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INTRODUCTION: Simulation-based training often fails to meet the needs of low- and middle-income countries with limited access to high-cost models. We built on an existing surgical simulation curriculum for medical students in Rwanda and assessed students' experience. METHODS: Based on a contextual simulation-based education curriculum that was piloted in 2022, our team designed and delivered an intensive week-long surgical simulation course for medical students. We increased interactive clinical scenarios using high-fidelity mannequins, improved and added benchtop models for training, and incorporated a new postcourse assessment of students' experiences using a survey on the first Kirkpatrick level to determine sessions with the highest utility. Modules included informed consent, preoperative patient preparation, trauma simulations, and procedural skills. The final day focused on integrating and applying skills learned throughout the week in an interactive circuit. RESULTS: Thirty-six students participated in the 5-d simulation course and 24 completed an end of course survey. When asked about their exposure to simulation prior to the course, 20/24 (83%) students reported "a lot" and 4/24 (17%) reported "a little", 24/24 (100%) strongly agreed that simulation is a valuable educational tool and 23/24 (96%) felt that the week enhanced their knowledge and skills to "a great extent". The modules with the highest self-rated level of engagement were the interactive trauma simulations, knot-tying and suturing practice and competition, and a model-based session on cutaneous lesions. The lowest ranked session was the interactive circuit on integrated skills. CONCLUSIONS: Implementing a locally-informed and locally-sourced surgical simulation curriculum is feasible and effectively engages medical students in low-income settings.
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BACKGROUND: Medical simulation is essential for surgical training yet is often too expensive and inaccessible in low- and middle-income countries (LMICs). Furthermore, in otolaryngology-head and neck surgery (OHNS), while simulation training is often focused on senior residents and specialists, there is a critical need to target general practitioners who carry a significant load of OHNS care in countries with limited OHNS providers. This scoping review aims to describe affordable, effective OHNS simulation models for early-stage trainees and non-OHNS specialists in resource-limited settings and discuss gaps in the literature. METHODS: This scoping review followed the five stages of Arksey and O'Malley's Scoping Review Methodology. Seven databases were used to search for articles. Included articles discussed physical models of the ear, nose, or throat described as "low-cost," "cost-effective," or defined as <$150 if explicitly stated; related to the management of common and emergent OHNS conditions; and geared towards undergraduate students, medical, dental, or nursing students, and/or early-level residents. RESULTS: Of the 1706 studies screened, 17 met inclusion criteria. Most studies were conducted in HICs. Most models were low-fidelity (less anatomically realistic) models. The most common simulated skills were peritonsillar abscess aspiration and cricothyrotomy. Information on cost was limited, and locally sourced materials were infrequently mentioned. Simulations were evaluated using questionnaires and direct observation. CONCLUSION: Low-cost simulation models can be beneficial for early medical trainees and students in LMICs, addressing resource constraints and improving skill acquisition. However, there is a notable lack of contextually relevant, locally developed, and cost-effective models. This study summarizes existing low-cost OHNS simulation models for early-stage trainees and highlights the need for additional locally sourced models. Further research is needed to assess the effectiveness and sustainability of these models.
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Otolaringologia , Treinamento por Simulação , Humanos , Otolaringologia/educação , Treinamento por Simulação/economia , Competência Clínica , Internato e Residência , Análise Custo-Benefício , Países em DesenvolvimentoRESUMO
Introduction/Background: Safe and quality surgery is crucial for child health. In Rwanda, district hospitals serve as primary entry points for pediatric patients needing surgical care. This paper reports on the organizational readiness and facility capacity to provide pediatric surgery in three district hospitals in rural Rwanda. Methods: We administered the Children's Surgical Assessment Tool (CSAT), adapted for a Rwandan district hospital, to assess facility readiness across 5 domains (infrastructure, workforce, service delivery, financing, and training) at three Partners in Health supported district hospitals (Kirehe, Rwinkwavu, and Butaro District Hospitals). We used the Safe Surgery Organizational Readiness Tool (SSORT) to measure perceived individual and team readiness to implement surgical quality improvement interventions across 14 domains. Results: None of the facilities had a dedicated pediatric surgeon, and the most common barriers to pediatric surgery were lack of surgeon (68%), lack of physician anesthesiologists (19%), and inadequate infrastructure (17%). There were gaps in operating and recovery room infrastructure, and information management for pediatric outpatients and referrals. In SSORT interviews (n=47), the highest barriers to increasing pediatric surgery capacity were facility capacity (mean score=2.6 out of 5), psychological safety (median score=3.0 out of 5), and resistance to change (mean score=1.5 out of 5 with 5=no resistance). Conclusions: This study highlights challenges in providing safe and high-quality surgical care to pediatric patients in three rural district hospitals in Rwanda. It underscores the need for targeted interventions to address facility and organizational barriers prior to implementing interventions to expand pediatric surgical capacity.
