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3.
Vet J ; 271: 105655, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33840482

RESUMO

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 ß-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.


Assuntos
Orelha/patologia , Necrose/veterinária , Sus scrofa , Doenças dos Suínos/patologia , Animais , Antibacterianos/uso terapêutico , Abrigo para Animais , Infecções/veterinária , Necrose/microbiologia , Necrose/terapia , Fatores de Risco , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/etiologia , Desmame
4.
Sensors (Basel) ; 21(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922456

RESUMO

OBJECTIVES: This paper aims to validate the performance and physical design of a wearable, unobtrusive ear-centered electroencephalography (EEG) device, dubbed "EARtrodes", using early and late auditory evoked responses. Results would also offer a proof-of-concept for the device to be used as a concealed brain-computer interface (BCI). DESIGN: The device is composed of a custom-fitted earpiece and an ergonomic behind-the-ear piece with embedded electrodes made of a soft and flexible combination of silicone rubber and carbon fibers. The location of the conductive silicone electrodes inside the ear canal and the optimal geometry of the behind-the-ear piece were obtained through morphological and geometrical analysis of the human ear canal and the region around-the-ear. An entirely conductive generic earpiece was also developed to assess the potential of a universal, more affordable solution. RESULTS: Early latency results illustrate the conductive silicone electrodes' capability to record quality EEG signals, comparable to those obtained with traditional gold-plated electrodes. Additionally, late latency results demonstrate EARtrodes' capacity to reliably detect decision-making processes from the ear. CONCLUSIONS: EEG results validate the performance of EARtrodes as a circum-aural and intra-aural EEG recording system adapted for a wide range of applications in audiology, neuroscience, clinical research, and as an unobtrusive BCI.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Orelha , Meato Acústico Externo , Eletrodos , Potenciais Evocados Auditivos , Humanos
5.
Medicine (Baltimore) ; 100(8): e24753, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663090

RESUMO

BACKGROUND: Archery has existed in human history for millenniums. Being a unique exercise and precision sport, the keys to performance are emotional control, attention, and concentration rather than explosive force, muscle power, and endurance. During the execution of archery, attention is the key to performance in elite players, especially in the initial period while drawing the bow. Auricular acupoint stimulation is one of the therapeutic methods of traditional Chinese medicine and has been reported for its use in amplifying the anesthesia effect, weight reduction, cessation of substance abuse, and autonomic nervous modulation. METHODS: The study will recruit archery players in school teams among junior and senior high schools and colleges. The subjects will be randomly assigned to the ear and sham acupressure groups. This is a randomized controlled trial with crossover design. The outcome measures will be obtained, including the meridian activities and balance index with Ryodoraku device, the movement stability with WIMU tracking system, the continuous heart rate record, and the scores of the 2 sections as the performance. The subjects will rate their attention and fatigue levels through self-reported questionnaires. OBJECTIVES: This study aims to investigate the immediate effect of non-invasive auricular acupoint stimulation on the performance and meridian activities of archery athletes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04637607.


Assuntos
Acupressão/métodos , Atletas , Orelha/fisiologia , Pontos de Acupuntura , Adolescente , Atenção/fisiologia , Estudos Cross-Over , Fadiga/terapia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Meridianos
6.
J Laryngol Otol ; 135(2): 117-124, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33612142

