Cancer‐associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse‐strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage

Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal‐binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3′ end of the 5p miRNA strand of a pre‐mRNA hairpin. To investigate the effects of these cancer‐associated 'hotspot' mutations, we engineered mouse DICER1‐deficient ES cells to express wild‐type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal‐binding site mutations were compared to each other and to wild‐type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation‐carrying cells were distinct from both wild‐type and DICER1‐deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p‐derived miRNAs. We therefore conclude that cancer‐associated somatic hotspot mutations of DICER1, affecting any one of four metal‐binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Hepatic complications of COVID-19 and its treatment

Coronavirus disease 2019 (COVID-19) is highly contagious and has a variety of clinical manifestations, it can affect a number of other organs in addition to the lungs, and liver injury may occur. Severe acute respiratory syndrome coronavirus 2 can cause liver injury through systemic inflammatory response syndrome, cytokine storms, ischemia-reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via angiotensin-converting enzyme 2. Clinical studies have found that liver injury in COVID-19 patients mainly manifests as abnormal liver biochemical indicators, but there have been no reports of liver failure caused by this disease. The number of COVID-19 patients with liver injury is increasing, and the incidence of liver injury in COVID-19 patients with severe disease are higher than in patients with mild disease. Liver injury may be a risk factor, which worsens in patients with COVID-19, and hence it is necessary to pay attention to the occurrence of liver injury in the diagnosis and treatment of COVID-19.     

Comparison of two self-sampling methods for human papillomavirus (HPV) DNA testing among women with high prevalence rates

One major advantage of molecular assays for human papillomavirus (HPV) DNA detection is that these assays can be performed on self-collected samples unlike cytology or visual inspection with acetic acid (VIA). This cross-sectional study was carried out between March 2017 and April 2019 to compare the diagnostic performance in self-collected urine and vaginal samples for HPV DNA detection. Viral DNA was extracted from processed samples using a Qiagen viral DNA extraction Kit (QIAamp DNA Mini Kit). To detect four common high-risk HPV types (16, 18, 31, 45), multiplex real-time polymerase chain reaction (PCR) targeting the LCR/E6/E7 region of the HPV genome was performed in ABI 7500 cycler (Applied Biosystems). The negative samples were screened by conventional PCR targeting the L1 capsid region to exclude other HPV types. The overall agreement between the two self-collecting sampling methods was 64.04% with a κ value of 0.29 pointing towards a fair agreement (P < .01). The sensitivity of HPV DNA detection in urine samples was 57.95% (47.52%, 67.72), and specificity was 84.6% (66.47%, 93.85%) when compared with vaginal samples. The study concludes that self-collected vaginal HPV DNA testing is more sensitive than unpreserved-urine samples for HPV DNA detection in a hospital-based setting.     

Common Acute Upper Extremity Injuries In Sports

Familiarity with anatomical differences in the pediatric patient is necessary to properly identify and treat the variety of upper extremity musculoskeletal injuries encountered in the ED. The many unique characteristics of pediatric bone, the presence of physes, and degree of skeletal maturity all pose a challenge for the emergency physician's ability to diagnose and treat pediatric orthopedic injuries. The somewhat subtle findings both on physical and radiographic examination of many serious pediatric orthopedic injuries further complicate the evaluation process. The treatment of upper extremity injuries in children and young athletes requires heightened vigilance for classic mechanisms of injury, a thorough systematic approach to the orthopedic examination, and a broad knowledge of various injury patterns and treatments. With experience, the emergency or primary care physician will enjoy the challenge of caring for acute traumatic sports-related upper extremity injuries in children.