Understanding social needs screening and demographic data collection in primary care practices serving Maryland Medicare patients.

BACKGROUND: Health outcomes are strongly impacted by social determinants of health, including social risk factors and patient demographics, due to structural inequities and discrimination. Primary care is viewed as a potential medical setting to assess and address individual health-related social needs and to collect detailed patient demographics to assess and advance health equity, but limited literature evaluates such processes. METHODS: We conducted an analysis of cross-sectional survey data collected from n = 507 Maryland Primary Care Program (MDPCP) practices through Care Transformation Requirements (CTR) reporting in 2022. Descriptive statistics were used to summarize practice responses on social needs screening and demographic data collection. A stepwise regression analysis was conducted to determine factors predicting screening of all vs. a targeted subset of beneficiaries for unmet social needs. RESULTS: Almost all practices (99%) reported conducting some form of social needs screening and demographic data collection. Practices reported variation in what screening tools or demographic questions were employed, frequency of screening, and how information was used. More than 75% of practices reported prioritizing transportation, food insecurity, housing instability, financial resource strain, and social isolation. CONCLUSIONS: Within the MDPCP program there was widespread implementation of social needs screenings and demographic data collection. However, there was room for additional supports in addressing some challenging social needs and increasing detailed demographics. Further research is needed to understand any adjustments to clinical care in response to identified social needs or application of data for uses such as assessing progress towards health equity and the subsequent impact on clinical care and health outcomes.

MiR-592 activates the mTOR kinase, ERK1/ERK2 kinase signaling and imparts neuronal differentiation signature characteristic of Group 4 medulloblastoma.

Medulloblastoma, a common malignant brain tumor in children, consists of four molecular subgroups WNT, SHH, Group 3 and Group 4. Group 3, Group 4 tumors have an overlap in their expression profiles and genetic alterations but differ significantly in their clinical characteristics, with Group 3 having the worst 5-year overall survival of <60%. MiR-592 is overexpressed predominantly in Group 4 tumors. MiR-592 expression reduced the anchorage-independent growth, invasion potential and tumorigenicity of Group 3 medulloblastoma cells. DEPTOR, an endogenous inhibitor of the mTOR kinase, and EML1 were identified as novel targets of miR-592. The miR-592 mediated decrease in the DEPTOR expression levels activated both mTORC1 and mTORC2 complex in medulloblastoma cells. However, the miR-592 expression also decreased the AKT kinase activity, likely to be due to the activation of the inhibitory feedback of the mTOR signaling. MiR-592 expression upregulated several neuronal differentiation-related genes, a characteristic of Group 4 medulloblastoma in Group 3 cell lines. The expression of miR-592 also upregulated the activity of ERK1/ERK2 kinases indicating activation of the MAPK signaling pathway. The inhibition of MAPK signaling by the ERK1/ERK2 inhibitor and mTOR signaling by rapamycin abrogated the miR-592-mediated upregulation of neuronal differentiation-related genes. Group 4 medulloblastomas showed higher activity of the mTOR and MAPK signaling compared to Group 3 tumors. Thus, miR-592 overexpression appears to be a driver event and a determining factor of Group 4 biology, which activates the mTOR and MAPK signaling pathways and thereby imparts its characteristic expression profile of neuronal differentiation-related genes.

Team Physiological Dynamics: A Critical Review.

OBJECTIVE: Review the use of physiological measurement in team settings and propose recommendations to improve the state of the science. BACKGROUND: New sensor and analytical capabilities enable exploration of relationships between team members' physiological dynamics. We conducted a review of physiological measures used in research on teams to understand (1) how these measures are theoretically and operationally related to team constructs and (2) what types of validity evidence exist for physiological measurement in team settings. METHOD: We identified 32 articles that investigated task-performing teams using physiological data. Articles were coded on several dimensions, including team characteristics. Study findings were categorized by relationships tested between team physiological dynamics (TPD) and team inputs, mediators/processes, outputs, or psychometric properties. RESULTS: TPD researchers overwhelmingly measure single physiological systems. Although there is research linking TPD to inputs and outputs, the research on processes is underdeveloped. CONCLUSION: We recommend several theoretical, methodological, and statistical themes to expand the growth of the TPD field. APPLICATION: Physiological measures, once established as reliable indicators of team functioning, might be used to diagnose suboptimal team states and cue interventions to ameliorate these states.

