Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1 × 106 B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R−/−), which have high leptin levels, obese leptin-deficient(ob −/−), pair fed lean ob−/−, and lean ob+/− mice. Mean body weights were 29.7 ± 0.3 g (WT), 46.3 ± 1.9 g (MC4R−/−), 63.7 ± 0.9 g (ob−/−), 30.5 ± 1.0 g (pair fed ob−/−) and 31.6 ± 1.7 g (ob+/−). Tumors were much larger in the obese leptin deficientob−/− (5.1 ± 0.9 g) and obese MC4R−/− (5.1 ± 0.7 g) than in lean WT (1.9 ± 0.3 g) and ob+/− (2.8 ± 0.7 g) mice. prevention of obesity by pair feeding ob−/− mice dramatically reduced tumor weight (0.95 ± 0.2 g) to a level that was significantly lower than in WT mice of the same weight. Tumor VEGF levels were the highest in the obese mouse tumors (p < 0.05), regardless of the host leptin levels. Except for the lean ob+/−, MC4R−/− and ob−/− melanomas had the highest VEGF receptor 1 and VEGF receptor 2 protein expression (p < 0.01 and p < 0.05), respectively. These results indicate that obesity markedly increases melanoma tumor growth rate by mechanisms that may involve upregulation of VEGF pathways. although tumor growth does not require host leptin, melanoma tumor growth may be accelerated by leptin.
Objectives The primary objective was to survey pediatric emergency medicine (PEM) leaders and fellows regarding point‐of‐care ultrasound (POCUS) training in PEM fellowship programs, including teaching methods, training requirements, and applications taught. Secondary objectives were to compare fellows' and program leaders' perceptions of fellow POCUS competency and training barriers. Methods This was a cross‐sectional survey of U.S. PEM fellows and fellowship program leaders of the 78 fellowship programs using two online group‐specific surveys exploring five domains: program demographics; training strategies and requirements; perceived competency; barriers, strengths, and weaknesses of POCUS training; and POCUS satisfaction. Results Eighty‐three percent (65/78) of programs and 53% (298/558) of fellows responded. All participating PEM fellowship programs included POCUS training in their curriculum. Among the 65 programs, 97% of programs and 92% of programs utilized didactics and supervised scanning shifts as educational techniques, respectively. Sixty percent of programs integrated numerical benchmarks and 49% of programs incorporated real‐time, hands‐on demonstration as training requirements. Of the 19 POCUS applications deemed in the literature as core requirements for fellows, at least 75% of the 298 fellows reported training in 13 of those applications. Although less than half of fellows endorsed competency for identifying intussusception, ultrasound‐guided pericardiocentesis, and transvaginal pregnancy evaluation, a higher proportion of leaders reported fellows as competent for these applications (40% vs. 68%, p ≤ 0.001; 21% vs. 39%, p = 0.003; and 21% vs. 43%, p ≤ 0.001). Forty‐six percent of fellows endorsed a lack of PEM POCUS evidence as a training barrier compared to 31% of leaders (p = 0.02), and 39% of leaders endorsed a lack of local financial support as a training barrier compared to 23% of fellows (p = 0.01). Conclusions Although most PEM fellowship programs provide POCUS training, there is variation in content and requirements. Training does conform to many of the expert recommended guidelines; however, there are some discrepancies and perceived barriers to POCUS training remain.
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