In vitro model of reconstructed human corneal epithelium for the evaluation of ocular surface desiccation and protection with vitamin A enriched ophthalmic ointment.

The aim of this study was to evaluate the efficacy of a paraffin ointment enriched with vitamin A in the protection against severe desiccation using 2D and 3D corneal epithelial in vitro models. We used immortalized human corneal epithelial cell cultures to evaluate the efficacy of four compounds -a paraffin ointment enriched with vitamin A (vA-PFF) and its vehicle; an aqueous gel containing hydroxypropyl guar (HPG); and an aqueous gel containing sodium carboxymethylcellulose (CMC)- to preserve cell viability in an in vitro model of desiccation. WST-1 and Live/Dead assays were used to study cell viability.

Improved Tool for Predicting Skin Irritation on Reconstructed Human Epidermis Models Based on Electrochemical Impedance Spectroscopy.

The rabbit skin irritation test has been the standard for evaluating the irritation potential of chemicals; however, alternative methods that do not use animal testing are actively encouraged. Reconstructed human epidermis (RhE) models mimic the biochemical and physiological properties of the human epidermis and can be used as an alternative method. On RhE methods, the metabolic activity of RhE models is used to predict skin irritation, with a reduction in metabolic activity indicating a reduced number of viable cells and linking cell death to skin irritation processes.

A Simple, Safe, and Effective Method for Preparing Autologous Bio-Based Fibrin Glue for Ophthalmic Use.

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery.

In-house performance assessment of 3D QobuR-Reconstructed Human Cornea-Like Epithelium (RhCE) for the evaluation of eye hazard.

To replace the Draize eye irritation test (OECD Test Guideline 404), several test methods based on reconstructed cornea-like epithelium (RhCE) have been developed and adopted in the OECD TG 492. The objective of this study was to stablish the experimental procedures and evaluate the performance assessment of QobuR-RhCE, an in-house RhCE model to be used for the evaluation of eye hazard. We define the essential structural, functional and procedural elements of the test method components to help assuring that the proposed test method is based on the same concepts as the validated reference methods.

Polymerizable Skin Hydrogel for Full Thickness Wound Healing.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically.

Impedance-based non-invasive assay for ocular damage prediction on in vitro 3D reconstructed human corneal epithelium.

Reconstructed human cornea-like epithelium (RhCE) holds unprecedented promise for toxicological analyses and the replacement of animal use. However, current standards to evaluate potential ocular irritancy present a major downfall, the need to invasively alter tissue samples to evaluate cell viability. In this study, the applicability of impedance analysis was validated by monitoring the change in cell capacitance during tissue maturation and before and after chemical application using coupled electrodes.

Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial.

Background: Acute graft-versus-host disease (GVHD) is a common and life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT); there is an urgent unmet need for effective therapies. We aimed to evaluate the Janus kinase 1 inhibitor itacitinib versus placebo, both in combination with corticosteroids, for initial treatment of acute GVHD.

Methods: GRAVITAS-301 was an international, double-blind, adaptive (group sequential design) phase 3 study conducted at 129 hospitals and community practices in 19 countries.

Mini Cleanroom for the Manufacture of Advanced Therapy Medicinal Products (ATMP): Bioengineered Corneal Epithelium.

Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B environment). This makes ATMP expensive. Moreover, the production of many of these therapeutic products may also be unprofitable, as in most cases their use is limited to a few patients and to a single batch per manufacturing unit.

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion.

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs.

Reduced graphene oxide membranes in ocular regenerative medicine.

Biological membranes are currently used in Ophthalmology in order to treat different ocular disorders. These membranes have different properties such as cellular biocompatibility and promoting wound healing. Moreover, intrinsic antimicrobial properties could also be desirable because it would allow their use reducing the risk of infections.

[Sex-related differences in patients with ST-segment elevation myocardial infarction].

Objective: To determine the epidemiological characteristics, location of the infarction, type and times of reperfusion, as well as in-hospital adverse events, distributed by sex in patients with ST-segment elevation myocardial infarction (STEMI) in Peru.

Methods: It is a sub-analysis of the PEruvian Registry of ST-segment Elevation Myocardial Infarction (PERSTEMI), which was an observational, prospective and multicenter study about patients over 18 years-old, who were hospitalized for ST-segment elevation myocardial infarction. Epidemiological and clinical characteristics, management and in-hospital adverse events were compared according to sex.

Development of an in-house reconstructed human epidermis model as an alternative method in skin corrosion assessment.

Defining the corrosive properties of chemical products generally involves the use of animal models for human health safety assessment. However, a few alternatives to animal experimentation are currently internationally accepted in order to reduce animal suffering. One of these alternatives makes use of in vitro reconstructed human epidermis (RhE) models and predicts corrosive potential based on the evaluation of cell viability after topical exposure.

QobuR - A new in vitro human corneal epithelial model for preclinical drug screening.

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER.

Silk Fibroin Films for Corneal Endothelial Regeneration: Transplant in a Rabbit Descemet Membrane Endothelial Keratoplasty.

Purpose: Develop a silk fibroin (SF)-based artificial endothelial graft for its use in a rabbit Descemet membrane endothelial keratoplasty (DMEK).

Methods: Human and rabbit artificial corneal endothelial grafts were developed through the culture of human and rabbit corneal endothelial cells (CECs) on SF films. Rabbit artificial SF endothelial grafts were transplanted in a DMEK surgery into a rabbit in vivo model.

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task.

Horn fly larval survival in cattle dung is reduced by endophyte infection of tall fescue pasture.

Background: The potential for using endophytic microorganisms in pest control has increased during the last 40 years. In this study, we investigated the impact of endophyte (Neotyphodium coenophialum) infection of cattle pasture upon the survival of the horn fly, Haematobia irritans, a major agricultural pest affecting livestock in many parts of the world.

Results: In laboratory assays, where cattle dung collected from endophyte-infected (E+) tall fescue cultivar K-31 was used as the oviposition substrate, larval development was significantly reduced compared with development on cattle dung from steers that grazed uninfected (E-) tall fescue.

Keratin-chitosan membranes as scaffold for tissue engineering of human cornea.

Purpose: To study the attachment and growth of human corneal cells on keratin-chitosan membranes. The end goal is to develop a bioengineered cornea based on this material.

Methods: Keratin-chitosan membranes were prepared as previously described by Tanabe et al.

Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation.

Ninety-one children and adolescents 18 years or younger after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory Hodgkin lymphoma (HL) were analyzed. Fifty-one patients received reduced intensity conditioning (RIC); 40 patients received myeloablative conditioning (MAC). Nonrelapse mortality (NRM) at 1 year was 21% (+/- 4%), with comparable results after RIC or MAC.