RESUMO

BACKGROUND: Coronavirus disease 2019 imposed dramatic changes on ENT service delivery. Pre-pandemic, such changes would have been considered potentially unsafe. This study outlines the impact of lockdown on the incidence and management of ENT emergencies at a large UK centre. METHODS: After modification of pre-pandemic guidelines, ENT emergency referrals data during the UK lockdown were prospectively captured. A comparative analysis was performed with retrospective data from a corresponding period in 2019. RESULTS: An overall reduction (p < 0.001) in emergency referrals (n = 119) and admissions (n = 18) occurred during the lockdown period compared to the 2019 period (432 referrals and 290 admissions). Specifically, there were reduced admission rates for epistaxis (p < 0.0001) and tonsillar infection (p < 0.005) in the lockdown period. During lockdown, 90 per cent of patients requiring non-dissolvable nasal packing were managed as out-patients. CONCLUSIONS: Coronavirus disease 2019 compelled modifications to pre-pandemic ENT guidelines. The enforced changes to emergency care appear to be safe and successfully adopted. Arguably, the measures have both economic and patient-related implications post-coronavirus disease 2019 and during future similar pandemics and lockdowns.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , COVID-19 , Epistaxe/terapia , Hospitalização/estatística & dados numéricos , Abscesso Peritonsilar/terapia , Tonsilite/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Orelha , Otopatias/epidemiologia , Otopatias/terapia , Emergências , Serviço Hospitalar de Emergência , Epistaxe/epidemiologia , Feminino , Corpos Estranhos/epidemiologia , Corpos Estranhos/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Otorrinolaringopatias/epidemiologia , Otorrinolaringopatias/terapia , Abscesso Peritonsilar/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta/tendências , SARS-CoV-2 , Tonsilite/epidemiologia , Reino Unido/epidemiologia , Adulto Jovem
7.
J Am Board Fam Med ; 34(Suppl): S183-S185, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33622835

RESUMO

The worldwide spread of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic since its identification in Wuhan, China in December 2019.1 Few cases of COVID-19-associated dermatologic manifestations have been reported in the literature to date. This report describes the clinical features of a localized pruritic scarlatiniform rash of the ears and antecubital fossa on defervescence in a 29-year-old patient with COVID-19. Our case stands to further illuminate the dermatologic manifestations of this novel disease.


Assuntos
COVID-19/complicações , Dermatopatias/etiologia , Adulto , Orelha , Cotovelo , Humanos , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Dermatopatias/virologia
8.
Otol Neurotol ; 42(4): e476-e482, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534387

RESUMO

OBJECTIVE: To determine reasons for premature termination in surgery for congenital aural atresia (CAA). STUDY DESIGN: Retrospective chart review. SETTING: High-volume tertiary care center. PATIENTS: Patients undergoing primary surgical repair of CAA whose surgeries were aborted for various indications. INTERVENTION: Patients with CAA who underwent elective aural atresia surgery at the University of Virginia from July 2004 to January 2020 were identified from the medical record and an institutional database of patients with CAA. Patients undergoing revision surgery or surgery not for hearing correction were excluded. All included candidates were noted to be good surgical candidates for atresia repair based on preoperative Jahrsdoerfer score of 6 or greater. Reasons for terminating surgery prematurely were categorized by anatomical constraints (inability to identify middle ear space, position of the facial nerve, or other anatomic abnormality), stapes fixation, and middle ear and/or mastoid inflammatory disease. MAIN OUTCOME MEASURES: Reasons for premature termination in CAA surgery. RESULTS: Over the interval, 319 patients underwent primary surgery for CAA. Surgery was terminated prematurely without completing the primary objective in 14 patients (4.4%); surgery was terminated in 8 (57%) due to anatomic constraints, 4 (29%) due to stapes fixation, and 2 (14%) due to middle ear space and/or mastoid inflammatory disease. CONCLUSIONS: Premature termination in surgery for CAA is a rare occurrence with careful study of the preoperative high-resolution computed tomography of the temporal bone. Of the reasons for premature termination, anatomic constraints were the most common. Knowing limitations in surgery-both technical and anatomic-is critical to optimize outcomes and prevent complications.


Assuntos
Anormalidades Congênitas , Orelha , Audiometria de Tons Puros , Anormalidades Congênitas/cirurgia , Orelha/cirurgia , Orelha Média , Humanos , Processo Mastoide , Estudos Retrospectivos
9.
Biochem Biophys Res Commun ; 546: 124-129, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33582554

