Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands. Here we show that mice with diet-induced obesity display mislocalization of Par3, a regulator of cellular junctional complexes defining mammary epithelial polarity. We found that epithelial polarity loss also occurs in a 3D coculture system that combines acini with human mammary adipose tissue, and establish that a paracrine effect of the tissue adipokine leptin causes loss of polarity by overactivation of the PI3K/Akt pathway. Leptin sensitizes non-neoplastic cells to proliferative stimuli, causes mitotic spindle misalignment, and expands the pool of cells with stem/progenitor characteristics, which are early steps for cancer initiation. We also found that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of obesity have an altered distribution of apical polarity markers. This effect is associated with increased epithelial cell layers. Our results provide a molecular basis for early alterations in epithelial architecture during obesity-mediated cancer initiation.

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Between July 1985 and March 1988, 22 adult patients with congenital pulmonary stenosis underwent balloon pulmonary valvuloplasty. There were 10 males and 12 females aged 16-45 (average 25 +/- 9.9) years. All patients had additional mild to severe infundibular stenosis; 16 were restudied 6-36 (mean 12.6) months later by repeat catheterization. Student's t-test was used for comparison of data. Right ventricular (RV) systolic pressure before dilatation was 84-196 (mean 129 +/- 32.3) mm Hg, and the peak pulmonary gradient (PPG) was 60-176 (mean 111 +/- 33.2) mm Hg immediately after dilatation. The RV systolic pressure dropped to 32-140 (mean 59.2 +/- 27) (P less than 0.001); and PPG dropped to 10-113 (mean 37.8 +/- 26.4) (P less than 0.001), and the infundibular gradient ranged from 8 to 113 (mean 35.1 +/- 25.8) mm Hg. The infundibular diameter, before dilatation, ranged from 2 to 15 (mean 9.5 +/- 4) mm Hg. At repeat catheterization, the RV systolic pressure dropped further to 33-66 (mean 42.8 +/- 9.7) mm Hg and the PPG was reduced to 0-48 (mean 18.4 +/- 10.9) mm Hg (P less than 0.001). The infundibular gradient regressed to 0-34 (mean 15 +/- 8.8) mm Hg (P less than 0.001). The infundibular diameter increased to 8-25 (mean 15.8 +/- 5.4) (P less than 0.001). It is concluded that moderate to severe infundibular stenosis, in adults, can regress after successful pulmonary valvuloplasty.

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Objectives: Acute coronary syndrome (ACS) at a younger age is now becoming a crucial problem. This study determined the effect of gender on the clinical findings and outcomes of young patients (≤ 45 years) with ACS. Methodology: In this descriptive cross sectional study, young patients (≤45 years) who presented with ACS and underwent coronary angiography were recruited. The comparison of clinical profile, angiographic findings, in-hospital, and 90-days mortality between genders were made. Results: A total of 335 young patients with ACS were included, 80.6% of whom were men. A significant difference was found between men and women in terms of mean age: 38±6 vs. 40±5 (p=0.014), hypertension: 37.8% vs. 58.5% (p=0.002), diabetes: 17.4% vs. 35.4% (p=0.001), smoking: 50.4% vs. 6.2% (p≤0.001), use of smokeless tobacco: 14.1% vs. 4.6% (p=0.037), median time from symptom onset to first medical contact: 270 [420–165] minutes vs. 346 [499.5–240] minutes (p=0.047), ST-segment elevation myocardial infarction (STEMI) 89.6% vs. 78.5% (p=0.015), non-ST-elevation myocardial infarction (NSTEMI) 8.5% vs. 18.5% (p=0.019), and three-vessel disease (3VD) 10.7% vs. 21.5% (p=0.019), respectively. In-hospital and 90-day mortality rates were 0.4% vs. 3.1% (p=0.097) and 1.5% vs. 4.6% (p=0.136) for men and women, respectively. Conclusion: Women tended to have a higher age at presentation, more frequent traditional risk factors, late presentation after symptom onset, frequent NSTEMI, and 3VD, whereas men were distinct with frequent STEMI and higher tobacco use. In addition, women trended to have a higher in-hospital as well as short-term mortality than men did.

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