Recently, cannabinoids, such as cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), have been the subject of intensive research and heavy scrutiny. Cannabinoids encompass a wide array of organic molecules, including those that are physiologically produced in humans, synthesized in laboratories, and extracted primarily from the Cannabis sativa plant. These organic molecules share similarities in their chemical structures as well as in their protein binding profiles. However, pronounced differences do exist in their mechanisms of action and clinical applications, which will be briefly compared and contrasted in this review. The mechanism of action of CBD and its potential applications in cancer therapy will be the major focus of this review article.

Breast Cancer 1 (BRCA1) gene is a well-characterized tumor suppressor gene, mutations of which are primarily found in women with breast and ovarian cancers. BRCA1-associated RING domain 1 (BARD1) gene has also been identified as an important tumor suppressor gene in breast, ovarian, and uterine cancers. Underscoring the functional significance of the BRCA1 and BARD1 interactions, prevalent mutations in the BRCA1 gene are found in its RING domain, through which it binds the RING domain of BARD1. BARD1-BRCA1 heterodimer plays a crucial role in a variety of DNA damage response (DDR) pathways, including DNA damage checkpoint and homologous recombination (HR). However, many mutations in both BARD1 and BRCA1 also exist in other domains that significantly affect their biological functions. Intriguingly, recent genome-wide studies have identified various single nucleotide polymorphisms (SNPs), genetic alterations, and epigenetic modifications in or near the BARD1 gene that manifested profound effects on tumorigenesis in a variety of non-breast and non-gynecological cancers. In this review, we will briefly discuss the molecular functions of BARD1, including its BRCA1-dependent as well as BRCA1-independent functions. We will then focus on evaluating the common BARD1 related SNPs as well as genetic and epigenetic changes that occur in the non-BRCA1-dominant cancers, including neuroblastoma, lung, and gastrointestinal cancers. Furthermore, the pro- and anti-tumorigenic functions of different SNPs and BARD1 variants will also be discussed.

Distal esophageal spasm (DES) is a rare motility disorder presenting with dysphagia or chest pain. Although studies suggest a link between DES and gastroesophageal reflux disease (GERD), data supporting a distinct GERD-related phenotype are limited. This study aims to investigate demographic, symptomatic, and physiologic differences between DES subjects with and without GERD. A retrospective cohort analysis of DES patients determined by high resolution manometry (HRM) was conducted between February 2020 and January 2023. Demographics, medications, symptoms, and quantitative reflux testing data were collected. DES subjects with reflux (R-DES) were defined by presence of Los Angeles Grade B/C/D esophagitis, Barrett’s metaplasia, or abnormal pH testing. DES subjects without reflux (NR-DES) had normal parameters. Statistical analysis employed two-sided or Wilcoxon Rank-Sum, Chi-squared, or Fisher’s exact tests, and multivariate logistic regression. Of 69 DES subjects, 32 (46.3%) had GERD. R-DES and NR-DES patients had similar demographic variables except for higher BMI in R-DES (30.41 vs. 26.88, P = 0.01). R-DES and NR-DES shared similar symptom profiles (heartburn P = 0.67, dysphagia P = 0.448, chest pain P = 0.32). Proton pump inhibitor use was similar between groups (78.1% vs. 91.9%, P = 0.202). HRM metrics were comparable except for basal LES tone (20.7 mmHg vs. 32.99 mmHg, P = 0.03) and median IRP 11.82 mmHg versus 17.20 mmHg, P = 0.017). This study found no distinguishing clinical or physiologic differences between DES patients with and without GERD, challenging the historical emphasis of GERD in DES pathogenesis. The impact of GERD management on the natural history of DES remains uncertain.

Necrotizing soft tissue infection, NSTI, involves the soft tissue characterized by rapid spread of infection and consequent cell necrosis. NSTI, in particular necrotizing fasciitis (NF), is a significant disease burden in the US with an annual mortality of 4.8 per 1,000,000 person years. Here we describe a rare fungal pathogen, Kodamaea Ohmeri, as a cause of NF in a diabetic but otherwise healthy male patient. In the past K. Ohmeri has been described in children, immunocompromised individuals, and in cases with IV catheters and prolonged use of IV antibiotics. A febrile and hypotensive male (LRINEC score of 6) presented after sustaining abrasions of his right lower extremity. He was initially started on broad-spectrum antibiotics and underwent surgical exploration. During the following weeks, the patient developed sepsis and endured a total of four debridement. Wound cultures resulted K. Ohmeri with sensitivity to miconazole and voriconazole. Anti-fungal, silver dressings and wound vacuum, were utilized to assist in treatment and tissue granulation. To our knowledge, this is the first case describing Kodamea ohmeri as a causative agent of NF. K. Ohmeri should be on the radar of the health care providers taking care of patients with NF, especially in the context of intermittent bouts of sepsis and prolonged hospital course. Our case illustrates the fact that prompt identification, addition of fungal cultures and appropriate surgical treatment are crucial to improve patient outcomes.