Student well-being during dedicated preparation for USMLE Step 1 and COMLEX Level 1 exams.

BACKGROUND: Nearly all U.S. medical students engage in a 4-8 week period of intense preparation for their first-level licensure exams, termed a "dedicated preparation period" (DPP). It is widely assumed that student well-being is harmed during DPPs, but evidence is limited. This study characterized students' physical, intellectual, emotional, and social well-being during DPPs. METHODS: This was a cross-sectional survey sent electronically to all second-year students at four U.S. medical schools after each school's respective DPP for USMLE Step 1 or COMLEX Level 1 in 2019. Survey items assessed DPP characteristics, cost of resources, and perceived financial strain as predictors for 18 outcomes measured by items with Likert-type response options. Open-ended responses on DPPs' influence underwent thematic analysis. RESULTS: A total of 314/750 (42%) students completed surveys. DPPs lasted a median of 7 weeks (IQR 6-8 weeks), and students spent 70 h/week (IQR 56-80 h/week) studying. A total of 62 (20%) reported experiencing a significant life event that impacted their ability to study during their DPPs. Most reported 2 outcomes improved: medical knowledge base (95%) and confidence in ability to care for patients (56%). Most reported 9 outcomes worsened, including overall quality of life (72%), feeling burned out (77%), and personal anxiety (81%). A total of 25% reported paying for preparation materials strained their finances. Greater perceived financial strain was associated with worsening 11 outcomes, with reported amount spent associated with worsening 2 outcomes. Themes from student descriptions of how DPPs for first-level exams influenced them included (1) opportunity for synthesis of medical knowledge, (2) exercise of endurance and self-discipline required for professional practice, (3) dissonance among exam preparation resource content, formal curriculum, and professional values, (4) isolation, deprivation, and anguish from competing for the highest possible score, and (5) effects on well-being after DPPs. CONCLUSIONS: DPPs are currently experienced by many students as a period of personal and social deprivation, which may be worsened by perceived financial stress more than the amount of money they spend on preparation materials. DPPs should be considered as a target for reform as medical educators attempt to prevent student suffering and enhance their well-being.

First-Year Experience Implementing an Adaptive Learning Platform for First- and Second-Year Medical Students at the Lake Erie College of Osteopathic Medicine.

CONTEXT: The Lake Erie College of Osteopathic Medicine (LECOM) is a large, diverse medical school spread across 3 campuses, which makes it challenging to deliver comparable learning experiences to all students. Osmosis is a Web and mobile application that can integrate with a variety of existing curricula and, through its content creation and sharing features, can foster student cohesion in an online environment. OBJECTIVE: To analyze the first year of use for the Osmosis platform among LECOM students at each campus and to identify barriers to this use. METHODS: Medical education at LECOM is delivered across 3 campus locations using 3 main pathways: the lecture-discussion, problem-based learning, and directed-study pathways. Beginning in the 2016-2017 academic year, all LECOM first-year medical students could use the Osmosis platform free of charge; second-year students were informed about the platform but were required to pay for a subscription. For all students, engagement metrics were tracked within the platform, and periodic student surveys and informal student feedback supplemented these metrics. RESULTS: Of 1135 LECOM students, 567 (50%) signed up for an account, including 416 (73%) of 573 first-year and 151 (27%) of 562 second-year students. In aggregate, students created 17,901 items and answered 123,050 practice questions and flashcards. Student use of the platform varied considerably, with the highest use at the Erie campus, where the platform was championed by faculty, and among a portion of second-year students preparing for board examinations. Some students were "superusers"; 2 students completed more than 20,000 items, and 5 created more than 1000 items each. The greatest barriers to use of the platform were preferences for previous study methods and lack of time to learn new study habits. CONCLUSION: Although the use of the platform across LECOM campuses was uneven, it was greatest when there was overt support by faculty and when students were already motivated to use the platform. The lessons learned during the first year of the program will be used to improve use of the platform. The authors offer their insights into this new technology.

Periodontal diseases and adverse pregnancy outcomes: Is there a role for vitamin D?

Studies have shown a relationship between maternal periodontal diseases (PDs) and premature delivery. PDs are commonly encountered oral diseases which cause progressive damage to the periodontal ligament and alveolar bones, leading to loss of teeth and oral disabilities. PDs also adversely affect general health by worsening of cardiovascular and metabolic diseases. Moreover, maternal PDs are thought to be related to increasing the frequency of preterm-birth with low birth weight (PBLBW) in new-borns. Prematurity and immaturity are the leading causes of prenatal and infant mortality and is a major public health problem around the world. Inflamed periodontal tissues generate significantly high levels of proinflammatory cytokines that may have systemic effects on the host mother and the fetus. In addition, the bacteria that cause PDs produce endotoxins which can harm the fetus. Furthermore, studies have shown that microorganisms causing PDs can get access to the bloodstream, invading uterine tissues, to induce PBLBW. Another likely mechanism that connects PDs with adverse pregnancy outcome is maternal vitamin D status. A role of inadequate vitamin D status in the genesis of PDs has been reported. Administration of vitamin D supplementation during pregnancy could reduce the risk of maternal infections and adverse pregnancy outcomes. As maternal PDs are significant risk factors for adverse pregnancy outcome, preventive antenatal care for pregnant women in collaboration with the obstetric and dental professions are required.

