Transcription-replication interactions reveal bacterial genome regulation.

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription-replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics.

Magnetically induced stiffening for soft robotics.

Soft robots are well-suited for human-centric applications, but the compliance that gives soft robots this advantage must also be paired with adequate stiffness modulation such that soft robots can achieve more rigidity when needed. For this reason, variable stiffening mechanisms are often a necessary component of soft robot design. Many techniques have been explored to introduce variable stiffness structures into soft robots, such as pneumatically-controlled jamming and thermally-controlled phase change materials. Despite fast response time, jamming methods often require a bulkier pneumatic pressure line which limits portability; and while portable via electronic control, thermally-induced methods require compatibility with high temperatures and often suffer from slow response time. In this paper, we present a magnetically-controlled stiffening approach that combines jamming-based stiffening principles with magnetorheological fluid to create a hybrid mechanical and materials approach. In doing so, we combine the advantages of fast response time from pneumatically-based jamming with the portability of thermally-induced phase change methods. We explore the influence of magnetic field strength on the stiffening of our magnetorheological jamming beam samples in two ways: by exploiting the increase in yield stress of magnetorheological fluid, and by additionally using the clamping force between permanent magnets to further stiffen the samples via a clutch effect. We introduce an analytical model to predict the stiffness of our samples as a function of the magnetic field. Finally, we demonstrate electronic control of the stiffness using electropermanent magnets. In this way, we present an important step towards a new electronically-driven stiffening mechanism for soft robots that interact safely in close contact with humans, such as in wearable devices.

A Collapsible Soft Actuator Facilitates Performance in Constrained Environments.

Complex environments, such as those found in surgical and search-and-rescue applications, require soft devices to adapt to minimal space conditions without sacrificing the ability to complete dexterous tasks. Stacked Balloon Actuators (SBAs) are capable of large deformations despite folding nearly flat when deflated, making them ideal candidates for such applications. This paper presents the design, fabrication, modeling, and characterization of monolithic, inflatable, soft SBAs. Modeling is presented using analytical principles based on geometry, and then using conventional and real-time finite element methods. Both one and three degree-of-freedom (DoF) SBAs are fully characterized with regards to stroke, force, and workspace. Finally, three representative demonstrations show the SBA's small-aperture navigation, bracing, and workspace-enhancing capabilities.

Patient satisfaction with a pharmacist-led best possible medication discharge plan via tele-robot in a remote and rural community hospital.

INTRODUCTION: Medication reconciliation (MedRec) reduces the risk of preventable medication-related adverse events (ADEs). A best possible medication discharge plan (BPMDP) is a revised list of medications a patient will take when discharged from hospital; a pharmacist review ensures accuracy. For many hospitals, on-site pharmacists are non-existent. Extension of a visual presence via a mobile robotic platform with real-time audiovisual communication by pharmacists to conduct MedRec remains unstudied. This study explored patient perceptions of a pharmacist-led BPMDP using a telepresence robot. Time requirements, unintentional discharge medication discrepancies (UMD), programme inefficiencies/barriers and facilitators involved in pharmacist review of the discharge medication list and patient interviews were also described. METHODS: This prospective cohort study enrolled adult patients admitted to a 12-bed community hospital at high risk of an ADE. Remote pharmacists reviewed the discharge prescription list, identified/resolved UMDs, and interviewed/counselled patients using a telepresence robot. Thereafter, patients completed an anonymous satisfaction questionnaire. Prescriber discharge UMDs were classified, and barriers/inefficiencies and facilitators were documented. RESULTS: Nine patients completed an interview, with a 75% interview agreement rate. All patients were comfortable with the robot and 76% felt their care was better. With a median of 11 discharge medications/patient, the UMD rate was 78%; 71% had omitted medications, 43% involved a cardiovascular medication, 88% were due to a hospital system cause, and 43% were specifically due to an inaccurate best possible admission medication history. Median times for interview preparation, interview and UMD/drug therapy problem resolution were 45, 15 and 10 min, respectively. CONCLUSION: Using a telepresence robot to provide pharmacist-led BPMDPs is acceptable to patients and an innovative, effective solution to identify/resolve UMDs.

