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Background/aimsTo apply retinal nerve fibre layer (RNFL) optical texture analysis (ROTA) to investigate (1) the patterns of RNFL bundle defects, and (2) the frequency of papillomacular and papillofoveal bundle involvement across early, moderate and advanced glaucoma.MethodsAll eyes underwent 24–2 visual field (VF) testing and optical coherence tomography (OCT) for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular and papillofoveal bundles was determined for each eye. 24–2 VF stimulus projections were mapped onto the corresponding topographic areas of ROTA images. Multilevel logistic regression analysis was applied to evaluate the structure-function association.ResultsPapillomacular bundle defects were highly prevalent in glaucoma, increasing from 87.7% in early to 95.35% in moderate and 100% in advanced glaucoma. Papillofoveal bundle defects were also common, increasing from 29.7% in early to 36.05% in moderate and 60.98% in advanced glaucoma. Central four 24–2 test locations that projected onto the trajectories of papillomacular or papillofoveal RNFL bundle defects demonstrated significantly increased likelihood of VF sensitivity abnormality (ORs of 22.42 at PDP<5% and 20.26 at TDP<5%, respectively, p<0.001 for both).ConclusionROTA uncovers a wide spectrum of RNFL bundle defects spanning the entire glaucoma continuum. It also provides visualisation of the preserved RNFL bundles in advanced glaucoma. Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with early, moderate and advanced glaucoma, and, when detected, they significantly increase the likelihood of abnormality in the corresponding central 24–2 test locations.

Compared with optical coherence tomography (OCT) in the near-infrared domain, the visible-light OCT (vis-OCT) system affords a higher axial resolution for discerning subtle pathological changes associated with early diseases. However, the significant material dispersion at the visible-light range leads to a severe problem for dispersion management in vis-OCT systems, which results in a compromised axial resolution. While dispersion compensators (such as prism pairs) are commonly used, a digital method is still highly desirable and has been widely used to compensate for the residual dispersion imbalance between the reference and sample arms in an OCT system. In this paper, we develop a generic approach to effectively compensate for the system dispersion, especially the higher-order dispersion in the vis-OCT system, by using a single arbitrary measurement of the mirror-reflection (SAMMR) method and its resulting phase information. Compared with the previous methods, including the method based on the Taylor series iterative fitting and differential method, the proposed method does not need to extract the dispersion coefficients or use the metric functions and affords a better performance for axial resolution and the signal-to-noise ratio in vis-OCT systems. Its effectiveness is further validated in an OCT system operating in the near-infrared domain.

The time and energetic costs of behavioral responses to incidental and experimental sonar exposures, as well as control stimuli, were quantified using hidden state analysis of time series of acoustic and movement data recorded by tags (DTAG) attached to 12 sperm whales (Physeter macrocephalus) using suction cups. Behavioral state transition modeling showed that tagged whales switched to a non-foraging, non-resting state during both experimental transmissions of low-frequency active sonar from an approaching vessel (LFAS; 1–2 kHz, source level 214 dB re 1 μPa m, four tag records) and playbacks of potential predator (killer whale, Orcinus orca) sounds broadcast at naturally occurring sound levels as a positive control from a drifting boat (five tag records). Time spent in foraging states and the probability of prey capture attempts were reduced during these two types of exposures with little change in overall locomotion activity, suggesting an effect on energy intake with no immediate compensation. Whales switched to the active non-foraging state over received sound pressure levels of 131–165 dB re 1 μPa during LFAS exposure. In contrast, no changes in foraging behavior were detected in response to experimental negative controls (no-sonar ship approach or noise control playback) or to experimental medium-frequency active sonar exposures (MFAS; 6–7 kHz, source level 199 re 1 μPa m, received sound pressure level [SPL] = 73–158 dB re 1 μPa). Similarly, there was no reduction in foraging effort for three whales exposed to incidental, unidentified 4.7–5.1 kHz sonar signals received at lower levels (SPL = 89–133 dB re 1 μPa). These results demonstrate that similar to predation risk, exposure to sonar can affect functional behaviors, and indicate that increased perception of risk with higher source level or lower frequency may modulate how sperm whales respond to anthropogenic sound.

