Choroidal thickness profile and clinical outcomes in eyes with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the relationship between choroidal thickness (CT) profile and clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment in polypoidal choroidal vasculopathy (PCV). METHODS: Medical records of patients diagnosed with PCV who received anti-VEGF treatment over 12 months were reviewed. Subfoveal CT (SFCT) and peripapillary CT (PCT) were measured on swept-source optical coherence tomography images. Patients were divided into various groups based on choroidal profiles including SFCT, nasal PCT (nPCT) and ratio of SFCT to nPCT (SFCT/nPCT). Clinical outcomes were compared between the thin and thick CT groups. RESULTS: A total of 65 patients with PCV patients were included. After ant-VEGF treatment, SFCT was significantly decreased after anti-VEGF treatment (P = 0.001), but nasal PCT (nPCT) was not. Clinical outcomes were not different between the thin and thick SFCT groups. Total number of injections during the 12 months was significantly fewer in the thin nPCT group (3.4 ± 1.3) than in the thick nPCT group (4.5 ± 1.8) (P = 0.020). Complete resolution after loading injections was more frequently observed in the high SFCT/nPCT ratio (> 1.9) group (87.9%) than in the low SFCT/nPCT ratio (≤ 1.90) group (59.4%) (P = 0.009). The ratio of SFCT/nPCT showed the best predictive ability for poor responders (area under curve = 0.771). CONCLUSION: These results suggest that baseline nPCT and SFCT/nPCT ratio could be a good biomarker that reflects clinical outcomes after anti-VEGF treatment in PCV.

Ca2+/calmodulin-dependent protein kinase II and Dimethyl Sulfoxide affect the sealing frequencies of transected hippocampal neurons.

Traumatic injury often results in axonal severance, initiating obligatory Wallerian degeneration of distal segments, whereas proximal segments often survive. Calcium ion (Ca2+ ) influx at severed proximal axonal ends activates pathways that can induce apoptosis. However, this same Ca2+ -influx also activates multiple parallel pathways that seal the plasmalemma by inducing accumulation and fusion of vesicles at the lesion site that reduce Ca2+ -influx and enhance survival. We examined whether various inhibitors of Ca2+ /calmodulin-dependent protein kinases (CaMKs), and/or dimethyl sulfoxide (DMSO), a common solvent for biologically active substances, affected the ability of a hippocampal-derived neuronal cell line (B104 cells) to seal membrane damage following axotomy. Axolemmal sealing frequencies were assessed at different transection distances from the axon hillock and at various times after Ca2+ -influx (PC times) by observing whether transected cells took-up fluorescent dyes. Inhibition of CaMKII by tatCN21 and KN-93, but not inhibition of CaMKI and CaMKIV by STO-609, affected axonal sealing frequencies. That is, CaMKII is a component of previously reported parallel pathways that induce membrane sealing, whereas CaMKI and CaMKIV are not involved. The effects of these CaMKII inhibitors on plasmalemmal sealing depended on their mechanism of inhibition, transection distance, and PC time. DMSO at low concentrations (90 µM-28 mM or 0.00064%-0.2% v/v) significantly increased membrane-sealing frequencies at most PC times and transection distances, possibly by permeabilizing the plasmalemma to Ca2+ . Inhibition of CaMKII, DMSO, PC time, and the transection distance significantly affect plasmalemmal sealing that is critical to somal survival in traumatic lesions.

Correlations Between A1C and Diabetes Knowledge, Diabetes Numeracy, and Food Security in a Vulnerable Type 2 Diabetes Population.

Type 2 diabetes is over-represented in vulnerable populations. Vulnerable patients managing diabetes are challenged with less-than-optimal processes and outcomes of care; thus, Healthy People 2020 and the American Diabetes Association have renewed the focus on social determinants of health with regard to the management of chronic diseases such as diabetes. This study explored the correlations between A1C and social and personal factors, including diabetes knowledge, diabetes numeracy, and food security. The Diabetes Numeracy Test-15, the Spoken Knowledge in Low Literacy Diabetes Scale, and the U.S. Department of Agriculture Food Security Questionnaire were administered to a Caucasian study population (n = 96) receiving diabetes care at a federally qualified health center. Although the correlation coefficients generated by the results obtained from the three questionnaires and A1C levels were generally small, a correlation coefficient of 0.46 was found between food security and A1C. An improved understanding of factors that contribute to the successful self-management of diabetes is necessary to improve diabetes outcomes in vulnerable populations.

Simple fabrication method for a porous poly(vinyl alcohol) matrix by multisolvent mixtures for an air-exposed model of the lung epithelial system.

