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ABSTRACT Background Leber congenital amaurosis (LCA), the most severe form of inherited retinal dystrophy, is a rare, heterogeneous, genetic eye disease associated with severe congenital visual impairment. RPE65, one of the causative genes for LCA, encodes retinoid isomerohydrolase, an enzyme that plays a critical role in regenerating visual pigment in photoreceptor cells. Methods Exome sequencing (ES) was performed on a patient with suspected LCA. Results Here, we report a 33‐year‐old male patient diagnosed with RPE65‐related LCA caused by uniparental isodisomy (UPiD) who received gene therapy as treatment, fourth patient to receive it in Korea. His fundus examinations showed salt‐and‐pepper retinal dystrophy, with diffuse extinguished signal on fundus autofluorescence and attenuated amplitude on electroretinogram. A homozygous frameshift variant NM_000329.3:c.1067del (p.Asn356MetfsTer17) in RPE65 was identified by ES with the entire chromosome 1 proving to be paternal UPiD. Within 5 months after the molecular diagnosis, the patient was treated with subretinal voretigene neparvovec (VN) therapy and is being followed up for prognosis. Conclusions To our knowledge, this patient is the first UPiD case to receive VN treatment. Performing ES as a first‐tier test was favourable because it allowed to identify UPiD that needed to be detected in addition to the disease‐causing variant.

Abstract Background To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity. Methods In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS. Results A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P

Abstract This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was − 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Abstract As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate,

Abstract Background To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). Methods Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented. Results A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence. Conclusions The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

Recently, preoxidation is an effective pretreatment method of refractory gold ore, which has been widely used due to the high desulfurization, arsenic removal, low environmental pollution, and rapid reaction rate. In this paper, we describe the thermodynamic considerations of preoxidation of pyrite and arsenopyrite, the main minerals of the refractory gold ore, and the effect of the pressure oxidation, one of the preoxidation processes on the chlorination leaching. The thermodynamic results indicated that arsenopyrite under acidic conditions is easier to oxidize compared to pyrite and the oxidation decomposition of pyrite and arsenopyrite-type gold ore can be considered mainly for pyrite. The experiment has shown that the arsenic removal rate was higher than the desulfurization rate; it is confirmed that the thermodynamic conclusion of the oxidation of pyrite and arsenopyrite was correct. Comparing the XRD, SEM, and EDX analyses of gold concentrate and pressurized oxidation residue, it can be seen that the surface of pressurized oxidation residue is a fine porous structure and the dense and durable structure of sulfide ore is mainly destroyed.

Multiseam interactions are a major source of ground and pillar instability in many underground coal mines. The objective of this study is to propose a method for determining the optimal parameters of a panel layout for the room and pillar retreat mining with the rational extraction ratio and stability factor of pillar in multicoal seams. First, key factors to ensure high extraction ratio and pillar stability in room and pillar retreat mining are selected as four parameters, and their value range and levels are determined according to geological and mining conditions, previous experiences. Then, the numerical analysis for the stability of the pillar system in the retreat mining panel was implemented by the analysis of multiple seam stability software in combination with an orthogonal experimental table (L16(44)), and the influence of each factor on the extraction ratio and stability factor of pillar is evaluated. Finally, it was found that the effect of the number of entries on the recovery rate and pillar stability factor was the largest regardless of the undermining or overmining, and the extraction ratio and pillar stability factor for mining of #2 seam over #1 seam in the optimal mining panel with 8 of number of entries, 1.5 m of entry height, 7 m of entry width, and 20 m of crosscut spacing are 69.2% and 1.87%, respectively.

