Lead Decreases Bone Morphogenetic Protein-7 (BMP-7) Expression and Increases Renal Cell Carcinoma Growth in a Sex-Divergent Manner.

Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 µM lead acetate for 10 consecutive passages decreased E-cadherin expression and cell aggregation. Proliferation, colony formation, and wound healing were increased. When lead-challenged cells were injected into mice, tumor size at day 21 was increased; interestingly, this increase was seen in male but not female mice. When mice were challenged with 32 ppm lead in drinking water for 20 weeks prior to tumor cell injection, there was an increase in tumor size in male, but not female, mice at day 21. To investigate the mechanism underlying the sex differences, the expression of sex hormone receptors in Renca cells was examined. Control Renca cells expressed estrogen receptor (ER) alpha but not ER beta or androgen receptor (AR), as assessed by qPCR, and the expression of ERα was increased in tumors in both sexes. In tumor samples harvested from lead-challenged cells, both ERα and AR were detected by qPCR, yet there was a significant decrease in AR seen in lead-challenged tumor cells from male mice only. This was paralleled by a plate-based array demonstrating the same sex difference in BMP-7 gene expression, which was also significantly decreased in tumors harvested from male but not female mice; this finding was validated by immunohistochemistry. A similar expression pattern was seen in tumors harvested from the mice challenged with lead in the drinking water. These data suggest that lead promotes RCC progression in a sex-dependent via a mechanism that may involve sex-divergent changes in BMP-7 expression.

Reversal of warfarin anticoagulation in geriatric traumatic brain injury due to ground-level falls.

BACKGROUND: The efficacy of prothrombin complex concentrate (PCC) compared with fresh frozen plasma (FFP) for reversal of oral anticoagulants has not been investigated in geriatric patients suffering intracranial hemorrhage (ICH) due to a ground-level fall (GLF). METHODS: Patients 65 years and older who were treated at Santa Barbara Cottage Hospital between January 2011 and March 2018 with ICH after a GLF while taking warfarin were reviewed. Patients were reversed with either FFP (n=25) or PCC (n=27) and patient outcomes were compared. Separate analyses were conducted for patients who received adjuvant vitamin K administration and those who did not. RESULTS: Mortality rates, hospital length of stay, intensive care unit admission and length of stay were similar for both FFP and PCC intervention. There was no difference in radiological progression of hemorrhage within the first 24 hours of admission (FFP: 36%, PCC: 43%, p=0.365). In patients who had international normalized ratio (INR) values measured prior to intervention, 81% (17 out of 21) of the PCC group reached an INR value below 1.5 within an 8-hour period, whereas only 29% (4 out of 14) of the FFP group did (p=0.002). Vitamin K was concomitantly given to 28% of the patients receiving FFP, and 81% of those patients receiving PCC. No significant differences in outcomes were found whether adjunctive vitamin K was administered or not, in either FFP or PCC group. However, when vitamin K was not administered, the PCC group had a higher rate of INR reversal (80% vs. 10% for FFP, p=0.006). CONCLUSION: Administration of PCC is as effective in short-term outcomes as FFP in treating geriatric patients on warfarin sustaining an ICH after a GLF. INR reversal was more successful, significantly faster, and required lower infusion volumes in patients receiving PCC. LEVEL OF EVIDENCE: Level III.

Acetabular labral tear description and measures of pincer and cam-type femoroacetabular impingement and interobserver variability on 3 T MR arthrograms.

PURPOSE: To evaluate the inter-rater agreement for description of labral tears and measures of femoroacetabular impingement (FAI) on 3 T hip MR arthrography. MATERIALS AND METHODS: 53 hip MR arthrograms were reviewed by three musculoskeletal radiologists. Labral tears were described (Czerny classification) with extents recorded. Cam- and pincer-type FAI measures were performed. Intraclass correlation (ICC) and kappa statistic (κ) assessed inter-observer agreement. RESULTS: There was fair agreement for labral tear description (κ = 0.25-0.39) and for alpha angles (ICC = 0.54), and fair to excellent agreement for other measures of FAI (ICC = 0.51-0.90). CONCLUSION: There is moderate inter-observer variability reporting labral tears and measures of FAI.

Testing principal- versus medial-axis accounts of global spatial reorientation.

Determination of a direction of travel is a necessary component of successful navigation, and various species appear to use the geometric shape (global geometric cues) of an environment to determine direction. Yet, debate remains concerning which objective shape parameter is responsible for spatial reorientation via global geometric cues. For example, the principal axis of space, which runs through the centroid and approximate length of the space, and the medial axis of space, a trunk and branch system that fills the shape, have each been suggested as a basis to explain global spatial reorientation. As the principal- and medial-axis accounts appear to have substantial theoretical implications regarding the nature of shape perception, spatial memory, and the underlying psychological representations of space, it appears critical to empirically differentiate between these global geometric accounts. The present experiment explicitly placed predictions from the principal- and medial-axis-based accounts of global spatial reorientation in conflict for theoretical diagnostic purposes. We used a standard reorientation paradigm in which human participants first reoriented in a rectangular environment; subsequent testing in a critical I-shaped enclosure allowed dissociation of the principal- or medial-axis-based accounts. We show that reorientation in the I-shaped enclosure was consistent with the principal-axis account and inconsistent with the medial-axis account. We suggest that the use of the principal axis for spatial reorientation is a relatively simple and efficient way to establish directionality that would be advantageous over a more complex and less efficient medial-axis-based account. (PsycINFO Database Record