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Hospitais de Distrito , Cirurgiões , Humanos , Criança , Ruanda , Anestesiologistas , Hospitais RuraisRESUMO
Non-tuberculous mycobacterial (NTM) lymphadenitis typically presents as a unilateral, non-tender, slowly enlarging cervical, submandibular, or pre-auricular lymph node in children. Disseminated NTM infection is most often seen in immunocompromised children. Here, we present an unusual case of extensive bilateral cervical and retropharyngeal lymphadenitis caused by Mycobacterium Avium Complex (MAC) in an ostensibly immunocompetent pediatric patient.
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Linfadenite , Infecções por Mycobacterium não Tuberculosas , Criança , Humanos , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Linfadenite/etiologia , Linfadenite/microbiologia , Complexo Mycobacterium avium , Hospedeiro ImunocomprometidoRESUMO
BACKGROUND/AIMS: Paediatric surgical care is a critical component of child health and basic universal health coverage and therefore should be included in comprehensive evaluations of surgical capacity. This study adapted and validated the Children's Surgical Assessment Tool (CSAT), a tool developed for district and tertiary hospitals in Nigeria to evaluate hospital infrastructure, workforce, service delivery, financing, and training capacity for paediatric surgery, for use in district hospitals in Rwanda. METHODS: We used a three-round modified Delphi process to adapt the CSAT to the Rwandan context. An expert panel of surgeons, anaesthesiologists, paediatricians, and health systems strengthening experts were invited to participate based on their experience with paediatric surgical or anaesthetic care at district hospitals or with health systems strengthening in the Rwandan context. We used the Content Validity Index to validate the final tool. RESULTS: The adapted tool had a final score of 0.84 on the Content Validity Index, indicating a high level of agreement among the expert panel. The final tool comprised 171 items across five domains: facility characteristics, service delivery, workforce, financing, and training/research. CONCLUSION: The adapted CSAT is appropriate for use in district hospitals in Rwanda to evaluate the capacity for paediatric surgery. This study provides a framework for adapting and validating a comprehensive paediatric surgical assessment tool to local contexts in LMICs and used in similar settings in sub-Saharan Africa.
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Saúde da Criança , Hospitais de Distrito , Criança , Humanos , Ruanda , Países em Desenvolvimento , Assistência MédicaRESUMO
Importance: There is a notable lack of low-cost OHNS simulation models that are relevant for early medical trainees and students. By conducting this study, we will understand the current landscape of low-cost otolaryngology-head and neck surgery simulation for early medical trainees and students. Objectives: Medical simulation is essential for surgical training yet is often too expensive and inaccessible in low- and middle-income countries (LMICs). Furthermore, in otolaryngology-head and neck surgery (OHNS), while simulation training is often focused on senior residents and specialists, there is a critical need to target general practitioners who carry a significant load of OHNS care in countries with limited OHNS providers. This scoping review aims to describe affordable, effective OHNS simulation models for early-stage trainees and non-OHNS specialists in resource-limited settings and discuss gaps in the literature. Evidence Review: This scoping review followed the five stages of Arksey and O'Malley's Scoping Review Methodology. Seven databases were used to search for articles. Included articles discussed physical models of the ear, nose, or throat described as "low-cost," "cost-effective," or defined as <$150 if explicitly stated; related to the management of common and emergent OHNS conditions; and geared towards undergraduate students, medical, dental, or nursing students, and/or early-level residents. Findings: Of the 1706 studies screened, 17 met the inclusion criteria. Most studies were conducted in HICs. Most models were low fidelity (less anatomically realistic) models. The most common simulated skills were peritonsillar abscess aspiration and cricothyrotomy. Information on cost was limited, and locally sourced materials were infrequently mentioned. Simulations were evaluated using questionnaires and direct observation. Conclusion and Relevance: Low-cost simulation models can be beneficial for early medical trainees and students in LMICs, addressing resource constraints and improving skill acquisition. However, there is a notable lack of contextually relevant, locally developed, and cost-effective models. This study summarizes existing low-cost OHNS simulation models for early-stage trainees and highlights the need for additional locally sourced models. Further research is needed to assess the effectiveness and sustainability of these models.