Résumé Introduction: Le bilan comparatif des médicaments (BCM) réduit le risque d'événements indésirables liés aux médicaments pouvant être évités. Le meilleur schéma thérapeutique possible (MSTP) désigne une liste révisée de la médication qu'un patient devra prendre au congé de l'hôpital; l'examen du pharmacien en assure l'exactitude. Malheureusement, de nombreux hôpitaux n'ont pas de pharmacien sur place. Aucune étude n'a porté sur l'expansion d'une présence visuelle par plateforme robotique mobile avec communication audiovisuelle en temps réel des pharmaciens pour réaliser le BCM. Cette étude a porté sur la perception des patients à l'égard d'un MSTP dirigé par un pharmacien par l'entremise d'un robot de téléprésence. L'étude s'est aussi penchée sur le temps nécessaire, les erreurs liées aux médicaments, les inefficacités ou obstacles du programme et les modérateurs qui sont intervenus dans le BCM et les entrevues auprès des patients. Méthodes: Cette étude de cohorte prospective a inscrit des adultes à risque élevé d'événement indésirable lié aux médicaments ayant été admis dans un hôpital communautaire de 12 lits. Des pharmaciens ont révisé à distance la liste des ordonnances au congé, relevé et résolu les erreurs liées aux médicaments et ont interviewé/renseigné les patients à l'aide d'un robot de téléprésence. Les patients ont ensuite répondu anonymement à un questionnaire de satisfaction. Les erreurs liées aux médicaments ont été classifiées, et les obstacles ou inefficacités et les modérateurs ont été identifiés. Résultats: Neuf patients SE sont soumis à l'entrevue, avec un taux d'acceptation de l'entrevue de 75%. Tous les patients étaient à l'aise avec le robot, et 76% étaient d'avis qu'ils avaient reçu de meilleurs soins. Avec une médiane de 11 médicaments/patient au congé, le taux d'erreurs liées aux médicaments était de 78%; 71% avaient oublié des médicaments, 43% touchaient un médicament cardiovasculaire, 88% étaient causées par le système de l'hôpital et 43% étaient causées précisément par un MSTP inexact. Les délais médians pour la préparation de l'entrevue, l'entrevue, et la résolution des erreurs liées aux médicaments/problèmes de pharmacothérapie étaient respectivement de 45, 15 et 10 min. Conclusion: Un robot de téléprésence pour réaliser le MSTP dirigé par un pharmacien est acceptable pour les patients et est une solution innovante et efficace pour relever et résoudre les erreurs liées aux médicaments. Mots-clés: Rural, pharmacien, bilan comparatif des médicaments, télémédecine, hôpital, robot.

Hardware Methods for Onboard Control of Fluidically Actuated Soft Robots.

Soft robots provide significant advantages over their rigid counterparts. These compliant, dexterous devices can navigate delicate environments with ease without damage to themselves or their surroundings. With many degrees of freedom, a single soft robotic actuator can achieve configurations that would be very challenging to obtain when using a rigid linkage. Because of these qualities, soft robots are well suited for human interaction. While there are many types of soft robot actuation, the most common type is fluidic actuation, where a pressurized fluid is used to inflate the device, causing bending or some other deformation. This affords advantages with regards to size, ease of manufacturing, and power delivery, but can pose issues when it comes to controlling the robot. Any device capable of complex tasks such as navigation requires multiple actuators working together. Traditionally, these have each required their own mechanism outside of the robot to control the pressure within. Beyond the limitations on autonomy that such a benchtop controller induces, the tether of tubing connecting the robot to its controller can increase stiffness, reduce reaction speed, and hinder miniaturization. Recently, a variety of techniques have been used to integrate control hardware into soft fluidic robots. These methods are varied and draw from disciplines including microfluidics, digital logic, and material science. In this review paper, we discuss the state of the art of onboard control hardware for soft fluidic robots with an emphasis on novel valve designs, including an overview of the prevailing techniques, how they differ, and how they compare to each other. We also define metrics to guide our comparison and discussion. Since the uses for soft robots can be so varied, the control system for one robot may very likely be inappropriate for use in another. We therefore wish to give an appreciation for the breadth of options available to soft roboticists today.

