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Background: Tail docking is widely used to control tail biting in pigs, but it is a painful and stressful procedure. The impact of non-docking trials on tail damage (TD) and ear lesions (EL) from weaning to slaughter was assessed on four commercial farms., Methods: A total of 898 docked pigs (396 DP) or undocked pigs (502 UP) were assessed for tail damage and ear lesions at the beginning and end of the weaner stage, during fattening and at the abattoir during slaughter., Results: The percentage of UP with shortened tails increased significantly from weaning to fattening, but the percentage of non-inflamed tails and tails without fresh lesions increased. In terms of severity of lesion, a lower percentage of pigs scored as 'no visible lesion' at the end of weaning compared to fattening, both for UP and DP (p < 0.05). DP always had a lower percentage of TD, whereas UP had a lower percentage of EL at the end of weaning., Limitation: It was not possible to statistically compare different preventive strategies trialed on farms as alternatives to docking., Conclusion: This study highlights that combining tail length and lesion score at slaughter could be a reliable on-farm welfare indicator., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

In adult mammals, skin wounds typically heal by scarring rather than through regeneration. In contrast, "super-healer" Murphy Roths Large (MRL) mice have the unusual ability to regenerate ear punch wounds; however, the molecular basis for this regeneration remains elusive. Here, in hybrid crosses between MRL and non-regenerating mice, we used allele-specific gene expression to identify cis-regulatory variation associated with ear regeneration. Analyzing three major cell populations (immune, fibroblast, and endothelial), we found that genes with cis-regulatory differences specifically in fibroblasts were associated with wound-healing pathways and also co-localized with quantitative trait loci for ear wound-healing. Ectopic treatment with one of these proteins, complement factor H (CFH), accelerated wound repair and induced regeneration in typically fibrotic wounds. Through single-cell RNA sequencing (RNA-seq), we observed that CFH treatment dramatically reduced immune cell recruitment to wounds, suggesting a potential mechanism for CFH's effect. Overall, our results provide insights into the molecular drivers of regeneration with potential clinical implications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cartilage-cutting and cartilage-sparing techniques are the two types of otoplasty procedures. Because of the significant risk of haematoma, skin necrosis, and ear deformity, cartilage-cutting techniques have been questioned. As a result; suture-based cartilage-sparing procedures such as Mustarde and Furnas suture procedures have grown in popularity. However, these techniques have a tendency for deformity recurrence due to cartilage memory and suture fatigue, as well as the possibility of suture extrusion and pinpricking sensation of the sutures., Methods: In this study, we used a medially based adipo-dermal flap including perichondrium which is elevated from the back of the auricle to cover and support a cartilage-sparing otoplasty, thirty-four patients (14 female and 20 male) were operated using this technique. The medially based perichondrio-adipo-dermal flap is advanced anteriorly and fixed to the helical rim under cover of the distal skin flap. This procedure sought to cover the suture line preventing suture extrusion and support in the repair of the deformity preventing its recurrence., Results: The average operative time was 80min, ranging from 65 to 110min. The patients passed the early postoperative period uneventfully except for 2 patients; one patient (2.9%) developed haematoma, and the other patient developed a small area of necrosis on the new antihelical fold. In late the postoperative period recurrence of the deformity developed in one patient. No patients developed suture extrusion or granuloma., Conclusion: The treatment to repair prominent ears is easy and safe, with benefits such as a natural-looking antihelical fold and minimal tissue stress. The medially or proximally based adipo-dermal flap may help to lower recurrence rates and suture extrusion., (Copyright © 2021 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

We report 2 patients who underwent Mohs micrographic surgery (MMS) and operative closure on the ear. Both cases were complicated by necrosis resulting in the formation of auricular defects. These cases highlight the importance of the auricular vasculature and the associated watershed regions during operative planning for MMS as well as the complications that can arise with vascular compromise. This case report also provides a review of the auricular vasculature with special attention to these vulnerable watershed regions.

Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM&#95;006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1., (© 2021. The Author(s).)

Wideband Absorbance Immittance (WAI) has been available for more than a decade, however its clinical use still faces the challenges of limited understanding and poor interpretation of WAI results. This study aimed to develop Machine Learning (ML) tools to identify the WAI absorbance characteristics across different frequency-pressure regions in the normal middle ear and ears with otitis media with effusion (OME) to enable diagnosis of middle ear conditions automatically. Data analysis included pre-processing of the WAI data, statistical analysis and classification model development, and key regions extraction from the 2D frequency-pressure WAI images. The experimental results show that ML tools appear to hold great potential for the automated diagnosis of middle ear diseases from WAI data. The identified key regions in the WAI provide guidance to practitioners to better understand and interpret WAI data and offer the prospect of quick and accurate diagnostic decisions.

