation to the changing environment. However, the molecular basis that explains the conversion of the macrophage phenotype has so far been unexplored. We find that CD169⁺ macrophages change their phenotype by regulating the level of a transcription factor Maf both in vitro and in vivo in C57BL/6J mice. When CD169⁺ macrophages were exposed to bacterial components, they expressed an array of acute inflammatory response genes in Maf-dependent manner and simultaneously start to downregulate Maf. This Maf suppression is dependent on accelerated degradation through proteasome pathway and microRNA-mediated silencing. The downregulation of Maf unlocks the NF-E2–related factor 2–dominant, cytoprotective/antioxidative program in the same macrophages. The present study provides new insights into the previously unanswered question of how macrophages initiate proinflammatory responses while retaining their capacity to repair injured tissues during inflammation.

https://ift.tt/2m3uKS5

IL-36 and IL-1/IL-17 Drive Immunity to Oral Candidiasis via Parallel Mechanisms [INFECTIOUS DISEASE AND HOST RESPONSE]

Protection against microbial infection by the induction of inflammation is a key function of the IL-1 superfamily, including both classical IL-1 and the new IL-36 cytokine families. Candida albicans is a frequent human fungal pathogen causing mucosal infections. Although the initiators and effectors important in protective host responses to C. albicans are well described, the key players in driving these responses remain poorly defined. Recent work has identified a central role played by IL-1 in inducing innate Type-17 immune responses to clear C. albicans infections. Despite this, lack of IL-1 signaling does not result in complete loss of immunity, indicating that there are other factors involved in mediating protection to this fungus. In this study, we identify IL-36 cytokines as a new player in these responses. We show that C. albicans infection of the oral mucosa induces the production of IL-36. As with IL-1α/β, induction of epithelial IL-36 depends on the hypha-associated peptide toxin Candidalysin. Epithelial IL-36 gene expression requires p38-MAPK/c-Fos, NF-B, and PI3K signaling and is regulated by the MAPK phosphatase MKP1. Oral candidiasis in IL-36R^–/– mice shows increased fungal burdens and reduced IL-23 gene expression, indicating a key role played by IL-36 and IL-23 in innate protective responses to this fungus. Strikingly, we observed no impact on gene expression of IL-17 or IL-17–dependent genes, indicating that this protection occurs via an alternative pathway to IL-1–driven immunity. Thus, IL-1 and IL-36 represent parallel epithelial cell–driven protective pathways in immunity to oral C. albicans infection.

https://ift.tt/2uhLB7r

Regulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae [INFECTIOUS DISEASE AND HOST RESPONSE]

Chitinases and chitinase-like proteins are an evolutionary conserved group of proteins. In the absence of chitin synthesis in mammals, the conserved presence of chitinases suggests their roles in physiology and immunity, but experimental evidence to prove these roles is scarce. Chitotriosidase (chit1) is one of the two true chitinases present in mammals and the most prevalent chitinase in humans. In this study, we investigated the regulation and the role of chit1 in a mouse model of Klebsiella pneumoniae lung infection. We show that chitinase activity in bronchoalveolar lavage fluid is significantly reduced during K. pneumoniae lung infection. This reduced activity is inversely correlated with the number of neutrophils. Further, instilling neutrophil lysates in lungs decreased chitinase activity. We observed degradation of chit1 by neutrophil proteases. In a mouse model, chit1 deficiency provided a significant advantage to the host during K. pneumoniae lung infection by limiting bacterial dissemination. This phenotype was independent of inflammatory changes in chit1^–/– mice as they exerted a similar inflammatory response. The decreased dissemination resulted in improved survival in chit1^–/– mice infected with K. pneumoniae in the presence or absence of antibiotic therapy. The beneficial effects of chit1 deficiency were associated with altered Akt activation in the lungs. Chit1^–/– mice induced a more robust Akt activation postinfection. The role of the Akt pathway in K. pneumoniae lung infection was confirmed by using an Akt inhibitor, which impaired health and survival. These data suggest a detrimental role of chit1 in K. pneumoniae lung infections.

https://ift.tt/2m2r8zY