Pharmacy Distribution, Clinical, and Management Services: A Survey of Small Hospitals in Canada Supported by Telepharmacy Services.

BACKGROUND: The Canadian Society of Hospital Pharmacists' Hospital Pharmacy in Canada Report presents data from pharmacy departments that service hospitals with at least 50 acute care beds. This report provides valuable data on pharmacy distribution, clinical, and management services in relation to hospital size, type, and geographic region. Pharmacy and hospital leadership use these extensive data in identifying baseline, benchmarking current, and planning enhanced pharmacy services. However, for most of Canada's small hospitals, such data remain unknown, and leadership remains uninformed. OBJECTIVE: To gather and analyze data about current pharmacy distribution, clinical, and management services in hospitals with fewer than 50 acute care beds receiving third-party remote pharmacy (telepharmacy) services. METHODS: In April 2019, pharmacy administrators of hospitals in Ontario, Quebec, and Saskatchewan that had fewer than 50 acute care beds and were using third-party telepharmacy services were invited to complete a comprehensive survey addressing concepts similar to those in the Hospital Pharmacy in Canada Survey. The following data on clinical pharmacy practice were collected: models of care, assignments to patient care programs, pharmacists' activities, performance indicators, and professional evaluation. The description of pharmacy distribution services comprised type of system, technology, location, hours of operation, method of medication order entry and verification, and medication administration records. Details on facilities' parenteral admixture infrastructure, policy for and provision of sterile compounding, and pharmacy department human resources, including composition and staffing ratios, were also collected. RESULTS: Of the 27 hospitals in Ontario, Quebec, and Saskatchewan that were invited to participate, 24 (89%) completed the survey. The median facility size was 19 acute care beds. CONCLUSIONS: Previously unavailable in Canada, these quantitative data from small hospitals supported by telepharmacy services provide facts about pharmacy distribution, clinical, and management services to inform hospital and pharmacy leaders. Creation of a survey unique to small hospitals, whether or not they use telepharmacy services, could provide a valuable resource to assist in the benchmarking, planning, and enhancement of pharmacy services in remote and rural communities.

CONTEXTE: Le Rapport sur les pharmacies hospitalières canadiennes de la Société canadienne des pharmaciens d'hôpitaux expose les données provenant des services de pharmacie qui appuient les hôpitaux comptant au moins 50 lits de soins aigus. Il offre de précieuses données sur les services de distribution des médicaments, les services cliniques et de gestion en relation avec la taille, le type et la région géographique des hôpitaux. Les équipes de direction des pharmacies et des hôpitaux utilisent ces données exhaustives pour déterminer une base de référence, évaluer les services de pharmacie actuels et planifier l'amélioration des services. Cependant, la plupart des petits hôpitaux du Canada ne disposent pas de ce type de données, et les équipes de direction n'en sont pas informées. OBJECTIF: Réunir et analyser des données sur la distribution de médicaments, les services cliniques et la gestion des services pharmaceutiques actuels dans les hôpitaux comptant moins de 50 lits de soins aigus, qui reçoivent des services de pharmacie à distance (services de télépharmacie) fournis par des tiers. MÉTHODE: En avril 2019, les administrateurs de pharmacie d'hôpitaux en Ontario, au Québec et en Saskatchewan remplissant ces critères ont été invités à répondre à une enquête exhaustive abordant des concepts similaires à ceux de Sondage sur les pharmacies hospitalières canadiennes. Les données suivantes sur la pratique de la pharmacie clinique ont été recueillies: modèles de soins, affectation des pharmaciens à des programmes particuliers de soins des patients, activités des pharmaciens, indicateurs de performance et évaluation professionnelle. La description des systèmes de distribution des médicaments par les pharmacies comprenait: le type de système, la technologie, le lieu, les heures de service, le mode de saisie et de vérification des ordonnances de médicaments ainsi que les dossiers d'administration. Les détails concernant l'infrastructure pour l'administration de solutions parentérales, la politique relative aux composés stériles et à leur distribution ainsi que les ressources humaines des services de pharmacie, y compris la composition et les ratios en personnel, ont également été recueillis. RÉSULTATS: Sur les 27 hôpitaux en Ontario, au Québec et en Saskatchewan invités à participer à l'enquête, 24 (89 %) y ont répondu. La taille moyenne des installations était de 19 lits de soins aigus. CONCLUSIONS: Autrefois indisponibles au Canada, ces données quantitatives provenant de petits hôpitaux soutenus par des services de télépharmacie livrent des faits concernant le système de distribution des médicaments au sein des pharmacies, les services cliniques et de gestion, qui permettent de guider les cadres des hôpitaux et de la pharmacie. La création d'une enquête unique destinée aux petits hôpitaux, utilisant ou non des services de télépharmacie, pourrait constituer une précieuse ressource pour aider à évaluer, à planifier et à améliorer les services pharmaceutiques dans les communautés rurales et éloignées.

Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma.

PURPOSE: Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. METHODS: A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. RESULTS: A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. CONCLUSIONS: Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.

Effect of Palliative Care Curriculum on Serious Illness Conversation Preparedness.

BACKGROUND: A shortage of palliative pare (PC) specialists underscores the necessity that all clinicians feel comfortable with serious illness conversations (SICs). OBJECTIVE: To assess the effect of an intensive PC curriculum with multiple teaching modalities on Internal Medicine residents' confidence with SICs and advance care planning documentation. METHODS: Twelve PC modules consisting of didactic lectures, role-playing, and online interactive modules were integrated as continuing education during academic year 2018-2019. Surveys were administered precurriculum and at 3 and 6 months postcurriculum to measure the primary outcome of increasing resident preparedness for SICs. A retrospective chart review was used to analyze secondary outcomes of advance care planning documentation for patients cared for by residents exposed to the curriculum versus residents from the previous year who received monthly didactic PC lectures. RESULTS: Postintervention surveys demonstrated statistically significant improvement in resident confidence. An increase in patient code status confirmation rates (odds ratio, 1.81; 95% confidence interval, 1.12-2.94; P = 0.02) and a decrease in PC consultation (odds ratio, 0.56; 95% confidence interval, 0.33-0.97; P = 0.04) was observed when compared with the previous year. CONCLUSION: Among residents, the incorporation of an intensive PC curriculum that uses multiple teaching modalities improves confidence in SICs, which we believe is integral to the practice of goal-concordant patient care.

Physical and chemical model of ion stability and movement within the dynamic and voltage-gated STM tip-surface tunneling junction.

The interaction and mobility of ions in complex systems are fundamental to processes throughout chemistry, biology, and physics. However, nanoscale characterization of ion stability and migration remains poorly understood. Here, we examine ion movements to and from physisorbed molecular receptors at solution-graphite interfaces by developing a theoretical model alongside experimental scanning tunneling microscopy (STM) results. The model includes van der Waals forces and electrostatic interactions originating from the surface, tip, and physisorbed receptors, as well as a tip-surface electric field arising from the STM bias voltage (Vb). Our model reveals how both the electric field and tip-surface distance, dtip, can influence anion stability at the receptor binding sites on the surface or at the STM tip, as well as the size of the barrier for anion transitions between those locations. These predictions agree well with prior and new STM results from the interactions of anions with aryl-triazole receptors that order into functional monolayers on graphite. Scanning produces clear resolution at large magnitude negative surface biases (-0.8 V) while resolution degrades at small negative surface biases (-0.4 V). The loss in resolution arises from frequent tip retractions assigned to anion migration within the tip-surface tunneling region. This experimental evidence in combination with support from the model demonstrates a local voltage gating of anions with the STM tip inside physisorbed receptors. This generalized model and experimental evidence may help to provide a basis to understand the nanoscale details of related chemical transformations and their underlying thermodynamic and kinetic preferences.

