DNA methylation of Ad4BP/SF-1 suppresses Cyp11a1 and StAR transcripts in C2C12 myoblasts.

Steroidogenesis occurs locally in peripheral tissues and via adrenal and gonadal glands' biosynthesis. The C2C12 mouse myoblast cell line and rat skeletal muscles harbor a local steroidogenesis pathway for glucocorticoids, and corticosterone is biosynthesized from skeletal muscle cells. However, Cyp11a1 and StAR protein expressions are not observed in C2C12 cells or rat muscular tissues. In this context, this study investigated the relationship between DNA methylation and key steroidogenic genes. Bioinformatics analysis of methylated DNA immune precipitation showed that C2C12 myoblasts and myotubes did not have remarkable DNA methylated regions in the gene-body of Cyp11a1. However, a highly methylated region in the CpG island was detected in the intronic enhancer of Ad4BP/SF-1, known as the transcriptional factor for steroidogenic genes. After C2C12 myoblasts treatment with 5-aza-2-deoxycytidine, the gene expressions of Ad4BP/SF-1, Cyp11a1, and StAR were significantly time- and concentration-dependent upregulated. To clarify the contribution of Ad4BP/SF-1 on Cyp11a1 and StAR transcripts, we silenced Ad4BP/SF-1 during the 5-aza-2-deoxycytidine treatment in C2C12 myoblasts, resulting in significant suppression of both Cyp11a1 and StAR. Additionally, pregnenolone levels in the supernatants of C2C12 cells were enhanced by 5-aza-2-deoxycytidine treatment, whereas pregnenolone production by C2C12 myoblasts was significantly suppressed by Ad4BP/SF-1 knockdown. These results indicate that DNA methylation of Ad4BP/SF-1 might be involved in the downregulation of steroidogenic genes, such as Cyp11a1 and StAR in C2C12 myoblasts.

Morphological and biochemical characterization of Holstein cow skin at the tail root region susceptible to Chorioptes bovis and texanus parasitism.

Cattle mange causes extreme itchiness, and the associated stress is an animal welfare concern that leads to economic losses due to decreased cattle productivity and deworming costs. This study investigated the reason why Chorioptic mites, C. bovis and C. texanus, preferentially infest the tail root region (rTR) and performed histological and biochemical analysis focusing on the volatile components of host odors that serve as the starting point for infestation of parasitic arthropods. Skin samples were taken from the rTR, lateral abdominal, and central masseteric, with the latter two designated as comparison sites. The two and three-dimensional histological analysis measured each sebaceous and sweat gland percentage per unit volume. The q-PCR analyzed the expression levels of ALDH1A1 and LOC785756, which are genes associated with volatile odoriferous compounds that serve as repellency and attractive messengers for ticks. Immunohistochemistry stained three sites with anti-androgen binding protein beta-like (ABPß-like), encoded by LOC785756, antibody. The three-dimensional analysis showed that sebaceous glands in the rTR tend to be more continuous and existed in larger masses than in other regions. The expression level of LOC785756 was significantly higher in the rTR, and immunohistochemistry revealed the presence of ABPß-like in the sebaceous gland with strong positive signals in the rTR. These results suggest that C. bovis/texanus selectively infests the rTR because that skin has well-developed sebaceous glands, including a large amount of ABPß-like, which acts as a mite attractant.

Subjective perception of visual field defects using random noise-moving images in patients with glaucoma: A comparison of computer graphics and analog noises.

