F-box protein FBXL16 binds PP2A-B55α and regulates differentiation of embryonic stem cells along the FLK1+ lineage.

The programmed formation of specific tissues from embryonic stem cells is a major goal of regenerative medicine. To identify points of intervention in cardiac tissue formation, we performed an siRNA screen in murine embryonic stem cells to identify ubiquitin system genes that repress cardiovascular tissue formation. Our screen uncovered an F-box protein, Fbxl16, as a repressor of one of the earliest steps in the cardiogenic lineage: FLK1+ progenitor formation. Whereas F-box proteins typically form SCF ubiquitin ligases, shotgun mass spectrometry revealed that FBXL16 instead binds protein phosphatase 2A (PP2A) containing a B55 specificity subunit (PP2A(B55)). Phosphoproteomic analyses indicate that FBXL16 negatively regulates phosphorylation of the established PP2A(B55) substrate, vimentin. We suggest that FBXL16 negatively regulates the activity of B55α-PP2A to modulate the genesis of FLK1+ progenitor cells.

Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises.

The primary objective of this investigation was to identify which components of endurance training (e.g., modality, duration, frequency) are detrimental to resistance training outcomes. A meta-analysis of 21 studies was performed with a total of 422 effect sizes (ESs). Criteria for the study included were (a) compare strength training alone to strength plus endurance training (concurrent) or to compare combinations of concurrent training; (b) the outcome measures include at least one measure of strength, power, or hypertrophy; and (c) the data necessary to calculate ESs must be included or available. The mean ES for hypertrophy for strength training was 1.23; for endurance training, it was 0.27; and for concurrent training, it was 0.85, with strength and concurrent training being significantly greater than endurance training only. The mean ES for strength development for strength training was 1.76; for endurance training, it was 0.78; and for concurrent training, it was 1.44. Strength and concurrent training was significantly greater than endurance training. The mean ES for power development for strength training only was 0.91; for endurance training, it was 0.11; and for concurrent training, it was 0.55. Significant differences were found between all the 3 groups. For moderator variables, resistance training concurrently with running, but not cycling, resulted in significant decrements in both hypertrophy and strength. Correlational analysis identified significant negative relationships between frequency (-0.26 to -0.35) and duration (-0.29 to -0.75) of endurance training for hypertrophy, strength, and power. Significant relationships (p < 0.05) between ES for decreased body fat and % maximal heart rate (r = -0.60) were also found. Our results indicate that interference effects of endurance training are a factor of the modality, frequency, and duration of the endurance training selected.

Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia.

Farnesoid X receptor (FXR) plays important regulatory roles in bile acid, lipoprotein, and glucose homeostasis. Here, we have utilized Fxr(-/-) mice and mice deficient in scavenger receptor class B type I (SR-BI), together with an FXR-specific agonist and adenovirus expressing hepatocyte nuclear factor 4alpha or constitutively active FXR, to identify the mechanisms by which activation of FXR results in hypocholesterolemia. We identify a novel pathway linking FXR to changes in hepatic p-JNK, hepatocyte nuclear factor 4alpha, and finally SR-BI. Importantly, we demonstrate that the FXR-dependent increase in SR-BI results in both hypocholesterolemia and an increase in reverse cholesterol transport, a process involving the transport of cholesterol from peripheral macrophages to the liver for excretion into the feces. In addition, we demonstrate that FXR activation also induces an SR-BI-independent increase in reverse cholesterol transport and reduces intestinal cholesterol absorption. Together, these data indicate that FXR is a promising therapeutic target for treatment of hypercholesterolemia and coronary heart disease.

Analysis of 30-day readmissions among neurosurgical patients: surgical complication avoidance as key to quality improvement.

UNLABELLED: OBJECT.: In terms of measuring quality of care and hospital performance, an outcome of increasing interest is the 30-day readmission rate. Recent health care policy making has highlighted the necessity of understanding the factors that influence readmission. To elucidate the rate, reason, and predictors of readmissions at a tertiary/quaternary neurosurgical service, the authors studied 30-day readmissions for the Department of Neurosurgery at two University of California, Los Angeles (UCLA), hospitals. METHODS: Over a 3-year period, the authors retrospectively identified adult and pediatric patients who had been discharged from the UCLA Medical Center after having undergone a major neurosurgical procedure and being readmitted within 30 days. Data were obtained on demographics, follow-up findings, diagnosis and reason for readmission, major operations performed, and length of stay during index admission and readmission. Reasons for readmission were broadly categorized into surgical, medical diagnosis/complication, problem associated with the original diagnosis, neurological decompensation, pain management, and miscellaneous. For further characterization, subgroup analysis and in-depth chart review were performed. RESULTS: Over the study period, 365 (6.9%) of 5569 patients were readmitted within 30 days. The most common diagnosis at index admission was brain tumor (102 patients), followed by CSF shunt malfunction (63 patients). The most common reason for readmission was surgical complication (50.1%). Among those with surgical complications, the largest subgroup consisted of patients with CSF shunt-related problems (77 patients). The second and third largest subgroups were surgical site infection and CSF leakage (41 and 31 patients, respectively). Medical diagnosis/complication was the second most frequent (27.9%) reason for readmission. CONCLUSIONS: Surgical complications seem to be a major reason for readmission at the neurosurgical practice studied. Results indicate that the outcomes that are amenable to and would have the greatest effect on quality improvement are CSF shunt-related complications, surgical site infections, and CSF leaks.