RESUMEN
Mutations and common polymorphisms in interferon regulatory factor 6 ( IRF6) are associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP). To date, much of the focus on this transcription factor has been on identifying its direct targets and the gene regulatory network in which it operates. Notably, however, IRF6 is found predominantly in the cytoplasm, with its import into the nucleus tightly regulated like other members of the IRF family. To provide further insight into the role of IRF6 in the pathogenesis of CLP, we sought to identify direct IRF6 protein interactors using a combination of yeast 2-hybrid screens and co-immunoprecipitation assays. Using this approach, we identified NME1 and NME2, well-known regulators of Rho-type GTPases, E-cadherin endocytosis, and epithelial junctional remodeling, as bona fide IRF6 partner proteins. The NME proteins co-localize with IRF6 in the cytoplasm of primary palatal epithelial cells in vivo, and their interaction with IRF6 is significantly enhanced by phosphorylation of key serine residues in the IRF6 C-terminus. Furthermore, CLP associated IRF6 missense mutations disrupt the ability of IRF6 to bind the NME proteins and result in elevated activation of Rac1 and RhoA, compared to wild-type IRF6, when ectopically expressed in 293T epithelial cells. Significantly, we also report the identification of 2 unique missense mutations in the NME proteins in patients with CLP (NME1 R18Q in an IRF6 and GRHL3 mutation-negative patient with van der Woude syndrome and NME2 G71V in a patient with nonsyndromic CLP). Both variants disrupted the ability of the respective proteins to interact with IRF6. The data presented suggest an important role for cytoplasmic IRF6 in regulating the availability or localization of the NME1/2 complex and thus the dynamic behavior of epithelia during lip/palate development.
Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Factores Reguladores del Interferón/genética , Nucleósido Difosfato Quinasas NM23/genética , Animales , Embrión de Pollo , Variación Genética , Humanos , Inmunoprecipitación , Mutación , Fosforilación , Reacción en Cadena de la Polimerasa , Adherencias Tisulares/genética , Factores de Transcripción/genéticaRESUMEN
Management of pain is a primary concern in the treatment of burn patients. The intent of this study was to test the efficacy of music-based imagery and musical alternate engagement in assisting burn patients in managing their pain and anxiety during debridement. Twenty-five patients, 7 years of age and older, who were admitted to the Comprehensive Burn Care Center were enrolled in the study, which used a repeated-measures design with subjects serving as their own control. Subjects were randomly assigned to 1 of 2 groups. Those placed in Group A received music therapy intervention during their first dressing change, and no music therapy on the following day. Group B received no music therapy intervention during their first dressing change and music therapy during their next dressing, on the following day. Data were collected at 4 intervals in the medical procedure; in the patient's room before transfer to the treatment room, in the treatment room during debridement, in the treatment room after debridement, and upon returning to the patient's room. The measurements taken were pulse, patients' self-report of pain, patients' self-report of anxiety, and the nurse's observation of patients' tension. There was a significant reduction in the self-reporting of pain in those who received music therapy in contrast to those who did not receive music therapy (P < .03). Music therapy is a valuable noninvasive intervention for the treatment of pain after burn injury.
Asunto(s)
Quemaduras/cirugía , Desbridamiento/métodos , Musicoterapia/métodos , Manejo del Dolor , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Unidades de Quemados , Quemaduras/diagnóstico , Niño , Terapia Combinada , Femenino , Florida , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dimensión del Dolor , Satisfacción del Paciente , Probabilidad , Valores de ReferenciaRESUMEN
This study assessed music as reinforcement for non-nutritive sucking of 12 premature infants born at an average gestation of 29.3 weeks and an average birthweight of 1111.9 g. At the time of the study, the infants' average post conception age was 35.5 weeks, and their average weight was 1747.3 g. A pacifier was fitted with a pressure transducer so that a sufficient suck activated frequency and duration signals as well as 10 seconds of recorded music consisting of lullabies sung by female vocalists. A 14-minute ABAB study design included a silence baseline for 2 minutes, 5 minutes of contingent music, 2 minutes of silence, and 5 minutes of contingent music. Frequency data were recorded for each 5-second interval in which the duration light was activated for at least 3 seconds. Results demonstrated that sucking rates during the periods of contingent music were 2.43 times greater than baseline (silence) sucking rates. In this study, music contributed significantly to the development of non-nutritive sucking of premature infants.