PURPOSE: Random noise-moving images (noises) can make glaucoma patients with no subjective symptoms aware of visual field abnormalities. To explore this concept, we developed a noise using computer graphics (CG) and investigated the difference in the subjective perception of visual field abnormalities between CG and conventional analog noises. METHODS: We enrolled individuals with glaucoma (205 eyes), preperimetric glaucoma (PPG; 19 eyes), and normal eyes (35 eyes). For a CG noise, a series of still images was made by randomly selecting five monochromatic tones on 2-mm square dots, and these images were drawn at 60 frames per second (fps) to create a noise-moving image. The participants were asked to describe their perceived shadows on a paper. The results were categorized as follows based on the pattern deviation probability map of the Humphrey field analyzer (HFA): "agreement," "partial agreement," "disagreement," and "no response." The glaucoma stage was classified into four stages, from M1 to M4, based on the HFA's mean deviation. RESULT: The detection rates (agreement and partial agreement) were 80.5% and 65.4% for the CG and analog noises, respectively, with CG noise showing a significantly higher detection rate in all glaucoma eyes (P < 0.001). The detection rates tended to increase as the glaucoma stage progressed, and in Stage M3, these were 93.9% and 78.8% for the CG and analog noises, respectively. The PPG eyes did not exhibit subjective abnormalities for both noises. The specificity values were 97.1% and 100% for the CG and analog noises, respectively. CONCLUSION: The CG noise is more effective than the analog noise in evaluating the subjective perception of visual field abnormalities in patients with glaucoma.

What Happens 20 to 30 years After Radial Keratotomy? Case Series.

ABSTRACT: Radial keratotomy (RK) was commonly performed in the 1980s and 1990s. We aimed to clarify the current status of post-RK refractive correction and treatment. We retrospectively reviewed the charts of 70 patients with a history of RK. Of the 70 patients, 44 were identified for clinical outcomes. Refractive or therapeutic intervention (rigid gas-permeable contact lens fit, spectacle prescription, corneal surgery, and use of pilocarpine hydrochloride for photophobia) was possible in 59% of patients with postoperative visual deterioration after RK; in the remaining 41%, therapeutic intervention was not possible. Rigid gas-permeable contact lens fit for corneal irregular astigmatism was the most common refractive intervention and was effective in 36% of cases in the university hospital.

Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas.

PURPOSE: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas. SETTING: National Hospital Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance. RESULTS: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01). CONCLUSIONS: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.

Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases.

AIM: To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images. METHODS: This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases. RESULTS: The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for 'urgent', 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for 'semi-urgent', 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for 'routine' and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for 'observation', respectively. CONCLUSIONS: The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.

A Comprehensive Wavefront Assessment of Keratoconus Using an Integrated Scheimpflug Corneal Tomographer/Hartmann-Shack Wavefront Aberrometer.

OBJECTIVES: To characterize higher-order aberrations (HOAs) in different severities of keratoconus (KC) from the anterior and posterior corneal surfaces and whole eye using an integrated Scheimpflug corneal tomographer/Hartmann-Shack wavefront aberrometer. METHODS: This study included eyes with clinical KC, topographic KC (no clinical signs), fellow eyes with very asymmetric ectasia with normal topography and no clinical signs (VAE-NT), and control eyes. Corneal and ocular wavefront aberrations were obtained using an integrated Scheimpflug tomographer/Hartmann-Shack wavefront aberrometer. The diagnostic capability of distinguishing VAE-NT from the control was also tested. RESULTS: This study included 68 eyes with clinical KC, 44 with topographic KC, 26 with VAE-NT, and 45 controls. Clinical KC had significantly greater total HOAs and coma from the anterior and posterior corneal surfaces and whole eye than the other groups ( P <0.05). Although topographic KC had significantly greater values in all wavefront parameters than the control ( P <0.05), ocular and corneal HOAs did not differ between the VAE-NT and control groups. The coma from the anterior cornea in topographic KC was significantly greater than that in VAE-NT ( P <0.05); the coma from the posterior cornea and whole eye did not differ. Total HOAs from the anterior corneal surface exhibited the highest area under the receiver operating characteristic curve value of 0.774 (sensitivity, 73%; specificity, 78%). CONCLUSION: A comprehensive wavefront assessment can be used to quantitatively evaluate corneal and ocular HOAs across various severity of KC. Total HOAs from the anterior corneal surface exhibited the potential ability in distinguishing VAE-NT from the control eyes.

