A Contra Capture Protein Array Platform for Studying Post-translationally Modified (PTM) Auto-antigenomes.

Aberrant modifications of proteins occur during disease development and elicit disease-specific antibody responses. We have developed a protein array platform that enables the modification of many proteins in parallel and assesses their immunogenicity without the need to express, purify, and modify proteins individually. We used anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) as a model modification and profiled antibody responses to ∼190 citrullinated proteins in 20 RA patients. We observed unique antibody reactivity patterns in both clinical anticyclic citrullinated peptide assay positive (CCP+) and CCP- RA patients. At individual antigen levels, we detected antibodies against known citrullinated autoantigens and discovered and validated five novel antibodies against specific citrullinated antigens (osteopontin (SPP1), flap endonuclease (FEN1), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. We also demonstrated the utility of our innovative array platform in the identification of immune-dominant epitope(s) for citrullinated antigens. We believe our platform will promote the study of post-translationally modified antigens at a breadth that has not been achieved before, by both identifying novel autoantigens and investigating their roles in disease development. The developed platforms can potentially be used to study many autoimmune disease-relevant modifications and their immunogenicity.

Preparing Older Adults with Serious Illness to Formulate Their Goals for Medical Care in the Emergency Department.

BACKGROUND: Emergency department (ED) clinicians often lack training and resources to conduct advance care planning (ACP) conversations. The use of technology for health education is increasing, yet little is known if it can be used to engage older ED patients in ACP. OBJECTIVE: To determine the feasibility of using tablets to provide ACP education ( www.prepareforyourcare.org )(PREPARE) to older ED patients. DESIGN: A feasibility study conducted in late 2014 and early 2015. SETTING/SUBJECTS: Subjects were recruited from a parent cohort of older adults enrolled in a survey about Geriatric ED care. Inclusion criteria were ≥65 years age and English speaking; exclusions were hearing or vision impairment or if clinically unstable. MEASUREMENTS: Primary outcome was completion of ≥1 of 5 PREPARE modules. Secondary outcomes were ease of use (10-point scale; 1 = very hard, 10 = very easy) and the reasons for refusal to participate. RESULTS: Sixty-one subjects were approached; 24 (39%) were interested in viewing PREPARE after the Geriatric ED survey. Mean age was 75 years (standard deviation [SD] 9); 67% were female and 54% were nonwhite. Seventy-one percent of participants completed ≥1 module. Participants rated the website as easy to use for themselves (mean 8.4, SD 2.39) and for others (mean 7.3, SD 2.31). Of the subjects who declined, top reasons cited were fatigue (26%), already feeling prepared (13%), and technology limitations (11%). CONCLUSION: PREPARE has the potential to engage older adults who are not acutely ill in ACP during their ED visits. Further studies should explore optimal approaches for ED implementation.

A user-editable web-based platform to streamline clinical information flow.

Frequent turnover of staff in medical clinics creates challenges in the maintenance of clinical protocols, workflows, and information management. Care coordination between providers in such a setting can be complex; disruptions in communication may lead to poorer health outcomes and patient satisfaction. Furthermore, protocols change frequently in response to new guidelines, which demands rapid updates to maintain compliance. To address these challenges, we developed an intuitive, end-user editable web-based knowledge management system optimized for use on mobile devices. The resulting system served as a point of care information storage and retrieval tool that providers can reference quickly for operational tasks. Since launch, the platform has allowed our clinic to consolidate knowledge banks, standardize staff training, and streamline information flow during clinic, and is now used extensively by clinic staff. During a one-year period, 175 new pages have been created and 1686 edits have been submitted by users. We posit that a mobile platform for clinical information flow management has significant potential to improve information maintenance and facilitate transfer of up-to-date clinical protocols to new personnel.

Manipulating the epigenome for the treatment of urological malignancies.

Urological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.