Porcine ear necrosis (PEN) is a condition that mainly occurs in intensive pig production systems and mostly affects piglets after weaning. The syndrome manifests itself with lesions on the pinna, which can heal or become more severe resulting in partial loss of the ear. The pathogenesis of the condition is not fully known. Three different hypotheses for the development of PEN are described in this review: (1) damage of the epidermis due to Staphylococcal exfoliative toxins; (2) occlusion of small blood vessels; and (3) ear biting with subsequent β-hemolytic streptococcal infection. Risk factors have not been completely elucidated, but viral and bacterial infections, and husbandry factors such as environment, housing conditions and management, have been suggested. It is also possible that some cases are due to a combination of these factors. The role of parasitic infestations has been not investigated. Due to bacterial involvement, severely affected pigs can be treated with antimicrobials. Control and preventive measures should focus on reducing potential risk factors by implementing herd immunization, as well as improvement of sanitary conditions, feed quality (with respect to mycotoxin contamination), management (appropriate stocking density), and environmental conditions (e.g. number of drinkers and feeders and/or optimal ventilation). Further research is needed to better understand the precise etiology and pathogenesis of PEN, so that risk factors can be identified and more targeted control measures can be implemented., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.

Otorrhagia is generally associated with basilar skull fractures or diving accidents. In routine forensic medical practice, an accurate knowledge of the etiology of otorrhagia may have a key role to distinguish between traumatic and atraumatic causes and accidental, homicidal, or suicidal manners. The authors present the case of an unusual cause of atraumatic otorrhagia occurred in an elderly farmer found dead in a barn. He remained entrapped in a narrow tunnel created by some hay bales. The autopsy findings revealed only an intense polyvisceral congestion and subpleural petechiae, with no signs of traumatic injuries and no fractures of skull base or temporal pyramid. The cause of death was determined to be positional asphyxia, and the manner of death was deemed accidental. In fact, the head-down position resulted in diaphragm compression causing respiratory failure in combination with the stasis of the upper venous circle districts. Mechanical and gravitational forces related to upside-down position and increased vascular pressure also caused postmortem otorrhagia. In this case, the death scene investigation and circumstantial information allowed for reconstruction of the unique dynamics of the death. At the death scene, the position of the corpse must be accurately investigated because it can explain some cadaveric findings such as the ear bleeding or other markers of increased cephalic venous pressure like pink teeth, facial and conjunctival petechiae, or Tardieu spots. Therefore, forensic pathologists should consider that ear bleeding in dead bodies is not always the evidence of severe head blunt trauma or diving accidents, but it might be a postmortem phenomenon mostly related to body position.

Background: Congenital auricular deformities (CAD) are prevalent worldwide. The objective of this study is to investigate the effectiveness and safety of ear molding for children with CAD at their early days., Methods: One hundred and nighty children (under 3 days) with CAD will be included in the study. Participants will be randomly allocated to treatment or waiting list group (n = 95). The treatment group will receive ear molding within 3 days after birth for 2 weeks. The control group will receive usual care and receive the same ear molding at 6th week if spontaneously recover is not occur. Physician and parent assessment of improvement, parent's anxiety, depression, and quality of life and adverse events will be measured at baseline, 3rd and 6th week of initial treatment. The primary outcome recovery rate will be compared between groups using Chi square test. Secondary continuous outcomes will be compared using analysis of variance., Discussion: This study is the first randomized controlled trial to examine the effectiveness, safety and cost-effectiveness of ear molding for CAD comparing with waiting list, to inform clinical decision of CAD treatments and relevant guideline development.

Objective: To depict various temporal bone abnormalities on high-resolution computed tomography in congenital aural atresia patients, and correlate these findings with auditory function test results and microtia subgroup., Methods: Forty patients (56 ears) with congenital malformation of the auricle and/or external auditory canal were evaluated. Auricles were graded according to Marx's classification, divided into subgroups of minor (grades I and II) and major (III and IV) microtia. Other associated anomalies of the external auditory canal, tympanic cavity, ossicular status, oval and round windows, facial nerve, and inner ear were evaluated., Results: Minor and major microtia were observed in 53.6 and 46.4 per cent of ears respectively. Mean hearing levels were 62.47 and 62.37 dB respectively (p = 0.98). The malleus was the most commonly dysplastic ossicle (73.3 vs 80.8 per cent of ears respectively, p = 0.53). Facial nerve (mastoid segment) abnormalities were associated (p = 0.04) with microtia subgroup (80 vs 100 per cent in minor vs major subgroups)., Conclusion: Microtia grade was not significantly associated with mean hearing levels or other ear malformations, except for external auditory canal and facial nerve (mastoid segment) anomalies. High-resolution computed tomography is essential in congenital aural atresia, before management strategy is decided.

