Publications by authors named "Humayun M"

453 Publications

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites.

Mol Pharm 2020 12 2;17(12):4499-4509. Epub 2020 Sep 2.

Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California 90089, United States.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00589DOI Listing
December 2020

Novel probabilistic model of core vitreous traction using microsurgical vitrectomy tools.

Graefes Arch Clin Exp Ophthalmol 2021 Feb 18;259(2):405-412. Epub 2020 Aug 18.

USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics, Los Angeles, CA, USA.

Purpose: Traction exerted on the vitreous base during vitrectomy poses a risk for retinal tears. We aimed to quantify core vitreous traction during vitrectomy using spring return and pneumatic cutters.

Methods: Juvenile porcine vitreous was vacuum held in a vitreous bath while traction was measured using precision force gauge during vitrectomy. The parameters included were aspiration rate, cut-rate, cutter size, and machine types.

Results: An empirical probabilistic model was developed. The traction was proportional to the aspiration rate but insignificantly dependent on the cut-rate. The traction probability was inversely proportional to the exponential function of the traction (p < 0.05). The traction was < 0.003 N for 99% of the time using either 23- or 25-gauge cutters.

Conclusion: The tractions measured were considered similar to the causative forces of an iatrogenic retinal tear during a pars plana vitrectomy. The results provide a safety reference matrix of instrumental parameters during vitrectomy.
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http://dx.doi.org/10.1007/s00417-020-04836-zDOI Listing
February 2021

Microfluidic lumen-based systems for advancing tubular organ modeling.

Chem Soc Rev 2020 Sep;49(17):6402-6442

Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA. and University of Wisconsin Carbone Cancer Center, Madison, WI, USA and Department of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.

Microfluidic lumen-based systems are microscale models that recapitulate the anatomy and physiology of tubular organs. These technologies can mimic human pathophysiology and predict drug response, having profound implications for drug discovery and development. Herein, we review progress in the development of microfluidic lumen-based models from the 2000s to the present. The core of the review discusses models for mimicking blood vessels, the respiratory tract, the gastrointestinal tract, renal tubules, and liver sinusoids, and their application to modeling organ-specific diseases. We also highlight emerging application areas, such as the lymphatic system, and close the review discussing potential future directions.
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http://dx.doi.org/10.1039/d0cs00705fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521761PMC
September 2020

Transcranial Focused Ultrasound for Noninvasive Neuromodulation of the Visual Cortex.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 01 23;68(1):21-28. Epub 2020 Dec 23.

Currently, blindness cannot be cured and patients' living quality can be compromised severely. Ultrasonic (US) neuromodulation is a promising technology for the development of noninvasive cortical visual prosthesis. We investigated the feasibility of transcranial focused ultrasound (tFUS) for noninvasive stimulation of the visual cortex (VC) to develop improved visual prosthesis. tFUS was used to successfully evoke neural activities in the VC of both normal and retinal degenerate (RD) blind rats. Our results showed that blind rats showed more robust responses to ultrasound stimulation when compared with normal rats. ( , two-sample t-test). Three different types of ultrasound waveforms were used in the three experimental groups. Different types of cortical activities were observed when different US waveforms were used. In all rats, when stimulated with continuous ultrasound waves, only short-duration responses were observed at "US on and off" time points. In comparison, pulsed waves (PWs) evoked longer low-frequency responses. Testing different parameters of PWs showed that a pulse repetition frequency higher than 100 Hz is required to obtain the low-frequency responses. Based on the observed cortical activities, we inferred that acoustic radiation force (ARF) is the predominant physical mechanism of ultrasound neuromodulation.
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http://dx.doi.org/10.1109/TUFFC.2020.3005670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153235PMC
January 2021

Polymorphism in GSTM1 and GSTT1 genes influence DNA damage in personnel occupationally exposed to volatile anaesthetics (VA), from Peshawar, Pakistan.

Occup Environ Med 2020 11 27;77(11):769-774. Epub 2020 Jul 27.

Khyber College of Dentistry, Khyber Medical University, Peshawar, Pakistan.

Objectives: The objective of this study was to assess the influence of antioxidant gene GSTM1 and GSTT1 on DNA damage in personnel occupationally exposed to volatile anaesthetics (VA).

Methods: The study groups were composed of 50 exposed subjects (anaesthesia workers) and 49 controls. Blood samples were collected from both subjects. DNA damage was analysed through the comet assay technique. Biomarker genes GSTM1 and GSTT1 were inspected through PCR technique for polymorphism.

