RESUMEN
Hyper-beta-alaninemia is a rare metabolic condition that results in elevated plasma and urinary ß-alanine levels and is characterized by neurotoxicity, hypotonia, and respiratory distress. It has been proposed that at least some of the symptoms are caused by oxidative stress; however, only limited information is available on the mechanism of reactive oxygen species generation. The present study examines the hypothesis that ß-alanine reduces cellular levels of taurine, which are required for normal respiratory chain function; cellular taurine depletion is known to reduce respiratory function and elevate mitochondrial superoxide generation. To test the taurine hypothesis, isolated neonatal rat cardiomyocytes and mouse embryonic fibroblasts were incubated with medium lacking or containing ß-alanine. ß-alanine treatment led to mitochondrial superoxide accumulation in conjunction with a decrease in oxygen consumption. The defect in ß-alanine-mediated respiratory function was detected in permeabilized cells exposed to glutamate/malate but not in cells utilizing succinate, suggesting that ß-alanine leads to impaired complex I activity. Taurine treatment limited mitochondrial superoxide generation, supporting a role for taurine in maintaining complex I activity. Also affected by taurine is mitochondrial morphology, as ß-alanine-treated fibroblasts undergo fragmentation, a sign of unhealthy mitochondria that is reversed by taurine treatment. If left unaltered, ß-alanine-treated fibroblasts also undergo mitochondrial apoptosis, as evidenced by activation of caspases 3 and 9 and the initiation of the mitochondrial permeability transition. Together, these data show that ß-alanine mediates changes that reduce ATP generation and enhance oxidative stress, factors that contribute to heart failure.
Asunto(s)
Trastornos de Somnolencia Excesiva/metabolismo , Mitocondrias Cardíacas/metabolismo , Enfermedades Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Convulsiones/metabolismo , beta-Alanina/metabolismo , beta-Alanina/toxicidad , Animales , Trastornos de Somnolencia Excesiva/genética , Trastornos de Somnolencia Excesiva/patología , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Ratones , Mitocondrias Cardíacas/genética , Mitocondrias Cardíacas/patología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/patología , Miocitos Cardíacos/patología , Consumo de Oxígeno , Ratas , Convulsiones/genética , Convulsiones/patología , Taurina/biosíntesis , Taurina/genética , beta-Alanina/genéticaRESUMEN
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is a mitochondrial disease caused by one or more mutations of tRNA(Leu(UUR)). These mutations reduce both the aminoacylation of tRNA(Leu(UUR)) and a posttranslational modification in the wobble position of tRNA(Leu(UUR)). Both changes result in reduced transcription of mitochondria-encoded proteins; however, reduced aminoacylation affects the decoding of both UUG and UUA while the wobble defect specifically diminishes UUG decoding. Because 12 out of the 13 mitochondria-encoded proteins are more dependent on UUA decoding than UUG decoding, the aminoacylation defect should have a more profound effect on protein synthesis than the wobble defect, which more specifically alters the expression of one mitochondria-encoded protein, ND6. Taurine serves as a substrate in the formation of 5-taurinomethyluridine-tRNA(Leu(UUR)); therefore, taurine deficiency should mimic 5-taurinomethyluridine-tRNA(Leu(UUR)) deficiency. Hence, the wobble hypothesis predicts that the symptoms of MELAS mimic those of taurine deficiency, provided that the dominant defect in MELAS is wobble modification deficiency. On the other hand, if the aminoacylation defect dominates, significant differences should exist between taurine deficiency and MELAS. The present review tests this hypothesis by comparing the symptoms of MELAS and taurine deficiency.
Asunto(s)
Síndrome MELAS/complicaciones , Síndrome MELAS/metabolismo , Taurina/deficiencia , Animales , Crecimiento y Desarrollo , Humanos , Especificidad de Órganos , Taurina/metabolismoRESUMEN
OBJECTIVES: The use of video recording is commonplace in rhinology given the increased use of endoscopes when evaluating patients in the office and the operating room and for its educational potential. This study aimed to determine the quality of publicly available endoscopic videos in rhinology. METHODS: A video search was performed on YouTube in April 2020 and included all videos since its inception in 2005 using terms related to rhinology found in the Accreditation Council for Graduate Medical Education (ACGME) Case Log Coding Guide. Videos which met inclusion criteria were evaluated for video metrics and quality using validated scoring systems: Video Power Index (VPI), modified Journal of American Medical Association (JAMA) benchmark criteria, modified global quality score (GQS), and modified DISCERN criteria. RESULTS: A total of 138 videos were evaluated, 114 of which were uploaded independently, and 24 videos were uploaded by an academic institution. Academic-affiliated videos have higher like ratio at 91.7 ± 7.55% compared with 86.27 ± 17.44% (p = 0.018). Academic-affiliated videos have higher JAMA benchmark scores, DISCERN criteria scores, and GQS values (1.71 ± 0.55 vs. 1.66 ± 0.49 [p = 0.66]), (3.33 ± 0.56 vs. 2.85 ± 0.65 [p < 0.001]), (4.38 ± 0.81 vs. 3.43 ± 1.01 [p < 0.001])], respectively. There was no significant difference in VPI (p = 0.73). CONCLUSIONS: Endoscopic videos are rapidly growing in prominence and remain an important part of surgical education, but overall are heterogeneous in quality and reliability, necessitating an effort to establish both video sharing regulations and objective standards of quality.
