Design, prototype development and pre-clinical validation of a novel instrument with a compliant steerable tip to facilitate endoscopic ear surgery.

ola Kala shared this article with you from Inoreader Design, prototype development and pre-clinical validation of a novel instrument with a compliant steerable tip to facilitate endoscopic ear surgery. Μέσω pubmed: hearing and balance Related Articles Design, prototype development and pre-clinical validation of a novel instrument with a compliant steerable tip to facilitate endoscopic ear surgery. J Med Eng Technol. 2020 Nov 16;:1-13 Authors: Swarup A, Eastwood KW, Francis P, Chayaopas N, Kahrs LA, Leonard CG, Drake J, James A Abstract This work presents the design of a novel compliant steerable tip (CST) instrument to facilitate transcanal (or totally) endoscopic ear surgery (TEES). The evolution of the instrument's design is shown, where prototypes were evaluated by surgeons and their feedback was used to inform the design changes for the next prototype iteration. The final prototype enables the surgeon to articulate the compliant tip to achieve the desired bending curvature while automatically locking in place and providing dissection and suction capabilities. Pre-clinical validation testing was performed in goat and human cadaver models by two surgeons who successfully removed an allograft from the middle ear. Time and the number of blockages while suctioning saline in both cadaver models were measured and compared with current instruments used during TEES. The CST took significantly less time to suction saline within a flooded middle ear compared to the Panetti suction dissector (PSD) for atticus and u nderwent less blockages than the PSD for atticus, ear drum and sinus tympani instruments, Wilcoxon Method p < .05. Our study demonstrates the development and successful clinical evaluation of a minimally invasive surgical instrument designed to facilitate endoscopic approaches to the ear. PMID: 33191826 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy.

ola Kala shared this article with you from Inoreader Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy. Μέσω pubmed: hearing and balance Related Articles Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy. Front Genet. 2020;11:565216 Authors: Whatley M, Francis A, Ng ZY, Khoh XE, Atlas MD, Dilley RJ, Wong EYM Abstract Usher syndrome (USH) is an autosomal recessive (AR) disorder that permanently and severely affects the senses of hearing, vision, and balance. Three clinically distinct types of USH have been identified, decreasing in severity from Type 1 to 3, with symptoms of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP), and vestibular dysfunction. There are currently nine confirmed and two suspected USH-causative genes, and a further three candidate loci have been mapped. The proteins encoded by these genes form complexes that play critical roles in the development and maintenance of cellular structures within the inner ear and retina, which have minimal capacity for repair or regeneration. In the cochlea, stereocilia are located on the apical surface of inner ear hair cells (HC) and are responsible for transducing mechanical stimuli from sound pressure waves into chemical signals. These signals are then detected by the auditory nerve fibers, transmitted to the brain and in terpreted as sound. Disease-causing mutations in USH genes can destabilize the tip links that bind the stereocilia to each other, and cause defects in protein trafficking and stereocilia bundle morphology, thereby inhibiting mechanosensory transduction. This review summarizes the current knowledge on Usher syndrome with a particular emphasis on mutations in USH genes, USH protein structures, and functional analyses in animal models. Currently, there is no cure for USH. However, the genetic therapies that are rapidly developing will benefit from this compilation of detailed genetic information to identify the most effective strategies for restoring functional USH proteins. PMID: 33193648 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intratympanal administration of lidocaine in the management of Ménière's Disease.

ola Kala shared this article with you from Inoreader Intratympanal administration of lidocaine in the management of Ménière's Disease. Μέσω pubmed: "acta otolaryngol"[j... Related Articles Intratympanal administration of lidocaine in the management of Ménière's Disease. Acta Otolaryngol. 2020 Nov 16;:1-7 Authors: Bertlich M, Ihler F, Spiegel JL, Canis M, Weiss BG Abstract BACKGROUND: Ménière's Disease (MD) is a chronic condition where patients suffer recurrent vertigo attacks. Evidence for treatment concepts are to this date low. AIMS/OBJECTIVE: To evaluate the therapeutic effect of intratympanic lidocaine injections to reduce the number of attacks. METHODS: Twenty patients diagnosed with definitive MD that were treated with 34 intratympanic lidocaine injections were included. Main outcome measures were the number of vertigo attacks in the previous four weeks, the attack free period and the subjective improvement of the condition. RESULTS: Mean follow up after first lidocaine injection was 25.3 months (±22.2; range 1.9-79.7). Patients expressed subjective improvement in overall situation, vertigo, and aural fullness. The number of vertigo attacks before each assessment decreased from 7.1 (±5.9; range 2-20) per months at baseline to 1.9 (±3.8; range 0-15). 25% of the patients suffered no further attacks, the other patients had an average attack free period of 7.8 months (±15.4; range 0.2-58.4). Hearing thresholds remained unaffected. Repetitive injections proved effective. CONCLUSION AND SIGNIFICANCE: Intratympanic lidocaine is an effective nonsurgical and non-ablative therapy for MD. When patients experience an increase of attacks repetitive injections promise improvement. PMID: 33190578 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Urine Microbial Extracellular Vesicles Can Be Potential and Novel Biomarkers for Allergic Diseases.

ola Kala shared this article with you from Inoreader Urine Microbial Extracellular Vesicles Can Be Potential and Novel Biomarkers for Allergic Diseases. Μέσω pubmed: "allergy asthma immu... Related Articles Urine Microbial Extracellular Vesicles Can Be Potential and Novel Biomarkers for Allergic Diseases. Allergy Asthma Immunol Res. 2021 Jan;13(1):5-7 Authors: Choi Y, Park HS, Jee YK PMID: 33191673 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biology and Function of Eosinophils in Chronic Rhinosinusitis With or Without Nasal Polyps.

ola Kala shared this article with you from Inoreader Biology and Function of Eosinophils in Chronic Rhinosinusitis With or Without Nasal Polyps. Μέσω pubmed: "allergy asthma immu... Related Articles Biology and Function of Eosinophils in Chronic Rhinosinusitis With or Without Nasal Polyps. Allergy Asthma Immunol Res. 2021 Jan;13(1):8-22 Authors: Bochner BS, Stevens WW Abstract Chronic rhinosinusitis (CRS) with or without nasal polyposis is a complex medical condition characterized by varying patterns of chronic innate and adaptive mucosal inflammation. Treatment of CRS has been traditionally limited to corticosteroids and sinus surgery; however, novel biologics have more recently been evaluated as steroid- and surgery-sparing options. While it is clear that there are different subtypes or endotypes of CRS, perhaps the most frequent presentation involves the features of type 2 inflammation, including a prominent tissue eosinophilia component. The purpose of this review is to provide an update on eosinophil biology as well as on the potential contribution of eosinophils and their mediators to the pathophysiology of CRS, drawing mechanistic conclusions mainly from studies of human sinus mucosal tissues, nasal secretions, and benefits (or lack thereof) from the use of various pharmacotherapies. The unavoidable conclusion derived from this approach is t hat eosinophils themselves cannot fully explain the underlying pathophysiology of this complex disorder. PMID: 33191674 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bioengineering of Virus-like Particles for the Prevention or Treatment of Allergic Diseases.

ola Kala shared this article with you from Inoreader Bioengineering of Virus-like Particles for the Prevention or Treatment of Allergic Diseases. Μέσω pubmed: "allergy asthma immu... Related Articles Bioengineering of Virus-like Particles for the Prevention or Treatment of Allergic Diseases. Allergy Asthma Immunol Res. 2021 Jan;13(1):23-41 Authors: Pechsrichuang P, Namwongnao S, Jacquet A Abstract Recent findings on the mechanism of allergen-specific immunotherapy (AIT) have revisited the role of immunoglobulin G (IgG) as the development of specific blocking IgG antibodies appeared critical for the successful suppression of T-helper 2 (Th2)-biased allergic responses. Consequently, any form of molecular AIT-promoting potent allergen-specific neutralizing antibodies would be preferred to conventional administration of allergen extracts. The potent immunogenicity of virus-like particles (VLPs) could be harnessed for that purpose. The particle size (20-200 nm) optimizes uptake by antigen-presenting cells as well as lymphatic trafficking. Moreover, the display of antigens in repetitive arrays promotes potent B cell activation for the development of sustained antibody responses. The presentation of self-antigens on the particle surface was even capable to break B cell tolerance. In this review, we describe the immunomodulatory properties of the 3 VLP-based strategies designe d so far for the treatment of allergic disease: VLP packaged with CpG motifs as well as chimeric particles displaying pro-Th2/Th2 cytokines or allergens (full-length or B cell epitopes). PMID: 33191675 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Heterogeneity of Childhood Asthma in Korea: Cluster Analysis of the Korean Childhood Asthma Study Cohort.

