Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual impairment.The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced stages.In keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe procedure.CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks formation.The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols.Finally,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Synthesis and Charcterization of Silane Crosslinked Hydrogel to pH Sensitive Study

Eco-friendly and biodegradable novel hydrogel were prepared by blending and solution casting method. The designed hydrogel is based on chitosan/ PEG600/Gurgam with carbon nanofiller along silane crosslinked (TEOS) with pH sensitive response to controlled release of drug in biomedical materials and agriculture industry. The various concentration of carbon nanofiller is used to analyze its effect on the fabricated hydrogel characteristics by using FTIR, SEM, TGA, swelling studies (water, buffer and ionic solution). Spectra of FTIR reflected both established and newly developed groups (like hydrogel). COOH group presence is clearly observed in this range in the carbon filler reinforced hydrogel. The SEM micrographs show that CPG0.003 had a collection of polysaccharide chains as thin helices, which is attributed to the increase in the size of porosity. TGA shows to increase concentration of nanofiller enhanced the thermal stability of the designed hydrogels at temperature 25˚C to 550˚C mass loss percentage decrease upto 20% and increase thermal stability. This pH response made these resultant hydrogels as fruitful competitor against the many reported controlled release application.

Asymmetric expression of CA2 and CA13 linked to calcification in the bilateral mandibular condyles cause crossed beaks in chickens

Crossed beak is a complex mode of inheritance with prevalence ranging from 0.2 to 7.4% in at least 12 chicken strains worldwide.To reveal the intrinsic factors causing crossed beaks,genes expression patterns in bilateral mandibular condyle between affected and normal birds were characterized by RNA sequencing analysis in the present studies.Crossed beak was induced by short length of unilateral mandibular ramus,and a total of 110differentially expressed genes were up-or down-regulated in the affected(short)mandibular condyle side as compared to the normal side.Carbonic anhydrase 2(CA2)and Carbonic anhydrase 13(CA13)were enriched in the carbonate dehydratase activity,and high-expressed in mandibular condyle and osteoblasts(P<0.05).However,both were low-expressed in short mandibular condyle side of affected birds(P<0.05).The carbonate dehydratase inhibitor experiments confirmed that there is positive association between the calcification and carbonic anhydrase isoenzymes.Quantitative analysis with cetylpyridinium chloride showed a decrease in calcification when the cells were transfected with an anti-CA13 shRNA.Our research suggested that CA2 and CA13 are down-calcified in shortside mandibular condyle,and caused mandibular ramus to grow slowly.CA2 and CA13 have the critical role in crossed beaks by regulating calcification of mandibular condyle.

Computations of Cross-Link Forces and Vibrations for the Test Bed of the Full Channel Gas

In order to control the cross? link forces and the vibration frequencies of the test bed of the full channel gas within the allowable ranges, the analyses of forces and deformation of the test bed was done, for the variously restrained elastic movable frame and the rigid one, the vibration frequencies were computed respectively by means of the methods of mechanics of materials, elasticity and vibration mechanics, the cross link forces and the vibration frequencies of the test bed were tested. The results of theoretical computation comparatively approach the experimental results. The computational methods could be used to availably estimate the design parameters relevant to the test bed of the full channel gas.

Linkage analysis and integrated software GAPL for pure-line populations derived from four-way and eight-way crosses

Pure lines derived from multiple parents provide abundant variation for genetic study.However,efficient genetic analysis methods and user-friendly software are still lacking.In this study, we developed linkage analysis methods and integrated analysis software for pure-line populations derived from four-way and eight-way crosses.First, polymorphic markers are classified into different categories according to the number of identifiable alleles in the inbred parents.Expected genotypic probability is then derived for each pair of complete markers, and based on them a maximum likelihood estimate(MLE) of recombination frequency is calculated.An EM algorithm is proposed for calculating recombination frequencies in scenarios that at least one marker is incomplete.A linkage map can thus be constructed using estimated recombination frequencies.We describe a software package called GAPL for recombination frequency estimation and linkage map construction in multi-parental pure-line populations.Both simulation studies and results from a reported four-way cross recombinant inbred line population demonstrate that the proposed method and software can build more accurate linkage maps in shorter times than other published software packages.The GAPL software is freely available from www.isbreeding.net and can also be used for QTL mapping in multi-parental populations.

