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ABSTRACT IMPACT: Racial differences in the prevalence of hypertension and endothelial (dys)function are well established, yet research investigating the mechanism(s) underlying this disparity is still lacking. OBJECTIVES/GOALS: Investigate the influence of race and the effect of serum collected from hypertensive donors on Protein Phosphatase 2A (PP2A) and endothelial nitric oxide synthase (eNOS) expression and activity in human umbilical vein endothelial cells (HUVECs) from Caucasian (CA) and African American (AA) donors. METHODS/STUDY POPULATION: HUVECs from 3 CA & 3 AA donors were cultured in parallel. Experiments were conducted between passages 5-7. At ?90% confluency, cells were serum starved ˜12hrs prior to incubating for 24 or 48 hours in one of the following conditions: 1) Control (Fetal Bovine Serum), 2) serum from normotensives (NT; 5 CA & 5 AA donors), or 3) serum from hypertensives (HT; 5 CA & 5 AA donors). NT and HT serum was pooled from donors with the following characteristics: Male, 30-50 years, nonsmokers, no comorbidities, and non-obese (BMI < 30 kg/m2). Western blotting was used to measure protein expression of total eNOS, p-eNOSS1177, total PP2A, and p-PP2AY307. For activity p-eNOSS1177/total eNOS and p-PP2AY307/ total PP2A ratio was used. A two-way ANOVA was used for statistical analysis. RESULTS/ANTICIPATED RESULTS: Irrespective of the donors’ race, there was no influence of serum treatment or interaction effect in any of the measured proteins of interest. Moreover, compared to CA, HUVECs from AA had lower expression of eNOS irrespective of condition (race p=0.01). Compared to CA, HUVECs from AA tended to have lower expression of p-eNOSS1177 irrespective of condition (race p=0.07). However, there was no racial differences in eNOS activity (p=0.68). There was no racial difference in the expression of PP2A (p=0.35), p-PP2AY307 (p=0.30), or PP2A activity (p=0.97) in all conditions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our preliminary results suggest no influence serum constituents from hypertensive donors or race on PP2A or eNOS expression and activity in HUVECS. Future research should consider conducting proteomics profiling to compare NT and HT serum.
We applaud the goals and execution of the target article, but note that individual differences do not receive much attention. This is a shortcoming because individual differences can play a vital role in theory testing. In our commentary, we describe programs of research of this type and also apply similar thinking to the mechanisms proposed in the target article.
In his influential text, William James (1890) devoted separate chapters to the self and to its habits. His chapter on the self focused on the malleability of self-views and the manner in which they are diverse, encompassing disparate aspects such as the material, social and spiritual selves. By contrast, his chapter on habits highlighted the ways in which an individual becomes more and more like a particular type of person, with a particular type of disposition, over time. Whether functional or dysfunctional, habits coalescence into personality traits, and these personality traits become relatively fixed by the age of thirty.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The US Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) program sponsors the development of systematic reviews to inform clinical policy and practice. The EPC program sought to better understand how health systems identify and use this evidence.
Representatives from eleven EPCs, the EPC Scientific Resource Center, and AHRQ developed a semi-structured interview script to query a diverse group of nine Key Informants (KIs) involved in health system quality, safety and process improvement about how they identify and use evidence. Interviews were transcribed and qualitatively summarized into key themes.
All KIs reported that their organizations have either centralized quality, safety, and process improvement functions within their system, or they have partnerships with other organizations to conduct this work. There was variation in how evidence was identified, with larger health systems having medical librarians and central bureaus to gather and disseminate information and smaller systems having local chief medical officers or individual clinicians do this work. KIs generally prefer guidelines, especially those with treatment algorithms, because they are actionable. They like systematic reviews because they efficiently condense study results and reconcile conflicting data. They prefer information from systematic reviews to be presented as short digestible summaries with the full report available on demand. KIs preferred systematic reviews from reputable entities and those without commercial bias. Some of the challenges KIs reported include how to resolve conflicting evidence, the generalizability of evidence to local needs, determining whether the evidence is up-to-date, and the length of time required to generate reviews. The topics of greatest interest included predictive analytics, high-value care, advance care planning, and care coordination. To increase awareness of AHRQ EPC reviews, KIs suggest alerting people at multiple levels in a health-system when new evidence reports are available and making reports easier to find in common search engines.
Systematic reviews are valued by health system leaders. To be most useful they should be easy to locate and available in different formats targeted to the needs of different audiences.
Collaboration is used by the US National Security Council as a means to integrate inter-federal government agencies during planning and execution of common goals towards unified, national security. The concept of collaboration has benefits in the healthcare system by building trust, sharing resources, and reducing costs. The current terrorist threats have made collaborative medical training between military and civilian agencies crucial.
This review summarizes the long and rich history of collaboration between civilians and the military in various countries and provides support for the continuation and improvement of collaborative efforts. Through collaboration, advances in the treatment of injuries have been realized, deaths have been reduced, and significant strides in the betterment of the Emergency Medical System have been achieved. This review promotes collaborative medical training between military and civilian medical professionals and provides recommendations for the future based on medical collaboration.