Recent studies have shown that microRNA (miRNA) regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report new evidence in ...which miRNA may also function to induce gene expression. By scanning gene promoters in silico for sequences complementary to known miRNAs, we identified a putative miR-373 target site in the promoter of E-cadherin. Transfection of miR-373 and its precursor hairpin RNA (pre-miR-373) into PC-3 cells readily induced E-cadherin expression. Knockdown experiments confirmed that induction of E-cadherin by pre-miR-373 required the miRNA maturation protein Dicer. Further analysis revealed that cold-shock domain-containing protein C2 (CSDC2), which possesses a putative miR-373 target site within its promoter, was also readily induced in response to miR-373 and pre-miR-373. Furthermore, enrichment of RNA polymerase II was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection. Mismatch mutations to miR-373 indicated that gene induction was specific to the miR-373 sequence. Transfection of promoter-specific dsRNAs revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. In conclusion, we have identified a miRNA that targets promoter sequences and induces gene expression. These findings reveal a new mode by which miRNAs may regulate gene expression.
Purpose Students who earn their medical doctorate (MD) in the U.S. must pass the United States Medical Licensing Exam (USMLE) Step-1. The application process for students with disabilities who seek ...Step-1 accommodations can be arduous, barrier-ridden, and can impose a significant burden that may have long-lasting effects. We sought to understand the experiences of medical students with Type-1 Diabetes (T1D) who applied for Step-1 accommodations. Methods A Qualtrics survey was administered to students enrolled in Liaison Committee on Medical Education (LCME)-accredited MD programs who disclosed having a primary diagnosis of T1D. Basic counts and qualitative inductive analyses were conducted. Results Of the 21 surveys sent, 16 (76.2%) participants responded. Of the 16 respondents, 11 (68.8%) applied for USMLE Step-1 accommodations, whereas 5 (31.2%) did not. Of the 11 who applied for accommodations, 7 (63.6%) received the accommodations requested, while 4 (36.4%) did not. Of those who received the accommodations requested, 5/7 (71.4%) experienced at least one diabetes-related barrier on exam day. Of those who did not apply for Step-1 accommodations, 4/5 (80%) participants reported experiencing at least one diabetes-related barrier on exam day. Overall, 11/16 (68.8%) students experienced barriers on exam day with or without accommodations. Qualitative analysis revealed themes among participants about their experience with the process: frustration, anger, stress, and some areas of general satisfaction. Conclusions This study reports the perceptions of students with T1D about barriers and inequities in the Step-1 accommodations application process. Students with and without accommodations encountered T1D-related obstacles on test day.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The field of non-coding RNA (ncRNA) has expanded over the last decade following the discoveries of several new classes of regulatory ncRNA. A growing amount of evidence now indicates that ncRNAs are ...involved even in the most fundamental of cellular processes. The heat shock response is no exception as ncRNAs are being identified as integral components of this process. Although this area of research is only in its infancy, this article focuses on several classes of regulatory ncRNA (i.e., miRNA, IncRNA, and circRNA), while summarizing their activities in mammalian heat shock. We also present an updated model integrating the traditional heat shock response with the activities of regulatory ncRNA. Our model expands on the mechanisms for efficient execution of the stress response, while offering a more comprehensive summary of the major regulators and responders in heat shock signaling. It is our hope that much of what is discussed herein may help researchers in integrating the fields of heat shock and ncRNA in mammals.
Observations requiring evaluation and critical thinking can be powerful learning experiences. Video-recorded standardized patient encounters are underutilized resources for evaluation and research. ...The authors engaged premedical students in medical education research reviewing standardized patient encounters. This study aims to explore participant perceptions of the research experience and how they gained clinical skills.
This mixed-method study was completed between 2019-2022. Premedical participants coded medical students' clinical skills in video-recorded standardized patient encounters. Each participant also completed their own new patient history in a standardized patient encounter at both the beginning and end of their research project. Participants then completed an end-of-program debrief to discuss their experiences coding the clinical skills encounters. The authors coded communication skills implemented in the pre/post encounters and completed a thematic analysis of the debrief transcripts.
All 21 participants demonstrated significant clinical skills gain after their research project, which included spending more time with the patient (pre-M=5 minutes, post-M=19 minutes, t=13.2, P<0.001) and asking more questions (pre-M=13, post-M=40, t=9.3, P<0.001). Prior clinical experience did not influence pre- or post-outcomes, but the number of videos coded was associated with asking more questions in the post-encounter. Participants described learning actively and reflected that their clinical skills research project gave them greater insight into patient-care aspects of medical school and how medical students learn.