Accelerated versus standard corneal cross linking in the treatment of ectasia post refractive surgery and penetrating keratoplasty: a medium term randomized trial

AIM: To compare the clinical outcomes of the standard corneal cross linking(CXL) and the accelerated CXL in patients with progressive corneal ectasia post refractive surgery and penetrating keratoplasty.METHODS: Totally 120 eyes of 83 patients scheduled to receive either standard CXL(3 m W/cm^2 for a period of 30 min) or accelerated CXL(18 m W/cm2 for a period of 5 min). The main outcomes for comparison were the change in: maximum-K reading(K-max), manifest refractive spherical equivalent(SE), central corneal thickness(CCT), and the best corrected distance visual acuity(CDVA).RESULTS: One hundred and eleven eyes completed the study. The main outcome measurement was the K-max reading. Both group showed significant improvement in the value postoperatively at 6 and 12 mo. The mean change in the standard group was 1.21±0.11 D and in the accelerated group was 0.90±0.05 D at the end of 12 mo postoperatively, with no statistically significant difference between the 2 groups. Similarly, CDVA improved significantly from their preoperative value in the standard group by 2.98±0.11 letters, and in the accelerated group by 2.20±0.06 letters, with no statistically significant difference between the two groups. Both of the SE, and CCT showed no statistically significant difference at the end of follow up period in each group.CONCLUSION: Both standard CXL and accelerated CXL are safe and effective treatment in halting ectasia after corneal refractive surgery. The accelerated CXL results are comparable to the standard CXL with short time exposure of the cornea to ultraviolet irradiation, leading to reduced operation time, reduced operative ocular discomfort, and corneal haze.

Long term efficacy and stability of corneal collagen cross linking for post-LASIK ectasia: an average of 80mo follow-up

This study was designed to evaluate efficacy and stability of corneal collagen crosslinking(CXL) in halting the progression of post-laser in situ keratomileusis(LASIK) ectasia and provide long-term follow-up results with an average of 80 mo. Patients with post-LASIK ectasia were treated with CXL between December 2007 and January 2012. Main outcome measures were uncorrected distance visual acuities(UDVA) and corrected distance visual acuities(CDVA), minimum and maximum keratometry(K) values, spherical and cylindrical refraction, and corneal thickness. The study evaluated 17 eyes for 13 patients(8 men, 5 women) with mean age of 31y(range 23 to 39) and mean follow-up of 80.7±15(range 57 to 102)mo. UDVA and CDVA improved from logMAR 0.53±0.36(20/63) to 0.49±0.4(20/50)(P=0.43) and from 0.18±0.17(20/28) to 0.16±0.16(20/27)(P=0.55) respectively. In 15 eyes UDVA and in 13 eyes CDVA either remained stable or improved ≥1 Snellen lines(88.2%) and(76.5%) respectively. Although statistically insignificant, spherical and cylindrical refraction decreased post-CXL from-1.26±2.87 to-0.38±2.32 diopters(D)(P=0.054) and from-3.80±2.47 to-3.04±2.18 D(P=0.13) respectively. Kmax significantly decreased from 44.23±3.76 to 42.85±3.08 D(P=0.013) and Kmin decreased from 41.07±3.61 to 40.00±2.65 D(P=0.057). Corneal thickness decreased from 470±42 to 460±41 μm, but was statistically non-significant(P=0.063). Therefore, CXL is effective in halting and partially reversing the progression of postLASIK ectasia on the long-term(mean follow-up of more than 80mo), thus highlighting the stability and maintained effect of CXL for such cases.

Correlation between corneal demarcation line depth in epithelium-off and trans-epithelium accelerated corneal cross linking and keratoconus progression

