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Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.
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BACKGROUND: Many individuals with cystic fibrosis (CF) die from respiratory failure without referral for lung transplant. Physician practices that may expedite, delay, or preclude referral, are poorly understood. METHODS: Two parallel, web-based surveys focusing on lung transplant referral triggers and barriers, as well as pre-referral evaluation, were emailed to pulmonologists practicing in the New England region. One questionnaire was sent to CF providers (n = 61), and the second to general pulmonary providers practicing at the same institutions (n = 61). RESULTS: There were 43 (70%) responses to the CF provider survey, and 25 (41%) responses to the general pulmonary ('non-CF') provider survey. Primary reasons for CF providers to refer their patients included: rapidly declining lung function (91%) and a forced expiratory volume in 1 s (FEV1) below 30% predicted (74%). The greatest barriers to referral for both CF and non-CF providers included active tobacco use (65 and 96%, respectively, would not refer), and active alcohol or other substance use or dependence (63 and 80%). Furthermore, up to 42% of CF providers would potentially delay their referral if triple-combination therapy or other promising new, disease-specific therapy were anticipated. In general, non-CF providers perform a more robust pre-referral medical work-up, while CF providers complete a psychosocial evaluation in higher numbers. Across both groups, communication with lung transplant programs was reported to be inadequate. CONCLUSIONS: Physician-level barriers to timely lung transplant referral exist and need to be addressed. Enhanced communication between lung transplant programs and pulmonary providers may reduce these barriers.
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Fibrosis Quística/cirugía , Conocimientos, Actitudes y Práctica en Salud , Hipertensión Pulmonar/diagnóstico , Trasplante de Pulmón , Derivación y Consulta , Toma de Decisiones Clínicas , Fibrosis Quística/complicaciones , Volumen Espiratorio Forzado , Humanos , New England , Prioridad del Paciente , Neumólogos , Encuestas y CuestionariosAsunto(s)
Filaminas/genética , Enfermedades Pulmonares Intersticiales/diagnóstico , Pulmón/patología , Mutación , Prolapso de la Válvula Aórtica/complicaciones , Dolor en el Pecho/etiología , Tos/etiología , Diagnóstico Diferencial , Disnea/etiología , Femenino , Cardiopatías Congénitas/complicaciones , Heterocigoto , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/genética , Heterotopia Nodular Periventricular/genética , Enfisema Pulmonar/congénito , Enfisema Pulmonar/cirugía , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Adulto JovenAsunto(s)
Filaminas/genética , Heterotopia Nodular Periventricular/diagnóstico , Anomalías Múltiples , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Ecocardiografía , Insuficiencia de Crecimiento/etiología , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X , Trastornos del Crecimiento/etiología , Corazón/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Hemangioma/complicaciones , Hemangioma/diagnóstico , Humanos , Lactante , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Mutación , Linaje , Heterotopia Nodular Periventricular/complicaciones , Heterotopia Nodular Periventricular/genética , Radiografía Torácica , Insuficiencia Respiratoria/etiologíaRESUMEN
BACKGROUND: Social media has emerged as a potentially powerful medium for communication with adolescents and young adults around their health choices. OBJECTIVE: The goal of this systematic review is to identify research on the use of social media for interacting with adolescents and young adults in order to achieve positive health outcomes. METHODS: A MEDLINE/PubMed electronic database search was performed between January 1, 2002 and October 1, 2013, using terms to identify peer-reviewed research in which social media and other Web 2.0 technologies were an important feature. We used a systematic approach to retrieve papers and extract relevant data. RESULTS: We identified 288 studies involving social media, of which 87 met criteria for inclusion; 75 studies were purely observational and 12 were interventional. The ways in which social media was leveraged by these studies included (1) observing adolescent and young adult behavior (n=77), (2) providing health information (n=13), (3) engaging the adolescent and young adult community (n=17), and (4) recruiting research participants (n=23). Common health topics addressed included high-risk sexual behaviors (n=23), alcohol, tobacco, and other drug use (n=19), Internet safety (n=8), mental health issues (n=18), medical conditions (n=11), or other specified issues (n=12). Several studies used more than one social media platform and addressed more than one health-related topic. CONCLUSIONS: Social media technologies offer an exciting new means for engaging and communicating with adolescents and young adults; it has been successfully used to engage this age group, identify behaviors, and provide appropriate intervention and education. Nevertheless, the majority of studies to date have been preliminary and limited in their methodologies, and mostly center around evaluating how adolescents and young adults use social media and the resulting implications on their health. Although these explorations are essential, further exploration and development of these strategies into building effective interventions is necessary.