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PURPOSE OF REVIEW: Identify patient-perceived barriers to head and neck cancer care and compare differences in barriers by country income status. RECENT FINDINGS: Of the 37 articles, 51% ( n â=â19) were from low- and middle-income countries (LMICs), while 49% ( nâ=â 18) were from high-income countries. Of the papers from high-income countries, unspecified head and neck cancer (HNC) subtype (67%, nâ=â 12) were the most common cancer type, while upper aerodigestive tract mucosal malignancies (58%, nâ=â 11) were more common in LMICs ( P â=â0.02). Based on World Health Organization barriers, level of education ( P â=ââ<â0.01) and alternative medicine use ( P â=â0.04) were greater barriers in LMICs compared to high-income countries. At least 50% of articles listed barriers at all three 'Three Delays' timepoints. There were no significant differences by country income status for the 'Three Delays' timepoints of deciding to seek care ( P â=â0.23), reaching the healthcare facility ( P â=â0.75), or receiving care ( P â=â1.00). SUMMARY: Patients face barriers to care for head and neck cancer regardless of country income status. There is overlap in several barriers and a need for systemic improvement in access. The differences in education and alternative medicine may guide region-specific interventions to improve the provision of head and neck services.
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Países em Desenvolvimento , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/terapiaRESUMO
OBJECTIVE: The aim of this study was to develop an international expert consensus on priority pediatric otolaryngology-head and neck surgery (OHNS) conditions and procedures for which all national health systems globally should be capable of managing. STUDY DESIGN: The Delphi method is a multiround online questionnaire and was administered internationally to otolaryngologists with a focus on pediatric populations. This study was administered in parallel to a Delphi survey focusing on adult OHNS conditions amongst adult otolaryngology experts. SETTING: International online survey. METHODS: In round 1, participants listed the top 15 pediatric otolaryngological conditions and top 15 pediatric otolaryngology procedures for their World Bank region. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as at least 70% of the round 2 Likert responses being ranked as either "important" or "very important." Descriptive statistics were calculated for each round. RESULTS: The survey was distributed to 35 experts globally, with a 40% (n = 14) response rate. Fifty percent (n = 7) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. A list of 28 consensus surgical procedures and 11 consensus conditions were identified. CONCLUSION: This Delphi survey method of world experts in pediatric otolaryngology identified a core list of medical conditions and surgical procedures that should be a part of every national health system's clinical goals of treatment, research, and capacity building.
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Otolaringologia , Adulto , Criança , Humanos , Consenso , Otorrinolaringologistas , Técnica DelphiRESUMO
BACKGROUND: Although lateral lumbar interbody fusion (LLIF) is an effective surgical option for lumbar arthrodesis, postoperative plexopathies are a common complication. We characterized post-LLIF plexopathies in a large cohort and analyzed potential risk factors for each. METHODS: A single-institutional cohort who underwent LLIF between May 2015 and December 2019 was retrospectively reviewed for postoperative lumbar plexopathies. Plexopathies were divided based on sensory and motor symptoms and duration, as well as by laterality relative to the surgical approach. We assessed these subgroups for associations with patient and surgical characteristics as well as psoas dimensions. We then evaluated risk of developing plexopathies after intraoperative neuromonitoring observations. RESULTS: A total of 127 patients were included. The overall rate of LLIF-induced sensory or motor lumbar plexopathy was 37.8% (48/127). Of all cases, 42 were ipsilateral to the surgical approach (33.1%); conversely, 6 patients developed contralateral plexopathies (4.7%). Most (31/48; 64.6%) resolved with a follow-up interval of 402 days in the plexopathy group. Of ipsilateral cases, 24 patients experienced persistent (>90 days) postoperative sensory symptoms (18.9%), whereas 20 experienced persistent weakness (15.7%). More levels fused predicted persistent sensory symptoms (odds ratio, 1.714 [1.246-2.359]; P = 0.0085), whereas surgical duration predicted persistent weakness (odds ratio, 1.004 [1.002-1.006]; P = 0.0382). Psoas anatomic variables were not significantly associated with plexopathy. Nonresolution of intraoperative evoked motor potential alerts was a significant risk factor for developing plexopathies (relative risk, 2.29 [1.17-4.45]). CONCLUSIONS: Post-LLIF plexopathies are common but usually resolve. Surgical complexity and unresolved neuromonitoring alerts are possible risk factors for persistent plexopathy.