AIM:To compare corneal demarcation line(DL)depth in both accelerated epithelium-off and trans-epithelium cross linking(CXL)using anterior segment optical coherence tomography(AS-OCT)and its relation to maximum keratometry(Kmax)progression in both techniques.METHODS:A prospective comparative interventional study where patients with mild to moderate keratoconus(KC)were classified into two groups:accelerated epitheliumoff and trans-epithelium CXL based on corneal pachymetry.Assessment of corneal DL depth was carried out after 3mo by AS-OCT.Kmax readings were evaluated after one year follow up using the Scheimpflug imaging system.RESULTS:Study included 74 eyes of 44 patients.Group A underwent epithelium-off CXL(41 eyes),while Group B underwent trans-epithelium CXL(33 eyes).At 3mo follow up,mean corneal DL depth in Group A was 219.9±58.4μm while in Group B was 127.2±7.8μm(P<0.05).The mean Kmaxchangedfrom51.9±3.9to51.3±4.2dioptersin Group A and from 53.1±4.1 to 53.6±5 diopters in Group B with insignificant difference in Kmax changes in either group(P>0.05).In addition,no significant change in corneal pachymetry was found in both groups(meanchange at 1y:6.4±4.7 and-10.1±2.3μm in Groups A and B respectively).CONCLUSION:Despite a significantly deeper corneal DL depth created by accelerated epithelium-off CXL technique compared to accelerated trans-epithelium CXL,there is no significant impact on keratoconus progression.

Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of organoboronic acids with N-protected 4-iodophenyl alanine linked isoxazoles

Suzuki-Miyaura coupling reaction of N-protected 4-iodopheyl alanine isoxazoles with arylboronic acids,catalyzed by palladium,efficiently produce benzyl-N-（4-bipheyl）-2-（3-methyl-5（E）-2-aryl-1-ethenyl-4-isoxazolyl）-amino-2-oxoethyl）carba- mates in good yields.This process is first of its kind to construct carbon-carbon bond formation having biaryl motif on amino acid linked isoxazole moiety.

Systematic review and Meta-analysis comparing modified cross-linking and standard cross-linking for progressive keratoconus

AIM：To compare the effectiveness and safety between modified cross-linking（MC）and standard cross-linking（SC）in mild or moderate progressive keratoconus.METHODS：Eligible studies were retrieved from four electronic databases,including CENTRAL,Clinical Trials gov,Pup Med and OVID MEDLINE.We set post-surgical maximum K value（Kmax）as the primary outcome.In addition,uncorrected and corrected distant visual acuity（UDVA and UDVA）,spherical equivalent（SE）,endothelial cell density（ECD）,central cornea thickness（CCT）and depth of demarcation line（DDL）were Meta-analyzed as secondary outcomes.Mean differences for these outcomes were pooled through either a random-effect model or fixed-effect model according to data heterogeneity.RESULTS：Twenty-four comparative studies either on accelerated cross-linking（AC）compared with SC or on transepithelial cross-linking（TC）compared with SC were included and pooled for analysis.The results indicated that MC was significantly inferior to SC at delaying Kmax deterioration[AC vs SC 0.49（95%CI：0.04-0.94,I2=75%,P=0.03）;TC vs SC 1.15（95%CI：0.54-1.75,I2=50%,P=0.0002）].SE decreased significantly for SC when compared to AC[0.62（95%CI：0.38-0.86,I2=22%,P〈0.00001）].DDL of SC was more significantly deeper than that of TC[-133.49（95%CI：-145.94 to-121.04,I2=33%,P〈0.00001）].Other outcomes demonstrated comparable results between MC and SC.CONCLUSION：SC is more favorable at halting the progression of keratoconus,but visual acuity improvement showed comparable results between MCs and SC.

电动汽车电控液压制动系统CarSim/Simulink联合仿真研究

针对某款国产电动汽车的电控液压制动系统,文章基于滑移率的比例-积分-微分(PID)控制提出了防抱死制动系统(ABS)模型,以改善车辆制动性能,提高在对开路面上的制动有效性和安全性。首先,使用Simulink软件建立液压电控制动系统的动力学模型;然后,基于滑移率设计PID控制器,并通过1/4车辆模型验证其有效性;最后,利用S函数将ABS控制器的Simulink模型输入CarSim平台中,开展CarSim/Simulink双平台联合控制仿真。结果表明,基于滑移率的PID控制的ABS对比无ABS的车辆,制动性能更加优越,在对开路面上制动稳定性更加明显。

一种MAKLINK图多节点链路建模的路径规划研究

针对传统MAKLINK图规划路径线路改变时,其最优化路径易与环境约束条件冲突的问题,提出了在MAKLINK图中各链路上增加节点数目的方法,以提高系统建模的适应性和鲁棒性。设计的多节点链路通过dijkstra算法得到更为理想的次优化路径,由蚁群算法进行迭代计算获得最优化路径,实现了在保证路径适应度的前提下,提高优化路径对环境约束条件的适应性。实验结果表明,与基本MAKLINK图路径规划算法相比,多节点链路的建模路径规划算法可有效提高次优路径的建模精度,最优路径的适应度值较单节点链路减小了1.43%,具有一定的建模优势。

