Inactivating mutations of the adenomatous polyposis coli (APC) gene and consequential upregulation of the Wnt signaling pathway are critical initiators in the development of colorectal cancer (CRC), the third most common cancer in the United States for both men and women. Emerging evidence suggests APC mutations are also found in gastric, breast and other cancers. The APC gene, located on chromosome 5q, is responsible for negatively regulating the β-catenin/Wnt pathway by creating a destruction complex with Axin/Axin2, GSK-3β, and CK1. In the event of an APC mutation, β-catenin accumulates, translocates to the cell nucleus and increases the transcription of Wnt target genes that have carcinogenic consequences in gastrointestinal epithelial stem cells. A literature review was conducted to highlight carcinogenesis related to APC mutations, as well as preclinical and clinical studies for potential therapies that target steps in inflammatory pathways, including IL-6 transduction, and Wnt pathway signaling regulation. Although a range of molecular targets have been explored in murine models, relatively few pharmacological agents have led to substantial increases in survival for patients with colorectal cancer clinically. This article reviews a range of molecular targets that may be efficacious targets for tumors with APC mutations.

Clinically, infertility is defined as the inability to conceive after a certain period. In contrast, sterility is defined as the inability to produce a biological child; however, this is not a practical definition that can be applied in a clinical setting to a patient’s diagnosis. Unlike infertility, sterility is rarely discussed in biomedical and clinical literature and is often used synonymously with infertility. Infertility affects about 10% of couples globally, but the prevalence of sterility remains unknown. We divide sterility into three subtypes natural, clinical, and hardship. To estimate sterility prevalence, we analyzed primary literature and meta-analysis papers on the rates of live births and pregnancies throughout several treatments of infertile couples (e.g., untreated patients, in vitro fertilization-treated, and patients administered other treatments). This analysis indicates that all treatments fail in delivering a biological child to most couples, suggesting that most infertile couples may fail to conceive. More comprehensive primary studies are needed to provide a precise estimate of sterility. Furthermore, research is needed to study the causes of sterility, as well as develop methods for diagnosis and treatment that are financially affordable and emotionally tolerable. Altogether, sterility is an under-discussed condition that is more common than expected, as many infertile couples are unable to conceive and are, in effect, sterile.

Balloon angioplasty is the standard endovascular treatment for symptomatic infrapopliteal peripheral artery disease (PAD). However, recent trials have studied the effectiveness of drug-eluting stents (DES) for infrapopliteal PAD. This study investigated the use of DES compared with standard endovascular techniques for treatment of infrapopliteal artery disease. This is a comprehensive systematic review and meta-analysis of 9 recent randomized controlled trials. The primary clinical outcome assessed was primary patency. The secondary outcomes were target lesion revascularization (TLR), major limb amputation, and all-cause mortality. A total of 945 patients met the inclusion criteria. Patients treated with DES were found to have increased primary patency than control at maximum follow-up (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.58-2.97, P < .0001, I² = 62%). A similar result was seen in the subgroup of patients with critical limb ischemia (HR 2.58, 95% CI 1.49-4.49, P = .0008, I² = 75%). DES were associated with significantly lower rates of TLR than control at maximum follow-up (HR 0.48, 95% CI 0.33-0.68, P < .0001; I² = 11%). There was no statistical difference between DES versus control in rates of major limb amputation and mortality. DES have superior primary patency and TLR rates with no difference in amputation and all-cause mortality rates compared with conventional endovascular therapies in patients with infrapopliteal PAD.