Emerging Cholesterol Modulators for Atherosclerotic Cardiovascular Disease.

Experimental and clinical studies have conclusively demonstrated that lowering elevated low-density lipoprotein cholesterol levels results in fewer major adverse cardiac events. Over the past few decades, statins have become the mainstay of lipid-lowering therapy, contributing significantly to the reduction of lipids, and providing patients with a cost-effective approach. However, with growing evidence in support of combination therapies providing increased benefits to certain patient populations, such as those intolerant to statins, there is an urgent need to investigate the safety and efficacy of alternative lipid-lowering drugs. In this paper, we review the current alternative and adjuvant cholesterol targeting agents. We further discuss the clinical trials that have evaluated the safety and efficacy of these alternative and adjuvant therapies as well as their implications for practical use. These drugs target levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or lipoprotein(a) as treatments for hyperlipidemia and atherosclerotic cardiovascular disease.

Adolescent social instability stress leads to immediate and lasting sex-specific changes in the neuroendocrine-immune-gut axis in rats.

Social instability stress (SS; daily 1 h isolation and change of cage partner from postnatal day (P) 30-45) in adolescence produces elevations in corticosterone during the procedure in male and female rats, but no lasting changes in hypothalamic-pituitary-adrenal (HPA) responses to psychological stressors, although deficits in social and cognitive function are evident in adulthood. Here we investigated the effects of SS in corticosterone response to an immune challenge (lipopolysaccharide, LPS, 0.1 mg/kg), on gene expression in the hippocampus, and on gut microbiota, when tested soon- (P46) or long- (P70) after SS. The temporal pattern of corticosterone release after LPS differed between SS and control rats irrespective of the time since SS exposure in females, whereas in males, SS did not alter corticosterone release after LPS. Expression of genes in the hippocampus relevant to immune and HPA function differed between saline-treated SS and control rats depending on sex and time tested, but with lasting consequences of SS in both sexes. LPS-treatment altered hippocampal gene expression, with bigger effects of LPS evident in control than in SS female rats, and the opposite in male rats. Further, effects sometimes depended on the age at time of LPS treatment. SS and control rats differed in both fecal and colon microbiome composition in all but P46 males, and stress history, sex, and age influenced the effects of an immune challenge on the gut microbiome. In sum, adolescent stress history has consequences for immune function into adulthood that may involve effects on the gut microbiome.

Optimizing Neuro-Oncology Imaging: A Review of Deep Learning Approaches for Glioma Imaging.

Radiographic assessment with magnetic resonance imaging (MRI) is widely used to characterize gliomas, which represent 80% of all primary malignant brain tumors. Unfortunately, glioma biology is marked by heterogeneous angiogenesis, cellular proliferation, cellular invasion, and apoptosis. This translates into varying degrees of enhancement, edema, and necrosis, making reliable imaging assessment challenging. Deep learning, a subset of machine learning artificial intelligence, has gained traction as a method, which has seen effective employment in solving image-based problems, including those in medical imaging. This review seeks to summarize current deep learning applications used in the field of glioma detection and outcome prediction and will focus on (1) pre- and post-operative tumor segmentation, (2) genetic characterization of tissue, and (3) prognostication. We demonstrate that deep learning methods of segmenting, characterizing, grading, and predicting survival in gliomas are promising opportunities that may enhance both research and clinical activities.