Auriculocondylar syndrome (ARCND, MIM #614669, #602483, and #615706); also known as ''question-mark ear syndrome'' or ''dysgnathia complex'', is a rare craniofacial malformation of first and second branchial arches with a prevalence of <1/1,000,000. It is characterized by a distinctive auricular malformation (question mark ear (QME)) and highly variable mandibular anomalies. Variants found in PLCB4, GNAI3, and in EDN1 genes are responsible for >90% of tested ARCND patients. Whole exome sequencing in a multigenerational Egyptian kindred with high intrafamilial variability revealed a known heterozygous missense variant in PLCB4 (NM&#95;000933.3:c.1862G>A:p.(Arg621His)). This report increases the number of molecularly characterized ARCND patients to 29 and emphasizes the highly variable clinical presentation within families., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Competing Interests: None

The transcription factor, MafB, plays important role in the differentiation and functional maintenance of various cells and tissues, such as the inner ear, kidney podocyte, parathyroid gland, pancreatic islet, and macrophages. The rare heterozygous substitution (p.Leu239Pro) of the DNA binding domain in MAFB is the cause of Focal Segmental Glomerulosclerosis associated with Duane Retraction Syndrome, which is characterized by impaired horizontal eye movement due to cranial nerve maldevelopment in humans. In this research, we generated mice carrying MafB p.Leu239Pro (Mafb mt/mt ) and retrieved their tissues for analysis. As a result, we found that the phenotype of Mafb mt/mt mouse was similar to that of the conventional Mafb deficient mouse. This finding suggests that the Leucine residue at 239 in the DNA binding domain plays a key role in MafB function and could contribute to the diagnosis or development of treatment for patients carrying the MafB p.Leu239Pro missense variant., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

When the cartilage on the prominent ears is reshaped, the arising stress returns the tissue to its initial configuration. Laser irradiation of areas of maximal stress leads to stress relaxation and results in a stable configuration. Sixty auricles were harvested from 30 New Zealand white rabbits and cut into a rectangle measuring 50 mm by 25 mm with an average thickness of approximately 1.3 mm. Bilateral skin was included for ex vivo studies. Continuous cryogen spray cooling (CSC) with laser energy was delivered to the exposed cartilage for reshaping. In clinical applications, from January 2006 to December 2016, a total of 50 patients with 100 bat ears who underwent CO 2 laser reshaping (otoplasty) were assessed. A continuous cooling system (4 °C) in conjunction with a CO 2 laser was applied to make a retroauricular-approached incision and reshape the ear cartilage. The well cartilage bending correlated with the different parameters demonstrated in the continuous CSC protected group. All 100 (100%) of the subjects experienced early complications (≤ 1 month) related to laser exposure with swelling, while 5 (5%) experienced ecchymosis, 2 (2%) minimal hematoma, 2 (2%) scarring, 1 (1%) minor infection, 1 (1%) under correction, 1 (1%) overcorrection, and 1 (1%) relapse. These problems were corrected and/or had resolved after 3 months. All patients achieved good to excellent results in our final outcome assessment (> 6 months). Laser reshaping has a potential use in certain surgical procedures involving the cartilage. The appropriate conditions for laser ear reshaping clearly depend on the laser wavelength used, energy controlling, and tissue optical properties.

Cytarabine, a pyramidine analog, is used for treating various hematological malignancies such as acute leukemias and lymphomas. Side effects of cytarabine are dose dependent and include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, hepato-renal insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity and dermatological side effects. The dermatological side effects can be immediate or due to delayed hypersensitivity reactions. They have been attributed largely to release of cytokines. We present three such cases of delayed hypersensitivity to cytarabine affecting the ears bilaterally.

Transforming growth factor beta (TGFβ) signalling is involved in several aspects of regeneration in many organs and tissues of primitive vertebrates. It has been difficult to recognize the role of this signal in mammal regeneration due to the low ability of this animal class to reconstitute tissues. Nevertheless, ear-holes in middle-age female mice represent a model to study the limited epimorphic-like regeneration in mammals. Using this model, in this study we explored the possible participation of TGFβ signalling in mammal regeneration. Positive pSmad3 cells, as well as TGFβ1 and TGFβ3 isoforms, were detected during the redifferentiation phase in the blastema-like structure. Daily administration of the inhibitor of the TGFβ intracellular pathway, SB431542, during 7 days from the re-differentiation phase, resulted in a decreased level of pSmad3 accompanied by a transitory higher growth of the new tissue, larger cartilage nodules, and new muscle formation. These phenotypes were associated with a decrease in the number of α-SMA-positive cells and loose packing of collagen I. These results indicate that the modulation of the fibrosis mediated by TGFβ signalling contributes to enhancing the differentiation of cartilage and muscle during limited ear-hole regeneration.

Emerging immunotherapy agents, such as immune checkpoint inhibitors, have shown remarkable promise in the treatment of various malignancies. These drugs selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. Due to the novelty of these therapeutic agents, their toxicity profile is less well understood.Meta-analysis results reveal that the overall prevalence of oral mucositis, stomatitis, and xerostomia is lower with checkpoint inhibitors compared to conventional chemotherapy, and head and neck radiation therapy. However, the widespread use of immunotherapy reveals new oral mucosal barrier adverse events, including bullous pemphigoid, mucous membrane pemphigoid, and lichenoid mucositis. Audiovestibular dysfunction can occur from autoimmune-mediated pathways of immunotherapy (adoptive cell) with limited treatment options. Such auditory complications can lead to speech recognition deficits and sensorineural hearing loss. Ocular toxicities are among the most common adverse events resulting from the use of these agents. The majority of ocular immune-related adverse events (irAEs) are mild, low-grade, non-sight threatening, such as blurred vision, conjunctivitis, and ocular surface disease. Serious and sight-threatening events, including corneal perforation, optic neuropathy, and retinal vascular occlusion, can occur but are infrequent. In this chapter, we review the current evidence on the clinical manifestations of oral, audiovestibular, and ocular immune-related adverse events (i.e., irAEs).