We introduce a simple and easy method for fabricating a thin and porous matrix that can be used as an extracellular matrix (ECM). A porous poly(vinyl alcohol) (PVA) matrix was created through recrystallization by multiple solvents under distilled water (DW), isopropyl alcohol (IPA), and a combination of DW and IPA. The crysatllization was driven by precipitating and dissolving a solute in a solution of a solvent and a nonsolvent, which induced the formation of microspheres in the IPA. The crystal structure depended on the ratio of the solvent/nonsolvent and the concentration of the PVA aqueous solution; these properties were used to tune the thickness, size, and porosity of the matrices. The resulting PVA matrix was chemically stabilized through a reaction with glutaraldehyde in the IPA solution. We demonstrated that a very thin and porous PVA matrix provided an effective functional model of the lung epithelial system. Lung epithelial cells (A549) displayed a high affinity for this matrix, which was permeable to the culture medium. These properties facilitated culturing under the air environment.

Comparison of intraocular pressure fluctuation and glaucoma progression rate between phakic and pseudophakic eyes in pseudoexfoliation glaucoma.

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (-2.15 ± 2.66 dB/year vs. -0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (-2.92 ± 2.34 µm/year vs. -1.79 ± 1.71 µm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, -1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.

Digitally tunable physicochemical coding of material composition and topography in continuous microfibres.

Heterotypic functional materials with compositional and topographical properties that vary spatiotemporally on the micro- or nanoscale are common in nature. However, fabricating such complex materials in the laboratory remains challenging. Here we describe a method to continuously create microfibres with tunable morphological, structural and chemical features using a microfluidic system consisting of a digital, programmable flow control that mimics the silk-spinning process of spiders. With this method we fabricated hydrogel microfibres coded with varying chemical composition and topography along the fibre, including gas micro-bubbles as well as nanoporous spindle-knots and joints that enabled directional water collection. We also explored the potential use of the coded microfibres for tissue engineering applications by creating multifunctional microfibres with a spatially controlled co-culture of encapsulated cells.

Biometric imaginaries: Formatting voice, body, identity to data.

This article examines the sociotechnical imaginary within which contemporary biometric listening or VIA (voice identification and analysis) technologies are being developed. Starting from an examination of a key article on Voiceprint identification written in the 1940s, I interrogate the conceptual link between voice, body, and identity, which was central to these early attempts at technologizing voice identification. By surveying patents that delineate systems for voice identification, collection methods for voice data, and voice analysis, I find that the VIA industry is dependent on the conceptual affixion of voice to identity based on a reduction of voice that sees it as a fixed, extractable, and measurable 'sound object' located within the body. This informs the thinking of developers in the VIA industry, resulting in a reframing of the technological shortcomings of voice identification under the rubric of big data. Ultimately, this reframing rationalizes the implementation of audio surveillance systems into existing telecommunications infrastructures through which voice data is acquired on a massive scale.

Factors related to the location of pigment epithelial detachment in central serous chorioretinopathy.

Pigment epithelial detachment (PED) is common in eyes with central serous chorioretinopathy (CSC), and choroidal neovascularisation (CNV), which is almost always associated with PED, is found in a higher proportion than previously expected. Using en-face optical coherence tomography, this retrospective study aimed to investigate the PED location in relation to various geometric landmarks including the foveal centre (FC), greatest choroidal thickness (GCT) point and optic disc centre. In a total of 98 eyes, the distance from the FC to PED centroid was correlated with the ratio of GCT to subfoveal choroidal thickness (r = 0.278, P = 0.006) and the distance from the FC to GCT point (r = 0.371, P < 0.001). Eyes with CNV had a shorter distance between the PED centroid and FC (700 ± 439 µm) than those without (1191 ± 964 µm, P = 0.001). Analysis of covariance showed that the distance from the FC to the PED centroid was significantly correlated with the distance from the FC to the GCT point (P = 0.009) and the PED group with and without CNV (P = 0.020). This result suggests that the development of complicated PED with CNV can be related to both choroidal vascular abnormalities and retinal pigment epithelial insufficiency.

An integrated microfluidic culture device to regulate endothelial cell differentiation from embryonic stem cells.

We developed an integrated microfluidic culture device to regulate embryonic stem (ES) cell fate. The integrated microfluidic culture device consists of an air control channel and a fluidic channel with 4×4 micropillar arrays. We hypothesized that the microscale posts within the micropillar arrays would enable the control of uniform cell docking and shear stress profiles. We demonstrated that ES cells cultured for 6 days in the integrated microfluidic culture device differentiated into endothelial cells. Therefore, our integrated microfluidic culture device is a potentially powerful tool for directing ES cell fate.

Eversion carotid endarterectomy for recurrent stenosis after carotid angioplasty/stenting.