Effect of Segmented Optical Axial Length on the Performance of New-Generation Intraocular Lens Power Calculation Formulas in Extremely Long Eyes.

PURPOSE: To evaluate the performance of traditional vergence formulas with segmented axial length (AL) compared to traditional composite AL in extremely long eyes, and to determine whether the segmented AL can be extended to the new-generation formulas, including the Barrett Universal II, Emmetropia Verifying Optical 2.0 (EVO2), Hill-RBF 3.0 (Hill3), Kane, and Ladas Super formula (LSF) formulas in extremely long eyes. SETTING: National Hospital. Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients who underwent uncomplicated cataract surgery implanted with a three-piece intraocular lens between December 2015 and March 2021 were retrospectively reviewed. The composite AL was measured with a swept-source optical coherence tomography (SS-OCT) biometer using a mean refractive index. The segmented AL was calculated by summing the geometric lengths of the ocular segments (cornea, aqueous, lens, and vitreous) using multiple specific refractive indices based on the data obtained by the SS-OCT-based biometer. When refraction was measured at three months postoperatively, the median absolute errors (MedAEs) were calculated with two ALs for each formula. RESULTS: The study included 31 eyes of 22 patients. The segmented AL (30.45 ± 1.23 mm) was significantly shorter than the composite AL (30.71 ± 1.28 mm, p < 0.001). The MedAEs were significantly reduced when using segmented AL for SRK/T, Haigis, Hill3, and LSF, compared to those obtained using composite AL (0.38 vs. 0.62, 0.48 vs. 0.79, 0.50 vs. 0.90, 0.34 vs. 0.61, p < 0.001 for all formulas, respectively). On the contrary, the MedAE obtained by Kane with segmented AL was significantly worse compared to the one with composite AL (0.35 vs. 0.27, p = 0.03). CONCLUSION: In extremely high myopic eyes, the segmented AL improves the performance of SRK/T, Haigis, Hill3, and LSF formulas compared to the composite AL, while the segmented AL worsens the prediction accuracy of the Kane formula.

Mechanism of skeletal muscle atrophy by muscle fiber types in male rats under long-term fasting stress.

Fasting induces metabolic changes in muscles, which are differentiated by muscle fiber type. In this study, the mechanism of fasting-induced muscle atrophy in rats was examined to determine the differences between muscle fiber types in energy production. Fasting for 96 h did not alter the weight of the soleus (SOL), a fiber type I muscle, but did significantly reduce the weight of gastrocnemius (GM), a fiber type II muscle. GM, SOL and blood pregnenolone and testosterone levels decreased under fasting, which induced energy deprivation, whereas corticosterone (CORT) levels significantly increased. However, the expression of 3ß-HSD and P45011ß in GM was unaffected by fasting. The decrease in GM weight may be due to decreased levels of testosterone and reduced synthesis of mammalian target of rapamycin (mTOR). Significant increases in CORT both GM and SOL were associated with increases in the amount of branched-chain amino acids available for energy production. However, decreased levels of mTOR and IGF1 and increased levels of CORT and IL-6 in SOL suggest that GM proteolysis was followed by SOL proteolysis for additional energy production. In conclusion, IGF1 levels decreased significantly in SOL, whereas those of IL-6 significantly increased in SOL and blood but decreased in GM. Blood branched-chain amino acids (BCAA) levels were unaffected due to fasting, whereas an increase was noted in the levels of BCAA in GM and SOL. These results show that fasting for 96 h restricts energy supply, producing fast-twitch muscle atrophy followed by slow-twitch muscle atrophy.

Optical Quality and Visual Performance With Different Toric Contact Lens Designs.