The aim of this pilot study was to develop and evaluate an automated system for the assessment of ear and tail lesions as welfare indicators in pigs at the abattoir. A camera-based system was constructed to enable automatic assessment. This was evaluated in comparison to a standard observer, defined as skilled human veterinary observer, based on 5952 carcasses. We detected significant values for ear lesions (sensitivity, 77.0; specificity, 96.5; accuracy, 95.4%) and good values for tail lesions (sensitivity, 77.8%; specificity, 99.7%; accuracy, 99.5%). The reliabilities of assessments by four individual human observers directly at the abattoir and the camera system were calculated using Krippendorff's alpha. These varied between 0.42 and 0.67 for ear lesions and 0.42 and 0.55 for tail lesions, while better values were reached for the agreement between the system and picture-based evaluation (0.64 for ear lesions and 0.75 for tail lesions). More scientific evaluations at different abattoirs are now needed to further test and improve the camera-based system and its various scopes of application., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Immunoglobulin G4-related sclerosing disease (IgG4-RSD) is a chronic fibro-inflammatory disease involving systemic multi-organ lesions, such as the salivary and lacrimal glands, lymph nodes and pancreas. The diagnosis of this disease is reliant upon clinical manifestations, laboratory tests, histopathologic results and radiological data. Some studies have found that IgG4-RSD has otological manifestations, whereas there were few studies introducing the diagnosis, therapy and long-term follow-up results of solely otological IgG4-RSD., Case Summary: Here, we report a case of IgG4-RSD involving the ear alone. A female presenting with otalgia and hearing loss underwent surgery, without hormone therapy. The pathological diagnosis was otological IgG4-RSD and no clinical or radiological signs of recurrence were observed at seven and twenty-four months follow-up., Discussion: This case indicates that IgG4-RSD can invade the ear only, and that surgical therapy without hormone therapy is efficient for solely IgG4-RSD. Pathological results are crucial for diagnosis., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Hypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. However, there are currently no satisfactory drugs to prevent HS formation. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. In this study, we evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model., Methods: We established a rabbit ear wound model by generating full-thickness wounds in the ears of rabbits (n = 12) and treated wounds with MSC CM, BMC CM, or BMC-induced MSC CM. Dermal fibroblasts from human hypertrophic scar were stimulated with transforming growth factor beta 1 (TGF-β1) for 24 h and cultured in each culture medium for 72 h. We measured the hypertrophic scar (HS) formation during the skin regeneration by measuring the expression of several remodeling molecules and the effect of these conditioned media on active human HS fibroblasts., Results: Our results showed that BMC-induced MSC CM had greater antifibrotic effects than MSC CM and BMC CM significantly attenuated HS formation in rabbits. BMC-induced MSC CM accelerated wound re-epithelization by increasing cell proliferation. Additionally, BMC-induced MSC CM also inhibited fibrosis by decreasing profibrotic gene and protein expression, promoting extracellular matrix turnover, inhibiting fibroblast contraction, and reversing myofibroblast activation., Conclusions: BMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation.

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development., (© 2019 Wiley Periodicals, Inc.)

Background: Cisplatin is an extensively used anti-neoplastic agent for the treatment of various solid tumors. However, a high incidence of severe ototoxicity is accompanied by its use in the clinic. Currently, no drugs or therapeutic strategies have been approved for the treatment of cisplatin-induced ototoxicity by the FDA. Purpose: The purpose of this study was to investigate the otoprotective effects of dexamethasone (DEX)-loaded silk-polyethylene hydrogel (DEX-SILK) following round window membrane administration in the cisplatin-induced ototoxicity mouse model. Methods: The morphology, gelation kinetics, viscosity and secondary structure of the DEX-SILK hydrogel were analyzed. DEX concentration in the perilymph was tested at different time points following hydrogel injection on the RWM niche. Cultured cells (HEI-OC1), organ of Corti explants (C57/BL6, P0-2), and cisplatin-induced hearing loss mice model (C57/BL6) were used as in vitro and in vivo models for investigating the otoprotective effects of DEX-SILK hydrogel against cisplatin. Results: Encapsulation of DEX with a loading of 8% (w/v) did not significantly change the silk gelation time, and DEX was evenly distributed in the Silk-PEG hydrogel as visualized by scanning electron microscopy (SEM). The concentration of Silk majorly influenced DEX distribution, morphological characteristics, viscosity, and gelation time. The optimized DEX-SILK hydrogel (8% w/v loading, 15% silk concentration, 10 μl) was administered directly onto the RWM of the guinea pigs. The DEX concentration in the perilymph was maintained above 1 μg/ml for at least 21 days for the DEX-SILK, while it was maintained for less than 6 h in the control sample of free DEX. DEX-SILK (5-60 ng/ml) exhibited significant protective effects against cisplatin-induced cellular ototoxicity and notably reduced the production of reactive oxygen species (ROS). Eventually, pretreatment with DEX-SILK effectively preserved outer hair cells in the cultured organ of Corti explants and demonstrated significant hearing protection at 4, 8, and 16 kHz in the cisplatin-induced hearing loss mice as compared to the effects noted following pretreatment with DEX. Conclusion: These results demonstrated the clinical value of DEX-SILK for the therapy of cisplatin-induced ototoxicity., Competing Interests: The authors declare that they have no competing interests in this work.