RESUMO

Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) and prostacyclin (PGI2) synthase (PGIS) are PG terminal synthases that work downstream of cyclooxygenase and synthesize PGE2 and PGI2, respectively. Although the involvement of PG receptors in acquired cutaneous immune responses was recently shown, the roles of these PG terminal synthases remain unclear. To identify the pathophysiological roles of mPGES-1 and PGIS in cutaneous immune systems, we applied contact hypersensitivity (CHS) to mPGES-1 and PGIS knockout (KO) mice as a model of acquired immune responses. Mice were treated with 1-fluoro-2,4-dinitrobenzene (DNFB) and evaluated for ear thickness and histopathological features. The results showed that the severity of ear swelling in both gene-deficient mice was much lower than that in wild-type (WT) mice. Histological examination of DNFB-treated ears showed that inflammatory cell infiltration and edema in the dermis were also less apparent in both genotypic mice. LC-MS analysis further showed that the increment in PGE2 levels in DNFB-treated ear tissue was reduced in mPGES-1 KO mice, and that 6-keto PGF1α (a stable metabolite of PGI2) was not detected in PGIS KO mice. Furthermore, we made bone marrow (BM) chimera and found that transplantation of WT mouse-derived BM cells restored the impaired CHS response in mPGES-1 KO mice but did not restore the response in PGIS KO mice. These results indicated that mPGES-1 in BM-derived cells and PGIS in non-BM-derived cells might play critical roles in DNFB-induced CHS. mPGES-1-derived PGE2 and PGIS-derived PGI2 might coordinately promote acquired cutaneous immune responses.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Dermatite de Contato/enzimologia , Oxirredutases Intramoleculares/metabolismo , Prostaglandina-E Sintases/metabolismo , Transferência Adotiva , Animais , Células da Medula Óssea , Sistema Enzimático do Citocromo P-450/deficiência , Sistema Enzimático do Citocromo P-450/genética , Dermatite de Contato/etiologia , Dermatite de Contato/genética , Dinitrofluorbenzeno/efeitos adversos , Orelha/patologia , Feminino , Interferon gama/metabolismo , Interleucinas/metabolismo , Oxirredutases Intramoleculares/deficiência , Oxirredutases Intramoleculares/genética , Camundongos , Camundongos Knockout , Prostaglandina-E Sintases/deficiência , Prostaglandina-E Sintases/genética , Prostaglandinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Sensors (Basel) ; 21(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401407

RESUMO

In this work, a binaural model resembling the human auditory system was built using a pair of three-dimensional (3D)-printed ears to localize a sound source in both vertical and horizontal directions. An analysis on the proposed model was firstly conducted to study the correlations between the spatial auditory cues and the 3D polar coordinate of the source. Apart from the estimation techniques via interaural and spectral cues, the property from the combined direct and reverberant energy decay curve is also introduced as part of the localization strategy. The preliminary analysis reveals that the latter provides a much more accurate distance estimation when compared to approximations via sound pressure level approach, but is alone not sufficient to disambiguate the front-rear confusions. For vertical localization, it is also shown that the elevation angle can be robustly encoded through the spectral notches. By analysing the strengths and shortcomings of each estimation method, a new algorithm is formulated to localize the sound source which is also further improved by cross-correlating the interaural and spectral cues. The proposed technique has been validated via a series of experiments where the sound source was randomly placed at 30 different locations in an outdoor environment up to a distance of 19 m. Based on the experimental and numerical evaluations, the localization performance has been significantly improved with an average error of 0.5 m from the distance estimation and a considerable reduction of total ambiguous points to 3.3%.


Assuntos
Sinais (Psicologia) , Estimulação Acústica , Orelha , Humanos , Impressão Tridimensional , Localização de Som
11.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443188

RESUMO

Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in keratinocytes contributes to ACD and other skin disorders remain elusive. In this study, we generated conditional knockout mice in which the Hmgb1 gene is specifically deleted in keratinocytes, and examined its role in ACD models. Interestingly, the mutant mice showed exacerbated skin inflammation, accompanied by increased ear thickening in 2,4-dinitrofluorobenezene-induced ACDs. The mRNA expression of interleukin-24 (IL-24), a cytokine known to critically contribute to ACD pathogenesis, was elevated in skin lesions of the mutant mice. As with constitutively expressed, IL-4-induced Il24 mRNA, expression was also augmented in the Hmgb1-deficient keratinocytes, which would account for the exacerbation of ACD in the mutant mice. Mechanistically, we observed an increased binding of trimethyl histone H3 (lys4) (H3K4me3), a hallmark of transcriptionally active genes, to the promoter region of the Il24 gene in the hmgb1-deficient cells. Thus, the nuclear HMGB1 is a critical "gate keeper" in that the dermal homeostasis is contingent to its function in chromatin remodeling. Our study revealed a facet of nuclear HMGB1, namely its antiinflammatory function in keratinocytes for the skin homeostasis.