Focal adhesion kinase family is involved in matrix contraction by transdifferentiated Müller cells.

Transdifferentiated Müller cells that adopt a fibroblastic/myofibroblastic phenotype have been identified in epiretinal membranes (ERMs) in several ocular disorders, and have been implicated to play a role in the formation and/or the contraction of ERMs. We have previously demonstrated that dasatinib, a dual inhibitor of Src-family kinases and Abl kinase, can prevent matrix contraction by transdifferentiated Müller cells. In this study, we examined molecules involved in matrix contraction downstream of primary dasatinib targets. Tyrosine phosphorylation of focal adhesion kinase (FAK) family members FAK and PYK2 was significantly reduced by dasatinib, and select inhibitors for these kinases PF431396, which inhibits both FAK and PYK2, and PF573228, which only inhibits FAK and not PYK2, significantly reduced matrix contraction by transdifferentiated Müller cells. Dasatinib and PF431396 significantly reduced phosphorylation of Hic-5, a protein implicated to play a role in focal adhesions and cell signaling. Our data shows that FAK family members are involved in matrix contraction by transdifferentiated Müller cells, and also implicates that Hic-5 is situated downstream of the FAK family within the signaling pathway.

Dasatinib affects focal adhesion and myosin regulation to inhibit matrix contraction by Müller cells.

Epiretinal membrane (ERM) contraction is associated with a variety of ocular diseases that cause macular dysfunction. Trans-differentiated Müller cells have been identified in ERMs, and have been implicated to be involved in the contractile process. In this study, we tested the effect of dasatinib, an FDA-approved tyrosine kinase inhibitor, on matrix contraction caused by Müller cells, and examined molecular mechanism of action. Type I collagen matrix contraction assays were used to examine the effect of drugs on matrix contraction by trans-differentiated Müller cells. Fluophore-conjugated phalloidin was used for the detection of actin cytoskeleton, and Western-blot analyses were carried out to examine protein expression and phosphorylation status. Dasatinib inhibited collagen matrix contraction by trans-differentiated Müller cells that was associated with decreased cell spreading and reduction of actomyosin stress fibers. Concomitantly, dasatinib-treated Müller cells had reduced phosphorylation of Src family kinase, paxillin, as well as myosin II light chain. Specific inhibitors of Rho/ROCK and myosin II confirmed the critical role played by this pathway in Müller cell contraction. Our data demonstrate that dasatinib significantly reduced matrix contraction by Müller cells via inhibition of focal adhesion, as well as actomyosin contraction.

Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles.

Cooperative binding of ion pairs to receptors is crucial for the manipulation of salts, but a comprehensive understanding of cooperativity has been elusive. To this end, we combine experiment and theory to quantify ion-pair binding and to separate allostery from electrostatics to understand their relative contributions. We designed aryl-triazole-ether macrocycles (MC) to be semiflexible, which allows ion pairs (NaX; X = anion) to make contact, and to be monocyclic to simplify analyses. A multiequilibrium model allows us to quantify, for the first time, the experimental cooperativity, α, for the equilibrium MC·Na(+) + MC·X(-) ⇌ MC·NaX + MC, which is associated with contact ion-pair binding of NaI (α = 1300, ΔGα = -18 kJ mol(-1)) and NaClO4 (α = 400, ΔGα = -15 kJ mol(-1)) in 4:1 dichloromethane-acetonitrile. We used accurate energies from density functional theory to deconvolute how the electrostatic effects and the allosteric changes in receptor geometry individually contribute to cooperativity. Computations, using a continuum solvation model (dichloromethane), show that allostery contributes ∼30% to overall positive cooperativity. The calculated trend of electrostatic cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to experimental observations (NaI > NaClO4). We show that intrinsic ionic size, which dictates charge separation distance in contact ion pairs, controls electrostatic cooperativity. This finding supports the design principle that semiflexible receptors can facilitate optimal electrostatic cooperativity. While Coulomb's law predicts the size-dependent trend, it overestimates electrostatic cooperativity; we suggest that binding of the individual anion and cation to their respective binding sites dilutes their effective charge. This comprehensive understanding is critical for rational designs of ion-pair receptors for the manipulation of salts.

Living on the edge: Tuning supramolecular interactions to design two-dimensional organic crystals near the boundary of two stable structural phases.

One of the benefits of supramolecular assemblies that form at dynamic interfaces is the opportunity to develop condensed phase systems that respond to environmental stimuli. A prerequisite of this responsive behavior is that the supramolecular system be designed to sit very near the stability of two or more crystal structures. We have created such a bi-phasic system with aryl-triazole oligomers by investigating how phase morphology is controlled by the interplay between interactions that involve the oligomer's dipolar cores (Δµ = 3.5 debye), van der Waals contacts of their pendant alkyl chains (C4-C18), and close-contact hydrogen bonding. Scanning tunneling microscopy experiments conducted at the solution-graphite interface allow sub-molecular resolution of the ordered monolayers to unambiguously determine the packing and structure of two principle phases, α and ß. The system is balanced very near the edge of phase stability, evidenced by co-existent phases present over short time frames and by the changes in preference between the two 2D supramolecular assemblies that occur with small modifications to the molecular structure. We demonstrate that the bi-phasic behavior can be understood as a balance between electrostatic interactions and van der Waals contacts, two variables within a larger parameter space, allowing synthetic design to move this solution-surface system across the stability boundary of different condensed-phase structures. These findings are a foundation for the development of environmentally responsive 2D supramolecular arrays.

Selective anion-induced crystal switching and binding in surface monolayers modulated by electric fields from scanning probes.

Anion-selective (Br(-) and I(-)) and voltage-driven crystal switching between two differently packed phases (α ⇆ ß) was observed in 2D crystalline monolayers of aryl-triazole receptors ordered at solution-graphite interfaces. Addition of Br(-) and I(-) was found to stimulate the α → ß phase transformation and to produce ion binding to the ß phase assembly, while Cl(-) and BF4(-) addition retained the α phase. Unlike all other surface assemblies of either charged molecules or ion-templated 2D crystallization of metal-ligand or receptor-based adsorbates, the polarity of the electric field between the localized scanning tip and the graphite substrate was found to correlate with phase switching: ß â†’ α is driven at -1.5 V, while α → ß occurs at +1.1 V. Ion-pairing between the countercations and the guest anions was also observed. These observations are supported by control studies including variation of anion species, relative anion concentration, surface temperature, tip voltage, and scanning time.

Quantifying chloride binding and salt extraction with poly(methyl methacrylate) copolymers bearing aryl-triazoles as anion receptor side chains.

Copolymers of methyl methacrylate and aryl-triazole based anion receptors were quantitatively analyzed. Transfer of structural features (1 : 1 and 2 : 1 complexes) and Cl(-) affinities from the parent receptors was demonstrated. Cl(-)-induced cross-linking changed the polymer's hydrodynamic radius. Extraction of tetrapropylammonium Cl(-) from water to dichloromethane was enhanced over PMMA.

Anion-induced dimerization of 5-fold symmetric cyanostars in 3D crystalline solids and 2D self-assembled crystals.

Anions stabilize stacking of C5-symmetric macrocycles, called cyanostars, into dimers in solution and herein we demonstrate this stacking in solid-state crystals. We further show that this guest binding can be applied as a route to bilayer growth at the solution-graphite interface.

