Objective
Although early proof-of-concept studies of somatic in
vivo genome editing of the mouse ortholog of proprotein
convertase subtilisin/kexin type 9 (Pcsk9) in mice have
established its therapeutic potential for the prevention of cardiovascular
disease, the unique nature of genome-editing technology—permanent
alteration of genomic DNA sequences—mandates that it be tested
in vivo against human genes in normal human cells with
human genomes in order to give reliable preclinical insights into the
efficacy (on-target mutagenesis) and safety (lack of off-target mutagenesis)
of genome-editing therapy before it can be used in patients.
Approach and Results
We used a clustered regularly interspaced short palindromic repeats
(CRISPR)-CRISPR-associated 9 (Cas9) genome-editing system to target the
human PCSK9 gene in chimeric liver-humanized mice bearing
human hepatocytes. We demonstrated high on-target mutagenesis (approaching
50%), greatly reduced blood levels of human PCSK9 protein, and
minimal off-target mutagenesis.
Conclusions
This work yields important information on the efficacy and safety of
CRISPR-Cas9 therapy targeting the human PCSK9 gene in human
hepatocytes in vivo, and it establishes humanized mice as a
useful platform for the preclinical assessment of applications of somatic
in vivo genome editing.
Coronavirus Disease 2019 (COVID-19) is a new pandemic that originated in China in December 2019. Cancer patients are immunosuppressed and very susceptive to acquiring infections; thus, they are at greater risk of developing more severe forms of COVID-19. People infected with COVID-19 display increased plasma levels of pro-inflammatory cytokines. Excessive inflammation may cause damage to the body's tissues, thereby potentially contributing to alveolar damage and the severity of COVID-19. We hypothesize that since a pro-inflammatory state may worsen COVID-19 prognosis, modulating systemic inflammation through dietary modification may be efficacious in improving the clinical sequelae of COVID-19. The aim of this review is to present current nutritional and dietary approaches in the context of inflammation with a specific focus on cancer patients with and without COVID-19. The main topics reviewed include nutrition in inflammation and immunity. A systematic literature search on Google Scholar, Medline, and PubMed databases was performed between March 22, 2020 and May 6, 2020 using the keywords "COVID-19," "coronavirus," "cancer," "inflammation," "probiotics," "vitamin D," and "nutrition prevention." Healthy dietary habits, omega-3-rich diets, probiotics use, and vitamin D supplementation, as well as obesity prevention, are likely the most efficacious preventive approaches to controlling hyperinflammation, improving immune function, and decreasing the severity of inflammatory diseases.
A physically active 90-year-old man underwent endovascular repair of an asymptomatic but enlarging abdominal aortic aneurysm. Postoperative computed tomography demonstrated entanglement of nonadjacent proximal bare-metal stents. This was associated with graft infolding and a type IA endoleak. The patient underwent percutaneous transluminal angioplasty and placement of a Palmaz stent. Subsequent surveillance imaging showed resolution of the type I endoleak >1 year later. This report demonstrates an uncommon cause of stent graft infolding, an already rare complication of endovascular aneurysm repair, and highlights the need to carefully assess the morphologic appearance of the proximal fixation stents after graft deployment.
We assessed the efficacy of traditional lectures versus online modules with respect to student learning in an undergraduate introductory biochemistry course in two successive years. In the first year, students had the options of attending live lectures by the course instructor and viewing online modules pre-recorded by the instructor, with the lectures and modules covering identical content; in addition, all students had a mandatory weekly application session. Utilizing pre-course and post-course tests as an instrument with which to measure learning during the course, we observed significantly increased learning (0.7 standard deviations) with attendance of traditional lectures and decreased learning with use of online modules, even after adjustment for grade point average. In the second year, the course had the same curriculum, but students were randomized to either live lectures or online modules for the first half of the course, crossing over to the other modality during the second half. With randomization, no difference in learning was observed between the two groups. Furthermore, we found that students self-reported greater engagement when viewing online modules than when attending lectures in person. These findings suggest some aspects of the lecture experience can be shifted to online modules in STEM courses without impacts on student learning so as to use classroom time more fully for application-based active learning interventions.
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