Assuntos
Montagem e Desmontagem da Cromatina , Dermatite Alérgica de Contato/metabolismo , Proteína HMGB1/metabolismo , Histonas/metabolismo , Interleucinas/metabolismo , Queratinócitos/metabolismo , Animais , Dermatite Alérgica de Contato/genética , Dermatite Alérgica de Contato/prevenção & controle , Dinitrofluorbenzeno/toxicidade , Modelos Animais de Doenças , Orelha/patologia , Deleção de Genes , Regulação da Expressão Gênica/genética , Proteína HMGB1/deficiência , Proteína HMGB1/genética , Inflamação/genética , Inflamação/metabolismo , Interleucina-4/farmacologia , Interleucinas/genética , Camundongos , Camundongos Knockout , Regiões Promotoras Genéticas , Pele/imunologia , Pele/metabolismo , Pele/patologia , Quimeras de Transplante
12.
Vet Surg ; 50(3): 677-686, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33491783

RESUMO

OBJECTIVES: To describe the use of near infrared fluorescence (NIRF) imaging with indocyanine green (ICG) for vascular visualization in two caudal auricular axial pattern flaps (APF). ANIMALS: Two client-owned cats with upper eyelid masses. STUDY DESIGN: Clinical case report. METHODS: Wide surgical excision with enucleation was performed by using a caudal auricular APF for closure. Flap margins and perforating artery location were approximated with anatomical landmarks. The caudal auricular artery origin was then visualized percutaneously by using an exoscope with NIRF camera and light source after a single 2.5-mg dose of IV ICG. Margins were adjusted as required. The flaps were routinely elevated with continued intraoperative visualization of the artery and rotated to complete closure. RESULTS: After IV ICG administration, fluorescence was initially visualized after 15 to 18 seconds and remained visible for up to 26 minutes. The achieved visualization led to flap margin adjustments in cat 1. Both cats recovered with minimal flap congestion, excellent hair regrowth, and no long-term complications (>186 days). Cat 1 experienced 100% flap survival. Cat 2 experienced 10% partial thickness flap necrosis, but revision was not required, and the flap was healed at recheck 85 days postoperatively. CONCLUSION: The use of ICG for APF vessel visualization prior to and during flap elevation resulted in transcutaneous visualization of the perforating vessel and improved awareness of vessel location intraoperatively. These two cats experienced excellent flap survival without major complications. This report highlights the potential benefits of ICG NIRF in APF for animals undergoing reconstructive surgery.


Assuntos
Doenças do Gato/diagnóstico por imagem , Corantes/administração & dosagem , Otopatias/veterinária , Orelha/diagnóstico por imagem , Verde de Indocianina/administração & dosagem , Imagem Óptica/veterinária , Retalhos Cirúrgicos/veterinária , Animais , Doenças do Gato/cirurgia , Gatos , Orelha/cirurgia , Otopatias/diagnóstico por imagem , Otopatias/cirurgia , Raios Infravermelhos , Masculino
13.
Trop Anim Health Prod ; 53(1): 74, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400045

RESUMO

The current study was undertaken to evaluate some morphological traits of the goat breeds raised in Southwest China. The field experimentation and data collection were from 434 animals presenting seven breeds of the Dazu black goat (DBG; n = 203), Saanen milk goat (SMG; n = 50), Black Boer × Dazu black goat (BXC; n = 28), Hechuan white goat (HWG; n = 49), Inner Mongolia Cashmere goat (IMCG; n = 25), IMCG × DBG (F1; n = 57) and F1 × F1 (F2; n = 22). All studied animals were adult and selected to be at the same age (36.50 ± 0.75 months). After editing, more than 20 morphological and production traits like body condition score (BCS), testicle measurements, coat colour, fibre traits, skin colour, horn colour, horn shape, horn orientation, wattles, front hair, beard, ear shape, ear size, rump angle, hind leg angulation and physiological variables were analysed. BXC and DBG had dark coat colour, whilst SMG, HWG and IMCG had light colour, whilst F1 and F2 ranged from light to dark coat colour. Concerning BCS, the breeds BXC and DBG were characterized as fat goats, whilst SMG, HWG, F1 and F2 were average, whilst IMCG was thin. The maximum values for testis measurements were recorded for BXC, SMG and DBG. For fibre traits, IMCG, F1 and F2 were the most superior. BXC and DBG males have good fertility parameters. The highest values for rectal temperature, skin temperature and breath rate were recorded for SMG. These findings revealed the presence of a wide range of morphological differences among studied goat breeds. Such diversity in the performance of goat breeds raised in Southwest China is crucial to implement reliable selection strategies for breeding goats in this area.


