Oxidized polyunsaturated fatty acid promotes colitis and colitis-associated tumorigenesis in mice.

Background And Aims: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD.

LKB1 isoform expression modulates T cell plasticity downstream of PKCθ and IL-6.

Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation.

Effects of Linoleic Acid-Rich Diet on Plasma Profiles of Eicosanoids and Development of Colitis in -10 Mice.

Dietary intake of linoleic acid (LA, 18:2ω-6) has risen dramatically in recent decades. Previous studies have suggested a high intake of LA could increase tissue concentrations of proinflammatory and protumorigenic ω-6-series eicosanoid metabolites, increasing risks of inflammation and associated diseases. However, the effects of a LA-rich diet on in vivo profiles of eicosanoids and development of inflammatory diseases are understudied.

Cell-Penetrating Anti-Protein Kinase C Theta Antibodies Act Intracellularly to Generate Stable, Highly Suppressive Regulatory T Cells.

Regulatory T cells maintain immunological tolerance and dampen inflammatory responses. Administering regulatory T cells can prevent the immune-mediated tissue destruction of graft-versus-host disease, which frequently accompanies hematopoietic stem cell transfer. Neutralizing the T cell-specific kinase, protein kinase C theta, which promotes T cell effector functions and represses regulatory T cell differentiation, augments regulatory T cell immunosuppression and stability.

CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.

Notch signaling provides an important cue in the mammalian developmental process. It is a key player in T cell development and function. Notch ligands such as Delta-like ligands (DLL) 1, 3, 4, and JAG1, 2 can impact Notch signaling positively or negatively, by -activation or -inhibition.

Triclocarban Exposure Exaggerates Spontaneous Colonic Inflammation in Il-10-/- Mice.

Triclocarban (3,4,4'-trichlorocarbanilide, TCC) is a high-volume chemical used as an antimicrobial ingredient in many consumer and personal care products. In 2016, the Food and Drug Administration removed TCC from over-the-counter hand washing products. However, TCC remains approved to use in many other products and is a ubiquitous contaminant in the environment; furthermore, many common food crops can efficiently accumulate environmental TCC, resulting in potential human exposure through oral ingestion of contaminated food products.

Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease.

The immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for treating GvHD. We characterized Cymerus™ MSCs, which are derived from adult, induced pluripotent stem cells (iPSCs), and show they display surface markers and tri-lineage differentiation consistent with MSCs isolated from bone marrow (BM).

Rotenone Treatment Reveals a Role for Electron Transport Complex I in the Subcellular Localization of Key Transcriptional Regulators During T Helper Cell Differentiation.

Recent advances in our understanding of tumor cell mitochondrial metabolism suggest it may be an attractive therapeutic target. Mitochondria are central hubs of metabolism that provide energy during the differentiation and maintenance of immune cell phenotypes. Mitochondrial membranes harbor several enzyme complexes that are involved in the process of oxidative phosphorylation, which takes place during energy production.

Ultrasound study of elbow ulnar collateral ligament changes in collegiate baseball players: A pilot study.

Objective: To assess changes in elbow ulnar collateral ligament length in college baseball pitchers over the course of a single season.

Design: Cohort Feasibility Study.

Methods: Diagnostic ultrasound was used to assess both the dominant and non-dominant medial elbow joint space in four pitchers and five fielders and compared to in-game pitching data.

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation.

Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding.

Standardization in patient safety: the WHO High 5s project.

Quality Problem: Despite its success in other industries, process standardization in health care has been slow to gain traction or to demonstrate a positive impact on the safety of care.

Intervention: The High 5s project is a global patient safety initiative of the World Health Organization (WHO) to facilitate the development, implementation and evaluation of Standard Operating Protocols (SOPs) within a global learning community to achieve measurable, significant and sustainable reductions in challenging patient safety problems.

Goals: The project seeks to answer two questions: (i) Is it feasible to implement standardized health care processes in individual hospitals, among multiple hospitals within individual countries and across country boundaries? (ii) If so, what is the impact of standardization on the safety problems that the project is targeting?

Method: The two key areas in which the High 5s project is innovative are its use of process standardization both in hospitals within a country and in multiple participating countries, and its carefully designed multi-pronged approach to evaluation.