Abstract Background We present a case of retinal occlusive vasculitis following brolucizumab administration and the first report of optical coherence tomography angiography (OCTA) findings after treatment. Case presentation A 71-year-old man complained of vision loss in the left eye 6 weeks after brolucizumab injection. His visual acuity was counting fingers, and examination revealed 1 + anterior chamber cells with 2 + vitreous cells. Fundus examination demonstrated vitreous haze, retinal whitening, and vascular sheathing. Fluorescein angiography revealed filling defects in the retinal arteries and veins, and OCTA showed extensive capillary nonperfusion. Under the diagnosis of brolucizumab-associated intraocular inflammation (IOI) and retinal occlusive vasculitis, topical, sub-Tenon, and systemic corticosteroids were administered. After the treatment, visual acuity improved to 20/200, and OCTA revealed gradual improvement in capillary dropout; however, with the limited improvement of reperfusion in the perifoveal areas. Conclusions Prompt evaluation and intensive corticosteroid treatments are required for brolucizumab-associated IOI. OCTA imaging provides detailed information on microvascular changes in the retinal vascular plexuses in brolucizumab-associated retinal occlusive vasculitis.

Abstract This observational cohort study aimed to evaluate the progression pattern of diffuse chorioretinal atrophy (DCA) according to its severity. Highly myopic eyes with DCA were graded according to its extent in the 532-nm (green) and 633-nm (red) wavelengths images of the Optos ultra-widefield scanning laser ophthalmoscope at baseline: grade 1 and 2 were defined when increased reflectance at peripapillary region, not beyond the fovea, were observed in red laser image only and in both laser images, respectively; grade 3 and 4 were defined when increased reflectance beyond the fovea were observed in red laser image only and in both laser images, respectively. A total of 307 eyes (221 patients) were included, and progression of myopic maculopathy during follow-up of ≥ 3 years was evaluated. The mean visual acuity and subfoveal choroidal thickness (CT) differed among DCA grades (P = 0.015 and P

A D bolt, an energy-absorbing rock bolt, is a smooth steel bar with a number of anchors along its length. The anchors, which can be spaced evenly or unevenly along its length, are firmly fixed within a borehole using either cement grout or resin, while the smooth sections of the bolt between the anchors may freely deform in response to rock dilation. A series of numerical simulations have been conducted using the finite difference method to investigate the effects of D bolt on the displacement increase of rock mass around a roadway in comparison with normal fully encapsulated rebar. As a result, the displacement of 49 mm at the top of roadway roof in the D bolts supported model is much larger than 30.08 mm in the fully encapsulated rebar bolts supported model so that the former is capable of absorbing potential deformation energy of rock mass around a roadway to tolerate the large deformation of rock. Plans of spacing arrangement of D bolt’s anchor have a significant effect on stress redistribution of the bolt. The numerical simulation result shows that for the D bolt with its whole length of 2.4 m, the length of its exposed section of 0.1 m, and the 4 anchors with the length of 0.1 m, the maximum tensile stress of 3.25 GPa generated in the D bolt with the ratio of the spacing between anchors (RSA) of 30 : 40 : 50 : 70 is lower about 1.13–1.31 times than the other D bolts with different ratio of spacing, and the changing range of stress is also the smallest, where the ratio of 30 : 40 : 50 : 70 indicates a ratio of lengths of deformable sections which is determined by turns from the innermost section of rock mass around roadway to the outermost section of roadway space. This study demonstrates that it is reasonable to employ the RSA of D bolt which makes it bring out its energy-absorbing capability to the full.

The bundle-series initiation is currently used as the method for simultaneously transmitting blast signals from a detonator to a large number of shock tubes for blasting using shock tubes and its initiation modes affect the ability and probability of signal transmission. A numerical study of the influence of initiation modes on the pressure impulse generated by detonators and transmitted to a large number of shock tubes has been undertaken with ANSYS AUTODYN code and validated through experimental results of signal transmission probability of shock tubes. Numerical simulations and experiments used lateral and frontal bundle-series initiation modes for a large number of shock tubes. For a bundle of many shock tubes, peak pressures of pressure impulses affected within all shock tubes beside the first layer around a detonator, and signal transmission probabilities were higher for frontal bundle-series initiation mode than for lateral bundle-series initiation mode. The magnitude of a numerically obtained pressure impulse to a bundle of shock tubes shows a good correlation with the experimentally obtained signal transmission probability of shock tubes. Finally, the results are employed in the application of a frontal bundle-series initiation mode with the simultaneous bundle-series initiating a large number of shock tubes for blastings in mining and construction.

This paper focuses on simulating the collision breakage process between the agglomerate and hammer in a hammer crusher by the discrete element method (DEM) as the interaction between particles. This enables us to consider the energy change in the collision breakage process of the hammer. The agglomerate model is built by using the EDEM 2.7 software according to the principle of closest packing in crystallography, while the hammer model is modeled into an assembly of different sizes of spherical particles to make the collision breakage process between the agglomerate and hammer as the one of interrelation of particles. With these models, we mainly investigated collision force, collision impulse, energy breaking agglomerate, and the relationship between the specific breakage energy and agglomerate damage ratio. The collision force is represented as Gaussian function, the collision impulse is represented by the function of the mass ratio of agglomerate to hammer and the product of agglomerate mass and collision velocity, and the relationship between the specific breakage energy and agglomerate damage ratio is represented by exponential function. Finally, it can be seen from this study that, when crushing the agglomerate by hammer impact, it is necessary to increase the specific breakage energy by 1.75 times in order to increase the agglomerate damage ratio from 85% to 90% but 2.13 times in order to increase 95%. The proposed method can be used for the further development and design of the various types of crusher.

Abstract It has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.

Abstract In this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 μm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = − 0.548 to − 0.357, all P

PurposeThe study aimed to evaluate risk factors for macular atrophy (MA) associated with myopic choroidal neovascularization (mCNV) during long-term follow-up after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in highly myopic eyes.MethodsThe medical records of patients who received intravitreal injection of anti-VEGF agents as mCNV treatment and were followed-up for more than 36 months were retrospectively reviewed. The risk factors for the development of mCNV-MA, which is the fovea-involving patchy atrophy lesion adjacent to mCNV, were investigated using the Cox proportional hazard model.ResultsA total of 82 eyes (74 patients) were included in the study. The mean age at anti-VEGF treatment was 56.3 ± 12.5 years (range, 26-77), and the mean follow-up period was 76.3 ± 33.5 months (range, 36-154). During follow-up, mCNV-MA developed in 27 eyes (32.9%), and its occurrence was estimated to be 24.5% at 3 years and 37.3% at 5 years after the first anti-VEGF treatment. Old age (hazard ratio [HR] = 1.054, 95% confidence interval [CI]: 1.018-1.091; P = 0.003) and greater CNV size at baseline (HR = 2.396, CI: 1.043-5.504; P = 0.040) were significant factors for mCNV-MA development. Eyes with a thinner subfoveal choroid were more likely to show faster enlargement of the mCNV-MA during follow-up.ConclusionsIn mCNV eyes treated with intravitreal anti-VEGF agents, older age and greater mCNV size at baseline were risk factors for the development of MA during long-term follow-up, which was associated with a poor visual prognosis.

It can be a great expense to examine individually the stability of earth and rockfill dams on rapid drawdown in civil engineering practice. The aim of this present work is to clarify the safe type on the rapid drawdown among the most common types of earth and rockfill dams and to introduce cheaply the types in dam design. First, a transient analysis of saturated-unsaturated seepage coupled with stress is carried out in the cross sections of typical earth and rockfill dams the during rapid drawdown, and the safety factors of the upstream slopes are determined by the shear strength reduction method. Then, the typical dams are compared for the stability characteristics so that designers can select the safe type of earth and rockfill dams on rapid drawdown. The obtained results show that the decreasing rate of safety factor in a central core dam is 0.72–0.85 times than one of the homogeneous dams and 0.17–0.40 times than one of the sloping upstream core dams so that it is more stable than other earth and rockfill dams during rapid drawdown.

Mechanical power loss in pneumatic hammers comes from the friction between parts in relative motion, and wear is among the failure mechanisms of the top hammer. Therefore, it is important for high performance and a longer service life of pneumatic hammers to reduce the friction force between parts in relative motion. This study presented a novel approach to quantitatively determine the friction force and consider it in the simulation model of pneumatic hammer. First, the friction force between piston and cylinder in a small pneumatic hammer was measured using an experimental setup at different inlet pressures. We could find from the experimental result that the friction force was about 0.8 N under the horizontal installation when there was no pressure supply, but it increased significantly, was 20 times greater than that without pressure supply, due to aerodynamic action by compressed air leaked from the annular gaps between the cylindrical matching surfaces of the components. In addition, it increased from 10.27 to 16.7 N due to an increase in inlet pressure and mechanical power loss in the pneumatic hammer that was about 10% of impact energy. Then, numerical analysis for a small pneumatic hammer performance was performed by a model considered the friction force using AMESim software. Finally, it can be seen from the simulation results that the proposed approach could significantly reduce the error between the simulated and the measured values for the impact energy because of ignoring the friction force. This approach will be used to predict service life of piston and find a low friction piston of pneumatic hammer in practical engineering.

Purpose To investigate the functional and anatomical parameters and their postoperative changes according to the ectopic inner foveal layer (EIFL) staging scheme for idiopathic epiretinal membrane (ERM). Methods In this prospective study, patients with idiopathic ERM underwent pars plana vitrectomy and ERM removal, and were followed-up for 6 months. The associations of EIFL with pre- and postoperative functional and anatomical parameters were analyzed. Results A total of 84 eyes (84 patients) were included: 39 (46.4%), 33 (39.3%), and 12 (14.3%) as EIFL stages 2, 3, and 4, respectively. At 6 months after surgery, the mean best-corrected visual acuity (BCVA) significantly improved in all EIFL stages (P ≤ 0.003); however, metamorphopsia improved only in eyes with EIFL stage 2 (P = 0.039) and 3 (P = 0.011). The aniseikonia and foveal avascular zone (FAZ) area showed no significant postoperative changes in any of the EIFL stages. Both preoperatively and during 6 months after surgery, the EIFL stage showed a significant correlation with BCVA (P ≤ 0.033), metamorphopsia (P ≤ 0.008), central macular thickness (P < 0.001), and FAZ parameters (P ≤ 0.016) at each time point, but not with aniseikonia. Significant correlations of EIFL thickness with BCVA (P = 0.028) and metamorphopsia (P = 0.006) before surgery were not persistent after surgery. Conclusion Both pre- and postoperatively, the staging of EIFL, rather than its thickness, is a simple and adequate surrogate marker for visual acuity and metamorphopsia in eyes with idiopathic ERM.

The present study was conducted to investigate recent trends of refractive surgery rates and analyze subjects undergoing refractive surgery using large-scale population studies over the past 8 years. We used the dataset of the Korean National Health and Nutrition Examination Surveys, a nationwide population-based cross-sectional study which were performed from 2008 to 2015. Of the 21,415 participants aged 20 to 49 years, 1,621 had refractive surgeries. Seventy three percent of them were females and 81% of them were aged under 40 years old. Over the past 8 years, cumulative prevalence of refractive surgery rate increased more than 10%. Although young (< 40 years, odds ratio (OR) 0.31, P

For years, the mammary gland serves as a perfect example to study the self-renew and differentiation of adult stem cells, and the regulatory mechanisms of these processes as well. To assess the function of given genes and/or other factors on stemness of mammary cells, several In vitro assays were developed, such as mammospheres formation assay, detection of stem cell markers by mRNA expression or flow cytometry and so on. However, the capacity of reconstruction of whole mount in the cleared fat pad of recipient female mice is a golden standard to estimate the stemness of the cells. Here we described a step-by-step protocol for in vivo mammary gland formation assay, including preparation of “cleared” recipients and mammary cells for implantation, the surgery process and how to assess the experimental results. Combined with manipulation of mammary cells via gene editing and /or drug treatment, this protocol could be very useful in the researches of mammary stem cells and mammary development.

Background: We report a case of different types of maculopathy in eyes after a high-voltage electrical shock injury. Case Report: A 43-year-old male suffered high-voltage electrical injury through his left arm. He underwent cataract surgery in both eyes 3 months after the injury, but there was no vision improvement. Ocular examination, including spectral domain optical coherence tomography, revealed diffuse retinal atrophy in the left eye which did not change until the final visit. In the right eye, an impending macular hole was observed but regressed spontaneously 9 months after the injury, and the visual acuity improved to 20/32 at the final visit. Conclusion: Two different types of maculopathy can occur in each eye after high-voltage electrical shock injury, and this might be due to asymmetric pathogenesis of the eyes according to the proximity to the route of electrical current.

Abstract The paper studies the estimation and the portmanteau test for double AR(p) $\operatorname{AR}(p)$ model with Laplace(a,b) $\operatorname{Laplace}(a,b)$ distribution. The double AR(p) $\operatorname{AR}(p)$ model is investigated to propose firstly the quasi-maximum exponential likelihood estimator, design a portmanteau test of double AR(p) $\operatorname{AR}(p)$ on the basis of autocorrelation function, and then establish some asymptotic results. Finally, an empirical study shows that the estimation and the portmanteau test obtained in this paper are very feasible and more effective.

Bovine spongiform encephalopathy (BSE) is a fatal disease caused by miss folded prion protein. Studies in the cattle, comparing genetic data from BSE diseased and healthy animals have shown that indel polymorphisms in the promoter and intron 1 of PRNP gene were associated with disease susceptibility. Several studies were conducted to find out allele and genotypic frequencies of indel polymorphisms in promoter and intron 1 of the cattle PRNP gene. Unlike domestic cattle and bison, no indel polymorphisms of the PRNP promoter and intron 1 were examined in any population of the water buffalo ( Bubalus bubalis). Aim of this study was to analyse frequencies of allele, genotype, and haplotype of the indel polymorphisms (23 bp indel in promoter and 12 bp indel in intron 1) in prion protein coding gene ( PRNP) of water buffalo. Therefore a PCR based procedure, previously used in cattle to detect indel polymorphisms of PRNP promoter and intron 1 locus, was applied to 106 Anatolian water buffalo DNAs. Our results have revealed high frequency of in variants and in23/ in12 haplotype for PRNP promoter and intron 1 indel polymorphisms in water buffalo. The results of the study have demonstrated that frequencies of allele, genotype, and haplotype of the indel polymorphisms in PRNP gene of the Anatolian water buffalo are significantly different those from cattle and bison PRNP indel polymorphisms. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients. Methods This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic association with visual and anatomic outcome measures at 12 months after initial treatment, including mean change in best-corrected visual acuity (BCVA) and total foveal thickness, visual gain of ≥ 15 letters, dry status on optical coherence tomography (OCT), pigment epithelial detachment (PED) regression on OCT, polyp regression on indocyanine green angiography, and injection numbers, were investigated using regression models with adjustment for non-genetic covariates under additive genetic model. Results In 81 patients who completed 12-month anti-VEGF monotherapy without photodynamic therapy, significant pharmacogenetic association was found between ARMS2 rs10490924 and PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for TG, and 63.6% for GG genotype, showing additive effect of G allele for higher chance of PED regression (OR, 2.96; 95% CI, 1.38–6.36; corrected P = 0.043). For entire 95 patients, no significant association was found between candidate polymorphisms and receiving photodynamic therapy within 12 months. Conclusions In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic response to anti-VEGF, suggesting pharmacogenetic relationship.

In this paper, we study a representation of generalized Mehler semigroup in terms of Fourier–Gauss transforms on white noise functionals and then we have an explicit form of the infinitesimal generator of the generalized Mehler semigroup in terms of the conservation operator and the generalized Gross Laplacian. Then we investigate a characterization of the unitarity of the generalized Mehler semigroup. As an application, we study an evolution equation for white noise distributions with n-th time-derivative of white noise as an additive singular noise.

PurposeVitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.MethodsThis prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).ResultsPDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).ConclusionsVitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.

PURPOSE:This study evaluated changes in choroidal vascularity after half-fluence photodynamic therapy (HF-PDT) in patients with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (SS-OCT) en face imaging. METHODS:This retrospective comparative case series included 50 eyes of 25 patients with unilateral CSC who underwent HF-PDT and 50 age-and sex-matched normal healthy control eyes. En face SS-OCT images of the choriocapillaris, Sattler's layer, and Haller's layer were converted into binary images. The vascular proportions were defined as the percentage of the area of vascular lumen against the area of the 3.0-mm-diameter circular area. The main outcome measures were the vascular proportions before HF-PDT and at 6 weeks, 6 months, and 12 months after HF-PDT. RESULTS:At baseline, the vascular proportions in the CSC eyes were significantly greater than those in the control eyes in all layers (choriocapillaris: 51.8% ± 15.5% vs. 41.3 ± 18.7%, P = 0.018; Sattler's: 58.6% ± 13.4% vs. 49.7% ± 15.7%, P = 0.017; Haller's: 65.3% ± 15.3% vs. 53.0% ± 13.4%, P = 0.001). In the CSC eyes, the vascular proportion in the choriocapillaris significantly decreased at 6 weeks (36.6% ± 16.9%, P < 0.001), 6 months (34.0% ± 12.3%, P < 0.001), and 12 months (34.8% ± 17.6%, P < 0.001) after HF-PDT compared with baseline. The vascular proportions in Sattler's and Haller's layers did not show a significant decrease at 6 weeks (Sattler's: 49.7% ± 17.3%, P = 0.052 and Haller's: 58.3% ± 12.9%, P = 0.558) but decreased significantly at 6 months (Sattler's: 48.9% ± 12.4%, P < 0.001 and Haller's: 57.7% ± 15.7%, P = 0.027) and 12 months after HF-PDT from the baseline values (Sattler's: 45.8% ± 10.4%, P < 0.001 and Haller's: 56.8% ± 15.7%, P < 0.001). CONCLUSION:After HF-PDT, the choriocapillaris showed the earliest decrease in vascular proportion of en face images, Sattler's and Haller's layers showed later decreases. The temporal differences in the response of each layer may reflect the pathophysiology of CSC and the therapeutic mechanism of HF-PDT.

This paper investigated the antifungal and antibiofilm activity of silver nanoparticles synthesized with Lycopersicon esculentum extracts against Candida species. Lycopersicon esculentum extracts obtained by homogenization were mixed with silver nitrate to synthesize silver nanoparticles. Analysis of the particle characteristics by UV−Vis spectrophotometry, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDAX), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR) confirmed that the Lycopersicon esculentum extracts effectively served as reductants and capping agents. Minimum inhibitory concentration (MIC) tests were conducted to confirm antifungal activity against Candida species. In all the tested species, the silver nanoparticles inhibited the growth of Candida. Moreover, the SEM images of Candida species treated with silver nanoparticles synthesized using natural extracts of Lycopersicon esculentum showed that silver nanoparticles adhered to the surface of Candida, which induced pore formation in the membranes and prevented their normal growth. Ultimately, these abnormal forms of Candida were thought to be less able to form biofilms than normal Candida. The antifungal and antibiofilm activities of silver nanoparticles against Candida are expected to be utilized in various fields and contribute in particular to developments in nanomedicine.

Behçet’s disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçet’s uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU.

BACKGROUND AND OBJECTIVES: Multipotent mesenchymal stem cells (MSCs) represent a promising cell-based therapy for a number of degenerative conditions. Understanding the effect of aging on MSCs is crucial for both autologous therapy development and allogenic donors in older subjects whom degenerative diseases typically afflict. In this study, we investigated the influence of donor age on the characteristics, proliferation, and differentiation potential of in vitro cultures of multipotent human turbinated mesenchymal stem cells (hTMSCs) from patients of various age groups. SUBJECTS AND METHODS: Twelve patients comprised the four age groups: (I) 60 years. Inferior turbinate tissues were discarded from patients undergoing partial turbinectomy. After isolating hTMSCs, the expression of the hTMSC surface markers CD14, CD19, CD34, CD73, CD90, CD105, and HLA-DR was assessed by FACS analysis, and cell proliferation was assessed using a cell counting kit (CCK)-8. The differentiation potential of hTMSCs was evaluated in osteogenic media by histology and determination of osteoblastic gene expression. RESULTS: FACS analysis revealed that hTMSCs were negative for CD14, CD19, CD34, and HLA-DR, and positive for CD73, CD90, and CD105, representing a characteristic MSC phenotype, and showed no significant differences among the age groups. Cellular proliferation and osteogenic differentiation potential of hTMSCs also showed no significant differences among the age groups. CONCLUSIONS: We conclude that donor age does not affect the characteristics, proliferation, and osteogenic differentiation potential of hTMSCs. Donor age may be excluded as a criterion in the guidelines for clinical use of the autologous or allogenic transplantation of hTMSCs.

Toxoplasma gondii is an apicomplexan parasite infecting all mammals including humans and causes toxoplasmosis. There is no vaccine available for humans and thus vaccine development efforts continue using novel antigens and/or vaccine platforms. Since our previous microarray screening study showed that ROP6 is a suitable antigen to be used in vaccine studies, in this study, we aimed to design an optimized mRNA construct encoding the ROP6 protein and then demonstrate its efficiency and immunogenicity using in vitro methods. For this, we constructed a pT7CFE1-Chis/ROP6 vector encoding optimized ROP6 mRNA containing EMCV 5'UTR with IRES and a 20 nucleotides fragment from alpha globin 3' UTR. Then, we generated the optimized ROP6 mRNAs with anti-reverse cap analogue (ARCA) and approximately 150 nucleotide long poly-A tail. Next, HEK293T cells were transfected with the optimized ROP6 mRNAs to show recombinant ROP6 protein expression capability. Moreover, we expressed in vitro recombinant ROP6 protein in HeLa cell lysate using the pT7CFE1-Chis/ROP6 vector to reveal the immunogenicity of recombinant ROP6 protein using sera samples collected from mice infected with PRU strain of T. gondii. The IFA and Western blot results showed that the optimized ROP6 mRNAs successfully expressed the recombinant ROP6 protein in HEK293T cells. Moreover the recombinant ROP6 protein expressed in HeLa cell lysate strongly reacted with sera samples collected from mice. The absorbance difference detected among positive and negative mice serum samples analyzed was statistically significant, indicating that the recombinant ROP6 protein was immunogenic (P = 0.0003). In conclusion, this study demonstrated that the optimized ROP6 mRNAs can be used in the development of mRNA vaccines against toxoplasmosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monkeypox virus (MPXV) belonging to poxviridae family causes chronic viral disease in various mammals including human and monkeys. Conventional vaccines developed against smallpox of poxviridae, are not specific against Mpox. Also, they can cause various side effects after vaccination. In this study, we aimed to analyze the A17L, A28L, A37R, A43R, E8L, H3L, B6R, and M1R structural proteins of MPXV and identify epitopes in them which can be used to generate vaccine antigens. Among the proteins analyzed, the M1R protein was predicted to be more appropriate for use in vaccine research due to its high antigenicity value and other physicochemical features. Also, A17L, B6R and E8L had high antigenicity values. E8L protein was more conserved while the A37R, A43R, and B6R proteins had signal peptides. Although a total of eight B cell epitopes were predicted in all proteins analyzed, CNGETK epitope belonging to B6R protein had the highest antigenicity value (1.7083), as well as was non-allergenic, non-toxic, and soluble. Based on T cell epitope analyses performed on all proteins, fourteen MHC-I/II epitopes were predicted that are antigenic, non-allergenic and non-toxic, as well as soluble. Among them, MHC-I related-HEIYDRNVGF epitope in A28L protein had the highest antigenicity value (1.6650) and MHC-II related-IGNIKIVQIDIRDIK epitope in A37R protein had the highest antigenicity value (2.0280). In conclusion, eight structural proteins of MPXV were successfully analyzed and 22 important epitopes were identified that could serve as vaccine antigens or in serological studies to develop diagnostic tools., (Copyright © 2024 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Toxoplasma gondii is an obligate intracellular parasite that can infect a variety of mammals including humans and causes toxoplasmosis. Unfortunately, a protective and safe vaccine against toxoplasmosis hasn't been developed yet. In this study, we developed a DNA vaccine encoding the SRS13 protein and immunized BALB/c mice thrice with pVAX1-SRS13 through the intramuscular route (IM) or intradermally using an electroporation device (ID + EP). The immunogenicity of pVAX1-SRS13 was analyzed by ELISA, Western blot, cytokine ELISA, and flow cytometry. The protective efficacy of the pVAX1-SRS13 was investigated by challenging mice orally with T. gondii PRU strain tissue cysts. The results revealed that pVAX1-SRS13 administered through IM or ID + EP routes induced high level of anti-SRS13 IgG antibody responses (P = 0.0037 and P < 0.0001). The IFN-γ level elicited by the pVAX1-SRS13 (ID + EP) was significantly higher compared to the control group (P = 0.00159). In mice administered with pVAX1-SRS13 (ID + EP), CD8 + cells secreting IFN-γ was significantly higher compared to pVAX1-SRS13 (IM) (P = 0.0035) and the control group (P = 0.0068). Mice vaccinated with the SRS13 DNA vaccine did not induce significant IL-4 level. Moreover, a significant reduction in the number of tissue cysts and the load of T. gondii DNA was detected in brains of mice administered with pVAX1-SRS13 through ID + EP and IM routes compared to controls. In conclusion, the SRS13 DNA vaccine was found to be highly immunogenic and confers strong protection against chronic toxoplasmosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Maedi Visna Virus (MVV) is a retrovirus that can infect sheep. There is still no effective therapy or vaccine against this virus and timely diagnosis is important to combat the complications of the disease. In this study, we aimed to develop an ELISA using peptides derived from gag protein as antigen. For this purpose, B cell epitopes of gag protein were predicted and a docking analysis with the B cell receptor was performed to select peptides to be used in ELISA. After three soluble epitopes with the highest antigenicity were produced as peptides, the immunogenicity of each peptide was determined by ELISA using sheep serum samples categorized as MVV positive (n=24) and negative (n=13). Subsequently, in house ELISA using above mentioned immunogenic peptides as antigen was used to investigate MVV seroprevalence in sheep (n=88). According to the results, among three peptides, two of them strongly reacted with MVV positive serum samples and the mean absorbance values detected among positive and negative serum samples were statistically significant, indicating that these peptides were immunogenic (P=0.016 and P=0.038). The third peptide also reacted with positive serum samples but the mean absorbance value was not statistically significant and this peptide was considered non-immunogenic (P=0.175). The immunogenic two peptides showed the same high sensitivity and specificity values of 91.60 and 92.80 according to the commercial kit. Moreover, MVV seroprevalence detected by peptide-ELISAs using CKQGSKE and CRPQGKAGHKG peptides as antigen was 3.40 % and 4.5 %, respectively. As a result, it was shown that these peptides can be successfully used for serological diagnosis of MVV., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)