Improving interprofessional practice and cultural competence with interprofessional education

Challenge/Issue: Interprofessional education (IPE) and cultural competence (CC) training have become a staple in healthcare education programs with the ultimate goal of improving patient care. IPE, where students from two or more professions learn from, about, and with each other to optimize care, resulting in great team building, sharing of knowledge, communication, and collaboration. CC involves an individual’s ability to recognize, assess, appreciate, and respect unique backgrounds such as race, ethnicity, sexual minorities, gender, identity, religion, and age, to make greater informed decisions in healthcare and minimize inequities. Within educational programs, both constructs can occur simultaneously to optimize learning and patient-centered outcomes.Objective: To identify the impact of a Diversity, Equity, and Inclusion IPE single-day event on the perceptions of interprofessional practice and ability to provide culturally competent care instudents enrolled in Doctor of Osteopathy (DO), Pharmacy, and Athletic Training (AT) education programs.Approach: An experimental design used pre- and post-test measures of IPE and CC knowledge with a one day conference as the intervention. Participants included students (205- pre and 200- post) enrolled in DO, pharmacy, and AT programs at two Midwestern universities. Participants completed the Interprofessional Collaborative Competences Attainments Survey (ICCAS) and three modified components of the Tool for Assessing Cultural Competence Training (mTACCT) before and after the event that included baseline information about the different professions, three CC presentations, and two case studies with small group discussions. Due to uneven sample sizes in the pre- and post-test, and violations of normality and homogeneity of variance, Kruskal Wallis tests were used to assess differences in the intervention.Results: Five items on the ICCAS and all items on the mTACCT demonstrated statistical significance. On the ICCAS, students demonstrated increases in their ability to; “actively list to Interprofessional (IP) team members’ ideas and concerns”, “working effectively with IP members to enhance care", “recognizing how others’ skills and knowledge complement and overlap with their own”, “to develop an effective care plan with IP team members”, and “negotiate responsibilities with overlapping scopes of practice”. This demonstrated that discussing the professions in general and utilizing case studies and small group discussions allowed students to understand the roles, skills, and responsibilities of their peer professionals which will lead to better communication and teamwork resulting in improved patient outcomes and satisfaction for both patients and staff. The results of the mTACCT demonstrated overall improvement in skills but highlighted students are consciously incompetent, where they recognize a deficiency but demonstrate a desire for greater understanding. Students felt that initially they lacked the ability to identify bias and stereotyping in healthcare but after the intervention felt better equipped. It is important to note that while we found improvements within CC, a single event should not be the only point of CC inclusion within curriculums. Our intervention provided students from three different healthcare programs with an educational opportunity to strengthen their skills in both IPE and C

Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Acidolysis of α‑O‑4 Aryl-Ether Bonds in Lignin Model Compounds: A Modeling and Experimental Study

Lignocellulosic biomass offers a vast, renewable resource for the sustainable production of fuels and chemicals. To date, a commonly employed approach to depolymerize the polysaccharides in plant cell walls employs mineral acids, and upgrading strategies for the resulting sugars are under intense development. Although the behavior of cellulose and hemicellulose is reasonably well characterized, a more thorough understanding of lignin depolymerization mechanisms in acid environments is necessary to predict the fate of lignin under such conditions and ultimately to potentially make lignin a viable feedstock. To this end, dilute acid hydrolysis experiments were performed on two lignin model compounds containing the α-O-4 ether linkage at two temperatures concomitant with dilute acid pretreatment. Both primary and secondary products were tracked over time, giving insight into the reaction kinetics. The only difference between the two model compounds was the presence or absence of a methyl group on the α-carbon, with the former being typical of native lignin. It was found that methylation of the α-carbon increases the rate of reaction by an order of magnitude. Density functional theory calculations were performed on a proposed mechanism initiated by a nucleophilic attack on the α-carbon by water with a commensurate protonation of the ether oxygen. The values for the thermodynamics and kinetics derived from these calculations were used as the basis for a microkinetic model of the reaction. Results from this model are in good agreement with the experimental kinetic data for both lignin model compounds and provide useful insight into the primary pathways of α-O-4 scission reactions in acid-catalyzed lignin depolymerization. The distribution of primary and secondary products is interpreted as a function of two barriers of formation exhibiting opposite trends upon methylation of the α-carbon (one barrier is lowered while the other is increased). Such insights will be needed to construct a comprehensive model of how lignin behaves in a common deconstruction approach

Optimization of Isothiazolo[4,3‑<i>b</i>]­pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity

There is an urgent need for strategies to combat dengue and other emerging viral infections. We reported that cyclin G-associated kinase (GAK), a cellular regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2, regulates intracellular trafficking of multiple unrelated RNA viruses during early and late stages of the viral lifecycle. We also reported the discovery of potent, selective GAK inhibitors based on an isothiazolo­[4,3-<i>b</i>]­pyridine scaffold, albeit with moderate antiviral activity. Here, we describe our efforts leading to the discovery of novel isothiazolo­[4,3-<i>b</i>]­pyridines that maintain high GAK affinity and selectivity. These compounds demonstrate improved in vitro activity against dengue virus, including in human primary dendritic cells, and efficacy against the unrelated Ebola and chikungunya viruses. Moreover, inhibition of GAK activity was validated as an important mechanism of antiviral action of these compounds. These findings demonstrate the potential utility of a GAK-targeted broad-spectrum approach for combating currently untreatable emerging viral infections