Late-presenting with a tumor-like mass giant cell reaction related to retropubic midurethral sling.

Stress urinary incontinence (SUI) is a condition that most commonly affects aging women. Synthetic mid-urethral slings (MUS) have become the most common surgical treatment for SUI; however, complications such as mesh erosion and dyspareunia have been reported. This case report describes an 84-year-old female who presented with a tumor-like mass giant cell reaction surrounding the MUS and the management of this mass.

Inhibitory control and negative affect in relation to food intake among youth.

Negative affect and poor inhibitory control are related to disinhibited eating behaviors in youth and may contribute to the development and/or maintenance of obesity. Although few studies have jointly examined these constructs in youth, it has been theorized that poor inhibitory control may be driven by negative affect. If supported, impaired inhibitory control, driven by negative affect, could represent a modifiable neurocognitive treatment target for disinhibited eating. The current study examined whether inhibitory control mediates the relationship between negative affect and eating among youth. Youth (8-17 years) participated in a Food Go/No-Go neurocognitive task to measure inhibitory control as the percentage of commission errors. A composite negative affect score was created from self-report measures of anxiety and depression. A laboratory buffet meal modeled to simulate disinhibited eating was used to measure total and snack food intake. Cross-sectional mediation models with bias-corrected bootstrap confidence intervals (CI) were conducted using negative affect as the independent variable, inhibitory control as the mediator, and intake patterns as dependent variables. One-hundred-eighty-one youths (13.2 ± 2.7y; 55% female; BMIz 0.6 ± 1.0) were studied. Total Go/No-Go commission errors mediated the relationship between negative affect and total intake (95%CI = [0.3, 31.6]), but not snack intake (95%CI = [-2.5, 7.3]). Commission errors for Food-Go blocks significantly mediated the relationship between negative affect and total intake (95%CI = [7.7, 44.4]), but not snack intake (95%CI = [-3.4, 9.5]). Commission errors on Neutral-Go blocks did not significantly mediate any of these relationships. Negative affect may lead to poorer inhibitory control as well as a stronger approach tendency toward food, increasing the likelihood of engaging in disinhibited eating. Future research should determine if, in combination with approaches to reduce negative affect, improved inhibitory control could help prevent overeating in youths with depressive or anxiety symptoms.

Mentoring to Help Prevent Physician Burnout.

The importance of a person's spirit and eternal destiny are eclipsed in American medi- cine. The most alarming effect of this eclipse is that the prevalence of burnout among physicians is high (about 46 percent) and growing.' It is alarming because trends that deplete the physician's spirit tragically impair the physician's capacity as a healer and as one who renews the spirit.

Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival.

BACKGROUND: The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. METHODS: We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. RESULTS: We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. CONCLUSIONS: Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth.

Isoaspartate accumulation in mouse brain is associated with altered patterns of protein phosphorylation and acetylation, some of which are highly sex-dependent.

Isoaspartate (isoAsp) formation is a major source of protein damage that is kept in check by the repair function of protein L-isoaspartyl methyltransferase (PIMT). Mice deficient in PIMT accumulate isoAsp-containing proteins, resulting in cognitive deficits, abnormal neuronal physiology and cytoarchitecture, and fatal epileptic seizures 30-60 days after birth. Synapsins I and II, dynamin-1, collapsin response mediator protein 2 (CRMP2), and α/ß-tubulin are major targets of PIMT in brain. To investigate links between isoAsp accumulation and the neurological phenotype of the KO mice, we used Western blotting to compare patterns of in vivo phosphorylation or acetylation of the major PIMT targets listed above. Phosphorylations of synapsins I and II at Ser-9 were increased in female KO vs. WT mice, and acetylation of tubulin at Lys-40 was decreased in male KO vs. WT mice. Average levels of dynamin-1 phosphorylation at Ser-778 and Ser-795 were higher in male KO vs. WT mice, but the statistical significance (P>0.1) was low. No changes in phosphorylation were found in synapsins I and II at Ser-603, in CRMP2 at Ser-522 or Thr-514, in DARPP-32 at Thr-34, or in PDK1 at Ser-241. General levels of phosphorylation assessed with Pro-Q Diamond stain, or an anti-phosphotyrosine antibody, appeared similar in the WT and KO mice. We conclude that isoAsp accumulation is associated with altered functional status of several neuronal proteins that are highly susceptible to this type of damage. We also uncovered unexpected differences in how male and female mice respond to isoAsp accumulation in the brain.