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Medios de Comunicación Sociales , Humanos , Difusión de la Información , Reproducibilidad de los Resultados , Grabación en Video , Educación de Postgrado en MedicinaRESUMEN
The purpose of this study is to describe the morbidity in patients undergoing endoscopic skull base surgery (ESBS) with and without intra-operative lumbar drain (LD) placement. A retrospective review of all patients undergoing ESBS from July 2018 to August 2020 at a tertiary academic skull base surgery program was conducted. Those with LD placement for aiding in suprasellar dissection and/or for CSF diversion following skull base repair were included. LD-related medical and technical complications were combined as composite outcomes to assess overall event rates in those with and without LD. 104 patients were included. Of the 104 participants, 64 (61.5%) had LD placed. Of these 64, 1 (0.96%) and 2 (1.9%) experienced postoperative medical (hypophysitis) and related technical (2 blood patches) complications, respectively. There was one case of postoperative CSF leak (in LD group) and no cases of DVT/PE or meningitis. LD use was not associated with increased risk of any complication (p = 0.165) compared to those without LD. There were no significant differences in rates of postoperative epistaxis (p = 0.427), readmission (p = 0.629), or reoperation (p = 0.165) between groups. Female sex was the only predictor of increased overall complication rates in patients with LD (OR, 1.122, 95% CI, 1.010-1.247, p = 0.032). Our findings suggest judicious use of a LD in endoscopic skull base surgery within a reasonable time does not increase the incidence of overall medical or technical complications, readmission, and reoperation.
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Pérdida de Líquido Cefalorraquídeo , Complicaciones Posoperatorias , Pérdida de Líquido Cefalorraquídeo/epidemiología , Pérdida de Líquido Cefalorraquídeo/etiología , Endoscopía/efectos adversos , Femenino , Humanos , Morbilidad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Base del Cráneo/cirugíaRESUMEN
OBJECTIVES/HYPOTHESIS: The objective of this study is to evaluate the impact of patient and surgical factors, including approach and reconstruction type, on postoperative nausea and vomiting episodes following endoscopic skull base surgery. STUDY DESIGN: Retrospective review. METHODS: We performed a retrospective chart review from July 2018 to August 2020 of 99 consecutive patients undergoing endoscopic skull base surgery at a tertiary academic skull base surgery program. All patients were treated with a standardized postoperative protocol consisting of scheduled ondansetron, along with promethazine and scopolamine for breakthrough nausea and vomiting episodes. Cumulative nausea and vomiting episodes throughout hospital stay were recorded for each patient. RESULTS: Of the 99 patients identified, the mean number of nausea and vomiting episodes per patient were 0.4 ± 1.2 and 0.3 ± 0.7, respectively. Female sex (ß = .65, P = .034) and extended surgical approach (ß = .90, P = .027) were associated with increased risk for postoperative nausea. Furthermore, female sex (ß = .44, P = .018), cavernous sinus dissection (ß = .52, P = .002), and extended approach (ß = .79, P = .025) significantly increased odds of postoperative vomiting episodes. There was no association between total operative time or total postoperative opioid dose and nausea and vomiting episodes (all Ps > .05). Neither increased nausea nor vomiting episodes significantly increased odds of prolonged hospitalization (P = .105 and .164, respectively). CONCLUSION: This report highlights novel risk factors for patients undergoing endoscopic skull base surgery. Upfront standing antiemetic therapy may be considered when treating patients with independent predictors of postoperative nausea and vomiting, including female sex, cavernous sinus dissection, and extended surgical approach. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:761-768, 2022.
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Antieméticos , Náusea y Vómito Posoperatorios , Antieméticos/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Ondansetrón/efectos adversos , Ondansetrón/uso terapéutico , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Estudios Retrospectivos , Base del Cráneo , Vómitos/inducido químicamenteRESUMEN
A direct observation strategy (Standardized Observation Analogue Procedure, SOAP) was used in a large-scale randomized trial of parent training versus parent education in young children with autism spectrum disorder (ASD) and disruptive behavior. The 16-minute SOAP, modified from an earlier version of this same measure, included parentchild interaction to assess child behavior in a clinical laboratory setting. Despite study entry criteria for all child participants requiring moderate levels of disruptive behavior in this project, 126 of 168 children with complete SOAP data at baseline showed no disruptive behavior on this measure. Although the primary purpose of the study was to determine whether the SOAP could detect differences between the two conditions (i.e.,parent training (PT) and parent education (PE)), baseline observation data was not consistent with parent ratings at baseline or subsequent follow up visits, leaving little room to demonstrate improvement with this observation measure. This and the challenging, time-consuming and resource intensive effort involved in using such a measure in a large randomized scale trial, raises fundamental questions about the validity of the SOAP as an outcome measure in such a study. Further consideration related to the feasibility and practicality of using direct observation as a primary measure in larger scale efforts overall are also discussed.