Assuntos
Cabras/anatomia & histologia , Cabras/fisiologia , Animais , Grupo com Ancestrais do Continente Asiático , Cruzamento , China , Cruzamentos Genéticos , Orelha/anatomia & histologia , Cabras/classificação , Cabelo/anatomia & histologia , Cor de Cabelo , Membro Posterior/anatomia & histologia , Cornos/anatomia & histologia , Humanos , Masculino , Leite , Fenótipo , Pigmentação da Pele , Testículo/anatomia & histologia
14.
Methods Mol Biol ; 2193: 85-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32808261

RESUMO

Lymphangiogenesis, the formation of lymphatic vessels from preexisting ones, is an important process in wound-healing physiology. Deregulation of lymphangiogenesis and lymphatic vascular remodeling have been implicated in a range of inflammatory conditions, such as lymphedema, lymphadenopathy, tumor growth, and cancer metastasis. Any attempt in understanding various parameters of the lymphangiogenic process and developing desirable therapeutic targets requires recapitulating these conditions in in vivo models. One pitfall with some experimental models is the absence of immune response, an important regulatory factor for lymphangiogenesis. We overcome this issue by using immune competent mice. In this chapter, by using Angiopoietin-2 (Ang2), a protein that belongs to the Ang/Tie signaling pathway, we describe the ear sponge assay with important adaptations, highlighting a reproducible and quantitative tool for assessment of in vivo lymphangiogenesis.


Assuntos
Bioensaio/métodos , Orelha/fisiopatologia , Linfangiogênese/fisiologia , Vasos Linfáticos/fisiologia , Angiopoietina-2/genética , Animais , Orelha/cirurgia , Humanos , Imunidade/imunologia , Imunidade/fisiologia , Linfangiogênese/genética , Linfangiogênese/imunologia , Vasos Linfáticos/imunologia , Camundongos , Transdução de Sinais/genética , Remodelação Vascular/genética , Remodelação Vascular/imunologia , Remodelação Vascular/fisiologia , Cicatrização/genética , Cicatrização/fisiologia
15.
Methods Mol Biol ; 2223: 87-100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226589

RESUMO

Allergic contact dermatitis (ACD) is a common skin disease with high prevalence in work environments. Human allergic contact dermatitis is triggered by the exposure to haptens that leads to an initial phase known as sensitization. During this phase, hapten-protein complexes presented by antigen-presenting cells activate a T-cell-mediated response, leading to the generation of memory cells against the hapten. Upon re-exposure to the same hapten, the elicitation phase is initiated. This phase is characterized by a quicker acute inflammatory response involving activation and/or infiltration of a variety of immune cell populations. Human ACD can be studied through the use of animal models of contact hypersensitivity (CHS). The 2,4-dinitrofluorobenzene (DNFB)-induced CHS model is a commonly used mouse model that has been helpful in the study of the mechanisms as well as potential therapeutic interventions of ACD. In this chapter I will provide a detailed protocol to develop acute DNFB-induced CHS in mice in a period of 7 days. In addition, I will discuss several key considerations for experimental design including best controls, potential expected outcomes, and sample collection.