Early microvascular damage in diabetes (e.g. capillary nonperfusion and ischemia) can now be assessed and quantified with optical coherence tomography-angiography (OCT-A). The morphology of vascular tissue is indeed affected by different factors; however, there is a paucity of data examining whether OCT-A metrics are influenced by ocular, systemic and demographic variables in subjects with diabetes. We conducted an observational cross-sectional study and included 434 eyes from 286 patients with diabetes. Foveal avascular zone (FAZ) area, FAZ circularity, total and parafoveal vessel density (VD), fractal dimension (FD), and vessel diameter index (VDI) from the superficial capillary plexus OCT-angiogram were measured by a customized automated image analysis program. We found that diabetic retinopathy (DR) severity was associated with increased FAZ area, decreased FAZ circularity, lower VD, lower FD, and increased VDI. Enlarged FAZ area was correlated with shorter axial length and thinner central subfield macular thickness. Decreased FAZ circularity was correlated with a reduction in visual function. Decreased VD was correlated with thinner macular ganglion-cell inner plexiform layer. Increased VDI was correlated with higher fasting glucose level. We concluded that the effects of ocular and systemic factors in diabetics should be taken into consideration when assessing microvascular alterations via OCT-A.

AimsTo evaluate the distributions of quantitative optical coherence tomography angiography (OCT-A) metrics and its associated factors in children.Methods1059 children aged 6–8 years were recruited from the Hong Kong Children Eye Study. All the participants underwent OCT-A with a swept-source OCT. Retinal microvasculature on superficial capillary plexus was assessed and quantified by a customised automated image analysis programme. Univariable and multiple linear regression analyses were performed to determine systemic (body mass index (BMI), waist circumference, head circumference and blood pressure), demographic and ocular (axial length (AL), macular thickness and volume, retinal nerve fibre layer (RNFL) thickness and visual acuity) variables (independent variables) associated with OCT-A metrics (dependent variables).ResultsIn multiple linear regression analyses, enlarged foveal avascular zone area was associated with female gender (β=0.110, p<0.001), decreased AL (β=−0.097, p<0.001) and decreased central macular thickness (β=−0.008, p<0.001). Decreased vessel density was associated with increased BMI (β=−4.12×10−4, p=0.006), decreased AL (β=0.003, p<0.001) and decreased central macular thickness (β=7.87×10−5, p=0.001). Increased vessel diameter index was associated with female gender (β=0.020, p=0.007) and decreased AL (β=−0.020, p<0.001). Decreased fractal dimension was associated with older age (β=−0.001, p=0.008). There were no significant correlations between OCT-A metrics with visual acuity, RNFL thickness, central corneal thickness, waist circumference, head circumference and blood pressure (all p>0.05).ConclusionOur findings provides new information on baseline morphology of retinal microvasculature and its associated factors in school children, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinal microvasculature.

ObjectiveTo compare the cost-effectiveness of drug-coated balloon angioplasty (DCB) versus plain old balloon angioplasty (POBA) for treatment of arteriovenous fistula (AVF) stenosis.MethodsA Markov model was created to compare DCB versus POBA for AVF stenosis over a 2-year time horizon from a United States payer’s perspective. Probabilities related to complications, restenosis, retreatment, and all-cause mortality were obtained from published literature. Costs were calculated using Medicare reimbursement rates and data from published cost analyses, inflation-adjusted to 2021. Health outcomes were measured with quality-adjusted life years (QALY). Probabilistic and deterministic sensitivity analyses were performed with a willingness-to-pay threshold of$100,000/QALY.ResultsBase case calculation showed better quality-of-life outcomes but increased cost with POBA compared to DCB, with an incremental cost-effectiveness ratio of $ 27,413/QALY, making POBA the more cost-effective strategy in the base case model. Sensitivity analyses showed that DCB becomes cost-effective if the 24-month mortality rate after DCB is no more than 3.4% higher than that after POBA. In secondary analyses where mortality rates were equalized, DCB was more cost-effective than POBA until its additional cost reached more than$4213 per intervention.ConclusionWhen modeled from a payer’s perspective over 2 years, the cost utility of DCB versus POBA varies with mortality outcomes. POBA is cost-effective if 2-year all-cause mortality after DCB is greater than 3.4% higher than after POBA. If 2-year mortality after DCB is less than 3.4% higher than after POBA, DCB is cost-effective until its additional cost per procedure exceeds $ 4213 more than POBA.Level of Evidence IV: Historically Controlled Study.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster . Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner. Since ROS are also involved in determining the lifespan, we discovered that the absence of T-type and cacophony decreased the lifespan while the absence of D-type maintained a similar lifespan to that of the wild-type strain. VGCCs are also responsible for electrical signaling in cardiac cells. The cardiac function of each mutant was evaluated through optical coherence tomography (OCT), which revealed that α1-subunits of VGCCs are essential in maintaining cardiac rhythmicity and cardiac function in an age-dependent manner. Our results establish specific roles of α1-subunits of VGCCs in the functioning of the aging heart.