RESUMEN
OBJECTIVE: Systematically review and critically evaluate all available published data on the use of topical mitomycin C (MMC) as an adjunctive in airway surgery. DATA SOURCES: Published studies indexed in MEDLINE, EMBASE, or Cochrane databases. Inclusion criteria were English language, sample size greater than five, and publication of data applicable to the analysis of topical MMC and airway surgery outcomes. REVIEW METHODS: Evidence tables were compiled to include sample size, study design, and evidence level. Summary statistics, random-effects modeling, and subgroup analysis were performed. RESULTS: Twenty manuscripts (eight human, 12 animal) met the inclusion criteria. Seven of eight (87.5%) of the human studies and eight of 12 (66%) animal studies concluded topical MMC was beneficial to airway surgical outcomes. Eleven of twelve animal studies included randomization and a control group, compared with only two of eight human studies. Random-effects modeling of human studies (k=7) indicated that 81.4 percent (95% CI, 72.0%-90.9%; P < 0.001) of patients had improved outcomes attributable to MMC. Random-effects modeling of animal data included modeling of change in airway diameter (Hedge's G = -0.03; 95% CI, -0.66-0.60; P = 0.924) and the change in histologic measures (Hedge's G = 1.26; 95% CI, 0.596-1.92; P < 0.001) in MMC-treated animals vs controls. CONCLUSION: The majority of the published literature individually suggests the use of topical MMC improves airway surgery outcomes. However, heterogeneity within the clinical studies, the lack of controlled data, and the lack of significance in the pooled animal data (other than histologic outcomes) suggest that the utility of MMC is still undetermined.
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Obstrucción de las Vías Aéreas/cirugía , Cicatriz/prevención & control , Mitomicina/uso terapéutico , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Administración Tópica , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/patología , Animales , Cicatriz/etiología , Cicatriz/patología , Humanos , Mitomicina/administración & dosificación , Inhibidores de la Síntesis del Ácido Nucleico/administración & dosificación , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
The retrospective pre-post design affords many benefits to program staff and, accordingly, has piqued renewed interest among applied program evaluators. In particular, the field has witnessed increasing application of a post-program-only data collection strategy in which only posttest and retrospective pretest data are collected. A post-program-only assessment strategy takes considerably less time than is required for collecting pre-program data and presumably has the added benefit of eliminating the impact of response-shift bias. Response-shift bias occurs when the knowledge, skills, or experiences participants gain through program participation leads them to interpret questionnaire items in a qualitatively different manner at pretest versus posttest. In this article, we discuss the strengths and weaknesses associated with administering retrospective pretest assessments and underscore the importance of thoroughly evaluating any application of a retrospective measurement strategy prior to its broader implementation. We provide a practical illustration of this evaluation process using a mixed-method study that assesses one measure of parenting education program effectiveness-the Parenting Skills Ladder.
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Responsabilidad Parental/psicología , Padres/educación , Padres/psicología , Evaluación de Programas y Proyectos de Salud/métodos , Adolescente , Adulto , California , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Oregon , Relaciones Padres-Hijo , Proyectos Piloto , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Patients with an acute ischemic stroke (AIS) following cardiac catheterization (CC) generally do not receive intravenous thrombolysis [intravenous tissue plasminogen activator (IV-tPA)] as it is contraindicated due to the coagulopathy related to the heparin used during the procedure. We report a case of AIS successfully treated with IV thrombolysis following protamine reversal of heparin effect. CASE REPORT: An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent elective transradial CC following an abnormal stress test. He had 2 drug-eluting stents for severe stenosis of mid-circumflex and right coronary arteries and received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. Computed tomographic scan of the brain and computed tomographic angiogram of head and neck were unremarkable. Bedside activated clotting time was 181. Protamine 40 mg was administered and 30 minutes later, the activated clotting time level was normalized. IV-tPA was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Magnetic resonance imaging of brain showed no acute infarction 24 hours after stroke. CONCLUSIONS: There are limited reports of protamine reversal of heparin before IV-tPA administration. To our knowledge, there are only 6 AIS cases including ours. Three cases received 0.6 mg/kg of tPA dose. All have favorable outcomes and no intracranial hemorrhage was reported. Protamine reversal of heparin for AIS after CC seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy.