Dimensionality Matters: Exploiting UV-Photopatterned 2D and Two-Photon-Printed 2.5D Contact Guidance Cues to Control Corneal Fibroblast Behavior and Collagen Deposition.

In the event of disease or injury, restoration of the native organization of cells and extracellular matrix is crucial for regaining tissue functionality. In the cornea, a highly organized collagenous tissue, keratocytes can align along the anisotropy of the physical microenvironment, providing a blueprint for guiding the organization of the collagenous matrix. Inspired by this physiological process, anisotropic contact guidance cues have been employed to steer the alignment of keratocytes as a first step to engineer in vitro cornea-like tissues.

Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures.

Functional tissue repair after injury or disease is governed by the regenerative or fibrotic response by cells within the tissue. In the case of corneal damage, keratocytes are a key cell type that determine the outcome of the remodeling response by either adapting to a fibroblast or myofibroblast phenotype. Although a growing body of literature indicates that geometrical cues in the environment can influence Myo(fibroblast) phenotype, there is a lack of knowledge on whether and how differentiated keratocyte phenotype is affected by the curved tissue geometry in the cornea.

Generation of Multicue Cellular Microenvironments by UV-photopatterning of Three-dimensional Cell Culture Substrates.

The extracellular matrix is an important regulator of cell function. Environmental cues existing in the cellular microenvironment, such as ligand distribution and tissue geometry, have been increasingly shown to play critical roles in governing cell phenotype and behavior. However, these environmental cues and their effects on cells are often studied separately using in vitro platforms that isolate individual cues, a strategy that heavily oversimplifies the complex in vivo situation of multiple cues.

3D Interfacial and Spatiotemporal Regulation of Human Neuroepithelial Organoids.

Neuroepithelial (NE) organoids with dorsal-ventral patterning provide a useful three-dimensional (3D) in vitro model to interrogate neural tube formation during early development of the central nervous system. Understanding the fundamental processes behind the cellular self-organization in NE organoids holds the key to the engineering of organoids with higher, more in vivo-like complexity. However, little is known about the cellular regulation driving the NE development, especially in the presence of interfacial cues from the microenvironment.

Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines.

Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature.

Mechanical Properties of Bioengineered Corneal Stroma.

For the majority of patients with severe corneal injury or disease, corneal transplantation is the only suitable treatment option. Unfortunately, the demand for donor corneas greatly exceeds the availability. To overcome shortage issues, a myriad of bioengineered constructs have been developed as mimetics of the corneal stroma over the last few decades.

CD8 and CD4 T Cell Populations in Human Kidneys.

Background: At border sites, and in internal organs, tissue resident memory T cells (T contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidney tissue.

Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis.

Cystic fibrosis (CF) is caused by mutations in the gene encoding the epithelial chloride channel CF transmembrane conductance regulator (CFTR) protein. The most common mutation is a deletion of three nucleotides leading to the loss of phenylalanine at position 508 (p.Phe508del) in the protein.

TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A Receptor-Mediated Signaling.

TLR-induced signaling potently activates cells of the innate immune system and is subject to regulation at different levels. Inflammatory conditions are associated with increased levels of extracellular adenosine, which can modulate TLR-induced production of cytokines through adenosine receptor-mediated signaling. There are four adenosine receptor subtypes that induce different signaling cascades.

Training Can Increase Students' Choices for Written Solution Strategies and Performance in Solving Multi-Digit Division Problems.

Making adaptive choices between solution strategies is a central element of contemporary mathematics education. However, previous studies signal that students make suboptimal choices between mental and written strategies to solve division problems. In particular, some students of a lower math ability level appear inclined to use mental strategies that lead to lower performance.

Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases.

Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques.

Statins amplify TLR-induced responses in microglia via inhibition of cholesterol biosynthesis.

Statins inhibit the endogenous intracellular mevalonate pathway and exposure to statins affects innate and adaptive immune responses. Different statins are currently under evaluation as (co)therapy in neuro-inflammatory diseases like multiple sclerosis. However, there are important discrepancies in the reported effects of statins on innate immune responses in different cell types.

Solution Strategies and Achievement in Dutch Complex Arithmetic: Latent Variable Modeling of Change.

In the Netherlands, national assessments at the end of primary school (Grade 6) show a decline of achievement on problems of complex or written arithmetic over the last two decades. The present study aims at contributing to an explanation of the large achievement decrease on complex division, by investigating the strategies students used in solving the division problems in the two most recent assessments carried out in 1997 and in 2004. The students' strategies were classified into four categories.

How to Measure and Explain Achievement Change in Large-Scale Assessments: A Rejoinder.

In this rejoinder, we discuss substantive and methodological validity issues of large-scale assessments of trends in student achievement, commenting on the discussion paper by Van den Heuvel-Panhuizen, Robitzsch, Treffers, and Köller (2009). We focus on methodological challenges in deciding what to measure, how to measure it, and how to foster stability. Next, we discuss what to do with trends that are found.

Differential expression of adenosine A3 receptors controls adenosine A2A receptor-mediated inhibition of TLR responses in microglia.

Microglia activation is a prominent feature in many neuroinflammatory disorders. Unrestrained activation can generate a chronic inflammatory environment that might lead to neurodegeneration and autoimmunity. Extracellular adenosine modulates cellular activation through adenosine receptor (ADORA)-mediated signaling.

Terminology modeling for an enterprise laboratory orders catalog.

Laboratory test orders are used in a variety of clinical information systems at Partners HealthCare. At present, each site at Partners manages its own set of laboratory orders with locally defined codes. Our current plan is to implement an enterprise catalog, where laboratory test orders are mapped to reference terminologies and codes from different sites are mapped to each other.

Challenges in creating an enterprise clinical rules service.

At Partners HealthCare, we are engaged in developing and implementing a strategy for our Clinical Decision Support systems and services that will enable CDS to be made available across the enterprise, allow development of consistent standards of care regardless of where a patient presents, and permit migration of current CDS functions to a supportable and scalable model. We report here on progress toward these goals, describe steps taken and proposed, and consider remaining challenges.

Enhancing clinical problem lists through data mining and natural language processing.

The availability of timely, accurate, comprehensive, and coded clinical problem lists is essential for supporting a range of healthcare activities. Evidence and experience suggest, however, that problem lists are frequently out-of-date, sometimes omit clinically important problems, and contain uncoded entries. Here, we describe a study being performed at Partners HealthCare System to explore automated techniques for enhancing existing problem lists.

Differentiation of primary adult microglia alters their response to TLR8-mediated activation but not their capacity as APC.

Activated microglia are found in a variety of neuroinflammatory disorders where they have attributed roles as effector as well as antigen-presenting cells (APC). Critical determinants for the multifaceted role of microglia are the differentiation potential of microglia and their mode of activation. In this study, we have investigated the effects of M-CSF and GM-CSF-mediated differentiation of adult primate microglia on their cellular phenotype, antigen presentation, and phagocytic function as well as on Toll-like receptor (TLR)-mediated responses.

Design and implementation of an application and associated services to support interdisciplinary medication reconciliation efforts at an integrated healthcare delivery network.

Confusion about patients' medication regimens during the hospital admission and discharge process accounts for many preventable and serious medication errors. Many organizations have begun to redesign their clinical processes to address this patient safety concern. Partners HealthCare, an integrated delivery network in Boston, Massachusetts, has answered this interdisciplinary challenge by leveraging its multiple outpatient electronic medical records (EMR) and inpatient computerized provider order entry (CPOE) systems to facilitate the process of medication reconciliation.

Designing an electronic medication reconciliation system.

Unintended medication discrepancies at hospital admission and discharge potentially harm patients. Explicit medication reconciliation (MR) can prevent unintended discrepancies among care settings and is mandated by JCAHO for 2005. Enterprise-wide, we are linking pre-admission and discharge medication lists in our outpatient electronic health records (EHR) with our inpatient order entry applications (OE) - currently not interoperable - to support MR and inform the development of comprehensive MR among hospitalized patients.

Personality disorders in the elderly compared to four younger age groups: a cross-sectional study of community residents and mental health patients.

The notion is expressed in the DSM-IV that some personality disorders (PDs) tend to remit with age whereas other types do not. This notion is supported by the literature and the study reported here. Studies published between 1951 and 2000 show that (1) in old age, PDs are prevalent both in normal subjects and to a greater extent in the mentally ill; (2) the evidence for general age-relatedness of PDs is scarce and contradictory; (3) there is evidence for specific age-relatedness of PDs in old age.

Goal orientation, perceived task outcome and task demands in mathematics tasks: effects on students' attitude in actual task settings.

Background: In earlier studies, it has been found that students' domain-specific cognitions and personal learning goals (goal orientation) influence task-specific appraisals of actual learning tasks. The relations between domain-specific and task-specific variables have been specified in the model of adaptive learning. In this study, additional influences, i.