Developing scientifically validated bias and diversity trainings that work: empowering agents of change to reduce bias, create inclusion, and promote equity.

Purpose ­: Research consistently shows that non-scientific bias, equity, and diversity trainings do not work, and often make bias and diversity problems worse. Despite these widespread failures, there is considerable reason for hope that effective, meaningful DEI efforts can be developed. One approach in particular, the bias habit-breaking training, has 15 years of experimental evidence demonstrating its widespread effectiveness and efficacy. Design/methodology/approach ­: This article discusses bias, diversity, equity, and inclusion (DEI) efforts from the author's perspective as a scientist-practitioner - the author draws primarily on the scientific literature, but also integrates insights from practical experiences working in DEI. The author provides a roadmap for adapting effective, evidence-based approaches from other disciplines (e.g. cognitive-behavioral therapy) into the DEI context and reviews evidence related to the bias habit-breaking training as one prominent demonstration of a scientifically-validated approach that effects lasting, meaningful improvements on DEI issues within both individuals and institutions. Findings ­: DEI trainings fail due to widespread adoption of the information deficit model, which is well-known as a highly ineffective approach. Empowerment-based approaches, in contrast, are highly promising for making meaningful, lasting changes in the DEI realm. Evidence indicates that the bias habit-breaking training is effective at empowering individuals as agents of change to reduce bias, create inclusion, and promote equity, both within themselves and the social contexts they inhabit. Originality/value ­: In contrast to the considerable despair and pessimism around DEI efforts, the present analysis provides hope and optimism, and an empirically-validated path forward, to develop and test DEI approaches that empower individuals as agents of change.

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines.

Recent advances have suggested that non-coding miRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of oral cancer chemotherapeutic responsiveness. This study evaluated whether these specific miRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU). Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) revealed differing resistance and chemosensitivity to these agents-with SCC9 and SCC25 demonstrating the most resistance to all chemotherapeutic agents. SCC9 and SCC25 were also the only cell lines that expressed miR-375, and were the only cell lines that did not express miR-27. In addition, the expression of miR-375 was associated with the upregulation of Rearranged L-myc fusion (RLF) and the downregulation of Centriolar protein B (POC1), whereas lack of miR-27 expression was associated with Nucleophosmin 1 (NPM1) expression. These data have revealed important regulatory pathways and mechanisms associated with oral cancer proliferation and resistance that must be explored in future studies of potential therapeutic interventions.

Rational design of metabolically stable HDAC inhibitors: An overhaul of trifluoromethyl ketones.

Epigenetic regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to their poor pharmacokinetic properties and lack of isoform selectivity. Trifluoromethylketones (TFMK) developed as alternatives to hydroxamates are rapidly metabolized to inactive trifluoromethyl alcohols in vivo, which prevented their further development as potential drug candidates. In order to overcome this limitation, we designed trifluoropyruvamides (TFPAs) as TFMK surrogates. The presence of an additional electron withdrawing group next to the ketone carbonyl group made the hydrate form of the ketone more stable, thus preventing its metabolic reduction to alcohol in vivo. In addition, this structural modification reduces the potential of the TFMK group to act as a covalent warhead to eliminate off-target effects. Additional structural changes in the cap group of the inhibitors gave analogues with IC50 values ranging from upper nanomolar to low micromolar in the cytotoxicity assay, and they were more selective for cancer cells over normal cells. Some of the most active analogues inhibited HDAC enzymes with low nanomolar IC50 values and were found to be more selective for HDAC8 over other isoforms. These molecules provide a new class of HDAC inhibitors with a metabolically stable metal-binding group that could be used to develop selective HDAC inhibitors by further structural modification.

The Use of Removed Mesquite Brush as a Fiber Replacement in Silage Production.

Mesquite (Prosopis L.) is considered an invasive browse species in most of the American Southwest. Mechanical intervention removes yields an excess of organic debris. Anecdotal evidence in the past has supported using such browse as feed for livestock. Thus, our objectives were to (1) determine the nutritive value and fermentation characteristics of silage produced with mesquite biomass, and (2) evaluate solvent treatment of mesquite biomass prior to ensiling. In Experiment 1, we evaluated mesquite inclusion rate (0, 250, 500, 750, or 1000 g kg−1 DM), length of fermentation (28, 56, or 84 d), and silage inoculant. In Experiment 2, we evaluated the effects of mesquite pre-treatment with acid (H2SO4) or alkali (NaOH) solutions. Concentrations of NDF, ADF, and ADL, as well as IVTD, decreased (p < 0.05) with increasing mesquite inclusion. However, 250 g mesquite kg−1 DM did not differ from grass silage. There was no effect (p > 0.05) of inoculation, though increasing length of incubation did increase (p < 0.05) VFA production and decrease (p < 0.05) silage pH. Solvent treatment did not improve ensiling properties. Results are interpreted to mean that mesquite biomass may be effectively incorporated into silage at levels up to 250 g kg−1.