OBJECTIVES: To evaluate the optical quality of different toric contact lens (CL) designs and compare their on-eye visual correction performance. METHODS: Twenty soft CL wearers aged 20 to 39 years were enrolled. Two daily disposable silicone-hydrogel toric CLs were tested: the "Eyelid Stabilized Design" (ESD-CL) and prism-ballast design (PB-CL); a spherical daily disposable silicone hydrogel CL (spherical CL) was used as a control. On-eye performance was compared for corrected distance visual acuity (CDVA), astigmatism, and ocular higher-order aberrations (HOAs); astigmatism and ocular HOAs were measured with a wavefront sensor. The subjective quality of vision, rated for "blurred vision" and "double vision," lens rotation, and fitting were also compared. RESULTS: The ESD-CLs, PB-CL, and no-CL provided better CDVA than spherical CL ( P <0.05). Compared with spherical CL and no CL, PB-CL and ESD-CLs caused significantly lesser astigmatism ( P <0.05). Coma was significantly lesser with ESD-CLs than that with PB-CL ( P <0.05); total HOAs did not differ among the four conditions. The subjective ratings for blurred and double vision were significantly lower with ESD-CLs than those with spherical CL ( P <0.05). CONCLUSIONS: Toric CLs provide a better CDVA than spherical CLs. However, differences in coma and subjective symptoms may occur because of the design of toric CLs.

Molecular and clinical correlates of HER3 expression highlights its potential role as a therapeutic target in melanoma.

Overexpression of the epidermal growth factor receptor family member HER3 (erbB3) has been implicated in several types of cancer and recently drugs targeting HER3 have shown promising clinical activity. In melanoma, HER3 overexpression has been linked to both metastasis formation and resistance to drug therapy in cell culture models. Here, we sought to characterise the expression of HER3 in 187 melanoma biopsies (149 cutaneous, 38 mucosal) using immunohistochemistry, as well as to analyse the association between HER3 expression and molecular, clinical and pathological variables. A subset of the cutaneous melanoma specimens was taken prior to treatment with immune checkpoint blockade therapy (pre-ICB) (n=79). HER3 expression (≥1+) was observed in 136 of 187 samples (∼73%). HER3 expression was found to be markedly lower in the mucosal melanomas, with 17 of the 38 tumours (∼45%) demonstrating no HER3 expression. In cutaneous melanomas, there was a negative association between HER3 expression and mutational load, a positive association with NRAS mutational status, and a trend of negative association with PD-L1 expression. In the pre-ICB cohort, an association was found between high HER3 expression (≥2+) and overall survival after anti-PD-1-based immunotherapy. Overall, our results indicate that HER3 is a promising therapeutic avenue in cutaneous melanoma worthy of further clinical evaluation.

Long-Term Corneal Refractive Power Changes Two Decades After Radial Keratotomy With Microperforations.

ABSTRACT: We retrospectively examined corneal refractive power in three patients who had been followed up for more than 20 years after radial keratotomy (RK) with microperforations (MPs). All patients underwent RK in both eyes and were referred to our clinic because of postoperative decreased vision. MP was observed in five of the six eyes at the initial visit. The corneal refractive power of the anterior and posterior surfaces of the 6-mm-diameter cornea was examined using Fourier analysis based on corneal shape analysis using anterior segment optical coherence tomography. The spherical components decreased in all three cases. The asymmetry and higher-order irregularity components and fluctuations in corneal refractive power were markedly greater in the two cases with MP in both eyes. Fluctuations in corneal refractive power were observed at more than 20 years after RK with MP. Therefore, careful observation is necessary, even after a long-term postoperative follow-up period.

Physicochemical properties of wooden breast-extracted myosin and rheological properties of its heat-induced gel.

BACKGROUND: It is reported that broilers with 'wooden breast' have poor processing properties, such as low binding and water-holding capacities. However, the reason for the poor functional characteristics has not been clarified. In this study, myosin was extracted from a wooden breast. Its physicochemical properties were investigated to clarify the relationship between the structure and physicochemical properties of the heating gel of myosin obtained from the wooden breast. RESULTS: The turbidity of myosin solution extracted from wooden breast increased with increase in the heat treatment to a higher value than that from the normal breast meat myosin. The solubility of myosin collected from a wooden breast after heating decreased like normal breast muscle myosin. The surface hydrophobicity of myosin removed from wooden breast increased continually above 60 °C, unlike the change in surface hydrophobicity of normal breast myosin. The free thiol group of myosin extracted from the wooden breast was higher than normal breast myosin before and after heating. The apparent elasticity of heat-induced gels and chicken meat sausages was significantly lower in sausages and gel with wooden breast than normal ones (P < 0.05). The microstructure of the heated gel of normal myosin showed a fine network structure. In contrast, the heat-induced gel of wooden breast-extracted myosin showed a structure with loosely connected aggregates and many gaps. CONCLUSION: The coarseness of the internal gel structure of myosin extracted from wooden breast was shown to affect the apparent elasticity of the gel and sausages made from the chicken meat. © 2023 Society of Chemical Industry.

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil.

The hepatitis E virus (HEV) causes a common infectious disease that infects pigs, wild boars, deer, and humans. In most cases, humans are infected by eating raw meat. Some essential oils have been reported to exhibit antiviral activities. In this study, in order to investigate the anti-HEV properties of essential oils, the immunoreactivities of HEV antigen proteins against the relevant antibodies were analyzed after the HEV antigens underwent treatment with various essential oils. The essential oils extracted from the tea tree, which was previously reported to exhibit antiviral activity, lavender, and lemon had strongly reduced activity. We found that treatment with the essential oil prepared from Sakhalin spruce was associated with the strongest reduction in immunoreactivity of HEV antigen protein(s) among the tested substances. The main volatile constituents of Sakhalin spruce essential oil were found to be bornyl acetate (32.30 %), α-pinene (16.66 %), camphene (11.14 %), camphor (5.52 %), ß-phellandrene (9.09 %), borneol (4.77 %), and limonene (4.57 %). The anti-HEV properties of the various components of the essential oils were examined: treatment with bornyl acetate, the main component of Sakhalin spruce oil, α-pinene, the main component of tea tree oil, and limonene, the main component of lemon oil, resulted in a strong reduction in HEV antigen immunoreactivity. These results indicate that each main component of the essential oils plays an important role in the reduction of the immunoreactivity of HEV antigen protein(s); they also suggest that Sakhalin spruce essential oil exhibits anti-HEV activity. In a formulation with the potential to eliminate the infectivity of HEV in foodborne infections, this essential oil can be applied as an inactivating agent for meat processing and cooking utensils, such as knives and chopping boards.

Comparison of Ocular Wavefront Aberration Measurements Obtained Using Two Hartmann-Shack Wavefront Aberrometers.

OBJECTIVES: To assess agreement between measurements of ocular wavefront aberrations obtained using the Pentacam AXL Wave (Oculus Optikgeräte GmbH) (Aberrometer A) and KR-1W (Topcon Corp) (Aberrometer B), both of which are based on the Hartmann-Shack principle. METHODS: In this prospective case-control study, ocular wavefront aberrations measurements were obtained using both aberrometers in patients with keratoconus (KC) and control participants. Ocular wavefront aberrations were measured through the natural pupil without dilation using both devices in a dark room. For both aberrometers, accommodation was inhibited by automatically adding fogging. The individual Zernike coefficients from the second to fourth order were compared between the two aberrometers for a 4-mm pupil diameter. RESULTS: Twenty-six KC and 29 control eyes were assessed. Statistically significant correlations ( P <0.05) were observed for all Zernike coefficients, except for Z 4-2 in the control group. Bland-Altman analysis indicated good agreement between aberrometers and no statistically significant differences in the control group. However, in the KC group, patterns of proportional error were observed in vertical coma Z 3-1 (r=0.338, P =0.008), trefoil Z 4-4 (r=0.701, P =0.003), secondary astigmatism Z 4-2 (r=0.348, P =0.025), and spherical aberrations Z 40 (r=0.407, P =0.012). CONCLUSIONS: The Zernike coefficient values measured by the two aberrometers were well correlated in the control and KC groups. However, in eyes with KC, Aberrometer B tended to present greater values in several Zernike coefficients than Aberrometer A, suggesting that wavefront measurements obtained using the two aberrometers are not interchangeable in patients with KC.