Results: The comet assay technique showed that the Total Comet Score (TCS) in exposed subjects was significantly higher (p=0.0001) than the control. Age and smoking had significant effects on TCS in the study groups (p<0.05). Duration of occupational exposure had significant positive correlation (r=0.755, p<0.001) with DNA damage. The null polymorphism in GSTM1 and GSTT1 gene showed a significant effect (p<0.001 and p<0.000) on the DNA damage.

Conclusions: The polymorphism in GSTM1 and GSTT1 gene significantly damage DNA in personnel occupationally exposed to VA.
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http://dx.doi.org/10.1136/oemed-2020-106561DOI Listing
November 2020

Elemental constraints on the amount of recycled crust in the generation of mid-oceanic ridge basalts (MORBs).

Sci Adv 2020 Jun 26;6(26):eaba2923. Epub 2020 Jun 26.

National High Magnetic Field Laboratory and Department of Earth, Ocean and Atmospheric Science, Florida State University, 1800 E. Paul Dirac Drive, Tallahassee, FL 32310, USA.

Mid-oceanic ridge basalts (MORBs) are depleted in incompatible elements, but ridge segments far from mantle plumes frequently erupt chemically enriched MORBs (E-MORBs). Two major explanations of E-MORBs are that these basalts are generated by the melting of entrained recycled crust (pyroxenite) beneath ridges or by the melting of refertilized peridotites. These two hypotheses can be discriminated with compatible element abundances from Sc to Ge, here termed the ScGe elements. Here, we demonstrate that E-MORBs have systematically lower Ge/Si and Sc contents and slightly higher Fe/Mn and Nb/Ta ratios than depleted MORBs (D-MORBs) due to the mixing of low-degree pyroxenite melts. The Ge/Si ratio is a new tracer that effectively discriminates between melts derived from peridotite sources and melts derived from mixed pyroxenite-peridotite sources. These new data are used to estimate the distribution of pyroxenite in the mantle sources of global MORB segments.
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http://dx.doi.org/10.1126/sciadv.aba2923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319763PMC
June 2020

MEASUREMENT OF THE HYDRAULIC CONDUCTIVITY OF THE VITREOUS HUMOR.

J Porous Media 2020 ;23(2):195-206

Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453.

The hydraulic conductivity of the vitreous humor has been measured for the bovine eye. The experiment was carried out by placing it within upright cylindrical chamber, open at both ends, and letting its liquid content drain out of the bottom opening by gravity, through a 20m nylon mesh filter. Additional negative pressure was provided at the exit by a hanging drainage tube. The diminishing vitreous volume was measured in terms of the height in the chamber and recorded as a function of time. The reduction in the vitreous liquid content also caused the hydraulic conductivity to reduce and this parameter was quantified on the basis of previously-developed theories of fibrous porous media that have been very well established. A theoretical model with a fully analytical expression for the vitreous volume undergoing drainage was developed and used as a least-squares best fit to deliver the initial hydraulic conductivity value of /=(7.8 ± 3.1) × 10 m (Pa-s). The measurements were made with the hyaloid membrane intact and therefore represents an effective conductivity for the entire system, including possible variations within the vitreous.
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http://dx.doi.org/10.1615/JPorMedia.2020028229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269170PMC
January 2020

Fabrication of BiFeO-g-CN-WO Z-scheme heterojunction as highly efficient visible-light photocatalyst for water reduction and 2,4-dichlorophenol degradation: Insight mechanism.

J Hazard Mater 2020 Oct 20;397:122708. Epub 2020 Apr 20.

Engineering Research Center for Functional Ceramics of the Ministry of Education, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, PR China; China-EU Institute for Clean and Renewable Energy, HuazhongUniversity of Science and Technology, Wuhan 430074, PR China. Electronic address:

In this work, a Z-scheme BiFeO-g-CN-WO (BFO-CN-WO) photocatalyst has been synthesized via a wet chemical method and utilized in photocatalysis for hydrogen generation and 2,4-dichlorophenol (2,4-DCP) degradation under visible light irradiation. The resultant photocatalyst showed 90 μmol·h g H evolution activity and 63% 2,4-DCP degradation performance, which is 12 and 4.2 times higher than the pristine g-CN respectively. The fascinating photocatalytic performance is attributed to the strong interfacial contact between g-CN and the coupled BiFeO and WO component, which greatly improved the visible light absorption and charge carriers' separation. The designed Z-scheme heterojunction is a successful strategy for enhancing the separation efficiency of photo-induced charge carriers at the interface while retaining outstanding redox ability. During 2,4-DCP degradation, LC/MS technique was used to detect the reaction intermediates. According to the LC/MS results, several new intermediates such as 2,3-dichloro-6-(2,4-dichlorophenoxy)phenol (m/z = 306), 2,4-dichlorophenyl hydrogen carbonate (m/z = 207), 2,4-dichlorobenzen-1,3-diol (m/z = 177) and phenyl hydrogen carbonate (m/z = 137) were detected. Based on these intermediates, 2,4-DCP degradation pathway is proposed. The fluorescence (FL) and electron paramagnetic resonance (EPR) results reveal that the •OH plays an important role in the 2,4-DCP degradation. The fabricated photocatalyst can be utilized in the field of photocatalysis for practical applications.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122708DOI Listing
October 2020

