TAp73 depletion accelerates aging through metabolic dysregulation

Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.     

Continuing Medical Education Activity in Echocardiography

Article Title: Transesophageal Echocardiographic Assessment of Pulmonary Veins and Left Atrium in Patients Undergoing Atrial Fibrillation Ablation (Echocardiography 2011;28:774)     

Impact of Student- Versus Instructor-Directed Case Discussions on Student Performance in a Pharmacotherapy Capstone Course

Objective. To evaluate the impact of incorporating student-directed (SD) vs instructor-directed (ID) active learning on student performance in a pharmacotherapy capstone course.Design. This 9-credit course was redesigned from exclusively ID case discussions to a format in which half were SD and half were ID. Student performance on evaluation questions derived from SD sessions was compared with that from ID sessions.Assessment. Overall, students (n=299) performed better on ID-session questions than on SD-session questions (78.7% vs 75.3%, correctly answered, respectively; p<0.001). For written evaluations, students performed better on ID-session questions than on SD-session questions (79.8% vs 73.9%, respectively; p<0.001). For verbal evaluations, students performed better on SD-session questions than on ID-session questions (79.5% vs 74.5%, respectively; p<0.001). After the course revision, student confidence regarding their ability to think critically, solve problems, make decisions, and pursue lifelong learning was high, and student and faculty feedback was positive.Conclusion. Student performance in a pharmacotherapy capstone course remained acceptable when a combination of SD and ID active learning was used, but the addition of SD learning did not translate to better performance on course evaluations.     

Methylmalonic acidemia mimicking diabetic ketoacidosis and septic shock in infants

Methylmalonic acidemia (MMA) is most common inherited type of organic acidemia. It has diverse presentation in older infants without any initial apparent symptoms. MMA sometimes present with sudden metabolic decompensation, which may mimics common emergencies like septic shock and diabetic ketoacidosis (DKA) without early recognition can be fatal. In born error of metabolism especially organic acidemia should be suspected in any infant presented with severe high anion gap metabolic acidosis. We report two cases of MMA in infants presented acutely mimicking DKA and septic shock.     

Application of diffusional kurtosis imaging to detect occult brain damage in multiple sclerosis and neuromyelitis optica

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are two common types of inflammatory demyelinating disease of the central nervous system. Early distinction of NMO from MS is crucial but quite challenging. In this study, 13 NMO spectrum disorder patients (Expanded Disability Status Scale (EDSS) of 3.0 ± 1.7, ranging from 2 to 6.5; disease duration of 5.3 ± 4.7 years), 17 relapsing–remitting MS patients (EDSS of 2.6 ± 1.4, ranging from 1 to 5.5; disease duration of 7.9 ± 7.8 years) and 18 healthy volunteers were recruited. Diffusional kurtosis imaging was employed to discriminate NMO and MS patients at the early or stable stage from each other, and from healthy volunteers. The presence of alterations in diffusion and diffusional kurtosis metrics in normal‐appearing white matter (NAWM) and diffusely increased mean diffusivity (MD) in the cortical normal‐appearing gray matter (NAGM) favors the diagnosis of MS rather than NMO. Meanwhile, normal diffusivities and kurtosis metrics in all NAWM as well as increases in MD in the frontal and temporal NAGM suggest NMO. Our results suggest that diffusion and diffusional kurtosis metrics may well aid in discriminating the two diseases.     

Exposure to childhood neglect and physical abuse and developmental trajectories of heavy episodic drinking from early adolescence into young adulthood

BackgroundAlthough the literature suggests that childhood maltreatment (CM) relates to adolescent heavy episodic drinking (HED), few studies have examined the long-term effects of CM on adolescent HED. This study is the first to examine associations between exposure to CM and trajectories of HED from adolescence to young adulthood for the US population.MethodsFour waves of data from the National Longitudinal Study of Adolescent Health were used. A total of 8503 adolescents followed from adolescence (7th–12th grades) into young adulthood (ages 24–32) were assessed on CM and past-year HED frequency. Using growth curve modeling, trajectories of adolescent HED were examined, with subtype, frequency, and severity of CM as the primary independent variables. All of our analyses controlled for common risk factors for adolescent HED, including demographics, parental and peer alcohol use, parental education and employment, family income, parent–child relationship, and adolescent depression.ResultsAfter controlling for potential risk factors, neglect and physical abuse, both individually and in conjunction, were associated with faster increases in HED during adolescence and persistently elevated HED over much of adolescence and young adulthood. The frequency of neglect and physical abuse, individually and in conjunction, was also associated with the trajectory of HED, such that additional instances of these types of maltreatment were associated with faster increases in HED during adolescence and higher rates of peak use during young adulthood.ConclusionChild neglect and physical abuse appear to have long-lasting adverse effects on HED beyond adolescence and throughout much of young adulthood.