ola Kala shared this article with you from Inoreader Heterogeneity of Childhood Asthma in Korea: Cluster Analysis of the Korean Childhood Asthma Study Cohort. Μέσω pubmed: "allergy asthma immu... Related Articles Heterogeneity of Childhood Asthma in Korea: Cluster Analysis of the Korean Childhood Asthma Study Cohort. Allergy Asthma Immunol Res. 2021 Jan;13(1):42-55 Authors: Yoon J, Eom EJ, Kim JT, Lim DH, Kim WK, Song DJ, Yoo Y, Suh DI, Baek HS, Shin M, Kwon JW, Jang GC, Yang HJ, Lee E, Kim HS, Seo JH, Woo SI, Kim HY, Shin YH, Lee JS, Jung S, Han M, Yu J Abstract PURPOSE: Asthma is a heterogeneous airway disease occurring in children, and it has various clinical phenotypes. A clear differentiation of the clinical phenotypes can provide better asthma management and prediction of asthma prognosis. Little is currently known about asthma phenotypes in Korean children. This study was designed to identify asthma phenotypes in school-aged Korean children. METHODS: This study enrolled 674 children with physician-diagnosed asthma from the Korean childhood Asthma Study (KAS) cohort. The physicians verified the relevant histories of asthma and comorbid diseases, as well as airway lability and hyper-responsiveness from the results of pulmonary function tests and bronchial provocation tests. Questionnaires regarding the participants' baseline characteristics, their environment and self-rating of asthma control were collected at the time of enrollment. Laboratory tests were performed to assess allergy and airway inflammation. Children with asthma were classified by hierarchical cluster analysis. RESULTS: Of the 674 patients enrolled from the KAS cohort, 447 were included in the cluster analysis. Cluster analysis of these 447 children revealed 4 asthma phenotypes: cluster 1 (n = 216, 48.3%) which was characterized by male-dominant atopic asthma; cluster 2 (n = 79, 17.7%) which was characterized by early-onset atopic asthma with atopic dermatitis; cluster 3 (n = 47, 10.5%) which was characterized by puberty-onset, female-dominant atopic asthma with the low lung function; and cluster 4 (n = 105, 23.5%) which was characterized by early-onset, non-atopic dominant asthma. CONCLUSIONS: The asthma phenotypes among Korean children can be classified into 4 distinct clusters. Long-term follow-up with these phenotypes will be needed to define their prognosis and response to treatment. PMID: 33191676 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bacterial Microbiota-derived Extracellular Vesicles in Children With Allergic Airway Diseases: Compositional and Functional Features.