Supramolecular polymers self-assemble into nanofibers, micelles, and other nanostructures through weak noncovalent interactions between subunits. Such systems possess attractive properties for use in a variety of practical settings such as energy, sustainability, and healthcare. In regenerative medicine, a common approach involves implanting a supramolecular material containing cell and growth factor binding motifs directly into a diseased or traumatized tissue defect, whereupon it interacts with and/or recruits components of the biological system to induce tissue healing. Here we introduce a supramolecular therapeutic in which tissue regeneration is orchestrated by a supramolecular polymer prodrug implanted subcutaneously in a remote tissue. Our approach exploits a hydrophobic small-molecule inhibitor of prolyl hydroxylase enzyme as both a regeneration-inducing therapeutic and a structure-directing agent in a supramolecular polymer that forms shear-thinning nanofiber hydrogels. Subcutaneous injection of the supramolecular hydrogel in the back of mice wounded with a critical-sized defect in the ear led to transient upregulation of hypoxia inducible factor-1α and regeneration of ear tissue in a manner reminiscent of epimorphic regeneration. This drug-induced regeneration strategy utilizes a simple and translatable supramolecular design, eliminates the need for delivery of biologics ( e. g., growth factors, cells), and avoids implantation of a foreign material directly in a tissue defect.

Keloid is a benign fibroblastic tumor which is most often secondary to a scar, but it can occur spontaneously in a subject with black skin. We report the case of a 19-year old patient, electrician, presenting with giant right retroauricular mass evolving over two years. For some time, the patient has experienced a feeling of heaviness on the pavilion of the right ear. The lesion had manifested as a hard, pruritic, non-painful patch gradually increasing in size. The patient had received several topical and antiseptics treatments without any effect. He had a history of traumatic injury in the right retroauricular sulcus. A month after, pruritic hypertrophic scar occurred. Physical examination showed voluminous hard, fixed, retroauricular tumor (10 × 6 cm) with normal skin color, non-painful on movement (A). Its base was sessile. The remainder of the physical examination was normal. Ultrasound showed little vascularized skin tumor of the right retroauricular sulcus with more or less sharp margins, measuring 9 x 5 cm. Two diagnoses were suspected: post-traumatic keloid (most likely) and Darier Ferrand dermatofibrosarcoma. Biopsy was performed and histological examination showed keloid. The patient underwent intramarginal excision (B). The surgical specimens weighed 75 grams (C). The postoperative course was simple with disappearance of the feeling of heaviness.

Purpose: This study analyzed the late ear complications of radiotherapy for nasopharyngeal cancer (NPC) and compared the conventional and intensity-modulated radiotherapy (2D-RT and IMRT, respectively)., Methods: At 2-21 years after the end of NPC treatment, 104 ears of 52 patients were evaluated with the otoscopic examination, pure tone audiometry test, tympanometry, and subjective complaints by being blinded to the radiotherapy technique., Results: There were no differences in terms of the pathology of the external, middle or inner ear, air and bone-conduction hearing thresholds, and the air-bone (A-B) gap at 500, 1000, 2000, and 4000 Hz, and tympanometry types between 2D-RT and IMRT groups (p > 0.05). There were positive correlations between the values of A500 and A1000 thresholds; gap 500, 4000, and mean cochlear RT dose (p < 0.05). There were positive correlations between the values of A500, A1000, and A4000 thresholds; gap 500, 1000, 2000, 4000, and maximum cochlear RT dose (p < 0.05)., Conclusion: IMRT was not found to be superior to 2D-RT to prevent RT-induced ear complications. The solution of the middle ear problems must be the goal of the strategies for complications treatment.

Temporal bone high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are valuable tools in the evaluation of pediatric hearing loss. Computed tomography is important in the evaluation of pediatric conductive hearing loss and is the imaging modality of choice for evaluation of osseous abnormalities. MR imaging is the modality of choice for evaluation of sensorineural hearing loss. A broad spectrum of imaging findings can be seen with hearing loss in children. HRCT and MR imaging provide complementary information and are often used in conjunction in the preoperative evaluation of pediatric candidates for cochlear implantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Hypertrophic scars cause cosmetic and functional problems for patients, and their treatment remains challenging. Mechanical micronization of adipose tissue can remove adipocytes and concentrate functional cells. Stromal vascular fraction (SVF)-gel is obtained by a series of simple mechanical processes, including shifting between syringes and centrifugation. This study aimed to assess the therapeutic effect of SVF-gel on hypertrophic scars., Methods: A model of hypertrophic scars was established in rabbit ears. SVF-gel and SVF cells were obtained from rabbit inguinal fat pads and injected into scars. Phosphate-buffered saline (PBS) was used as a control. Scars were structurally characterized by histologic and immunohistochemical analyses. Expression of inflammatory and fibrogenic genes was evaluated., Results: Hypertrophic scars became less visible and softer following injection of SVF-gel or SVF cells. Dermal thickness was significantly lower in the groups treated with SVF-gel and SVF cells than in the PBS-treated group. Treatment with SVF-gel restored subcutaneous fat tissue in scars, while treatment with SVF cells and PBS did not. Injection of SVF-gel and SVF cells reduced macrophage infiltration in the dermal layer and decreased mRNA expression of interleukin-6 and monocyte chemoattractant protein-1. In addition, the level of myofibroblasts and collagen deposition were reduced in the groups treated with SVF-gel and SVF cells., Conclusions: SVF-gel has therapeutic effects on hypertrophic scars. Injection of SVF-gel into hypertrophic scars restores subcutaneous fat tissue and reduces the levels of macrophages and myofibroblasts; thus, it decreased the dermal thickness of the scar.

In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.

The dermis and the subcutaneous space vary in many fundamental characteristics, which include composition of lymphatic vessels, density of blood vasculature, and cells of the immune response. Traditional approaches employ the subcutaneous space as the preferred layer of the skin to inoculate Yersinia pestis for bubonic plague studies. Because fleas transmit Y. pestis in nature, and because these insects target the dermal layer of the skin, an intradermal model of infection is more biologically relevant than a subcutaneous model. Among many features, the use of an intradermal model results in robust and reproducible colonization of lymph nodes, blood, and deeper tissues. Remarkably, intradermal inoculation in the murine ear pinna also allows for the study of cutaneous infection without severely disrupting the architecture and physiology of the skin.

Objective: To explore the influence of hyperbaric oxygen on scar formation in rabbit ears., Methods: A total of 20 New Zealand rabbits were selected to establish the hypertrophic scar model on the ears. The rabbits were randomly divided into control group and experimental group (7d, 14d, 21d, and 28d group according to different HBO treatment days),each experimental group received hyperbaric oxygen treatment after the operation at the same time everyday for 1 hour. After the day 29, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining, and transmission electrical microscope. The expression of bax, bcl-2, and the cell apoptosis rate was detected by immunohistochemical method., Results: (i) Both number of fibroblast and amount of collagen fibrils in experimental group were significantly reduced compared with those in control group. In Masson staining, arrangement of collagen fibrils in experimental group was much more irregular and coarse than control groups. (ii) HI value can be found much smaller in the experimental groups than the control (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05). (iii) Expression of Bax could be detected up-regulated in experimental group (P < .05). While the expression of Bcl-2 is detected significantly down-regulated in experimental group than that in control group (P < .05). Compared with the 7d group, the expression of Bax and Bcl-2 has significant difference in 14d group (P < .05), and the expression of this two factors in 21d group has significant difference comparing with 14d group(P < .05),but there is no significant difference between 28d group and 21d group(P > .05). (iv) Significant difference of cell apoptosis rate can be detected between the experimental groups and the control group (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05)., Conclusion: The hyperbaric oxygen can up-regulate bax/bcl-2 value, increase the cell apoptosis rate, and inhibit the early hypertrophic scar in rabbit ears., (© 2018 The Authors Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)

To evaluate the therapeutic effect of micro-plasma radio frequency on hypertrophic scars in rabbit ears to provide an experimental basis and theoretical foundation for the treatment of hypertrophic scars. Hypertrophic scars were established on the ventral surface of the ears of six New Zealand white rabbits. Left and right ears were randomly divided into two groups: experimental group treated with micro-plasma radio frequency and control group with no treatment. H&E staining and CD34 labeling of microvessels were performed to analyze ear specimens, and immunohistochemical staining was conducted to detect IL-8 and MCP-1 in the scars. Compared with the control group, scar tissue in the experimental group was improved by color and texture. H&E-stained collagen fiber bundles were more organized after treatment as assessed by optical microscopy. The number of microvessels in the experimental group was decreased compared with that in the control group. Microvascular density was significantly reduced in the experimental group compared with the control group (27.16 ± 5.64 and 48.75 ± 8.25 mm 2 , respectively; P < 0.01). The mean optical densities of IL-8 and MCP-1 were significantly reduced in the experimental group compared with the control group (IL-8 0.016 ± 0.011 and 0.078 ± 0.023, respectively; MCP-1 0.018 ± 0.016 and 0.054 ± 0.038, respectively; both P < 0.01). The micro-plasma radio-frequency technique has a therapeutic effect on hypertrophic scars in rabbit ears.

Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat because of the wide spectrum of clinical manifestations. Therefore, the current clinical management strategies are nonspecific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch, and immune dysregulation. However, the precise roles played by effector cells and cytokines have not been fully elucidated. To address this, we established a prolonged model of AD, using MC903. The phenotype of this MC903 model closely resembles the one observed in AD patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, thereby providing a platform to evaluate targets for the treatment of AD. This model exposed cells and cytokines that are critically associated with disease severity, including eosinophils, TSLP, and IL-4/IL-13. Indeed, eosinophil depletion significantly ameliorated AD pathology, most notably barrier dysfunction, to a similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6. Thus, this study has identified eosinophils to be critical for the development and maintenance of AD, thereby proposing these effector cells as therapeutic targets for the treatment of AD., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Vertigo and dizziness are frequent chief complaints in clinical practice. Symptoms may originate from otological, neurological, medical and psychiatric etiologies, which poses an interdisciplinary challenge. Systematic analysis of case history and clinical examination generally allow classification into peripheral-, central- or non-vestibular disorders. The most important criteria for differentiation are the timeline, quality of symptoms, modulating factors and accompanying symptoms. As concerns the clinical examination, the following tests are relevant: head impulse test, test for spontaneous nystagmus, positional nystagmus, central ocular motor signs and the Romberg test. However, neuro-otological disorders with combined peripheral and central vestibular pathology do exist. Occlusion of the anterior inferior cerebellar artery results in ischemia of the labyrinth and cerebellum and therefore causes acute vestibular syndrome and unilateral hearing loss. Repetitive attacks of vertigo or dizziness which are accompanied by ear symptoms and headaches may be due to an overlap syndrome of Menière's disease and vestibular migraine. In this case patients often have to be treated with a dual prophylactic medication to control symptoms. In case of chronic dizziness and instability of gait a subsample of patients may suffer from CANVAS, which is a combination of bilateral vestibulopathy, a cerebellar syndrome and polyneuropathy. Chronic dizziness with signs of peripheral and central vestibular dysfunction can also originate from tumors of the cerebellopontine angle with compression of central structures. In conclusion, the diagnostic algorithm in the workup of patients with vertigo and dizziness should always include tests for peripheral and central vestibular and ocular motor function.

Purpose: Tendon tears are common injuries that heal with scar formation. Interestingly, MRL/MpJ mice heal without scar in several tissues, including tendon. Most hypotheses regarding scarless healing implicate the systemic environment. However, the tissue-specificity of this regenerative response and our previous findings showing regeneration of sub-rupture tendon injuries, which lack an overt systemic response, motivate a tissue-driven hypothesis. Our objective is to investigate the potential of the local tendon environment in driving scarless healing (1) by comparing the systemic response and the healing capacity associated with ear and tendon injuries in MRL/MpJ mice, and (2) by comparing intrinsic healing properties between MRL/MpJ and normal healer C57Bl/6 tendons., Methods: We examined the systemic inflammatory and local structural environments of ear and tendon punch injuries in MRL/MpJ and C57Bl/6 mice. Systemic differences were analyzed to assess effects of different injuries on the inflammatory response. Correlations were assessed between MRL/MpJ ear and tendon injuries to compare the extent of healing between regenerative tissues., Results: Analysis showed similarities between the systemic environment in MRL/MpJ post ear or tendon injuries. However, comparable inflammatory responses did not translate into analogous healing between tissues, suggesting that the systemic environment is not the driver of regeneration. Supporting the regenerative role of the local environment, healing MRL/MpJ tendons exhibited improved matrix and cell alignment and a distinct composition of growth factors and Hyaluronan from C57Bl/6., Conclusion: These findings support the tissue-driven hypothesis for MRL/MpJ tendon regeneration and motivate further investigation regarding specific roles of extracellular factors in scarless healing.

Acne vulgaris (acne) is a common inflammatory skin disorder, and Propionibacterium acnes plays a major role in the development and progression of acne inflammation. Herbs possessing antimicrobial and anti-inflammatory activity have been applied as a medical option for centuries. In this study, we examined the suppressive effect of ethanolic oregano ( Origanum vulgare ) extract on live P. acnes -induced in vivo and in vitro inflammation. Following ethanol extraction of oregano leaves, four compounds with strong antioxidant activity, including rosmarinic acid, quercetin, apigenin, and carvacrol, were identified by high-performance liquid chromatography. Using the mouse ear edema model, we demonstrated that ethanol oregano extracts (EOE) significantly suppressed P. acnes -induced skin inflammation, as measured by ear thickness (32%) and biopsy weight (37%). In a separate study, using the co-culture of P. acnes and human THP-1 monocytes, EOE reduced the production of interleukin (IL)-8, IL-1β and tumor necrosis factor (TNF)-α up to 40%, 37%, and 18%, respectively, as well as the expression of these three pro-inflammatory mediators at the transcriptional level. Furthermore, EOE inhibited the translocation of nuclear factor-kappa B (NF-κB) into the nucleus possibly by inactivating toll-like receptor-2 (TLR2). The suppressive effect of EOE on live P. acnes -induced inflammatory responses could be due, in part, to the anti-inflammatory and antioxidant properties, but not the anti-microbial effect of EOE.