Corneal collagen crosslinking in keratoconus and other eye disease

Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. Corneal collagen crosslinking(CXL) with riboflavin and Ultraviolet-A(UVA) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. Studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative spherical equivalent(SEQ) was reduced by an average of more than 1 D and refractive cylinder decreased by about1 D. The major indication for the use of CXL is to inhibit the progression of corneal ecstasies, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photo ablation. This treatment has been used to treat infectious corneal ulcers with apparent favorable results. Most recent studies demonstrate the beneficial impact of CXL for iatrogenic ecstasies, pellucid marginal degeneration, infectious keratitis, bullous keratopathy and ulcerative keratitis. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subject to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze,permanent scars, endothelial damage, treatment failure,sterile infiltrates, bullous keratopathy and herpes reactivation are the other reported complications of this procedure.

Clinical Observation of Transepithelial Corneal Collagen Cross-linking by Iontophoresis of Riboflavin in Treatment of Keratoconus

Purpose: To evaluate the efficacy and safety of transepithelial collagen cross-linking by iontophoretic delivery of riboflavin in treatment of progressive keratoconus.Methods:.Eleven patients(15 eyes) with progressive keratoconus were enrolled. After 0.1% riboflavin-distilled water solution was deliveried via transepithelial iontophpresis for 5 min with 1 m A current, and ultraviolet radiation(370 nm,.3 m W /cm2) was performed at a 1.5 cm distance for 30 min. The follow up were 6 months in all eyes. The uncorrected visual acuity, corrected visual acuity,endothelial cell counting, corneal thickness,.intraocular pressure, corneal curvature, corneal topography,.OCT and corneal opacity before and 6-month after surgery were analyzed.Results: At 6 month postoperatively, mean uncorrected visual acuity and corrected visual acuity changed from 0.36 to 0.30 and from 0.42 to 0.57 without statistical significance..The mean value of each index of corneal curvature declined without statistical significance.Kmax value dereased from 60.91 to59.91, and the astigmatism declined from 3.86 to 3.19. Central corneal thickness decreased from 460.93 μm to 455.40μm,.and thinnest corneal thickness declined from 450.87 μm to 440.60 μm with no statistical significance..Intraocular pressure was significantly elevated from 10.85 mm Hg to 12.62 mm Hg. Endothelial cell count did not change significantly. No corneal haze occurred. Mean depth of corneal demarcation line was 288.46 μm at 1 month postoperatively..Conclusion:.Transepithelial corneal collagen cross-linking by iontophoresis is effective and safe in the treatment of progressive keratoconus, and yields stable clinical outcomes during 6-month follow up..However,.long-term follow up is urgently required.

PERVAPORATION PROPERTIES OF PDMS MEMBRANES CURED WITH DIFFERENT CROSS-LINKING REAGENTS FOR ETHANOL CONCENTRATION FROM AQUEOUS SOLUTIONS

Ethanol perm-selective PDMS/PVDF composite membranes were prepared by curing polydimethylsiloxane (PDMS) with various cross-linking reagents,such as tetraethoxylsilane(TEOS),γ-aminopropyltriethoxylsilane(APTEOS), phenyltrimethoxylsilane(PTMOS) and octyltrimethoxylsilane(OTMOS) as well.The cross-linking density and surface properties of the PDMS active layer were adjusted by varying cross-linking reagents.The pervaporation performance of PDMS membranes cured with different cross-linking reagents was investig...