Role of retinal pigment epithelial cell ß-catenin signaling in experimental proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is caused by the contraction of fibrotic membranes on the epiretinal surface of the neurosensory retina, resulting in a traction retinal detachment and loss of visual acuity. Retinal pigment epithelial (RPE) cells play an important role in formation of such fibrotic, contractile membranes. We investigated the role of Wnt/ß-catenin signaling, a pathway implicated in several fibrotic diseases, in RPE cells in proliferative vitreoretinopathy. In vitro culture of swine RPE sheets resulted in nuclear translocation of ß-catenin in dedifferentiated RPE cells. FH535, a specific inhibitor of ß-catenin signaling, reduced the outgrowth of cultured RPE sheets and prevented dedifferentiated RPE cell proliferation and migration. It also inhibited formation of contractile membranes by dedifferentiated RPE cells on collagen I matrices. Expression and function of the ß-catenin signaling target connexin-43 were down-regulated by FH535, and functional blockade of connexins with carbenoxolone also prevented the in vitro formation of fibrotic, contractile membranes. Intravitreal injection of FH535 in swine also inhibited formation of dense, contractile membranes on the epiretinal surface and prevented development of traction retinal detachment. These findings demonstrate that ß-catenin signaling is involved in formation of contractile membranes by dedifferentiated RPE cells and suggest that adjunctive treatment targeting this pathway could be useful in preventing proliferative vitreoretinopathy.

Inhibition of PVR with a tyrosine kinase inhibitor, dasatinib, in the swine.

PURPOSE: We tested the efficacy of dasatinib, a Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor, to prevent proliferative vitreoretinopathy (PVR). METHODS: The effect of dasatinib on RPE sheet growth was determined by measuring enlargement of cultured RPE sheets in the presence or absence of dasatinib. Epithelial-mesenchymal transition (EMT) of RPE cells was assessed by expression of S100A4. A scratch wound assay, cell number count, and type I collagen contraction assay were used to examine the effect of dasatinib on migration, proliferation, and extracellular matrix (ECM) contraction, respectively. Our swine model of experimental PVR with green fluorescent protein-positive (GFP+) RPE cells was used to assess the efficacy of dasatinib in preventing traction retinal detachment (TRD) caused by PVR. Full-field electroretinography and histologic examination were used to determine the retinal toxicity of dasatinib. RESULTS: Dasatinib prevented RPE sheet growth, cell migration, proliferation, EMT, and ECM contraction in a concentration-dependent manner. 0.1 µM dasatinib inhibited nearly 80% of vitreous fluid-stimulated collagen gel contraction. Dasatinib also prevented TRD caused by PVR in vivo. Only 1/11 eyes had a TRD in the presence of dasatinib, while all 11 controls eyes had a TRD. Dasatinib did not cause any detectable toxicity of the retina. CONCLUSIONS: Dasatinib significantly inhibited PVR-related RPE changes in vitro and prevented TRD in an experimental PVR model in the swine without any detectable toxicity. Our data suggested that dasatinib may be effective in the prevention of PVR.

Storytellers as partners in developing a genetics education resource for health professionals.

Advances in genetics are bringing unprecedented opportunities for understanding health and disease, developing new therapies and changes in healthcare practice. Many nurses and midwives lack competence and confidence in integrating genetics into professional practice. One approach to enhance understanding of genetics is to simulate clinical exposure through storytelling. Stories are acknowledged as a powerful learning tool, being understandable and memorable, stimulating critical thinking, and linking theory to practice. Telling Stories, Understanding Real Life Genetics is a freely accessible website that sets people's stories within an education framework. The links between the stories and professional practice are made explicit and additional features support learning and teaching. Care of the storytellers within an ethical framework is of paramount importance. Storytellers are viewed as partners in the project. The challenges encountered include preserving the authentic voice and dignity of the storyteller. Project team members have also experienced 'professional shame' when negative experiences have been recounted, and the stories have had an impact on the team. The experience of working with storytellers has been positive. The storytellers want to be heard so that others will benefit from their stories. They serve as a reminder of why this work is important.