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Promoción de la Salud/métodos , Medios de Comunicación Sociales , Adolescente , Comunicación , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Conducta Sexual , Red Social , Adulto JovenRESUMEN
OBJECTIVE: Emerging evidence suggests that neuronal guidance cues, typically expressed during development, are involved in both physiological and pathological immune responses. We hypothesized that endothelial expression of such guidance cues may regulate leukocyte trafficking into the vascular wall during atherogenesis. APPROACH AND RESULTS: We demonstrate that members of the netrin, semaphorin, and ephrin family of guidance molecules are differentially regulated under conditions that promote or protect from atherosclerosis. Netrin-1 and semaphorin3A are expressed by coronary artery endothelial cells and potently inhibit chemokine-directed migration of human monocytes. Endothelial expression of these negative guidance cues is downregulated by proatherogenic factors, including oscillatory shear stress and proinflammatory cytokines associated with monocyte entry into the vessel wall. Furthermore, we show using intravital microscopy that inhibition of netrin-1 or semaphorin3A using blocking peptides increases leukocyte adhesion to the endothelium. Unlike netrin-1 and semaphorin3A, the guidance cue ephrinB2 is upregulated under proatherosclerotic flow conditions and functions as a chemoattractant, increasing leukocyte migration in the absence of additional chemokines. CONCLUSIONS: The concurrent regulation of negative and positive guidance cues may facilitate leukocyte infiltration of the endothelium through a balance between chemoattraction and chemorepulsion. These data indicate a previously unappreciated role for axonal guidance cues in maintaining the endothelial barrier and regulating leukocyte trafficking during atherogenesis.
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Aterosclerosis/metabolismo , Endotelio Vascular/metabolismo , Efrina-B2/fisiología , Regulación de la Expresión Génica , Homeostasis , Factores de Crecimiento Nervioso/fisiología , Semaforina-3A/fisiología , Proteínas Supresoras de Tumor/fisiología , Animales , Aterosclerosis/patología , Adhesión Celular , Movimiento Celular , Células Cultivadas , Efrina-B2/genética , Humanos , Leucocitos/fisiología , Ratones , Ratones Endogámicos C57BL , Factores de Crecimiento Nervioso/genética , Netrina-1 , Semaforina-3A/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
The airway epithelium plays a pivotal role in regulating mucosal immunity and inflammation. Epithelial barrier function, homeostasis of luminal fluid, and mucociliary clearance are major components of mucosal defense mechanisms. The epithelial sodium channel (ENaC) is one of the key players in controlling airway fluid volume and composition, and characteristic cytokines cause ENaC and barrier dysfunctions following pulmonary infections or allergic reactions. Given the limited understanding of the requisite duration and magnitude of cytokines to affect ENaC and barrier function, available treatment options for restoring normal ENaC activity are limited. Previous studies have demonstrated that distinct amino acids can modulate epithelial ion channel activities and barrier function in intestines and airways. Here, we have investigated the time- and concentration-dependent effect of representative cytokines for Th1- (IFN-γ and TNF-α), Th2- (IL-4 and IL-13), and Treg-mediated (TGF-ß1) immune responses on ENaC activity and barrier function in human bronchial epithelial cells. When cells were exposed to Th1 and Treg cytokines, ENaC activity decreased gradually while barrier function remained largely unaffected. In contrast, Th2 cytokines had an immediate and profound inhibitory effect on ENaC activity that was subsequently followed by epithelial barrier disruption. These functional changes were associated with decreased membrane protein expression of α-, ß-, and γ-ENaC, and decreased mRNA levels of ß- and γ-ENaC. A proprietary blend of amino acids was developed based on their ability to prevent Th2 cytokine-induced ENaC dysfunction. Exposure to the select amino acids reversed the inhibitory effect of IL-13 on ENaC activity by increasing mRNA levels of ß- and γ-ENaC, and protein expression of γ-ENaC. This study indicates the beneficial effect of select amino acids on ENaC activity in an in vitro setting of Th2-mediated inflammation suggesting these amino acids as a novel therapeutic approach for correcting this condition.
