17 research outputs found
Biocompatibility and functionality of a tissue-engineered living corneal stroma transplanted in the feline eye
PURPOSE. Corneal tissue shortage has become a major concern worldwide, which has
motivated the search for alternative solutions to eye bank human eyes for corneal
transplantation. Minimally invasive lamellar transplantation and tissue engineering may offer
new opportunities for the rehabilitation of diseased corneas. The aim of this study was to
evaluate the biocompatibility and functionality of stromal lamellar grafts tissue-engineered
(TE) in vitro and transplanted in vivo in the cornea of a feline model.
METHODS. The corneal stromas were engineered in culture from corneal stromal cells using
the self-assembly approach, without the addition of exogenous material or scaffold. Eight
healthy animals underwent two intrastromal grafts in one eye and the contralateral eye was
used as a control. Animals were followed with slit-lamp ophthalmic examination, corneal
esthesiometry and optical coherent tomography. Confocal microscopy, immunofluorescence,
histology, and transmission electron microscopy (TEM) were performed at 4 months.
RESULTS. Four months after transplantation, the TE-stromal grafts were transparent, functional,
and well tolerated by the eye. All grafts remained avascular, with no signs of immune
rejection, despite a short course of low-dose topical steroids. Corneal sensitivity returned to
preoperative level and reinnervation of the grafts was confirmed by confocal microscopy and
immunofluorescence. Histology and TEM of the TE-grafts showed a lamellar stromal structure
with regular collagen fibril arrangement.
CONCLUSIONS. These results open the way to an entirely new therapeutic modality. Intracorneal
filling using a biocompatible, transparent, and malleable TE-stroma could be the basis for
multiple types of novel therapeutic options in corneal interventional surgery
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Effect of quiescence on integrin α5ÎČ1 expression in human retinal pigment epithelium
The retinal pigment epithelium (RPE) is a monolayer of polarized epithelial cells located between the photoreceptor outer segments of the neural retina and the choroidal blood supply The interactions between a cell and its ECM are, in part, mediated by a family of cell surface glycoproteins called integrins Integrins are heterodimers consisting of variable αand ÎČsubunits. The different combinations of these subunits determine the receptor specificity for the different ECM molecules The FN integrin α5ÎČ1 also appears to play pathogenic roles in a variety of proliferative diseases. Indeed, changes in α5ÎČ1 expression have been correlated with malignancy of uveal melanoma Integrins have been postulated to play a major role in PV
âThe medications are the decision-makersâŠâ Making reproductive and medication use decisions among female patients with rheumatoid arthritis: a constructivist grounded theory
Objective
To examine how female patients with RA form decisions about having children, pregnancy, and medication use.
Methods
We employed a constructivist grounded theory design and recruited female participants who are 18 years or older, have a rheumatologist-confirmed RA diagnosis, live in Canada, and are able to communicate in English or French. We collected data through semi-structured individual and focus group interviews using telephone or video conferencing technology. Data collection and analysis were iterative, employed theoretical sampling, reflexive journaling, and peer debriefing, and culminated in a theoretical model.
Results
We recruited 21 participants with a mean age of 34 years and median 10 years since RA diagnosis. Overall, 33% had never been pregnant, 57% had previously been pregnant, and 10% were pregnant at the time of interview. Of those who had experienced pregnancy, 64% had at least one pregnancy while diagnosed with RA and of those, 56% used DMARD(s) during a pregnancy. We constructed a patient-centred framework depicting the dynamic relationships between 4 decision-making processesâ(1) using medications, (2) having children, (3) planning pregnancy, and (4) parentingâand the substantial impact of healthcare providers on patientsâ experiences making these decisions. These processes were further influenced by participantsâ intersecting identities and contextual factors, particularly attitudes towards health and medications, disease onset and severity, familial support system, and experiences interacting with the healthcare system.
Conclusion
Our framework provides insight into how patients make reproductive decisions in the context of managing RA and the opportunities for providers to support them at each decision-making process. A patient-centred care approach is suggested to support female patients with RA in making reproductive and medication choices aligning with their individual desires, needs, and values.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCMedicine, Department ofObstetrics and Gynaecology, Department ofRheumatology, Division ofReviewedFacultyResearcherOthe
Mo1297 Mode of Delivery in Inflammatory Bowel Disease Patients: A Population-Based Study
Ulcerative colitis-associated hospitalization costs:a population-based study
BACKGROUND: Hospitalization costs for ulcerative colitis (UC) following the introduction of infliximab have not been evaluated
Wildlife in the line of fire: evaluating the stress physiology of a critically endangered Australian marsupial after bushfire
Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells
Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition. Protein encapsulated in T-cell-bound nanoparticles was released following culture of CTLs with target cells in an antigen dose- and perforin-dependent manner and coincided with target cell lysis. Using this approach, we demonstrate the capacity of HIV-specific CTLs to deliver an immunotherapeutic agent to an anatomical site of viral replication. This strategy provides a novel means to couple drug delivery to the action of therapeutic cells in vivo.Ragon Institute of MGH, MIT and HarvardNational Institutes of Health (U.S.) (IH (AI111860