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.

Major adverse cardiovascular events (MACE) remain the major cause of mortality and morbidity in patients with STEMI (ST-elevation myocardial infarction). The current literature is aimed to analyze the occurrence of MACE following STEMI irrespective of treatment provided, and follow up after the first diagnosis of STEMI. A PubMed search for Studies of STEMI identified 24,244 articles. After applying our inclusion/exclusion criteria, we found out 75 articles of relevance wherein MACE and its components were considered to be the primary endpoint. These 75 articles included eight Cohort Studies, 13 clinical trials including five randomized controlled trials (RCT), one case-control Study, one cross-sectional study, one review article, and 51 other observational studies. Our analysis shows that MACE remains one of the strongest adverse outcomes among STEMI patients. The current literature review found out the incidence of MACE was 4.2 % to 51% irrespective of the mode of treatment, and follow-ups lasting up to 10 years from the time of STEMI diagnosis.

No abstract

No abstract

Clinical microbiologist are facing challenge to defeat the bacterial infections like Methicillin ResistantStaphylococcus aureus (MRSA) in humans; due to unique resistance in bacterial strain. There are limited medication options left to conquer this deadly toxicities, if holistic approach is ignored. Also the linked complications and consequences of infections may increase beyond threshold levels; if exercise only a single array of drug therapy. This empirical study aims to create synergy by adopting an integrated drug therapy approach for optimum treatment. This research article is based on primary microbial data collection (from sputum, urine and blood) in hospital; where the experiment focuses to investigate the highest risk vulnerable area. The result depicts high prevalence of MRSA in blood sample (50 %) among in-door patients of age above 50. The preventive and curative measures are discussed along with alternative multiple array of medication with prudent selection to achieve targeted and optimum outcome.