Methodology for Low-Field, Portable Magnetic Resonance Neuroimaging at the Bedside.

Neuroimaging is a critical component of triage and treatment for patients who present with neuropathology. Magnetic resonance imaging and non-contrast computed tomography are the gold standard for diagnosis and prognostication of patients with acute brain injuries. However, these modalities require intra-hospital transport to strict, access-controlled environments, which puts critically ill patients at risk for complications and secondary injuries. A novel, portable MRI (pMRI) device that can be deployed at the patient's bedside provides a needed solution. In a dual-center investigation, Yale New Haven Hospital has obtained regular neuroimaging on patients using the pMRI as part of routine clinical care in the Emergency Department and Intensive Care Unit (ICU) since August of 2020. Massachusetts General Hospital has begun using pMRI in the Neuroscience Intensive Care Unit since January 2021. This technology has expanded the population of patients who can receive MRI imaging by increasing accessibility and timeliness for scan completion by eliminating the need for transport and increasing the potential for serial monitoring. Here we describe our methods for screening, coordinating, and executing pMRI exams and provide further detail on how to scan specific patient populations.

Brain-derived Neurotropic Factor val66met is a Strong Predictor of Decision Making and Attention Performance on the CONVIRT Virtual Reality Cognitive Battery.

The val66met polymorphism of the brain-derived neurotrophic factor gene has been associated with changes in components of executive functioning such as decision making; however, this relationship remains unclear. Val66met-related changes in attention and visual processing speed may explain potential changes in decision making. Furthermore, chronic stress disrupts executive functions and alters autonomic activity. Because the relationship between val66met and cognition has not been investigated in the context of chronic stress or stress-related autonomic changes, in this study 55 healthy university students completed self-report measures of chronic stress and mental health. Participants then completed a virtual reality cognitive test battery (CONVIRT) measuring decision making, attention, and visual processing reaction times. To measure autonomic activity, saliva alpha amylase and heart rate variability (HRV) were assessed at baseline and after CONVIRT testing. Saliva samples were used to identify val66met genotype. Regression analyses demonstrated that val66met was the strongest predictor of decision making and attention, but not visual processing, where valine/methionine (Val/met) participants had faster reaction times than Val/val participants. Val/met participants also had higher perceived chronic stress and heightened increases in sympathetic activity, but not parasympathetic activity. Neither stress nor autonomic activity moderated the effect of val66met on decision making or attention. This study is the first to investigate the role of val66met in decision making, attention, and visual processing while taking into account chronic stress and autonomic activity. This multifactorial approach revealed that carriers of the Val/met genotype may have better decision making and attention than Val/val carriers.

Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes.

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.

Knowledge, attitude and recommendations for practice regarding dengue among the resident population of Queensland, Australia

Objective: To investigate levels of awareness of dengue among the inhabitants of Queensland (QLD), a dengue-prevalent state in the north east of Australia. Methods: A computer-assisted telephone interviewing survey was conducted in mid 2014. A total of 1. 223 randomly selected respondents (≥ 18 years) across QLD completed a structured questionnaire covering all aspects of dengue. Results: 97.55% had heard of dengue and participated further. Among them, 54.70% had travelled overseas (48.11% to dengue-risk countries) in the last five years. A total of 94.47% said transmission is by mosquito bite. In addition, 84.83% knew of current transmission of dengue in QLD, while 80.97% knew the focus is Far North and North QLD. Furthermore, 2.35% and 8.97% had experienced an infection in their life or that of their immediate family/partner, respectively. 85.03% identified correctly at least one means of prevention. A total of 69.72% advised to use insect repellent, wear covered clothing and avoid visiting mosquito-prone areas while 20.93% advised fumigation and clearing water containers around residences. There was a significant difference (P 0.05). Conclusions: Although many people throughout QLD have heard of dengue, about 15% appear unaware of local transmission, its symptoms and of methods to reduce risk of infection. A lack of knowledge regarding prevention of mosquito breeding is evident in South East QLD, where dengue is not currently reported. The study suggests that future dengue awareness campaigns should target communities in both endemic and potentially endemic areas throughout Queensland.