ola Kala shared this article with you from Inoreader Bacterial Microbiota-derived Extracellular Vesicles in Children With Allergic Airway Diseases: Compositional and Functional Features. Μέσω pubmed: "allergy asthma immu... Related Articles Bacterial Microbiota-derived Extracellular Vesicles in Children With Allergic Airway Diseases: Compositional and Functional Features. Allergy Asthma Immunol Res. 2021 Jan;13(1):56-74 Authors: Samra MS, Lim DH, Han MY, Jee HM, Kim YK, Kim JH Abstract PURPOSE: Bacterial extracellular vesicles (EVs) play crucial roles in bacteria-host interactions. Due to their cargo, EVs are considered fingerprints of the parent cell, which are detectable in body fluids. We studied the composition and function of bacterial microbiota-derived EVs genes in urine to evaluate whether they have specific characteristics concerning allergic airway disease. METHODS: Subjects were from elementary school surveys and classified into 3 groups according to questionnaires and sensitization to aeroallergens: the allergic airway group (AA, n = 16), atopic controls (AC, n = 7) and healthy controls (HC, n = 26). The bacterial EVs were isolated from voided urine samples, their nucleic acid was extracted for 16S ribosomal RNA pyrosequencing and then characterized using α-diversity, β-diversity, network analysis, intergroup comparison of bacterial composition and predicted functions, and correlation with total immunoglobulin E (IgE), eosinophils% and fractional exhaled NO. RESULTS: The compositional α-diversity was the highest in AA, while functional α-diversity was the highest in HC. AA had a distinct clustering with the least intersample variation. Klebsiella, Haemophilus, members from Lachnospiraceae and Ruminococcaceae, and the pathways of sphingolipid and glycerolipid metabolism, and biosynthesis of peptidoglycan and lysine were the highest in AA and positively correlated with total IgE or eosinophil%. Genetic information processing function contributed to 48% of the intergroup variance and was the highest in AA. Diaphorobacter, Acinetobacter, and the pathways of short-chain fatty acids and anti-oxidants metabolism, lysine and xenobiotic degradation, and lipopolysaccharide biosynthesis were the lowest in AA and negatively correlated with total IgE or eosinophil%. The bacterial composition and function in AC were closer to those in HC. The bacterial network was remarkably dense in HC. CONCLUSIONS: The bacterial microbiota-derived EVs in urine possess characteristic features in allergic airway disease with a remarkable correlation with total IgE and eosinophil%. These findings suggest that they may play important roles in allergic airway diseases. PMID: 33191677 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Urine Microbe-Derived Extracellular Vesicles in Children With Asthma.

ola Kala shared this article with you from Inoreader Urine Microbe-Derived Extracellular Vesicles in Children With Asthma. Μέσω pubmed: "allergy asthma immu... Related Articles Urine Microbe-Derived Extracellular Vesicles in Children With Asthma. Allergy Asthma Immunol Res. 2021 Jan;13(1):75-87 Authors: Lee YS, Kim JH, Lim DH Abstract PURPOSE: Several studies have found significant associations between asthma and microbiome. However, it is challenging to obtain-sputum and bronchoalveolar lavage samples from pediatric patients. Thus, we used voided urine to show that urine microbe-derived extracellular vesicles (EVs) in asthma are an available source for clinical research. METHODS: Five urine samples were obtained at 2-3-month intervals from each patient with asthma (n = 20), and a single voided urine sample were obtained from each healthy child (n = 20). After isolating EVs, 16S rDNA pyrosequencing was performed. The Chao1 index and principal coordinate analysis (PCoA) were used to assess diversity. To predict microbiota functional capacities, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used based on the Kyoto Encyclopedia of Genes and Genomes pathway database. Eight covariates were included in the EnvFit analysis to identify significant factors in the asthma group. RESULTS: The asthma group showed lower Chao1 bacterial richness, and PCoA-based clustering differed significantly. Two phyla, and 13 families and genera were enriched or depleted. Functional profiling revealed significant differences between the asthma and control groups. EnvFit analysis of correlation to age, sex, body mass index, infection, season, asthma phenotype, severity, and symptoms was not significant except for infections associated with visit 1 and the season of visit 2. CONCLUSIONS: This study showed that microbe-derived EVs were constantly altered in the urine of children with asthma, consistent with the findings of previous studies indicating microbiome changes in the lung and gut. The urine may reflect the specific pattern of microbiome EVs in children with asthma. PMID: 33191678 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling.