Asunto(s)
Enfermedades del Prematuro/enfermería , Musicoterapia , Conducta en la Lactancia , Régimen de Recompensa , Peso Corporal , Femenino , Humanos , Lactante , Recién Nacido , Cuidado Intensivo Neonatal , MasculinoRESUMEN
To assess the benefits of lullaby singing and multimodal stimulation on premature infants in neonatal intensive care, 40 infants in a Level III Newborn Intermediate Care Unit were divided into control (n = 20) and experimental (n = 20) groups by pair matching on the basis of gender, birthweight, gestational age at birth and severity of medical complications. Participants met these project criteria: (a) corrected gestational age > 32 weeks; (b) age since birth > 10 days; and (c) weight > 1700 g. All participants had been referred for developmental stimulation by the medical staff. Experimental infants received reciprocal, multimodal (ATVV) stimulation paired with line singing of Brahms' Lullaby. Stimulation was provided for 15-30 minutes, one or two times per week from referral to discharge. Dependent variables were (a) days to discharge, (b) weight gain/day, and (c) experimental infants' tolerance for stimulation. Results showed that music and multimodal stimulation significantly benefited females' days to discharge and increased weight gain/day for both males and females. Both male and female infants' tolerance for stimulation showed marked and steady increase across the stimulation intervals with females' tolerance increasing more rapidly than males.
Asunto(s)
Recien Nacido Prematuro/fisiología , Recien Nacido Prematuro/psicología , Cuidado Intensivo Neonatal/métodos , Cuidado Intensivo Neonatal/psicología , Musicoterapia/métodos , Estimulación Física/métodos , Peso Corporal , Femenino , Humanos , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Enfermería Neonatal/métodos , Caracteres SexualesRESUMEN
Aversive environment auditory stimuli is a common concern in neonatal intensive care. Recently, interest has developed regarding the use of music applications to mask such stimuli and to reduce the high risk for complications or failure to thrive. In this study of 20 oxygenated, low birth weight infants in a Newborn Intensive Care Unit of a regional medical center in the Southeastern United States, 10 infants listened to lullabies and 10 infants to recordings of their mother's voice through earphones for 20 minutes across three consecutive days. Oxygen saturation levels and frequency of oximeter alarms were recorded. Results indicated a differential response to the two auditory stimuli as listening time progressed. On Day 1, the infants listening to music had significantly higher oxygen saturation levels, but these effects disappeared by Days 2 and 3. On Days 2 and 3, however, the babies hearing music had significantly depressed oxygen saturation levels during the posttest intervals after the music was terminated. Infants hearing music had significantly fewer occurrences of Oximeter alarms during auditory stimuli than did those listening to the mothers' voice. Implications for the therapeutic use of auditory stimuli in the Newborn Intensive Care Unit are discussed.
Asunto(s)
Recien Nacido Prematuro/psicología , Madres , Musicoterapia/métodos , Voz , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Unidades de Cuidado Intensivo Neonatal , Masculino , Oximetría , Oxígeno/sangre , Factores de TiempoRESUMEN
Music therapy is a profession which meets multiple physical, social, and psychological needs. Music therapists can facilitate health objectives by reducing the intensity or duration of pain, alleviating anxiety, and decreasing the amount of analgesic medication needed. Rehabilitative objectives can include activities which incorporate exercise, range of motion therapy, or gait training. Reduction of fear, anxiety, stress, or grief are common psychological objectives. Music therapy is particularly effective in promoting social objectives such as increased interaction, verbalization, independence, and cooperation; enhanced relationships with health care personnel and family members; and increased stimulation during long-term hospitalization or isolation. Counseling techniques are often paired with music to achieve emotional objectives such as expression, adjustment, stability, or locus of control. The purpose of this article is to synthesize the extant music/medical research literature and clarify how music therapy can provide a quintessential combination of physical, social, and psychological benefits to enhance the health care of pediatric oncology patients.
Asunto(s)
Investigación en Enfermería Clínica , Musicoterapia , Enfermería Oncológica , Enfermería Pediátrica , Niño , Humanos , Musicoterapia/educación , Musicoterapia/métodos , Enfermería Oncológica/educación , Enfermería Oncológica/métodos , Enfermería Pediátrica/educación , Enfermería Pediátrica/métodosRESUMEN
This article is a comprehensive analysis and application of music therapy research in the general field of music in medicine, and consists of a thorough review of the literature and a meta-analysis of all empirical studies using music in actual medical/dental treatments. It also transfers research results to clinical applications of music therapy techniques and program development in a general hospital setting.