Background To test clinically relevant factors associated with quantitative artifact-free deep capillary plexus (DCP) metrics in patients with diabetes mellitus (DM). Methods 563 eligible eyes (221 with no diabetic retinopathy [DR], 135 with mild DR, 130 with moderate DR, and 77 with severe DR) from 334 subjects underwent optical coherence tomography-angiography (OCT-A) with a swept-source OCT (Triton DRI-OCT, Topcon, Inc., Tokyo, Japan). Strict criteria were applied to exclude from analysis those DCP images with artifacts and of poor quality, including projection artifacts, motion artifacts, blurriness, signal loss, B-scan segmentation error, or low-quality score. A customized MATLAB program was then used to quantify DCP morphology from the artifact-free DCP images by calculating three metrics: foveal avascular zone (FAZ), vessel density (VD), and fractal dimension (FD). Results 166 (29.5%) eyes were excluded after quality control, leaving in the analysis 397 eyes (170 with no DR, 101 with mild DR, 90 with moderate DR, 36 with severe DR) from 250 subjects. In the multiple regression models, larger FAZ area was associated with more severe DR (β = 0.687; p  = 0.037), shorter axial length (AL) (β = − 0.171; p  = 0.003), thinner subfoveal choroid thickness (β = − 0.122; p  = 0.031), and lower body mass index (BMI) (β = − 0.090; p  = 0.047). Lower VD was associated with more severe DR (β = − 0.842; p  = 0.001), shorter AL (β = 0.107; p  = 0.039), and poorer visual acuity (VA) (β = − 0.133; p  = 0.021). Lower FD was associated with more severe DR (β = − 0.891; p  < 0.001) and with older age (β = − 0.142; p  = 0.004). Conclusions Quantitative artifact-free DCP metrics are associated with VA, DR severity, AL, subfoveal choroidal thickness, age, and BMI in diabetic patients. The effects of ocular and systemic factors should be considered for meaningful interpretations of DCP changes in DM patients.

The large conductance, calcium, and voltage‐active potassium channels (BKCa) were originally discovered in Drosophila melanogaster as slowpoke (slo). They are extensively characterized in fly models as ion channels for their roles in neurological and muscular function, as well as aging. BKCa is known to modulate cardiac rhythm and is localized to the mitochondria. Activation of mitochondrial BKCa causes cardioprotection from ischemia–reperfusion injury, possibly via modulating mitochondrial function in adult animal models. However, the role of BKCa in cardiac function is not well‐characterized, partially due to its localization to the plasma membrane as well as intracellular membranes and the wide array of cells present in mammalian hearts. Here we demonstrate for the first time a direct role for BKCa in cardiac function and cardioprotection from IR injury using the Drosophila model system. We have also discovered that the BKCa channel plays a role in the functioning of aging hearts. Our study establishes the presence of BKCa in the fly heart and ascertains its role in aging heart function.

Angiomatoid fibrous histiocytoma (AFH) is a rare and slow-growing soft tissue lesion that typically arises in the extremities of young patients. Microscopically, AFH is characterized by pseudovascular, blood-filled spaces that are surrounded by a multinodular proliferation of spindle and/or round cells and lymphoid cuffs. However, there is a wide morphological spectrum, including a myxoid variant. Examples with a prominent myxoid matrix are rare and may pose great diagnostic difficulty. Specific gene fusions have been found to play a significant role in AFH tumorigenesis. Gene fusions of Ewing sarcoma breakpoint region 1 (EWSR1) with members of the cAMP response element-binding protein family (CREB) of transcription factors (CREB1, activating transcription factor 1 (ATF1), and cAMP response element modulator (CREM)) have been described in histopathologically diverse mesenchymal neoplasms such as AFH, hyalinising clear cell carcinomas of salivary glands, primary pulmonary myxoid sarcoma, and clear cell sarcoma. Classically, EWSR1-CREB is known to be the prominent gene fusion in AFH. Recently, a small series of intracranial mesenchymal tumors with EWSR1-CREB family gene fusions has been reported. These tumors seem to show histologic, immunophenotypic, and cytogenic features similar to those observed in the myxoid variant of AFH; therefore, there is a debate on whether these tumors merely represent a variant of AFH or a novel entity. This case report is of a 58-year-old woman presenting with the first episode of generalized seizure due to an extra-axial lesion with homogenous contrast enhancement in the right parietal lobe, which was initially diagnosed as a World Health Organization (WHO) grade I meningioma. Following a series of pathological investigations, the diagnosis of an intracranial myxoid variant of AFH was made. This case report illustrates the need to consider the myxoid variant of intracranial AFH in the differential diagnosis of meningioma-like tumors. A high index of suspicion is required if the meningioma behaves abnormally with a much higher recurrence rate.