ola Kala shared this article with you from Inoreader The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling. Μέσω pubmed: "allergy asthma immu... Related Articles The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling. Allergy Asthma Immunol Res. 2021 Jan;13(1):88-105 Authors: Li R, Wang F, Wei J, Lin Y, Tang G, Rao L, Ma L, Xu Q, Wu J, Lv Q, Zhou R, Lei H, Zhao X, Yao D, Xiao B, Huang H, Zhang J, Mo B Abstract PURPOSE: Recent studies have demonstrated that macrophage migration inhibitory factor (MIF) is of importance in asthmatic inflammation. The role of MIF in modulating airway remodeling has not yet been thoroughly elucidated to date. In the present study, we hypothesized that MIF promoted airway remodeling by intensifying airway smooth muscle cell (ASMC) autophagy and explored the specific mechanisms. METHODS: MIF knockdown in the lung tissues of C57BL/6 mice was conducted by instilling intratracheally adeno-associated virus (AAV) vectors (MIF-mutant AAV9) into mouse lung tissues. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/-) was used to detect the role of autophagy in ovalbumin (OVA)-asthmatic murine models. Moreover, to block the expression of MIF and CD74 in vitro models, inhibitors, antibodies and lentivirus transfection techniques were employed. RESULTS: First, MIF knockdown in the lung tissues of mice showed markedly reduced airway remodeling in OVA murine mice models. Secondly, ASMC autophagy was increased in the OVA-challenged models. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/-) that were primed and challenged with OVA showed lower airway remodeling than genetically wild-type asthmatic mice. Thirdly, MIF can induce ASMC autophagy in vitro. Moreover, the cellular source of MIF which promoted ASMC autophagy was macrophages. Finally, MIF promoted ASMC autophagy in a CD74-dependent manner. CONCLUSIONS: MIF can increase asthmatic airway remodeling by enhancing ASMC autophagy. Macrophage-derived MIF can promote ASMC autophagy by targeting CD74. PMID: 33191679 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of an Antagonistic Peptide of CCR5 on the Expression of Autophagy-related Genes and β-Arrestin 2 in Lung Tissues of Asthmatic Mice.

ola Kala shared this article with you from Inoreader Effect of an Antagonistic Peptide of CCR5 on the Expression of Autophagy-related Genes and β-Arrestin 2 in Lung Tissues of Asthmatic Mice. Μέσω pubmed: "allergy asthma immu... Related Articles Effect of an Antagonistic Peptide of CCR5 on the Expression of Autophagy-related Genes and β-Arrestin 2 in Lung Tissues of Asthmatic Mice. Allergy Asthma Immunol Res. 2021 Jan;13(1):106-121 Authors: Liu J, Liang R, Huang H, Zhang Y, Xie A, Zhong Y Abstract PURPOSE: The mechanisms of CC chemokine receptor 5 (CCR5) in the process of autophagy remain unknown. In this study, we examined the role of HY peptide, which is an antagonistic peptide specifically binding the second extracellular loop of CCR5, in the expression of autophagy genes and β-arrestin 2 in lung tissues of asthmatic mice. METHODS: Experimental asthmatic mice were treated with HY peptide and dexamethasone sodium phosphate (Dex). Airway inflammation, autophagy-related genes, autophagic vacuoles (AVs) and β-arrestin 2 were examined in lung tissues, and the correlation between β-arrestin 2 and LC3 expression was assessed. RESULTS: HY peptide and Dex treatments alleviate airway inflammation. The expression of autophagy-related genes, such as BECN1, ATG5 and LC3, was decreased in the lung tissues of the asthmatic mice. However, HY peptide and Dex treatments increased the expression of these genes as well as the formation of AVs. Additionally, the expression of the β-arrestin 2 protein was significantly increased in the HY peptide-treated group, and positive cells expressing β-arrestin 2 were mainly located in the membrane and cytoplasm of bronchial epithelial cells. The β-arrestin 2 expression was positively correlated with the expression of LC3 in the model and HY peptide-treated groups. CONCLUSIONS: HY peptide inhibits airway inflammation, autophagic dysfunction exists in asthmatic mice, and targeting HY peptide increases the expression of autophagy-related genes. Thus, β-arrestin 2 may participate in the mechanisms underlying these processes. PMID: 33191680 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.