Towards an International Classification for Patient Safety: key concepts and terms.

Background: Understanding the patient safety literature has been compromised by the inconsistent use of language.

Objective: To identify key concepts of relevance to the International Patient Safety Classification (ICPS) proposed by the World Alliance For Patient Safety of the World Health Organization (WHO), and agree on definitions and preferred terms.

Methods: Six principles were agreed upon-that the concepts and terms should: be applicable across the full spectrum of healthcare; be consistent with concepts from other WHO Classifications; have meanings as close as possible to those in colloquial use; convey the appropriate meanings with respect to patient safety; be brief and clear, without unnecessary or redundant qualifiers; be fit-for-purpose for the ICPS.

Towards an International Classification for Patient Safety: a Delphi survey.

Objective: Interpretation and comparison of patient safety information have been compromised by the lack of a common understanding of the concepts involved. The World Alliance set out to develop an International Classification for Patient Safety (ICPS) to address this, and to test the relevance and acceptability of the draft ICPS and progressively refine it prior to field testing.

Design: Two-stage Delphi survey.

Towards an International Classification for Patient Safety: the conceptual framework.

Global advances in patient safety have been hampered by the lack of a uniform classification of patient safety concepts. This is a significant barrier to developing strategies to reduce risk, performing evidence-based research and evaluating existing healthcare policies relevant to patient safety. Since 2005, the World Health Organization's World Alliance for Patient Safety has undertaken the Project to Develop an International Classification for Patient Safety (ICPS) to devise a classification which transforms patient safety information collected from disparate systems into a common format to facilitate aggregation, analysis and learning across disciplines, borders and time.

Impact of a structured skills laboratory curriculum on surgery residents' intraoperative decision-making and technical skills.

Background: This project sought to study the effectiveness of a curriculum to enhance the intraoperative clinical judgment and procedural skill of surgical residents.

Method: A multiinstitutional, prospective, randomized study was performed. A cognitive task analysis of laparoscopic cholecystectomy (LC) was conducted on which instructional activities and measurement instruments were designed.

Teaching pediatrics residents how to obtain informed consent.

Background: Few physicians view informed consent as a critical component of the physician-patient relationship or as a way to improve individual and population health. We hypothesized that formal education about informed consent would affect first-year pediatrics residents' knowledge and attitudes.

Method: Twenty-seven first-year pediatrics residents participated in a randomized controlled trial with a wait-list control group.

Residents seeking informed consent: Are they adequately knowledgeable?

Purpose: The purpose of this study was to determine the extent to which first-year surgical residents are prepared to obtain informed consent from patients. The study was designed to answer the following research questions: 1) Are first-year residents who are asked to obtain informed consent sufficiently knowledgeable about the risks, benefits, and alternatives of the procedures? 2) Can first-year residents accurately answer the questions patients may pose about these procedures?

Methods: First-year residents (n = 18) were asked to list the risks, benefits, and alternatives for open inguinal hernia repair, laparoscopic cholecystectomy, total thyroidectomy, esophagogastrectomy, and abdominal aortic aneurysm repair, assuming the procedures were elective on otherwise healthy individuals. Residents were also asked to answer questions that patients may pose about each of the procedures.

Questioning skills: the effect of wait time on accuracy of medical student responses to oral and written questions.

Background: Pauses (wait time) after asking questions in pre-college classes result in improved discussion and answer accuracy. The authors hypothesized that this would extend to medical students.

Method: Third-year surgery clerks were randomized to three-second or six-second wait times after questions asked of them during a scripted lecture.

Recognizing clinical faculty's contributions in education.

Objective: A faculty productivity profile system was designed to recognize faculty's contributions to administrative, educational, and research activities. It has long been recognized that clinical faculty receive little recognition or compensation for their efforts in education. Our surgery department previously had in place a recognition program for research achievements, but not for educational contributions.

A critical evaluation of the morbidity and mortality conference.

Background: This study was designed to evaluate the impact of changes made to our morbidity and mortality (M&M) conference.

Methods: A 23-item survey using corresponding Likert-type scales was created. Faculty and residents were asked to anonymously complete the surveys in June 1999.