Restenosis requiring treatment after carotid angioplasty/stenting is uncommon in clinical practice. Treatment options include repeat angioplasty (with or without another stent) or carotid endarterectomy. This report describes a patient with recurrent stenosis treated with eversion carotid endarterectomy and stent removal.

Comparison of Regional Differences in the Choroidal Thickness between Patients with Pachychoroid Neovasculopathy and Classic Exudative Age-related Macular Degeneration.

Purpose: To compare the regional differences in the choroidal thickness (CT) between patients with pachychoroid neovasculopathy (PNV) and classic exudative age-related macular degeneration (ceAMD).Materials and Methods: We included both eyes of patients with unilateral macular neovascularization (MNV) due to ceAMD or PNV. Unilateral eyes of normal subjects were also included as a normal control group. The regional difference in CT was defined as a difference between the macular and extramacular areas, and calculated as the ratio of subfoveal CT (SFCT) to nasal peripapillary CT (PCT).Results: In normal subjects, the choroid was 2.25 ± 0.10 times thicker at the macula than at the extramacular area. The SFCT and PCT were significantly affected by age (P < .001 and P < .001, respectively), whereas the regional difference in CT were independent of age (P = .076). Analysis of covariance including age, sex, and MNV group showed that regional difference in CT were significantly affected by sex, nasal peripapillary CT, and MNV group (P = .023, P < .001, and P < .001, respectively). The estimated marginal mean of the regional difference in CT was significantly smaller in the ceAMD group (1.671 ± 0.103) than in the normal control (2.250 ± 0.095, P = .003) and PNV groups (2.0880 ± 0.086, P < .001).Conclusions: Regional differences in CT were consistent with aging. However, the difference varied with the presence of PNV or ceAMD. Measurement of regional differences in CT provides additional information for characterizing the choroid in patients with MNV.

Peripapillary Choroidal Vascularity Outside the Macula in Patients With Central Serous Chorioretinopathy.

Purpose: To investigate choroidal vascularity outside the macula in central serous chorioretinopathy (CSC). Methods: Fifty normal controls and 103 patients with a history of CSC (31 with acute CSC, 32 with chronic CSC, and 40 with resolved CSC) were included. Using swept-source optical coherence tomography, we measured choroidal thickness (CT) and choroidal vascularity index (CVI) at the subfoveal and nasal peripapillary areas. Results: Subfoveal CT in the acute CSC group was greater than that in all other groups (all P < 0.05). Peripapillary CT in the acute and chronic CSC groups was significantly greater than that in controls (all P ≤ 0.005). However, subfoveal and peripapillary CT in the resolved CSC group was not different from controls. Subfoveal CVI in the acute group (64.71% ± 2.68%) was higher than that in controls (61.68% ± 5.68%) (P = 0.015). Peripapillary CVIs in the acute (67.35% ± 6.04%) and chronic groups (64.90% ± 5.31%) were higher than controls (54.57% ± 7.02%) (all P < 0.001). Subfoveal CVI in the resolved CSC group was not different from controls (P = 0.252), whereas peripapillary CVI (62.61% ± 6.03%) was higher (P < 0.001). Conclusions: Unlike CT, CVI outside the macula was increased in all eyes with both current and past history of CSC. These findings suggest that the choroidal vascularity outside the macula may represent choroidal characteristics in addition to the subfoveal area. Translational Relevance: Peripapillary CVI outside the macula may provide additional information beyond what is known through subfoveal choroid studies.

Clustering of eyes with age-related macular degeneration or pachychoroid spectrum diseases based on choroidal thickness profile.

Choroidal changes have been suggested to be involved in the pathophysiology of both age-related macular degeneration (AMD) and pachychoroid spectrum diseases (PSD). To find out the choroidal characteristics of each disease groups, various groups of AMD and PSD were classified into several clusters according to choroidal profiles based on subfoveal choroidal thickness (CT), peripapillary CT, the ratio of subfoveal CT to peripapillary CT and age. We retrospectively analyzed 661 eyes, including 190 normal controls and 471 with AMD or PSDs. In the AMD groups, eyes with soft drusen or reticular pseudodrusen were belonged to the same cluster as those with classic exudative AMD (all p < 0.001). However, eyes with pachydrusen were not clustered with eyes from other AMD groups; instead, they were classified in the same cluster as eyes from the PSD group (all p < 0.001). In the PSD group, eyes with pachychoroid neovasculopathy were grouped in the same cluster of those with polypoidal choroidal vasculopathy (p < 0.001). The cluster analysis based on the CT profiles, including subfoveal CT, peripapillary CT, and their ratio, revealed a clustering pattern of eyes with AMD and PSDs. These findings support the suggestion that pachydrusen has the common pathogenesis as PSD.