Effect of an Intervention Package and Teamwork Training to Prevent Healthcare Personnel Self-contamination During Personal Protective Equipment Doffing.

BACKGROUND: More than 28 000 people were infected with Ebola virus during the 2014-2015 West African outbreak, resulting in more than 11 000 deaths. Better methods are needed to reduce the risk of self-contamination while doffing personal protective equipment (PPE) to prevent pathogen transmission. METHODS: A set of interventions based on previously identified failure modes was designed to mitigate the risk of self- contamination during PPE doffing. These interventions were tested in a randomized controlled trial of 48 participants with no prior experience doffing enhanced PPE. Contamination was simulated using a fluorescent tracer slurry and fluorescent polystyrene latex spheres (PLSs). Self-contamination of scrubs and skin was measured using ultraviolet light visualization and swabbing followed by microscopy, respectively. Doffing sessions were videotaped and reviewed to score standardized teamwork behaviors. RESULTS: Participants in the intervention group contaminated significantly fewer body sites than those in the control group (median [interquartile range], 6 [3-8] vs 11 [6-13], P = .002). The median contamination score was lower for the intervention group than the control group when measured by ultraviolet light visualization (23.15 vs 64.45, P = .004) and PLS swabbing (72.4 vs 144.8, P = .001). The mean teamwork score was greater in the intervention group (42.2 vs 27.5, P < .001). CONCLUSIONS: An intervention package addressing the PPE doffing task, tools, environment, and teamwork skills significantly reduced the amount of self-contamination by study participants. These elements can be incorporated into PPE guidance and training to reduce the risk of pathogen transmission.

Restoration of miR-30a expression inhibits growth, tumorigenicity of medulloblastoma cells accompanied by autophagy inhibition.

Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas. MicroRNAs are known to play vital roles in nervous system development as well as in cancer. MicroRNA profiling of medulloblastomas identified miR-30 family members' expression to be downregulated in medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH, Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore, established medulloblastoma cell lines Daoy, D283 and D425 were also found to underexpress miR-30a. Restoration of miR-30a expression using inducible lentiviral vector inhibited proliferation, clonogenic potential and tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a mediator of autophagy. MiR-30a expression was found to downregulate Beclin1 expression and inhibit autophagy in the medulloblastoma cell lines as judged by downregulation of LC3B expression and its turnover upon chloroquine treatment and starvation induced autophagy induction. MiR-30a therefore could serve as a novel therapeutic agent for the effective treatment of medulloblastoma by inhibiting autophagy that is known to play important role in cancer cell growth, survival and malignant behavior.

MiR-224 expression increases radiation sensitivity of glioblastoma cells.

Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30-55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85-90% on irradiation at a dose of 6Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55-65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy, therefore appear as promising options for the treatment of glioblastoma, which is refractory to the existing treatment strategies.

Barriers and facilitators to screen for and address social needs in primary care practices in Maryland: a qualitative study.

Background: Social needs screening can help modify care delivery to meet patient needs and address non-medical barriers to optimal health. However, there is a need to understand how factors that exist at multiple levels of the healthcare ecosystem influence the collection of these data in primary care settings. Methods: We conducted 20 semi-structured interviews involving healthcare providers and primary care clinic staff who represented 16 primary care practices. Interviews focused on barriers and facilitators to awareness of and assistance for patients' social needs in primary care settings in Maryland. The interviews were coded to abstract themes highlighting barriers and facilitators to conducting social needs screening. The themes were organized through an inductive approach using the socio-ecological model delineating individual-, clinic-, and system-level barriers and facilitators to identifying and addressing patients' social needs. Results: We identified several individual barriers to awareness, including patient stigma about verbalizing social needs, provider frustration at eliciting needs they were unable to address, and provider unfamiliarity with community-based resources to address social needs. Clinic-level barriers to awareness included limited appointment times and connecting patients to appropriate community-based organizations. System-level barriers to awareness included navigating documentation challenges on the electronic health record. Conclusions: Overcoming barriers to effective screening for social needs in primary care requires not only practice- and provider-level process change but also an alignment of community resources and advocacy of policies to redistribute community assets to address social needs.

A Systematic Review of Quantitative Methods for Evaluating Electronic Medication Administration Record and Bar-Coded Medication Administration Usability.