Quantitative analysis of drug distribution in heterogeneous tissues using dual-stacking capillary electrophoresis-mass spectrometry.

BACKGROUND AND PURPOSE: Intratumour heterogeneity frequently leads to drug resistance, which is a major issue in drug discovery. Drug distribution is one of the key factors for elucidating the resistance mechanism; however, quantitative and regional drug measurement is challenging. Here, we developed a novel ultra-sensitive analytical method and applied it to HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd), aiming to explore its payload (DXd) distribution within heterogeneous tissues. EXPERIMENTAL APPROACH: The developed analytical method is named LDMS-CE-MS, a capillary electrophoresis-mass spectrometry (CE-MS) coupled with a novel sample preconcentration/separation method called "large-volume dual-sample stacking by micelle collapse and sweeping (LDMS)". First, the analytical performance of LDMS-CE-MS for DXd detection was evaluated. Subsequently, we evaluated the bystander effect of HER3-DXd, where tumour tissues were excised from xenograft models and clinical specimens after administration of HER3-DXd. HER3-high expression, adjacent, and HER3-low expression regions were then sampled by laser microdissection to quantify the released DXd. KEY RESULTS: LDMS concentrated DXd by 1000-fold and separated it from the hydrophilic bio-matrix through continuous capture and release by the charged micelles, allowing quantification at sub-attomole-level. DXd concentrations decreased in the order of antigen-high expression > adjacent > antigen-low expression regions in the tumour xenograft model, whereas in clinical specimens, adjacent and antigen-high expression regions had approximately the same concentration. These distributions represent a bystander effect. CONCLUSIONS AND IMPLICATIONS: Our LDMS-CE-MS successfully visualized the attomole-level drug distributions in heterogeneous clinical specimens. This new platform opens a new era of quantitative pharmacokinetic analysis, facilitating drug discovery and development.

Assessment of the corneal biomechanical features of granular corneal dystrophy type 2 using dynamic ultra-high-speed Scheimpflug imaging.

PURPOSE: To evaluate the corneal biomechanical features of eyes with granular corneal dystrophy type 2 (GCD2) by analyzing corneal biomechanical indices obtained using a Corvis ST (CST) dynamic ultra-high-speed Scheimpflug imaging device. METHODS: In this retrospective case-control study, 35 CST parameters were compared in normal eyes (control) and eyes of patients with GCD2 treated at Osaka University Hospital, Osaka, Japan. The parameters included the Corvis Biomechanical Index (CBI), which is important in differentiating eyes with keratoconus from normal eyes. We measured the deposition rates of lesions in the central 7-mm region of the eye and assessed the correlation between the deposition rate and the CBI. RESULTS: Twenty-one eyes with GCD2 and 23 control eyes were analyzed. Eyes with GCD2 showed significantly less corneal stiffness in 15 CST parameters than did control eyes. In particular, the CBI was remarkably higher in eyes with GCD2 than in control eyes (P = 0.000006). Additionally, the deposition rate and the CBI were positively correlated. CONCLUSIONS: GCD2 eyes had softer corneas than did control eyes in most biomechanical CST parameters, and one of the parameters (the CBI) was linked to the rate of deposited lesions. Since IOP may be underestimated in GCD2 eyes, management should be especially careful in GCD2 cases complicated by glaucoma.

Clinical Performance of a Hydrophobic Acrylic Diffractive Trifocal Intraocular Lens in a Japanese Population.