Assuntos
Dermatite Alérgica de Contato/imunologia , Dinitrofluorbenzeno/farmacologia , Modelos Animais de Doenças , Histocitoquímica/métodos , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/patologia , Orelha , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microtomia , Inclusão em Parafina , Pele/imunologia , Pele/patologia
16.
Methods Mol Biol ; 2223: 151-157, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226593

RESUMO

The regulation of vascular permeability is critical in inflammation. It controls the distribution of water and plasma contents such as immunoglobulins in peripheral tissues. To regulate allergic diseases, it is important to study vascular biology especially in inflammation. Since the vascular permeability changes in minutes upon the exposure to proinflammatory mediators, intravital imaging system is a powerful technique to capture such dynamic responses. We here describe how to evaluate vascular permeability in vivo using multiphoton microscopy. We use various sizes of fluorescence-labeled dextran to visualize how leaky the blood vessels are in the steady state and in inflammation. Using this assay system, we can illustrate the dynamic kinetics of vascular permeability in vivo in real-time. This assay system provides a novel convenient way to study vascular biology that is beneficial in the assessment of various animal models of allergic disease.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Dextranos/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Histamina/farmacologia , Hipersensibilidade Imediata/diagnóstico por imagem , Microscopia Intravital/métodos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Animais , Orelha/irrigação sanguínea , Orelha/diagnóstico por imagem , Fluoresceína-5-Isotiocianato/metabolismo , Corantes Fluorescentes/metabolismo , Hipersensibilidade Imediata/induzido quimicamente , Injeções Intravenosas , Microscopia Intravital/instrumentação , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência por Excitação Multifotônica/instrumentação , Peso Molecular , Imagem com Lapso de Tempo
17.
Methods Mol Biol ; 2223: 295-335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226602

RESUMO

Allergic asthma is characterized by airway hyperresponsiveness, remodeling, and reversible airway obstruction. This is associated with an eosinophilic inflammation of the airways, caused by inhaled allergens such as house dust mite or grass pollen. The inhaled allergens trigger a type-2 inflammatory response with the involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high immunoglobulin E (IgE) antibody production by B cells and mucus production by airway epithelial cells. As a consequence of the IgE production, subsequent allergen reexposure results in a classic allergic response with distinct early and late phases, both resulting in bronchoconstriction and shortness of breath. Allergen-specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma. Both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have shown clinical efficacy in long-term suppression of the allergic response. Although AIT treatments are very successful for rhinitis, application in asthma is hampered by variable efficacy, long duration of treatment, and risk of severe side effects. A more profound understanding of the mechanisms by which AIT induces tolerance to allergens in sensitized individuals is needed to be able to improve its efficacy. Mouse models have been very valuable in preclinical research for characterizing the mechanisms of desensitization in AIT and evaluating novel approaches to improve its efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen adsorbed to aluminum hydroxide, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of allergen extracts as an immunotherapy treatment. Finally, mice are challenged by intranasal allergen administrations. We will also describe the protocols as well as the most important readout parameters for the measurements of invasive lung function, serum immunoglobulin levels, isolation of bronchoalveolar lavage fluid (BALF), and preparation of cytospin slides. Moreover, we describe how to perform ex vivo restimulation of lung single-cell suspensions with allergens, flow cytometry for identification of relevant immune cell populations, and ELISAs and Luminex assays for assessment of the cytokine concentrations in BALF and lung tissue.


Assuntos
Alérgenos/administração & dosagem , Asma/terapia , Modelos Animais de Doenças , Pólen/imunologia , Pyroglyphidae/imunologia , Imunoterapia Sublingual/métodos , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Alérgenos/imunologia , Hidróxido de Alumínio/administração & dosagem , Animais , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Misturas Complexas/administração & dosagem , Misturas Complexas/imunologia , Citocinas/genética , Citocinas/imunologia , Orelha , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Injeções Subcutâneas , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/patologia , Pólen/química , Pyroglyphidae/química , Análise de Célula Única/métodos
18.
Int J Pediatr Otorhinolaryngol ; 141: 110551, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338703