BACKGROUND: Although electronic medication administration records (eMARs) and bar-coded medication administration (BCMA) have improved medication safety, poor usability of these technologies can increase patient safety risks. OBJECTIVES: The objective of our systematic review was to identify the impact of eMAR and BCMA design on usability, operationalized as efficiency, effectiveness, and satisfaction. METHODS: We retrieved peer-reviewed journal articles on BCMA and eMAR quantitative usability measures from PsycInfo and MEDLINE (1946-August 20, 2019), and EMBASE (1976-October 23, 2019). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we screened articles, extracted and categorized data into the usability categories of effectiveness, efficiency, and satisfaction, and evaluated article quality. RESULTS: We identified 1,922 articles and extracted data from 41 articles. Twenty-four articles (58.5%) investigated BCMA only, 10 (24.4%) eMAR only, and seven (17.1%) both BCMA and eMAR. Twenty-four articles (58.5%) measured effectiveness, 8 (19.5%) efficiency, and 17 (41.5%) satisfaction. Study designs included randomized controlled trial (n = 1; 2.4%), interrupted time series (n = 1; 2.4%), pretest/posttest (n = 21; 51.2%), posttest only (n = 14; 34.1%), and pretest/posttest and posttest only for different dependent variables (n = 4; 9.8%). Data collection occurred through observations (n = 19, 46.3%), surveys (n = 17, 41.5%), patient safety event reports (n = 9, 22.0%), surveillance (n = 6, 14.6%), and audits (n = 3, 7.3%). CONCLUSION: Of the 100 measures across the 41 articles, implementing BCMA and/or eMAR broadly resulted in an increase in measures of effectiveness (n = 23, 52.3%) and satisfaction (n = 28, 62.2%) compared to measures of efficiency (n = 3, 27.3%). Future research should focus on eMAR efficiency measures, utilize rigorous study designs, and generate specific design requirements.

Pharmacogenomic testing in oncology: a health system's approach to identify oncology provider perspectives.

Aim: Identify oncology healthcare providers' attitudes toward barriers to and use cases for pharmacogenomic (PGx) testing and implications for prescribing anticancer and supportive care medications. Materials & methods: A questionnaire was designed and disseminated to 71 practicing oncology providers across the MedStar Health System. Results: 25 of 70 (36%) eligible oncology providers were included. 88% were aware of PGx testing and 72% believed PGx can improve care. Of providers who had ordered a medication with PGx implications in the past month, interest in PGx for anticancer (90-100%) and supportive care medications (>75%) was high. Providers with previous PGx education were more likely to have ordered a test (odds ratio: 7.9; 95% CI: 1.1-56; p = 0.0394). Conclusion: Oncology provider prescribing practices and interest in PGx suggest opportunities for implementation.

"Are we there yet?" Ten persistent hazards and inefficiencies with the use of medication administration technology from the perspective of practicing nurses.

OBJECTIVES: (1) Characterize persistent hazards and inefficiencies in inpatient medication administration; (2) Explore cognitive attributes of medication administration tasks; and (3) Discuss strategies to reduce medication administration technology-related hazards. MATERIALS AND METHODS: Interviews were conducted with 32 nurses practicing at 2 urban, eastern and western US health systems. Qualitative analysis using inductive and deductive coding included consensus discussion, iterative review, and coding structure revision. We abstracted hazards and inefficiencies through the lens of risks to patient safety and the cognitive perception-action cycle (PAC). RESULTS: Persistent safety hazards and inefficiencies related to MAT organized around the PAC cycle included: (1) Compatibility constraints create information silos; (2) Missing action cues; (3) Intermittent communication flow between safety monitoring systems and nurses; (4) Occlusion of important alerts by other, less helpful alerts; (5) Dispersed information: Information required for tasks is not collocated; (6) Inconsistent data organization: Mismatch of the display and the user's mental model; (7) Hidden medication administration technologies (MAT) limitations: Inaccurate beliefs about MAT functionality contribute to overreliance on the technology; (8) Software rigidity causes workarounds; (9) Cumbersome dependencies between technology and the physical environment; and (10) Technology breakdowns require adaptive actions. DISCUSSION: Errors might persist in medication administration despite successful Bar Code Medication Administration and Electronic Medication Administration Record deployment for reducing errors. Opportunities to improve MAT require a deeper understanding of high-level reasoning in medication administration, including control over the information space, collaboration tools, and decision support. CONCLUSION: Future medication administration technology should consider a deeper understanding of nursing knowledge work for medication administration.