INTRODUCTION: In this study, clinical performance of a hydrophobic acrylic diffractive trifocal intraocular lens (IOL) with double C-loop haptics was evaluated in Japanese cataract eyes. METHODS: Twenty-three patients had bilateral cataract surgery with the implantation of a trifocal IOL with double C-loop haptics. Postoperative examinations at 6 months included assessing uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA) at 5 m, uncorrected intermediate visual acuity (UIVA), distance-corrected intermediate visual acuity (DCIVA) at 80 cm, uncorrected near visual acuity (UNVA) and distance-corrected near visual acuity (DCNVA) at 40 cm. Binocular defocus, contrast sensitivity, spectacle independence, symptoms of photic phenomena and quality of vision (QOV) were also observed. RESULTS: Twenty-three patients received 46 IOLs binocularly. Manifest refraction spherical equivalent was - 0.227 ± 0.385 D (mean ± standard deviation) at 6 months postoperatively. Binocular UDVA, binocular UIVA and binocular UNVA were - 0.101 ± 0.065, - 0.021 ± 0.079 and 0.022 ± 0.095 logMAR units, respectively. Binocular CDVA, binocular DCIVA and binocular DCNVA were - 0.151 ± 0.044, - 0.042 ± 0.067 and - 0.011 ± 0.080 logMAR, respectively. Binocular CDVA of 0.00 logMAR or better was obtained in the defocus from - 3.0 D until + 0.5 D. Only 8.7% of patients required the use of spectacles postoperatively. There were no symptoms of glare, halo and light disturbance in 78.3%, 56.5% and 69.6% of patients, respectively. QOV scores significantly improved postoperatively (P < 0.0001). CONCLUSION: The hydrophobic acrylic trifocal IOL with double C-loop haptics provides good visual performance at all distances and produces high spectacle independence rate and patient satisfaction. TRIAL REGISTRATION NUMBER: NCT04699266 (Clinicaltrials.gov).

The location of protein oxidation in dystrophic skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe childhood disease characterised by progressive muscle wasting caused by widespread myofibre necrosis. Implicated in the pathology of DMD is oxidative stress, caused by excessive generation of reactive oxygen and nitrogen species (RONS). One consequence of RONS exposure is post-translational oxidative modifications to proteins, which can cause loss of protein function. This study used the dystrophic mdx mouse model for DMD to visualise the precise location of different oxidative modifications to proteins in dystrophic muscles, including both reversible (protein thiol oxidation and s-nitrosylation) and irreversible (carbonylation and dityrosine formation) oxidation at various stages of dystrophic muscle necrosis and regeneration. High levels of protein oxidation were observed in mdx myofibres undergoing degeneration and immune cell infiltration (myonecrosis). Since irreversible protein oxidation, especially dityrosine formation, was only colocalised to areas of myonecrosis, we suggest that this specific measurement could be a useful biomarker of myonecrosis. To test this we quantified dityrosines in muscle homogenates; this analysis showed significantly higher levels of dityrosines in mdx (compared with control normal) mice aged 23 days, an age when acute onset of extensive myonecrosis occurs in mdx muscles. These results indicate a major localised role of immune cells in RONS generation in dystrophic muscle, and strongly support a role for protein oxidation in myonecrosis and associated dystropathology. Consequently, the measurement of protein oxidation (specifically dityrosines) in dystrophic muscles may be a useful biomarker for indirectly quantifying myonecrosis in research studies using mdx mice and other animal models for DMD.

Potent and Selective PTDSS1 Inhibitors Induce Collateral Lethality in Cancers with PTDSS2 Deletion.

SIGNIFICANCE: This study identifies a specific dependency on PTDSS1 for phosphatidylserine synthesis following PTDSS2 deletion and introduces novel PTDSS1 inhibitors as a therapeutic option to induce collateral lethality in cancer with PTDSS2 loss.