A Novel Insight into Keratoconus: Mechanical Fatigue of the Cornea

An integrated model for keratectasia risk assessment has received much attention over many years. The objective of this article is to propose a more complete, conceptual model by which high risk individuals can be screened, even with no topographic irregularity or corneal thinning. In this model, corneal ectasia results from the fatigue effect of cyclic shear stress and tensile stress, caused by eye rubbing and fluctuating intraocular pressure (IOP), respectively, on corneal microstructures. The model clarifies the importance of the magnitude of shearing force applied by eye rubbing, the amplitude of IOP fluctuations, the frequency of eye rubbing and IOP fluctuations, the geometry of the cornea, the temperature of the cornea, and the effects of oxidative stress on the cornea in keratectasia development. Therefore, preoperative screening strategies based on these concepts can be designed to assess the risk of keratectasia at an early stage, and select the best candidates who can benefit from keratorefractive surgeries

A Novel Insight into Keratoconus: Mechanical Fatigue of the Cornea

An integrated model for keratectasia risk assessment has received much attention over many years. The objective of this article is to propose a more complete, conceptual model by which high risk individuals can be screened, even with no topographic irregularity or corneal thinning. In this model, corneal ectasia results from the fatigue effect of cyclic shear stress and tensile stress, caused by eye rubbing and fluctuating intraocular pressure (IOP), respectively, on corneal microstructures. The model clarifies the importance of the magnitude of shearing force applied by eye rubbing, the amplitude of IOP fluctuations, the frequency of eye rubbing and IOP fluctuations, the geometry of the cornea, the temperature of the cornea, and the effects of oxidative stress on the cornea in keratectasia development. Therefore, preoperative screening strategies based on these concepts can be designed to assess the risk of keratectasia at an early stage, and select the best candidates who can benefit from keratorefractive surgeries

Preventive maintenance effect on the aggregate production planning model with tow-phase production systems: modeling and solution methods

This paper develops two mixed integer linear programming (MILP) models for an integrated aggregate production planning (APP) system with return products, breakdowns and preventive maintenance (PM). The goal is to minimize the cost of production with regard to PM costs, breakdowns, the number of laborers and inventory levels and downtimes. Due to NP-hard class of APP, we implement a harmony search (HS) algorithm and vibration damping optimization (VDO) algorithm for solving these models. Next, the Taguchi method is conducted to calibrate the parameter of the metaheuristics and select the optimal levels of factors influencing the algorithm’s performance. Computational results tested on a set of randomly generated instances show the efficiency of the vibration damping optimization algorithm against the harmony search algorithm. We find VDO algorithm to obtain best quality solutions for APP with breakdowns and PM, which could be efficient for large scale problems. Finally, the computational results show that the objective function values obtained by APP with PM are better than APP with breakdown results

Reprogrammed Cell‐based Therapy for Liver Disease: From Lab to Clinic

A large number of patients are affected by liver dysfunction worldwide. Liver transplantation is the only efficient treatment in a variety of enduring liver disorders including inherent and end-stage liver diseases. The generation of human functional hepatocytes in high quantities for liver cell therapy is an important goal for ongoing therapies in regenerative medicine. Reprogrammed cells are considered as a promising and unlimited source of hepatocytes, mainly because of their expected lack of immunogenicity and minimized ethical concerns in clinical applications. Despite gained advances in the reprogramming of somatic cells to functional hepatocytes in vitro, production of primary adult hepatocytes that can proliferate in vivo still remains inaccessible. As part of efforts toward translation of cell reprogramming science into clinical practice, more careful cell selection strategies should be integrated into improvement of dedifferentiation and redifferentiation protocols, especially in precision medicine where gene correction is needed. Furthermore, advances in cellular reprogramming highlight the need for developing and evaluating novel standards addressing clinical research interests in this field

Učinci adheziva osjetljivih na tlak i kemijskih promotora na permeaciju fentanila kroz kožu štakora

Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of the PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that permeation rate or steady state flux (Jss) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak® 2054 and Duro-Tak® 2516 showed the highest Jss of 1.95 μg cm-2 h-1 and the lowest Jss of 1.43 μg cm-2 h-1, respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and lowest enhancement ratio (ER) on the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in adhesion property of PSA as measured by 180° peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that PG as a CPE and cosolvent in 10% m/m with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.Pripravljeni su transdermalni adhezivni flasteri fentanila (DIAPs) koristeći različite adhezive osjetljivih na tlak (PSAs) i kemijske promotore permeabilnosti (CPEs). Njihovi učinci na permeabilnost fentanila evaluirani su pomoću modificirane Franzove difuzijske ćelije s membranom od kože s abdomena štakora. Brzina permeabilnosti (Jss) ovisi o viskoznosti i vrsti akrilnih adheziva i o vrsti promotora. Najveća vrijednost Jss = 1,95 μg cm-2 h-1 postignuta je s Duro-Tak® 2054, a najmanja (Jss = 1,43 μg cm-2 h-1) s Duro-Tak® 2516. Među različitim promotorima propilen glikol i polietilen glikol 400 pokazali su najveći (1,61) i najmanji (1,18) omjer poboljšanja (ER) permeabilnosti. Oleinska kiselina i cetil alkohol umjereno su povećali permeabilnost fentanila. Za mjerenje adhezivnih svojstava upotrebljena je "metoda ljuštenja". Povećanje koncentracije CPE smanjilo je adhezivna svojstva PSA. Kada je udio fentanila u flasteru povišen s 1 na 3%, brzina permeabilnosti se povećala, dok daljnje povećanje udjela fentanila nije značajno utjecalo na brzinu. Pripravak s 10% propilen glikola i 3% fentanila u Duro-Tak 2054 pokazao se kao učinkoviti transdermalni terapijski sustav za fentanil

Učinci adheziva osjetljivih na tlak i kemijskih promotora na permeaciju fentanila kroz kožu štakora

Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of the PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that permeation rate or steady state flux (Jss) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak® 2054 and Duro-Tak® 2516 showed the highest Jss of 1.95 μg cm-2 h-1 and the lowest Jss of 1.43 μg cm-2 h-1, respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and lowest enhancement ratio (ER) on the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in adhesion property of PSA as measured by 180° peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that PG as a CPE and cosolvent in 10% m/m with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.Pripravljeni su transdermalni adhezivni flasteri fentanila (DIAPs) koristeći različite adhezive osjetljivih na tlak (PSAs) i kemijske promotore permeabilnosti (CPEs). Njihovi učinci na permeabilnost fentanila evaluirani su pomoću modificirane Franzove difuzijske ćelije s membranom od kože s abdomena štakora. Brzina permeabilnosti (Jss) ovisi o viskoznosti i vrsti akrilnih adheziva i o vrsti promotora. Najveća vrijednost Jss = 1,95 μg cm-2 h-1 postignuta je s Duro-Tak® 2054, a najmanja (Jss = 1,43 μg cm-2 h-1) s Duro-Tak® 2516. Među različitim promotorima propilen glikol i polietilen glikol 400 pokazali su najveći (1,61) i najmanji (1,18) omjer poboljšanja (ER) permeabilnosti. Oleinska kiselina i cetil alkohol umjereno su povećali permeabilnost fentanila. Za mjerenje adhezivnih svojstava upotrebljena je "metoda ljuštenja". Povećanje koncentracije CPE smanjilo je adhezivna svojstva PSA. Kada je udio fentanila u flasteru povišen s 1 na 3%, brzina permeabilnosti se povećala, dok daljnje povećanje udjela fentanila nije značajno utjecalo na brzinu. Pripravak s 10% propilen glikola i 3% fentanila u Duro-Tak 2054 pokazao se kao učinkoviti transdermalni terapijski sustav za fentanil