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Fusão Vertebral , Humanos , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Procedimentos Neurocirúrgicos , Fatores de Risco , Análise Multivariada , Vértebras Lombares/cirurgiaRESUMO
Background: Lateral lumbar interbody fusion (LLIF) is a minimally invasive fusion procedure that may be performed with or without supplemental instrumentation. However, there is a paucity of evidence on the effect of supplemental instrumentation technique on perioperative morbidity and fusion rate in LLIF. Methods: A single-institutional retrospective review of patients who underwent LLIF for lumbar spondylosis was conducted. Patients were grouped according to supplemental instrumentation technique: stand-alone LLIF, LLIF with laterally placed instrumentation, or LLIF with posterior percutaneous pedicle screw fixation (PPSF). Outcomes included fusion rates, peri-operative complication, and reoperation; estimated blood loss (EBL); surgery duration; length of stay; and length of follow-up. Results: 82 patients underwent LLIF at 114 levels. 35 patients (42.7%) received supplemental lateral instrumentation, 30 (36.6%) received supplemental PPSF, and 17 (20.7%) underwent stand-alone LLIF. More patients in the lateral instrumentation group had prior lumbar fusion at adjacent levels (23/35, 65.71%) versus stand-alone (3/17, 17.6%) or PPSF (2/30, 6.67%) groups (p = 0.003). 4/17 patients (23.5%) with stand-alone LLIF and 4/35 patients (11.42%) with lateral instrumentation underwent reoperation, versus 0/30 with PPSF (p = 0.030). There was no difference in fusion rates between groups (p = 0.717). Operation duration was longer in patients with PPSF (p < 0.005) and length of follow-up was longer for PPSF than lateral instrumentation (p = 0.001). Choice of instrumentation group was a statistically significant predictor of reoperation. Conclusions: While rates of complete radiographic fusion on imaging follow-up didn't differ, patients receiving PPSF were less likely than stand-alone or lateral instrumentation groups to require reoperation, though operative time was significantly longer. Further study of choice of supplemental instrumentation with LLIF is indicated.
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Background: Lateral lumbar interbody fusion (LLIF) is a minimally invasive surgical option for treating symptomatic degenerative lumbar spinal stenosis (DLSS) in select patients. However, the efficacy of LLIF for indirectly decompressing the lumbar spine in DLSS, as well as the best radiographic metrics for evaluating such changes, are incompletely understood. Methods: A single-institutional cohort of patients who underwent LLIF for DLSS between 5/2015 - 12/2019 was retrospectively reviewed. Diameter, area, and stenosis grades were measured for the central canal (CC) and neural foramina (NF) at each LLIF level based on preoperative and postoperative T2-weighted MRI. Baseline facet joint (FJ) space, degree of FJ osteoarthritis, presence of spondylolisthesis, interbody graft position, and posterior disc height were analyzed as potential predictors of radiographic outcomes. Changes to all metrics after LLIF were analyzed and compared across lumbar levels. Preoperative and intraoperative predictors of decompression were then assessed using multivariate linear regression. Results: A total of 102 patients comprising 153 fused levels were analyzed. Pairwise linear regression of stenosis grade to diameter and area revealed significant correlations for both the CC and NF. All metrics except CC area were significantly improved after LLIF (p < 0.05, 2-tailed t-test). Worse FJ osteoarthritis ipsilateral to the surgical approach was predictive of greater post-operative CC and NF stenosis grade (p < 0.05, univariate and multivariate ordinary least squares linear regression). Lumbar levels L3-5 had significantly higher absolute postoperative CC stenosis grades while relative change in CC stenosis at the L2-3 was significantly greater than other lumbar levels (p < 0.05, one-way ANOVA). There were no baseline or postoperative differences in NF stenosis grade across lumbar levels. Conclusions: Radiographically, LLIF is effective at indirect compression of the CC and NF at all lumbar levels, though worse FJ osteoarthritis predicted higher degrees of post-operative stenosis.
