Alexander R. Zheutlin

Carbon dioxide emissions and change in prevalence of obesity and diabetes in the United States: an ecological study.

Recent studies suggest that increasing levels of the greenhouse gas, carbon dioxide (CO2), may influence weight gain and thus may play a role in rising trends in obesity and diabetes. We conducted an ecological study to examine the associations between CO2 emissions from fossil fuel combustion and changes in the prevalence of obesity and diabetes in the United States. County-level data on CO2 emissions, prevalence of obesity and diagnosed diabetes, other sociodemographic factors and neighborhood characteristics related to urbanicity, and fine particles (PM2.5) between 2004 and 2008 were obtained from the Vulcan Project, Centers for Disease Control and Prevention, and American Community Survey. Linear mixed effect modeling of 3019 counties for the associations between average CO2 emissions and changes in diabetes and obesity prevalence between 2004 and 2008 was performed. The average obesity and diabetes prevalence increased between 2004 and 2008 by 3.65% (SD: 1.88%) and 1.65% (SD: 1.70%), respectively. A marginally significant positive association between CO2 emission and changes in obesity prevalence was found with adjustment for sociodemographic factors, indicators of urbanicity and spatial autocorrelation (p-trend=0.06). The association became weaker and nonsignificant with further adjustment for PM2.5 (p-trend=0.17). There was a significant positive association between CO2 emission and changes in diabetes prevalence before controlling for PM2.5 (p-trend=0.05) but the association became null after controlling for PM2.5 (p-trend=0.49), suggesting that PM2.5 is a critical confounder in the association between CO2 emission and changes in diabetes prevalence. This study does not support the hypothesis that CO2 emissions, a leading driver of climate change, may be linked to increasing trends in obesity and diabetes, though there was an indication of possible link between CO2 and obesity.

Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation

The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. Comparison of the xDO-BMSC and xDO groups demonstrated significantly improved osteocyte count (87.15 ± 10.19 vs. 67.88 ± 15.38, P = 0.00), and empty lacunae number (2.18 ± 0.79 vs 12.34 ± 6.61, P = 0.00). Quantitative analysis revealed a significant decrease in immature osteoid volume relative to total volume (P = 0.00) and improved the ratio of mature woven bone to immature osteoid (P = 0.02) in the xDO-BMSC compared with the xDO group. No significant differences were found between the Control and xDO-BMSC groups. In an isogenic murine model of DO, BMSC therapy assuaged XRT-induced cellular depletion, resulting in a significant improvement in histological and histomorphometric outcomes.

Prophylactic amifostine prevents a pathologic vascular response in a murine model of expander-based breast reconstruction

BACKGROUND Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.

Relapsing Polychondritis following Treatment with Secukinumab for Ankylosing Spondylitis: Case Report and Review of the Literature

Relapsing polychondritis (RP) is an autoimmune disorder that often occurs concomitantly with other autoimmune diseases, though RP has been infrequently associated with ankylosing spondylitis (AS). There is a small, but growing, body of the literature demonstrating case reports describing RP secondary to AS in patients treated with tumor necrosis alpha inhibitors (TNFis). We present the first case in which RP developed in AS while treated with an interleukin 17A inhibitor (IL-17Ai), secukinumab. With this case report, we hope to raise physician awareness of the possible autoimmune disorders that may arise subsequent to novel immunomodulation therapies, particularly that RP may develop subsequent to inhibition of IL-17A.

Impact of neoadjuvant chemotherapy on surgical outcomes among patients with hormone receptor positive breast cancer

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate for outcome, but not necessarily conversion to BCT eligibility. We sought to examine the impact of NACT on surgical decision making among HR+ patients.

Significant Differences in the Bone of an Isogenic Inbred Versus Nonisogenic Outbred Murine Mandible: A Study in Rigor and Reproducibility

Abstract Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors’ laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal. The authors hypothesized that little difference would be found within these metrics. The authors’ study utilized 20 male Lewis and Sprague Dawley rats, which underwent no manipulation other than final dissection and analysis. Ten rats from each strain underwent bone mineral density and biomechanical strength analysis. The remaining rats underwent histological analysis. Descriptive and bivariate statistics were computed and the P value was set at 0.05. Lewis rats had a significantly greater number of empty lacunae. Sprague Dawley rats exhibited a significantly greater ratio of bone volume-to-total volume, bone mineral density, tissue mineral density, bone volume fraction, and total mineral content. No differences were found during biomechanical testing. This study demonstrates that differences exist between the Lewis and Sprague Dawley rat within unaltered baseline mandibular tissue. However, these differences appear to have limited functional impact, as demonstrated by similar biomechanical strength metrics. Other specific differences not addressed in this manuscript may exist. However, the authors believe that researchers may confidently cross-compare results between the 2 strains, while taking into account the differences found within this study.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis

The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO).

Changes in Skin Vascularity in a Murine Model for Postmastectomy Radiation.

Background Postmastectomy radiation causes persistent injury to the breast microvasculature, and the prevailing assumption is that longer delays before breast reconstruction allow for recovery of blood supply. This study uses a murine model to examine the effects of radiation on skin vascularity to help determine when radiation-induced effects on the microvasculature begin to stabilize. Study Design Isogenic Lewis rats were divided into 2 groups: radiation therapy (XRT) (n = 24) and control (n = 24). The XRT rats received a breast cancer therapy human dose-equivalent of radiation to the groin, whereas control rats received no radiation. Animals were sacrificed at 4, 8, 12, and 16 weeks after completion of radiation. The vasculature was injected with Microfil, and groin skin was harvested for radiomorphometric analysis by microcomputed tomography. One-way analysis of variance with post hoc Tukey tests was used to determine significance between groups. Results Augmentation in vascularity was observed in the XRT group at 4 weeks after radiation compared to the control group (P = 0.045). Vessel number was decreased at 12 weeks (P = 0.002) and at 16 weeks (P = 0.001) in the XRT rats compared to control rats. Vessel separation in the XRT group was higher than that in the control group at 12 weeks (P = 0.009) and 16 weeks (P = 0.001). There was no change in vessel number and separation between weeks 12 and 16. Conclusions A period of augmented skin vascularity is seen after radiation injury followed by decreased vascularity which demonstrates stabilization at approximately 12 weeks in this murine model. This model can be used to further study breast flap vascularity and the optimization of the timing of delayed breast reconstruction.