Retina-electrode interface properties and vision restoration by two generations of retinal prostheses in one patient-one in each eye.

J Neural Eng 2020 04 9;17(2):026020. Epub 2020 Apr 9.

Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States of America. USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States of America. Authors to whom any correspondence should be addressed.

Objective: The Argus I implant is a first-generation epiretinal prosthesis approved for an investigational clinical trial in the U.S. Its successor, the Argus II implant, has a higher electrode density for increased spatial resolution and covers a larger retinal area to accommodate a wider visual angle. Both generations of Argus restored some vision to end-stage RP patients, but it remains unclear how the increased electrode count affected the visual percepts. Here we report a study of the first person on earth with two 'bionic eyes', with an Argus I implanted in one eye and Argus II in the other, to compare the retina-electrode interface and the visual outcome of the two devices.

Approach: The retina-electrode interface was examined by electrode impedance, perceptual threshold, and ophthalmic images such as ocular coherence tomography data and fundus imaging. The subject's visual outcomes were evaluated by computer-based visual function tests and subjective feedback.

Main Results: The electrode impedance of both Argus I and II slowly decreased overtime after implantation, accompanied by a gradual increase in the perceptual threshold. A quantitative analysis of the impedance and retina-electrode distance revealed somewhat different causes of impedance change in Argus I vs. II. Evaluation of the visual functions restored and feedback from the subject suggest that the Argus II device enables improved spatial visual ability over Argus I, but adaptation to prosthetic vision did not lead to a measurable performance improvement in the standard visual function tests.

Significance: This study of Argus I and II in the same subject directly compares for the first time the interface properties and prosthetic vision in two eyes that share the same disease mechanism and converged visual pathway in higher visual centers, offering exciting new insights into the influence of the electrode parameters and layout to prosthetic vision.

Trial Registration: Data collected within clinical trials registered at NIH (NCT00279500 & NCT01860092).
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http://dx.doi.org/10.1088/1741-2552/ab7c8fDOI Listing
April 2020

In Vivo Visualization of Eye Vasculature Using Super-Resolution Ultrasound Microvessel Imaging.

IEEE Trans Biomed Eng 2020 10 10;67(10):2870-2880. Epub 2020 Feb 10.

Objective: The choroidal vessels, which supply oxygen and nutrient to the retina, may play a pivotal role in eye disease pathogenesis such as diabetic retinopathy and glaucoma. In addition, the retrobulbar circulation that feeds the choroid shows an important pathophysiologic role in myopia and degenerative myopia. Owing to the light-absorbing retinal pigment epithelium (RPE) and optically opaque sclera, choroidal and retrobulbar vasculature were difficult to be observed using clinically accepted optical coherence tomography angiography (OCT-A) technique. Here, we have developed super-resolution ultrasound microvessel imaging technique to visualize the deep ocular vasculature.

Methods: An 18-MHz linear array transducer with compounding plane wave imaging technique and contrast agent - microbubble was implemented in this study. The centroid intensity of each microbubble was detected using image deconvolution algorithm with spatially variant point spread function, and then accumulated in successive frames in order to reconstruct microvasculature. The image deconvolution technique was first evaluated in a simulation study and experimental flow phantoms. The performance was then validated on normal rabbit eyes in vivo.

Results: The image deconvolution based super-resolution ultrasound microvessel imaging technique shows good performance on either simulation study or flow phantoms. In vivo rabbit eye study indicated that the micron-level choroidal and retrobulbar vessels around the optic nerve head were successfully reconstructed in multiple 2D views and 3D volume imaging.

Conclusions: Our results demonstrate the capability of using super-resolution ultrasound microvessel imaging technique to image the microvasculature of the posterior pole of the eye. This efficient approach can potentially lead to a routinely performed diagnostic procedure in the field of ophthalmology.
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http://dx.doi.org/10.1109/TBME.2020.2972514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546097PMC
October 2020

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

Retina 2020 Feb;40(2):303-311

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients.

Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing.

Results: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years.

Conclusion: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.
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http://dx.doi.org/10.1097/IAE.0000000000002394DOI Listing
February 2020

evaluation of posterior eye elasticity using shaker-based optical coherence elastography.

Exp Biol Med (Maywood) 2020 02 7;245(4):282-288. Epub 2020 Jan 7.

Department of Biomedical Engineering and NIH Ultrasonic Transducer Resource Center, University of Southern California, Los Angeles, CA 90089, USA.

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http://dx.doi.org/10.1177/1535370219897617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370597PMC
February 2020

Subretinal Implantation of a Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Monolayer in a Porcine Model.

Adv Exp Med Biol 2019 ;1185:569-574

Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

The goal of this study was to quantitatively assess retinal thickness using spectral domain optical coherence tomography (SD-OCT) after subretinal implantation of human embryonic stem cell-derived retinal pigment epithelium in a porcine model. The implant is called CPCB-RPE1 for the California Project to Cure Blindness-Retinal Pigment Epithelium 1. Data were derived from previous experiments on 14 minipigs that received either subretinal implantation of CPCB-RPE1 (n = 11) or subretinal bleb formation alone (sham; n = 3) using previously described methods and procedures (Brant Fernandes et al. Ophthalmic Surg Lasers Imaging Retina 47:342-51, 2016; Martynova et al. (2016) Koss et al. Graefes Arch Clin Exp Ophthalmol 254:1553-65, 2016; Hu et al. Ophthalmic Res 48:186-91, 2016; Martynova et al. ARVO Abstract 2016. SD-OCT retinal thickness (RT) and sublayer thickness over the implant were compared with topographically similar preimplantation regions as described previously Martynova et al. ARVO Abstract 2016. Imaging results were compared to postmortem histology using hematoxylin-eosin staining. RT overlying the CPCB-RPE1 postimplantation was not significantly different from preimplantation (308 ± 72 μm vs 292 ± 41 μm; p = 0.44). RT was not significantly different before and after implantation in any retinal sublayer at 1 month. Histology demonstrated grossly normal retinal anatomy as well as photoreceptor interdigitation with RPE.
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http://dx.doi.org/10.1007/978-3-030-27378-1_93DOI Listing
February 2020

Experimental and DFT Studies of Au Deposition Over WO/g-CN Z-Scheme Heterojunction.

Nanomicro Lett 2019 Dec 19;12(1). Epub 2019 Dec 19.

Engineering Research Center for Functional Ceramics of the Ministry of Education, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.

A typical Z-scheme system is composed of two photocatalysts which generate two sets of charge carriers and split water into H and O at different locations. Scientists are struggling to enhance the efficiencies of these systems by maximizing their light absorption, engineering more stable redox couples, and discovering new O and H evolutions co-catalysts. In this work, Au decorated WO/g-CN Z-scheme nanocomposites are fabricated via wet-chemical and photo-deposition methods. The nanocomposites are utilized in photocatalysis for H production and 2,4-dichlorophenol (2,4-DCP) degradation. It is investigated that the optimized 4Au/6% WO/CN nanocomposite is highly efficient for production of 69.9 and 307.3 µmol h g H gas, respectively, under visible-light (λ > 420 nm) and UV-visible illumination. Further, the fabricated 4Au/6% WO/CN nanocomposite is significant (i.e., 100% degradation in 2 h) for 2,4-DCP degradation under visible light and highly stable in photocatalysis. A significant 4.17% quantum efficiency is recorded for H production at wavelength 420 nm. This enhanced performance is attributed to the improved charge separation and the surface plasmon resonance effect of Au nanoparticles. Solid-state density functional theory simulations are performed to countercheck and validate our experimental data. Positive surface formation energy, high charge transfer, and strong non-bonding interaction via electrostatic forces confirm the stability of 4Au/6% WO/CN interface.
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http://dx.doi.org/10.1007/s40820-019-0345-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770730PMC
December 2019

Surgical Method for Implantation of a Biosynthetic Retinal Pigment Epithelium Monolayer for Geographic Atrophy: Experience from a Phase 1/2a Study.

Ophthalmol Retina 2020 03 7;4(3):264-273. Epub 2019 Oct 7.