Pharmacogenomic Clinical Decision Support: A Review, How-to Guide, and Future Vision.

Clinical decision support (CDS) is an essential part of any pharmacogenomics (PGx) implementation. Increasingly, institutions have implemented CDS tools in the clinical setting to bring PGx data into patient care, and several have published their experiences with these implementations. However, barriers remain that limit the ability of some programs to create CDS tools to fit their PGx needs. Therefore, the purpose of this review is to summarize the types, functions, and limitations of PGx CDS currently in practice. Then, we provide an approachable step-by-step how-to guide with a case example to help implementers bring PGx to the front lines of care regardless of their setting. Particular focus is paid to the five "rights" of CDS as a core around designing PGx CDS tools. Finally, we conclude with a discussion of opportunities and areas of growth for PGx CDS.

Identifying Electronic Medication Administration Record (eMAR) Usability Issues from Patient Safety Event Reports.

BACKGROUND: Improving our understanding of the association between medication errors and health information technology (health IT) usability has the potential to reduce errors and improve patient safety. This study used patient safety event reports (PSEs) to investigate the contribution of usability challenges associated with the electronic medication administration record (eMAR) to medication errors. METHODS: Free-text descriptions of 849 medication-related PSEs selected from 2.3 million reports were analyzed. Coders identified the specific health IT components, usability challenge categories, and nuanced usability themes that contributed to each PSE. Thematic analysis was conducted to refine categorizations and identify emerging themes. Final analysis was limited to PSEs involving a contribution from eMAR, either as the point of origin or as a downstream contributor to error. RESULTS: eMAR contributed to 473 PSEs. eMAR was the point of origin for 84 (17.8% of 473) PSEs. Usability challenge categories included Workflow support (n = 52, 11.0%) and Display/Visual clutter (n = 30, 6.3%). eMAR contributed downstream from the point of origin in 389 (82.2% of 473) PSEs, with errors stemming primarily from Pharmacy IT and computerized provider order entry (CPOE). Prominent secondary eMAR-associated usability challenges included Display/Visual clutter (n = 327, 69.1%) and Alerting (n = 32, 6.8%). CONCLUSION: This study identified several eMAR usability challenges, through the analysis of PSEs, that contribute to medication errors. Findings highlight the critical need for improving the eMAR user interface. Improved interface design, better vendor usability testing, eMAR-focused certification testing, consideration of work system factors, and eMAR-focused usability and safety testing by health care facilities can improve eMAR technology and patient safety.

Clinician Perceptions on the Use of Free-Text Communication Orders.

OBJECTIVE: The aim of this study was to investigate (1) why ordering clinicians use free-text orders to communicate medication information; (2) what risks physicians and nurses perceive when free-text orders are used for communicating medication information; and (3) how electronic health records (EHRs) could be improved to encourage the safe communication of medication information. METHODS: We performed semi-structured, scenario-based interviews with eight physicians and eight nurses. Interview responses were analyzed and grouped into common themes. RESULTS: Participants described eight reasons why clinicians use free-text medication orders, five risks relating to the use of free-text medication orders, and five recommendations for improving EHR medication-related communication. Poor usability, including reduced efficiency and limited functionality associated with structured order entry, was the primary reason clinicians used free-text orders to communicate medication information. Common risks to using free-text orders for medication communication included the increased likelihood of missing orders and the increased workload on nurses responsible for executing orders. DISCUSSION: Clinicians' use of free-text orders is primarily due to limitations in the current structured order entry design. To encourage the safe communication of medication information between clinicians, the EHR's structured order entry must be redesigned to support clinicians' cognitive and workflow needs that are currently being addressed via the use of free-text orders. CONCLUSION: Clinicians' use of free-text orders as a workaround to insufficient structured order entry can create unintended patient safety risks. Thoughtful solutions designed to address these workarounds can improve the medication ordering process and the subsequent medication administration process.

Identifying Health Information Technology Usability Issues Contributing to Medication Errors Across Medication Process Stages.