Purpose: To analyze the effects of micro-beam irradiation (MBI) on the normal tissues of the mouse ear., Methods and Materials: Normal mouse ears are a unique model, which in addition to skin contain striated muscles, cartilage, blood and lymphatic vessels, and few hair follicles. This renders the mouse ear an excellent model for complex tissue studies. The ears of C57BL6 mice were exposed to MBI (50-μm-wide micro-beams, spaced 200 μm between centers) with peak entrance doses of 200, 400, or 800 Gy (at ultra-high dose rates). Tissue samples were examined histopathologically, with conventional light and electron microscopy, at 2, 7, 15, 30, and 240 days after irradiation (dpi). Sham-irradiated animals acted as controls., Results: Only an entrance dose of 800 Gy caused a significant increase in the thickness of both epidermal and dermal ear compartments seen from 15 to 30 dpi; the number of sebaceous glands was significantly reduced by 30 dpi. The numbers of apoptotic bodies and infiltrating leukocytes peaked between 15 and 30 dpi. Lymphatic vessels were prominently enlarged at 15 up to 240 dpi. Sarcomere lesions in striated muscle were observed after all doses, starting from 2 dpi; scar tissue within individual beam paths remained visible up to 240 dpi. Cartilage and blood vessel changes remained histologically inconspicuous., Conclusions: Normal tissues such as skin, cartilage, and blood and lymphatic vessels are highly tolerant to MBI after entrance doses up to 400 Gy. The striated muscles appeared to be the most sensitive to MBI. Those findings should be taken into consideration in future micro-beam radiation therapy treatment schedules., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The right jugular foramen is usually larger than the left in Homo sapiens, but it is unknown if right-sided jugular dominance is also more common amongst those with unilateral congenital aural atresia. We hypothesized that the dominant (i.e. larger) jugular foramen in children with isolated, non-syndromic, unilateral congenital aural atresia would be contralateral to the atretic ear., Methods: We reviewed high-resolution computed tomography scans of the temporal bones of 70 children with isolated, non-syndromic, unilateral congenital aural atresia. Images were viewed in the transverse (axial) plane by a board-certified neuroradiologist and a board-certified otolaryngologist. Consensus opinion was recorded. Multiple logistic regression was used to assess the impact of age, sex, and side of aural atresia on jugular dominance., Results: Jugular foramen dominance was not associated with the side of aural atresia (P = 0.20), age (P = 0.50) or sex (P = 0.76). Right-sided jugular dominance (46/70, 65.7%) was more common in both left- and right-sided unilateral aural atresia (P = 0.004)., Conclusions: The side of jugular foramen dominance is not associated with the side of aural atresia in children with isolated, non-syndromic, unilateral congenital aural atresia. Right-sided jugular dominance is more common irrespective of unilateral aural atresia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vague complaints of ear pain can bring frustration in the neurology office as the differential is broad and often nonneurologic. Herein, we present a case of red ear syndrome, a treatable migraine variant that can cause significant distress and lead to delayed treatment if not considered as a diagnostic possibility., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of magnetic resonance imaging (MRI) for diagnosing superior semicircular canal dehiscence (SSCD)., Materials and Methods: The radiological records of patients who were admitted to our clinic with complaints of otologic and neuro-otologic symptoms between October 2014 and December 2015 were retrospectively reviewed. Among these patients, those who underwent both computed tomography and MRI and were reported to have SSCD in the temporal bone on at least one side were included in the study group. MRI records of patients with a confirmed diagnosis were then assessed for the presence of SSCD., Results: The left and right semicircular canals of 52 patients were evaluated in this study. The sensitivity and specificity of MRI in the diagnosis of SSCD was 89.06% and 90%, respectively. The positive and negative predictive values were 93.44% and 83.72%, respectively., Conclusion: The use of multiplanar reformats and angulation techniques during MRI assessment of patients with neuro-otologic symptoms can improve the diagnostic process for patients with SSCD. This may allow early diagnosis of the disease by using just one imaging method, which would also reduce the costs per patient during the diagnosis period.

Here, we present a protocol of a whole-mount adult ear skin imaging technique to study comprehensive three-dimensional neuro-vascular branching morphogenesis and patterning, as well as immune cell distribution at a cellular level. The analysis of peripheral nerve and blood vessel anatomical structures in adult tissues provides some insights into the understanding of functional neuro-vascular wiring and neuro-vascular degeneration in pathological conditions such as wound healing. As a highly informative model system, we have focused our studies on adult ear skin, which is readily accessible for dissection. Our simple and reproducible protocol provides an accurate depiction of the cellular components in the entire skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann cells), blood vessels (endothelial cells and vascular smooth muscle cells), and inflammatory cells. We believe this protocol will pave the way to investigate morphological abnormalities in peripheral nerves and blood vessels as well as the inflammation in the adult ear skin under different pathological conditions.

Analysis of neural structures in Menière's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.