These data demonstrate that observational studies in which premedical students evaluate standardized patient encounters gave the students context to medical education while enabling them to develop and transfer their own clinical skills. Studies observing standardized patient encounters provide rich insight into clinical skills development, and this work generates both research outcomes and actionable program evaluation data for medical educators. Purposefully engaging premedical students in such experiential learning opportunities benefits the students and helps cultivate early medical education pathways for these learners.
Purpose
Despite recent advocacy for transgender and nonbinary (TGNB) health competencies in medical education, there is little guidance on how to represent diverse gender identities for clinical ...skills training. Published literature is one of few resources available to inform educators’ decisions, so this study aims to summarize how medical education scholarship portrays TGNB identities in patient simulation.
Method
This scoping review used PRISMA guidelines with search strings encompassing diverse gender identities and patient simulation. This search was completed in July 2021, and all years of publication were included. The authors completed a 3-tiered review to identify relevant studies and then extracted data to summarize how TGNB patients were portrayed and training outcomes.
Results
After screening 194 total articles, 44 studies met the criteria for full review. Of these, 22 studies involved TGNB simulated patient cases. Within these, 15 (68%) reported the specific gender identities represented in the patient case, revealing mostly binary transgender identities. Sixteen studies (73%) reported the gender identities of all actors who portrayed the patient. The identities of all patients and actors matched in only 10 articles (45%), indicating that most programs portray TGNB identities with cisgender or unspecified standardized patients. Nearly all studies reported desirable learner outcomes. Several noted the advantage of authenticity in recruiting TGNB actors and the need to achieve more accurate representation of TGNB patients.
Conclusions
Educators are increasingly representing TGNB identities in clinical skills training. These results show a lack of nonbinary representation and discrepancies between TGNB patient cases and standardized patient identities. These data also suggest that simulation programs need and desire better recruitment strategies within TGNB communities. Because TGNB communities are not a monolith, reporting out and analyzing gender identities of simulation cases and people hired to portray TGNB patients helps ensure that TGNB care is taught effectively and respectfully.
KLF4/GLKF4 is a transcription factor that can have divergent functions in different malignancies. The role of KLF4 in prostate cancer etiology remains unclear. We have recently reported that small ...double-stranded RNA can induce gene expression by targeting promoter sequence in a phenomenon referred to as RNA activation (RNAa). In this study, we examine KLF4 levels in prostate cancer tissue and utilize RNAa as a tool for gene overexpression to investigate its function. Expression analysis indicated that KLF4 is significantly downregulated in prostate cancer cell lines compared with nontumorigenic prostate cells. Meta-analysis of existing cDNA microarray data also revealed that KLF4 is frequently depleted in prostate cancer tissue with more pronounced reduction in metastases. In support, tissue microarray analysis of tumors and patient-matched controls indicated downregulation of KLF4 in metastatic tumor samples. Logistic regression analysis found that tumors with a KLF4 staining score less than 5 had a 15-fold higher risk for developing metastatic prostate cancer (P = 0.001; 95% confidence interval, 3.0-79.0). In vitro analysis indicated that RNAa-mediated overexpression of KLF4 inhibited prostate cancer cell proliferation and survival and altered the expression of several downstream cell-cycle-related genes. Ectopic expression of KLF4 via viral transduction recapitulated the RNAa results, validating its inhibitory effects on cancer growth. Reactivation of KLF4 also suppressed migration and invasion of prostate cancer cells. These results suggest that KLF4 functions as an inhibitor of tumor cell growth and migration in prostate cancer and decreased expression has prognostic value for predicting prostate cancer metastasis.
Androgen receptor (AR) is a ligand-activated transcription factor belonging to the steroid hormone receptor family and is
very important for the development and progression of prostate cancer. The ...soy isoflavone genistein has been shown previously
to down-regulate AR in androgen-dependent prostate cancer cell lines such as LNCaP. However, the mechanism(s) by which AR
is down-regulated by genistein is still not known fully. We show a new mechanism by which genistein inhibits AR protein levels.
We show that genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated
via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The
increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by
its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase,
is inhibited by the antiestrogenic activity of genistein. Hence, in this study, we elucidate a novel mechanism of AR down-regulation
by genistein through inhibition of HDAC6-Hsp90 cochaperone function required to stabilize AR protein. Our results suggest
that genistein could be used as a potential chemopreventive agent for prostate cancers along with known inhibitors of HDAC6
and Hsp90. Mol Cancer Ther 2008;7(10):3195–202
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