OBJECTIVE: Different health information technology (health IT) systems are intended to support medication ordering, reviewing, and administration. We sought to identify the types of medication errors associated with health IT use, whether they reached the patient, where in the medication process those errors occurred, and the specific usability issues contributing to those errors. METHODS: Patient safety event reports from more than 595 healthcare facilities entered between January 2013 and September 2018 were analyzed. We computationally identified reports associated with health IT intended to support the medication process, including computerized provider order entry, electronic medication administration record, and barcode medication administration. From these, 2700 reports were manually reviewed to determine the type of medication error, medication process stage, and health IT usability issue. RESULTS: Of the 2700 manually reviewed reports, 1508 (55.9%) described a medication error that was associated with health IT use and 750 (49.7%) reached the patient. Improper dose errors were frequent (1214 of 1508, 80.5%) with most errors during ordering (673 of 1508, 44.6%) and reviewing medications (639 of 1508, 42.4%). Most health IT-associated medication error reports described usability issues (n = 1468 of 1508, 97.3%) including data entry, workflow support, and alerting. Data entry usability issues impacted few medication process stages, whereas workflow support and alerting impacted several stages. CONCLUSIONS: Health IT usability issues are a prevalent contributing factor to medication errors, many of which reach the patient. Data entry, workflow support, and alerting should be prioritized during usability and safety optimization efforts.

Restoration of miR-193a expression is tumor-suppressive in MYC amplified Group 3 medulloblastoma.

Medulloblastoma, a highly malignant pediatric brain tumor, consists of four molecular subgroups, namely WNT, SHH, Group 3, and Group 4. The expression of miR-193a, a WNT subgroup-specific microRNA, was found to be induced by MYC, an oncogenic target of the canonical WNT signaling. MiR-193a is not expressed in Group 3 medulloblastomas, despite MYC expression, as a result of promoter hypermethylation. Restoration of miR-193a expression in the MYC amplified Group 3 medulloblastoma cells resulted in inhibition of growth, tumorigenicity, and an increase in radiation sensitivity. MAX, STMN1, and DCAF7 were identified as novel targets of miR-193a. MiR-193a mediated downregulation of MAX could suppress MYC activity since it is an obligate hetero-dimerization partner of MYC. MYC induced expression of miR-193a, therefore, seems to act as a feedback inhibitor of MYC signaling. The expression of miR-193a resulted in widespread repression of gene expression that included not only several cell cycle regulators, WNT, NOTCH signaling genes, and those encoding DNA replication machinery, but also several chromatin modifiers like SWI/SNF family genes and histone-encoding genes. MiR-193a expression brought about a reduction in the global levels of H3K4me3, H3K27ac, the histone marks of active chromatin, and an increase in the levels of H3K27me3, a repressive chromatin mark. In cancer cells having high MYC expression, MYC brings about transcriptional amplification of all active genes apart from the induction of its target genes. MiR-193a, on the other hand, brought about global repression of gene expression. Therefore, miR-193a has therapeutic potential in the treatment of not only Group 3 medulloblastomas but possibly other MYC overexpressing aggressive cancers as well.

Understanding CancelRx: Results of End-to-End Functional Testing, Proactive Risk Assessment, and Pilot Implementation.

BACKGROUND: CancelRx allows prescribers to send electronic cancellation messages to pharmacies when medications are discontinued. Little is known about its functionality and impact on clinical workflows. OBJECTIVES: To understand CancelRx functionality, its potential impact on workflows and medication safety risks, and to develop mitigating strategies for risks introduced by implementation. METHODS: We conducted direct observations and semi-structured interviews to develop CancelRx use cases and assessed CancelRx in an end-to-end test environment, proactive risk assessment, and pilot implementation from April 16 to July 15, 2018. RESULTS: E-cancellations were sent upon discontinuation of e-prescriptions written within the electronic health record (EHR), but not other medications (e.g., printed prescriptions) and could be initiated by nonprescribers. In our proactive risk assessment, CancelRx implementation eliminated five of seven failure modes in outpatient prescribing to Johns Hopkins pharmacies, but introduced new risks, including (1) failure to act if an e-cancellation was not sent or was unsuccessful; (2) failure to cancel all prescriptions for a medication; (3) errors in manual matching; and (4) erroneous medication cancellations. We identified potential mitigation strategies for these risks. During pilot implementation, 92.4% (428/463) of e-cancellations had confirmed approval by the receiving pharmacy, while 4.5% (21/463) were denied, and 3.0% (14/463) had no e-cancellation response. Among e-cancellations received by the pilot pharmacy, 1.7% (7/408) required manual matching by pharmacy staff. Based on performance in testing, 73.4% (340/463) of completed e-cancellations would be expected to generate an in-basket message, including 21 (6.2%) denials and 319/340 (93.8%) approvals with a note from the pharmacy. CONCLUSION: CancelRx is an important functionality with the potential to decrease adverse events due to medication errors. However, changes in implementation in our EHR and pharmacy software and enhancements in the CancelRx standard are needed to maximize safety and usability. Further studies are needed to evaluate the impact of e-cancellation on medication safety.