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OBJECTIVE: The objective of this study was to develop an international expert consensus on priority otolaryngology-head and neck surgery conditions and procedures globally for which national health systems should be capable of caring. STUDY DESIGN: The Delphi method was employed via a multiround online survey administered to attending otolaryngologists in an international research collaborative of >180 otolaryngologists in >40 countries. SETTING: International online survey. METHODS: In round 1, participants listed the top 15 otolaryngologic conditions and top 15 otolaryngology procedures for their World Bank regions. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as 50% of the round 2 Likert responses being ranked as "important" or "very important." Descriptive statistics were calculated for each round. RESULTS: The survey was distributed to 53 experts globally, with a response rate of 38% (n = 20). Fifty percent (n = 10) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. Ten consensus surgical procedures and 10 consensus conditions were identified. CONCLUSION: This study identified a list of priority otolaryngology-head and neck surgery conditions and surgical procedures for which all national health systems around the world should be capable of managing. Acute and infectious conditions with preventative and emergent procedures were highlighted. These findings can direct future research and guide international collaborations.
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Otolaringologia , Consenso , Técnica Delphi , Humanos , Otorrinolaringologistas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: This study evaluated the effectiveness of a parent-completed questionnaire for detecting seizures in high-risk children. METHODS: A 2-part seizure screen for children up to 12 years of age with suspected autism spectrum disorder, developmental delay, or seizure, was implemented in 12 Massachusetts clinics serving populations with high health disparities. Primary care providers and developmental behavioral pediatricians administered part 1, a brief highly sensitive screen. If the result was positive, a research assistant administered part 2, a more detailed screen with higher specificity. Positive part 2 results prompted a specialized assessment by a pediatric neurologist. Screening data were evaluated for detection of seizures or other diagnoses, reason for conducting the screen, and appointment outcomes. Data analysis included chi-squared tests, percentages for categorical variables, and means for numerical data. RESULTS: Of 207 administered seizure questionnaires, 78% of children screened positive on part 1. Of those, 94% of families completed part 2 by telephone, and 64 individuals screened positive. The screen helped to detect 15 new seizure diagnoses and 35 other neurologic diagnoses. Average time to first scheduled appointment was 23.8 days. The no-show rate was 7%. CONCLUSIONS: The seizure questionnaire effectively identified seizures and other disorders in a diverse population of high-risk children. Broader use of this low-cost screening tool could improve access to care for children with suspected seizures, increase seizure recognition, and help allocate resources more effectively.
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Transtorno do Espectro Autista/complicações , Deficiências do Desenvolvimento/complicações , Epilepsia/complicações , Pais , Convulsões/diagnóstico , Convulsões/etiologia , Inquéritos e Questionários/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , MassachusettsRESUMO
OBJECTIVES: To evaluate outcome of concomitant tricuspid annuloplasty in mild or moderate regurgitation on perioperative outcome and on right ventricular function in patients undergoing major cardiac surgery. METHODS: Among 14 500 patients who underwent cardiac surgery at our institution between January 2000 and April 2016, 1023 patients had a documented history of tricuspid regurgitation (TR). Of those patients, 324 patients were diagnosed with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) and composed the study population. The decision to perform concomitant annuloplasty was subjected to the individual decision of the treating surgeon. Our analysis focused on a comparison between patients with concomitant TR-repair (group 1, n = 184) and patients without concomitant TR-repair (group 2, n = 140) after propensity score matching. RESULTS: Following a preliminary data preprocessing, we observed a mean age of 73.8 years, mean logistic EuroSCORE of 10.5%. Perioperative mortality was 4.4% in group 1 and 5.7% in group 2. There was no significant difference in mid-term mortality. TR after surgery was significantly higher in group 2. After propensity score matching regression analysis, patients who had a repaired tricuspid valve (group 1) had better right ventricle (RV) function than those without TR-repair (group 2) (P > 0.05 at 95% confidence interval following Kolmogorov-Smirnov Goodness of fit Test). CONCLUSIONS: Adding tricuspid valve repair in patients with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) to standard open heart surgery does not increase perioperative risk but improves right ventricular function. Therefore, standard tricuspid repair in this subgroup might be considered on a routine basis.