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Aminoácidos , Bronquios , Citocinas , Células Epiteliales , Canales Epiteliales de Sodio , Canales Epiteliales de Sodio/metabolismo , Canales Epiteliales de Sodio/genética , Humanos , Bronquios/citología , Bronquios/metabolismo , Bronquios/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Citocinas/metabolismo , Aminoácidos/farmacología , Células Th2/inmunología , Células Th2/metabolismo , Células Th2/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Línea Celular , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Interleucina-13/metabolismoRESUMEN
Importance: Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. Objective: To determine the effect of type of activity and mask usage on exhaled particle production in children. Methods: Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Results: Twenty-three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High-intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Interpretation: Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.
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This review of Pemphigoid of the Pulmonary System (POPS) is a comprehensive description of pulmonary involvement in patients with mucous membrane pemphigoid (MMP), which is an orphan autoimmune blistering disease. The objective of the review was to analyze clinical features of pulmonary involvement in MMP. This POPS review is a case series in which multiple search engines were utilized from inception to June 2022 for cases of MMP with biopsy and immunopathology proven tracheal and bronchial pemphigoid. Clinical profiles prior to pulmonary involvement, bronchoscopy findings, clinical course and therapy were recorded and cause of death was analyzed. Patients with documented MMP who developed tracheal, bronchial and pulmonary involvement were included in the POPS review. Histology and immunopathology documentation were essential diagnostic criteria. Comparison groups were not possible. Patients were treated with immunosuppressive therapy. Some required surgical interventions. Six of the 11 patients attained complete or partial remission on or off therapy. Five patients died from pulmonary complications. The POPS review had six females and five males. The mean age at onset was 20 years (range 4-76), while 80% of the patients were under 40 years. All had severe widespread MMP involving three to five mucosal tissues. 100% had oral, 82% had ocular and cutaneous involvement. Pulmonary involvement occurred at 24 mo (range 2-372) after the onset of MMP. Bronchoscopy revealed acute inflammation during active disease and scarring of the trachea and bronchi in the later stages. Systemic infections occurred in 45%, while pulmonary infection occurred in 36%. Mortality due to respiratory failure, at the median age of 20 years (range 18-76), occurred in 45% of the patients, and was considered disease related. In spite of the young age, while there are some similarities in the clinical profile and response to systemic therapy, there are definitive differences from other patients with MMP. Early diagnosis with appropriate management could produce better clinical outcomes and prevent mortality in this orphan disease. Consequently, there is a critical need for early identification and diagnosis of POPS.
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Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Preescolar , Niño , Penfigoide Ampolloso/patología , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Membrana Mucosa/patología , Vesícula , BiopsiaRESUMEN
Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.
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Antivirales/farmacología , Ebolavirus/metabolismo , Lectinas/química , Lectina de Unión a Manosa/química , Calreticulina/química , Línea Celular Tumoral , Química Farmacéutica/métodos , Proteínas del Sistema Complemento/química , Diseño de Fármacos , Humanos , Cinética , Microscopía de Fuerza Atómica/métodos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes/química , Resonancia por Plasmón de Superficie/métodos , FicolinasRESUMEN
We performed a retrospective chart review with a 6-month follow-up to examine the initial use of propranolol as an adjunctive treatment in children with severe recurrent respiratory papillomatosis. This is the first such report. Two of 3 children with severe recurrent respiratory papillomatosis demonstrated a response to oral propranolol therapy, as evidenced by an improved voice and by an increased time between surgical interventions. One child demonstrated no response to propranolol, and medication was halted. Both children who demonstrated a response had undergone more than 10 surgical interventions in the previous year, along with prior treatment including surgical excision and adjuvant therapy. Both children more than doubled the interval between treatments after propranolol administration, and the parents of both children noted marked improvement of the child's voice as measured by their Pediatric Voice-Related Quality of Life score (from 40 to 67.5 in one child and from 27 to 60 in the other child). No child experienced hypoglycemia or blood pressure abnormalities. We conclude that initial use of propranolol as an adjunctive measure in severe recurrent respiratory papillomatosis shows it to have some efficacy in delaying surgical intervention and improving voice. Previous reports have demonstrated relatively safe use of propranolol in children with hemangiomas. Further studies are needed to determine the long-term effectiveness, dosing strategies, and side-effect profile of propranolol for treatment of recurrent respiratory papillomatosis.