Novel PDMS cylindrical channels that generate coaxial flow, and application to fabrication of microfibers and particles.

In this paper, we introduce a novel cylindrical channel that generates coaxial flow without using glass microcapillary or complicated silicon processing, and we demonstrate the fabrication of microparticles and microfibers using this channel. The simple fabrication process for cylindrical channels employs the deflection of free-standing thin PDMS membranes. Using this channel, alginate microparticles and microfibers were fabricated without clogging the downstream channel, and the dimensions of these particles and fibers could be successfully controlled by regulating the flow rate through the channels. We also developed a method to integrate the coaxial flow channel into rectangular microfluidic channel devices, which have a broad array of established applications. As proof of concept of this technology, we fabricated a microfluidic chip that incorporated 12 rectangular micromixers to generate a stepwise gradient across discrete output streams. These output streams simultaneously fed into 5 coaxial flow channels, each of which produced a microfiber of a different chemical composition. The fibers or particles generated by the proposed method may be used in biomedical and tissue engineering, as well as in drug delivery. We expect that our method will facilitate the construction of microfluidic factories within single PDMS devices.

Development of a multi-layer microfluidic array chip to culture and replate uniform-sized embryoid bodies without manual cell retrieval.

We have developed a multi-layer, microfluidic array platform containing concave microwells and flat cell culture chambers to culture embryonic stem (ES) cells and regulate uniform-sized embryoid body (EB) formation. The main advantage of this platform was that EBs cultured within the concave microwells of a bottom layer were automatically replated into flat cell culture chambers of a top layer, following inversion of the multi-layer microfluidic array platform. This allowed EB formation and EB replating to be controlled simultaneously inside a single microfluidic device without pipette-based manual cell retrieval, a drawback of previous EB culture methods.

Microfluidic spinning of micro- and nano-scale fibers for tissue engineering.

Microfluidic technologies have recently been shown to hold significant potential as novel tools for producing micro- and nano-scale structures for a variety of applications in tissue engineering and cell biology. Over the last decade, microfluidic spinning has emerged as an advanced method for fabricating fibers with diverse shapes and sizes without the use of complicated devices or facilities. In this critical review, we describe the current development of microfluidic-based spinning techniques for producing micro- and nano-scale fibers based on different solidification methods, platforms, geometries, or biomaterials. We also highlight the emerging applications of fibers as bottom-up scaffolds such as cell encapsulation or guidance for use in tissue engineering research and clinical practice.

Micro/Nanometer-scale fiber with highly ordered structures by mimicking the spinning process of silkworm.

A new method for the microfluidic spinning of ultrathin fibers with highly ordered structures is proposed by mimicking the spinning mechanism of silkworms. The self-aggregation is driven by dipole-dipole attractions between polar polymers upon contact with a low-polarity solvent to form fibers with nanostrands. The induction of Kelvin-Helmholtz instabilities at the dehydrating interface between two miscible fluids generates multi-scale fibers in a single microchannel.

Large-scale, ultrapliable, and free-standing nanomembranes.

The creation and characterization of large-area ultrathin highly pliable free-standing PDMS membranes and their application to the study of cellular epithelia is described. The ultra-thin membranes permitted the straight forward calculation of cell monolayer moduli, derived from measured stress-strain curves. These measurements allowed the unprecedented detection of cellular-level injury in the epithelia caused by the rupture of cell-cell tight junctions in response to stretching.

Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects.

We have developed a three-dimensional (3D) liver-on-a-chip to investigate the interaction of hepatocytes and hepatic stellate cells (HSCs) in which primary 3D hepatocyte spheroids and HSCs are co-cultured without direct cell-cell contact. Here, we show that the 3D liver chip offers substantial advantages for the formation and harvesting of spheroids. The most important feature of this liver chip is that it enables continuous flow of medium to the cells through osmotic pumping, and thus requires only minimal handling and no external power source. We also demonstrate that flow assists the formation and long-term maintenance of spheroids. Additionally, we quantitatively and qualitatively investigated the paracrine effects of HSCs, demonstrating that HSCs assist in the maintenance of hepatocyte spheroids and play an important role in the formation of tight cell-cell contacts, thereby improving liver-specific function. Spheroids derived from co-cultures exhibited improved albumin and urea secretion rates compared to mono-cultured spheroids after 9 days. Immunostaining for cytochrome P450 revealed that the enzymatic activity of spheroids co-cultured for 8 days was greater than that of mono-cultured spheroids. These results indicate that this system has the potential for further development as a unique model for studying cellular interactions or as a tool that can be incorporated into other models aimed at creating hepatic structure and prolonging hepatocyte function in culture.