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Anuloplastia da Valva Cardíaca/métodos , Pontuação de Propensão , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Função Ventricular Direita/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/fisiopatologia , Adulto JovemRESUMO
In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the heterophilic cell adhesion proteins, DIPs and Dprs, are expressed in ORNs during glomerular formation. Many ORN classes express a unique combination of DIPs/dprs, with neurons of the same class expressing interacting partners, suggesting a role in class-specific self-adhesion between ORN axons. Analysis of DIP/Dpr expression revealed that ORNs that target neighboring glomeruli have different combinations, and ORNs with very similar DIP/Dpr combinations can project to distant glomeruli in the antennal lobe. DIP/Dpr profiles are dynamic during development and correlate with sensilla type lineage for some ORN classes. Perturbations of DIP/dpr gene function result in local projection defects of ORN axons and glomerular positioning, without altering correct matching of ORNs with their target neurons. Our results suggest that context-dependent differential adhesion through DIP/Dpr combinations regulate self-adhesion and sort ORN axons into uniquely positioned glomeruli.
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Proteínas de Drosophila/fisiologia , Drosophila/fisiologia , Condutos Olfatórios/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Animais , Axônios/fisiologia , Adesão Celular , Drosophila/genética , Proteínas de Drosophila/genética , Regulação da Expressão Gênica , Técnicas de Genotipagem , Modelos Teóricos , Análise de Sequência de RNARESUMO
BACKGROUND: Several classifications of adult asthma patients using cluster analyses based on clinical and demographic information has resulted in clinical phenotypic clusters that do not address molecular mechanisms. Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects. In this study, we aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients. METHODS: Breath samples were analyzed for VOC profiles by gas chromatography-mass spectrometry from asthma patients (n = 195) and healthy controls (n = 40). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate healthy from asthmatic subjects. 2-step cluster analysis based on clinical information and VOCs in exhaled air were used to form asthma endotypes. RESULTS: We identified 16 VOCs, which could distinguish between healthy and asthma subjects with a sensitivity of 100% and a specificity of 91.1%. Cluster analysis based on VOCs in exhaled air and the clinical parameters FEV1, FEV1 change after 3 weeks of hospitalization, allergic sensitization, Junipers symptoms score and asthma medications resulted in the formation of 7 different asthma endotype clusters. We identified asthma clusters with different VOC profiles but similar clinical characteristics and endotypes with similar VOC profiles, but distinct clinical characteristics. CONCLUSION: This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.
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Asma/diagnóstico , Testes Respiratórios , Expiração , Pulmão/metabolismo , Compostos Orgânicos Voláteis/análise , Adulto , Asma/classificação , Asma/metabolismo , Asma/fisiopatologia , Biomarcadores/análise , Estudos de Casos e Controles , Análise por Conglomerados , Análise Discriminante , Feminino , Volume Expiratório Forçado , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos TestesRESUMO
BACKGROUND: Asthma is a heterogeneous disease characterized by different clinical phenotypes and the involvement of multiple inflammatory pathways. During airway inflammation, many cytokines and chemokines are released and some are detectable in the sera. OBJECTIVE: Serum chemokines and cytokines, involved in airway inflammation in asthma patients, were investigated. METHODS: A total of 191 asthma patients were classified by hierarchical cluster analysis, including the following parameters: forced expiratory volume in 1 second (FEV1), eosinophil cationic protein (ECP) serum levels, blood eosinophils, Junipers asthma symptom score, and the change in FEV1, ECP serum levels, and blood eosinophils after 3 weeks of asthma therapy. Serum proteins were measured by multiplex analysis. Receiver operating characteristic (ROC) curves were used to evaluate the validity of serum proteins for discriminating between asthma clusters. RESULTS: Classification of asthma patients identified one cluster with high ECP serum levels, increased blood eosinophils, low FEV1 values, and good FEV1 improvement in response to asthma therapy (n=60) and one cluster with low ECP serum levels, low numbers of blood eosinophils, higher FEV1 values, and no FEV1 improvement in response to asthma therapy (n=131). Serum interleukin (IL)-8, eotaxin, vascular endothelial growth factor (VEGF), cutaneous T-cell-attracting chemokine (CTACK), growth-related oncogene (GRO)-α, and hepatocyte growth factor (HGF) were significantly different between the two clusters of asthma patients. ROC analysis for serum proteins calculated a sensitivity of 55.9% and specificity of 75.8% for discriminating between them. CONCLUSION: Serum cytokine and chemokine levels might be predictors for the severity of asthmatic inflammation, asthma control, and response to therapy, and therefore might be useful for treatment optimization.