Downregulation of miR-204 expression defines a highly aggressive subset of Group 3/Group 4 medulloblastomas.

Genome-wide expression profiling studies have identified four core molecular subgroups of medulloblastoma: WNT, SHH, Group 3 and Group 4. Molecular markers are necessary for accurate risk stratification in the non-WNT subgroups due to the underlying heterogeneity in genetic alterations and overall survival. MiR-204 expression was evaluated in molecularly classified 260 medulloblastomas from an Indian cohort and in 763 medulloblastomas from the MAGIC cohort, SickKids, Canada. Low expression of miR-204 in the Group 3 / Group 4 tumors identify a highly aggressive subset of tumors having poor overall survival, in the two independent cohorts of medulloblastomas. Downregulation of miR-204 expression correlates with poor survival within the Group 4 as well indicating it as a valuable risk-stratification marker in the subgroup. Restoration of miR-204 expression in multiple medulloblastoma cell lines was found to inhibit their anchorage-independent growth, invasion potential and tumorigenicity. IGF2R was identified as a novel target of miR-204. MiR-204 expression resulted in downregulation of both M6PR and IGF2R that transport lysosomal proteases from the Golgi apparatus to the lysosomes. Consistent with this finding, miR-204 expression resulted in reduction in the levels of the lysosomal proteases in medulloblastoma cells. MiR-204 expression also resulted in inhibition of autophagy that is known to be dependent on the lysosomal degradation pathway and LC3B, a known miR-204 target. Treatment with HDAC inhibitors resulted in upregulation of miR-204 expression in medulloblastoma cells, suggesting therapeutic role for these inhibitors in the treatment of medulloblastomas. In summary, miR-204 is not only a valuable risk stratification marker in the combined cohort of Group 3 / Group 4 medulloblastomas as well as in the Group 4 itself, that has paucity of good prognostication markers, but also has therapeutic potential as indicated by its tumor suppressive effect on medulloblastoma cells.

The Threat-Strategy Interview.

Operators in dynamic work environments use strategies to manage threats in order to achieve task goals. We introduce a structured interview method, the Threat-Strategy Interview (TSI), and an accompanying qualitative analysis to induce operator-level threats, strategies, and the cues that give rise to them. The TSI can be used to elicit knowledge from operators who are on the front line of managing threats to provide an understanding of strategic thinking, which in turn can be applied toward a variety of problems.

Tamoxifen-Induced Cell Death of Malignant Glioma Cells Is Brought About by Oxidative-Stress-Mediated Alterations in the Expression of BCL2 Family Members and Is Enhanced on miR-21 Inhibition.

High-grade gliomas are refractory to the current mode of treatment primarily due to their inherent resistance to cell death. Tamoxifen has been reported to inhibit growth and induce cell death of glioma cells in vitro, in an estrogen-receptor-independent manner. Delineating the molecular mechanism underlying tamoxifen-induced cell death of human glioma cells would help in identifying pathways/genes that could be targeted to induce tumor-cell-specific cell death. In the present study, tamoxifen was found to bring about autophagic cell death of human glioma cells that was accompanied by oxidative stress induction, JNK activation, downregulation of anti-autophagic BCL2 family members, viz. BCL2 and BCL-XL, and increased expression of the pro-autophagic members BCL-Xs and BAK. Oxidative stress induction appears to be primarily responsible for the tamoxifen-induced cell death since the cell death, JNK activation, and the alterations in the expression levels of BCL2 family members were abrogated on pretreatment with antioxidant vitamin E. MiR-21, an oncogenic miRNA, is known to be highly upregulated in malignant glioma. Inhibition of miR-21 activity was found to enhance tamoxifen-induced cell death of U87 MG malignant glioma cells. Tamoxifen treatment coupled with miR-21 inhibition could therefore be an effective strategy for the treatment of malignant gliomas.