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Neoplasias Laríngeas/tratamiento farmacológico , Papiloma/tratamiento farmacológico , Propranolol/administración & dosificación , Administración Oral , Adolescente , Niño , Preescolar , Disfonía/tratamiento farmacológico , Disfonía/fisiopatología , Femenino , Humanos , Neoplasias Laríngeas/fisiopatología , Neoplasias Laríngeas/cirugía , Masculino , Papiloma/fisiopatología , Papiloma/cirugía , Propranolol/efectos adversos , Recurrencia , Estudios Retrospectivos , VozRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted via respiratory droplets, aerosols, and to a lesser extent, fomites. Defining the factors driving infectivity and transmission is critical for infection control and containment of this pandemic. We outline the major methods of transmission of SARS-CoV-2, focusing on aerosol transmission. We review principles of aerosol science and discuss their implications for mitigating the spread of SARS-CoV-2 among children and adults.
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COVID-19/epidemiología , COVID-19/transmisión , Pandemias , SARS-CoV-2 , Adulto , Aerosoles , COVID-19/prevención & control , Niño , Fómites , Humanos , Control de InfeccionesRESUMEN
INTRODUCTION: Obstructive lung diseases (asthma and chronic obstructive pulmonary disease (COPD)) and smoking are associated with greater risk of respiratory infections and hospitalisations, but conflicting data exist regarding their association with severity of COVID-19, and few studies have evaluated whether these associations differ by age. OBJECTIVES: To examine the associations between asthma, COPD and smoking on the severity of COVID-19 among a cohort of hospitalised patients, and to test for effect modification by age. METHODS: We performed a retrospective analysis of electronic health record data of patients admitted to Massachusetts General Hospital, assigning the maximal WHO Clinical Progression Scale score for each patient during the first 28 days following hospital admission. Using ordered logistic regression, we measured the association between maximal severity score and asthma, COPD and smoking and their interaction with age. MEASUREMENTS AND MAIN RESULTS: Among 1391 patients hospitalised with COVID-19, we found an increased risk of severe disease among patients with COPD and prior smoking, independent of age. We also found evidence of effect modification by age with asthma and current smoking; in particular, asthma was associated with decreased COVID-19 severity among older adults, and current smoking was associated with decreased severity among younger patients. CONCLUSIONS: This cohort study identifies age as a modifying factor for the association between asthma and smoking on severity of COVID-19. Our findings highlight the complexities of determining risk factors for COVID-19 severity, and suggest that the effect of risk factors may vary across the age spectrum.
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COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Estudios de Cohortes , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Fumar/efectos adversosRESUMEN
The diagnosis of acute respiratory diseases in children can be challenging, and no single objective diagnostic test exists for common pediatric respiratory diseases. Previous research has demonstrated that ResAppDx, a cough sound and symptom-based analysis algorithm, can identify common respiratory diseases at the point of care. We present the study protocol for SMARTCOUGH-C 2, a prospective diagnostic accuracy trial of a cough and symptom-based algorithm in a cohort of children presenting with acute respiratory diseases. The objective of the study is to assess the performance characteristics of the ResAppDx algorithm in the diagnosis of common pediatric acute respiratory diseases.