Organization of mammalian cytoplasm.

Although the role of macromolecular interactions in cell function has attracted considerable attention, important questions about the organization of cells remain. To help clarify this situation, we used a simple protocol that measures macromolecule release after gentle permeabilization for the examination of the status of endogenous macromolecules. Treatment of Chinese hamster ovary cells with saponin under carefully controlled conditions allowed entry of molecules of at least 800 kDa; however, there were minimal effects on internal cellular architecture and protein synthesis remained at levels comparable to those seen with intact cells. Most importantly, total cellular protein and RNA were released from these cells extremely slowly. The release of actin-binding proteins and a variety of individual cytoplasmic proteins mirrored that of total protein, while marker proteins from subcellular compartments were not released. In contrast, glycolytic enzymes leaked rapidly, indicating that cells contain at least two distinct populations of cytoplasmic proteins. Addition of microfilament-disrupting agents led to rapid and extensive release of cytoplasmic macromolecules and a dramatic reduction in protein synthesis. These observations support the conclusion that mammalian cells behave as highly organized, macromolecular assemblies (dependent on the actin cytoskeleton) in which endogenous macromolecules normally are not free to diffuse over large distances.

Rapamycin sensitizes Akt inhibition in malignant human breast epithelial cells.

Akt and mTOR are therapeutic targets for the treatment of cancer. The effects of inhibiting mTOR, with rapamycin, and Akt, with A-443654, concurrently, on cell morphology, cell proliferation, the cell cycle, and apoptosis were examined using the benign MCF10A and malignant MCF10CA1a human breast epithelial cells. Rapamycin and A-443654 in combination produced the greatest morphological changes and inhibited cell proliferation by G2/M arrest. Rapamycin and A-443654 in combination induced apoptosis at earlier times and at lower A-443654 concentrations in MCF10CA1a tumor cells than in the benign MCF10A cells. Rapamycin and A-443654 increased p53 and p15(INK4B) protein levels, decreased anti-apoptotic Bcl-2 levels, and increased Bad levels in the MCF10CA1a tumor cells by approximately 5-fold. These results suggest that the combined inhibition of Akt and mTOR may have beneficial therapeutic and safety margin effects.

miRNAs: effectors of environmental influences on gene expression and disease.

Discovered less than a decade ago, micro-RNAs (miRNAs) have emerged as important regulators of gene expression in mammals. They consist of short nucleic acids, on average approximately 22 nucleotides in length. The miRNAs exert their effect by binding directly to target messenger RNAs (mRNAs) and inhibiting mRNA stability and translation. Each miRNA can bind to multiple targets and many miRNAs can bind to the same target mRNA, allowing for a complex pattern of regulation of gene expression. Once bound to their targets, miRNAs can suppress translation of the mRNA by either sequestration or degradation of the message. Thus, miRNAs function as powerful and sensitive posttranscriptional regulators of gene expression. This review will summarize what is known about miRNA biogenesis, expression, regulation, function, mode of action, and role in disease processes with an emphasis on miRNAs in mammals. We discuss some of the methodology employed in miRNA research and the potential of miRNAs as therapeutic targets. The role of miRNAs in signal transduction and cellular stress is reviewed. Lastly, we identify new exciting avenues of research on the role of miRNAs in toxicogenomics and the possibility of epigenetic effects on gene expression.

Toxicogenomic evaluation of microcystin-LR treated with ultrasonic irradiation.

Microcystins are a family of toxins produced by cyanobacteria found throughout the world in marine and freshwater environments. The most commonly encountered form of microcystin is microcystin-LR (MC-LR). Humans are exposed to MC-LR by drinking contaminated water. The toxin accumulates rapidly in the liver where it exerts most of its damage. Treatment of water containing MC-LR by ultrasonic irradiation leads to the breakdown of the toxin. Both the parent toxin and the treated toxin reaction products (TTRP) were evaluated for toxic effects in mice. Animals were exposed to purified MC-LR or an equivalent dose of the TTRP and sacrificed after 4 h or 24 h. Serum was collected and assayed for lactate dehydrogenase (LDH) activity as an indicator of hepatotoxicity. LDH activity was detected in the serum of MC-LR exposed mice indicative of liver damage, but not in control mice. Only a fraction of that activity was detectable in mice exposed to TTRP. Liver RNA was used for microarray analysis and real-time PCR. Individual animals varied in their overall genomic response to the toxin; however, only 20 genes showed consistent changes in expression. These include chaperones which may be part of a generalized stress response; cytochrome P450 which may be involved in metabolizing the toxin; and lipid dystrophy genes such as lipin-2, uridine phosphorylase and a homolog to tribbles, a stress-inducible gene involved in cell death. Of the genes that responded to the MC-LR, none showed significant changes in expression profile in response to TTRP. Taken together, the data indicate that ultrasonic irradiation of MC-LR effectively reduces hepatotoxicity in mice and therefore may be a useful method for detoxification of drinking water.