RESUMO

OBJECTIVES: Patients with microtia and aural atresia have multiple options for treatment of conductive hearing loss (CHL) and auricle reconstruction; however, little is known about the factors influencing treatment selection. This study aims to review the socioeconomic and clinical data of microtia/atresia patients to evaluate congruency with national data and whether these factors affect treatment decisions. METHODS: Retrospective review of patients evaluated in the microtia and atresia multidisciplinary clinic (MDC) at a tertiary academic children's hospital between 2008 and 2018. Outcomes included demographic, socioeconomic and clinical factors associated with hearing surgery and framework surgery. RESULTS: 373 patients were seen in the Microtia MDC: 193 (51.7%) were male, 187 (50.1%) identified as Hispanic and 23 (6.2%) identified as Asian. 267 (75.6%) patients received a nonsurgical bone conduction hearing device (BCHD); fitting at a younger age was associated with better nonsurgical BCHD compliance. Multivariate analysis was performed on the patients that were eligible for surgery based on age and appropriate follow-up. 70 (18.8%) patients had placement of an osseointegrated BCHD; inconsistent compliance with nonsurgical BCHD decreased the odds of proceeding with osseointegrated BCHD placement. 60 (16.1%) patients underwent framework surgery for external reconstruction. Placement of osseointegrated BCHD was the only factor that was associated with proceeding with framework surgery. Other assessed demographic and socioeconomic factors were statistically not associated with selection of surgical intervention. CONCLUSION: Fitting a nonsurgical BCHD at a younger age is associated with higher likelihood of nonsurgical BCHD compliance, that is in turn associated with patients and families proceeding with osseointegrated BCHD and framework surgery.


Assuntos
Anormalidades Congênitas , Microtia Congênita , Orelha/anormalidades , Criança , Auxiliares de Audição , Perda Auditiva Condutiva/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Fatores Socioeconômicos
19.
Cancer Lett ; 497: 154-164, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33080310

RESUMO

Solid tumors are composed of tumor cells and stromal cells including lymphatic endothelial cells (LEC), which are mainly viewed as cells forming lymphatic vessels involved in the transport of metastatic and immune cells. We here reveal a new mechanism by which tumor exposed-LEC (teLEC) exert mitogenic effects on tumor cells. Our conclusions are supported by morphological and molecular changes induced in teLEC that in turn enhance cancer cell invasion in 3D cultures and tumor cell proliferation in vivo. The characterization of teLEC secretome by RNA-Sequencing and cytokine array revealed that interleukine-6 (IL6) is one of the most modulated molecules in teLEC, whose production was negligible in unexposed LEC. Notably, neutralizing anti-human IL6 antibody abrogated teLEC-mediated mitogenic effects in vivo, when LEC were mixed with tumor cells in the ear sponge assay. We here assign a novel function to teLEC that is beyond their role of lymphatic vessel formation. This work highlights a new paradigm, in which teLEC exert "fibroblast-like properties", contribute in a paracrine manner to the control of tumor cell properties and are worth considering as key stromal determinant in future studies.


Assuntos
Células Endoteliais/patologia , Interleucina-6/metabolismo , Linfangiogênese , Neovascularização Patológica/patologia , Neoplasias Cutâneas/patologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Orelha/fisiopatologia , Células Endoteliais/metabolismo , Humanos , Interleucina-6/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Nat Commun ; 11(1): 6356, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353938

RESUMO

Minimally invasive medical procedures, such as endovascular catheterization, have considerably reduced procedure time and associated complications. However, many regions inside the body, such as in the brain vasculature, still remain inaccessible due to the lack of appropriate guidance technologies. Here, experimentally and through numerical simulations, we show that tethered ultra-flexible endovascular microscopic probes can be transported through tortuous vascular networks with minimal external intervention by harnessing hydrokinetic energy. Dynamic steering at bifurcations is performed by deformation of the probe head using magnetic actuation. We developed an endovascular microrobotic toolkit with a cross-sectional area that is orders of magnitude smaller than the smallest catheter currently available. Our technology has the potential to improve state-of-the-art practices as it enhances the reachability, reduces the risk of iatrogenic damage, significantly increases the speed of robot-assisted interventions, and enables the deployment of multiple leads simultaneously through a standard needle injection and saline perfusion.


Assuntos
Procedimentos Endovasculares/instrumentação , Reologia , Robótica , Animais , Cateteres , Simulação por Computador , Orelha/irrigação sanguínea , Orelha/cirurgia , Desenho de Equipamento , Humanos , Fenômenos Magnéticos , Microfluídica , Imagens de Fantasmas , Coelhos , Temperatura , Pesquisa Médica Translacional
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