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Tos , Teléfono Inteligente , Algoritmos , Niño , Ensayos Clínicos como Asunto , Estudios de Cohortes , Tos/diagnóstico , Humanos , Estudios Prospectivos , Ruidos Respiratorios/diagnósticoRESUMEN
BACKGROUND: Data on pediatric COVID-19 has lagged behind adults throughout the pandemic. An understanding of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. METHODS: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. RESULTS: 110 children with COVID-19 (median age 10 years, range 2 weeks-21 years) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first five days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. CONCLUSIONS: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.
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BACKGROUND: Nitrofen is a diphenyl ether that induces congenital diaphragmatic hernia (CDH) in rodents. Its mechanism of action has been hypothesized as inhibition of the retinaldehyde dehydrogenase (RALDH) enzymes with consequent reduced retinoic acid signaling. METHODS: To determine if nitrofen inhibits RALDH enzymes, a reporter gene construct containing a retinoic acid response-element (RARE) was transfected into HEK-293 cells and treated with varying concentrations of nitrofen in the presence of retinaldehyde (retinal). Cell death was characterized by caspace-cleavage microplate assays and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays. Ex vivo analyses of cell viability were characterized in fetal rat lung explants using Live/Dead staining. Cell proliferation and apoptosis were assessed using fluorescent immunohistochemistry with phosphorylated histone and activated caspase antibodies on explant tissues. Nile red staining was used to identify intracellular lipid droplets. RESULTS: Nitrofen-induced dose-dependent declines in RARE-reporter gene expression. However, similar reductions were observed in control-reporter constructs suggesting that nitrofen compromised cell viability. These observed declines in cell viability resulted from increased cell death and were confirmed using two independent assays. Ex vivo analyses showed that mesenchymal cells were particularly susceptible to nitrofen-induced apoptosis while epithelial cell proliferation was dramatically reduced in fetal rat lung explants. Nitrofen treatment of these explants also showed profound lipid redistribution, primarily to phagocytes. CONCLUSIONS: The observed declines in nitrofen-associated retinoic acid signaling appear to be independent of RALDH inhibition and likely result from nitrofen induced cell death/apoptosis. These results support a cellular apoptotic mechanism of CDH development, independent of RALDH inhibition.
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Aldehído Deshidrogenasa/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Isoenzimas/antagonistas & inhibidores , Éteres Fenílicos/toxicidad , Familia de Aldehído Deshidrogenasa 1 , Animales , Línea Celular , Epitelio/efectos de los fármacos , Epitelio/patología , Expresión Génica/efectos de los fármacos , Genes Reporteros/genética , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Ratas , Elementos de Respuesta/genética , Retinal-Deshidrogenasa , Coloración y Etiquetado , Tretinoina/farmacologíaRESUMEN
Advancement in technology has improved recognition of genetic etiologies of disease, which has impacted diagnosis and management of rare disease patients in the pediatric pulmonary clinic. This review provides an overview of genetic conditions that are likely to present with pulmonary features and require extensive care by the pediatric pulmonologist. Increased familiarity with these conditions allows for improved care of these patients by reducing time to diagnosis, tailoring management, and prompting further investigation into these disorders.
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Enfermedades Pulmonares/genética , Niño , Predisposición Genética a la Enfermedad , Humanos , Pulmón/anomalías , Pulmón/irrigación sanguínea , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/terapiaRESUMEN
Recognition of underlying genetic etiologies of disease is increasing at an exponential rate, likely due to greater access to and lower cost of genetic testing. Monogenic causes of disease, or conditions resulting from a mutation or mutations in a single gene, are now well recognized in every subspecialty, including pediatric pulmonary medicine; thus, it is important to consider genetic conditions when evaluating children with respiratory disease. In the pediatric pulmonary clinic, genetic testing should be considered when multiple family members present with similar or related clinical features and when individuals have unusual clinical presentations, such as early-onset disease or complex, syndromic features. This review provides a practical guide for genetic diagnosis in the pediatric pulmonary setting, including a review of genetic concepts, considerations for test selection and results in interpretation, as well as an overview of genetic differential diagnoses for common pediatric pulmonary phenotypes. Genetic conditions that commonly present to the pediatric pulmonary clinic are reviewed in a companion article by Yonker et al.