Experimental study on the treatment of rabbit corneal melting after alkali burn with Collagen cross-linking

AIM: To evaluate the effect of Collagen cross-linking on the prevention of melting in rabbit corneas after alkali burn. METHODS: Twenty New Zealand white rabbits were randomly divided into model control group and collagen cross-linking treatment group. The second group of rabbits received collagen cross linked treatment. Both groups were applied with antibiotic eye drops to prevent infection. The corneas were evaluated for melting, opacity, pathological and immunohistochemistry, record the changes when 28 days after the animals were killed. RESULTS: In the control group, 6 out of 8 rabbits showed corneal melting after injury (14 +/- 4) days, while two corneal perforated. In collagen cross-linking treatment group, one rabbit showed corneal melting after injury 23 days, without corneal perforation; corneal dissolution rate between the two groups was significantly different (P <0.05). Pathological examination suggested that in the treatment group, mild corneal edema, mild damage to collagen fibers, inflammatory cell infiltration was significantly less than the control group. Immunohistochemistry showed that corneal collagen fibers arranged in neat rows in the control group. CONCLUSION: Collagen cross-linking treatment not only can prevent and delay the corneal melting after alkali burn, but also can reduce the destruction of corneal collagen fibers and infiltration of inflammatory cells in the corneal tissue.

Applications of Crown Ether Cross-Linked Chitosan for the Analysis of Lead and Cadmium in Environmental Water Samples

A new type of crown ether cross-linked chitosan was synthesized by the reaction of chitosan with 4,4′-dibromodibenzo-18-crown-6 (Br-DBC). Its token structure was analyzed with FT-IR and NMR and the adsorption behaviors for lead and cadmium in environmental water samples by FAAS were studied. In addition the best analysis conditions were discussed and the adsorption mechanism was explained. As the enrichment factor is above 100, both recoveries are 94%–106%, the detection limits of lead and cadmium are 0.5μg·L?1 and 0.04 μg·L?1 and the relatively standard deviations of lead and cadmium are 3.1% and 2.8% respectively, this new method was successfully applied to the determination of environmental water samples. This method is fast and simple and it greatly enhances the determination ability of FAAS for lead and cadmium.

Study on the Structure of Peroxide Cross-Linked Polyethylene Pipes with Several Stabilizers

Cross-linked polyethylene (PEX) pipes used in hot water supply are required for high mechanical strength and high creep resistance at high temperature. Especially PEX-a pipes which are made by peroxide cross-linking have better performance, such as creep resistance and thermal shock resistance than the pipes made by the other cross-linking method. Because the PEX-a pipes indicate the higher cross-link degree as compared with the other PEX pipes. In this study, the PEX-a pipes which were mixed with several stabilizers were tested to evaluate the effects on cross-link degree and the oxygen induction time. And also they are evaluated with the chlorine aqueous solution by the performance of the long-term hydrostatic pressure test and the long-term hydro dynamic pressure test. As a result, it was found that the combination of antioxidants for PEX-a pipes plays an important role to prolong the oxygen induction time without inhibiting the cross-linking. From the results of the 1H pulsed NMR measurement over the melting point of polyethylene, it was found that each peroxide PEX pipe with different antioxidant combinations indicated the different proportion and crosslink density of cross-linked region, in addition, that these pipes had the effective structure of cross-linking for the hydrostatic and hydrodynamic pressure test with the chlorine aqueous solution. Therefore, it was considered to be useful results for studies of the stricture of cross-linking of polyethylene.

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas

AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure.RESULTS: The mean thinnest thickness of the cornea was 408.5 ±29.0 μm before treatment and reduced to369.8 ±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0 ±26.5 μm before CXL and recover to 412.5 ±22.7 μm at 3mo after treatment, P =0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6 ±4.0 diopters, and slightly decreased(54.7±4.9 diopters) after surgery(P =0.085). Mean best-corrected visual acuity was 0.55 ±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery(P =0.879).The endothelial cell density was 2706.4 ±201.6 cells/mm2 before treatment, and slightly decreased( 2641. 2 ±218.2 cells/mm2) at last fellow up(P =0.002).CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Research Progress in Corneal Cross-linking Agents

Corneal collagen cross-linking with UVA-riboflavin is currently the only method for preventing the progression of keratoconus from the pathological perspective. Topical application of a direct cross-linking agent is now attracting widespread attention in clinical settings..This article reviews the research progress in the application of indirect or direct cross-linking agents(e.g., riboflavin, glucose, ribose, glutaraldehyde,formaldehyde,.glyceraldehyde,.short chain aliphatic β-nitro alcohol, and genipin) in the treatment of corneal diseases and analyzes the cross-linking efficacy,.toxicity,.and merits and disadvantages of each cross-linking agent,.providing clinical information for further studies.