USC Roski Eye Institute, USC Institute for Biomedical Therapeutics and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Biomedical Engineering, Denney Research Center, University of Southern California, Los Angeles, California. Electronic address:

Purpose: To report the intraoperative methods and anatomic results for subretinal implantation of an investigational human embryonic stem cell-derived retinal pigment epithelium (RPE) monolayer seeded on a synthetic substrate (California Project to Cure Blindness Retinal Pigment Epithelium 1 [CPCB-RPE1]) in geographic atrophy (GA).

Design: Single-arm, open label, prospective, nonrandomized, Phase 1/2a study.

Participants: Advanced non-neovascular age-related macular degeneration (NNAMD).

Methods: The worse-seeing eye (≤20/200) of each subject underwent subretinal implantation of a single 3.5×6.25 mm CPCB-RPE1 implant with a preplanned primary end point of safety and efficacy at 365 days. Commercially available 23-gauge vitrectomy equipment, custom surgical forceps, and operating microscope with or without intraoperative OCT (iOCT) were used. Exact Wilcoxon rank-sum tests and Spearman rank correlation coefficients were used to assess the association of the percentage of the GA area covered by the implant with patient and surgery characteristics. The partial Spearman correlation coefficient was calculated for the correlation between duration of surgery and baseline GA size after adjustment for surgeon experience.

Main Outcome Measures: Intraoperative exploratory measures are reported, including area of GA covered by implant, subretinal position of implant, duration of surgery, and incidence of adverse events. Operative recordings and reports were used to determine exploratory outcome measures.

Results: Sixteen subjects were enrolled with a median age of 78 years (range, 69-85 years). Median duration of the surgery for all subjects was 160 minutes (range, 121-466 minutes). Intraoperative OCT was used to guide subretinal placement in 9 cases. Intraoperative OCT was potentially useful in identifying pathology not evident with standard intraoperative visualization. Median GA area at baseline was 13.8 mm (range, 6.0-46.4 mm), and median GA area left uncovered by the implant was 1.7 mm (range, 0-20.4 mm). On average, 86.9% of the baseline GA area was covered by the implant. In 5 subjects, >90% of the GA area was covered. Baseline GA size was inversely correlated with percentage of GA area covered by the implant (r=-0.72; P = 0.002). No unanticipated serious adverse events related to the implant or surgery were reported.

Conclusions: Surgical implantation of CPCB-RPE1 targeted to the area of GA in subjects with advanced NNAMD is feasible in an outpatient setting. Intraoperative OCT is not necessary but potentially useful in identifying subretinal pathology and confirming implant location.
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http://dx.doi.org/10.1016/j.oret.2019.09.017DOI Listing
March 2020

Quantitative confocal optical coherence elastography for evaluating biomechanics of optic nerve head using Lamb wave model.

Neurophotonics 2019 Oct 15;6(4):041112. Epub 2019 Nov 15.

University of Southern California, Roski Eye Institute, Los Angeles, California, United States.

The mechanosensitivity of the optic nerve head (ONH) plays a pivotal role in the pathogenesis of glaucoma. Characterizing elasticity of the ONH over changing physiological pressure may provide a better understanding of how changes in intraocular pressure (IOP) lead to changes in the mechanical environment of the ONH. Optical coherence elastography (OCE) is an emerging technique that can detect tissue biomechanics noninvasively with both high temporal and spatial resolution compared with conventional ultrasonic elastography. We describe a confocal OCE system in measuring ONH elasticity , utilizing a pressure inflation setup in which IOP is controlled precisely. We further utilize the Lamb wave model to fit the phase dispersion curve during data postprocessing. We present a reconstruction of Young's modulus of the ONH by combining our OCE system with a Lamb wave model for the first time. This approach enables the quantification of Young's modulus of the ONH, which can be fit using a piecewise polynomial to the corresponding IOP.
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http://dx.doi.org/10.1117/1.NPh.6.4.041112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857697PMC
October 2019

Economic Value of Anti-Vascular Endothelial Growth Factor Treatment for Patients With Wet Age-Related Macular Degeneration in the United States.

JAMA Ophthalmol 2020 01;138(1):40-47

Roski Eye Institute, University of Southern California, Los Angeles.

Importance: Anti-vascular endothelial growth factor (anti-VEGF) is a breakthrough treatment for wet age-related macular degeneration (wAMD), the most common cause of blindness in western countries. Anti-VEGF treatment prevents vision loss and has been shown to produce vision gains lasting as long as 5 years. Although this treatment is costly, the benefits associated with vision gains are large.

Objective: To estimate the economic value of benefits, costs for patients with wAMD, and societal value in the United States generated from vision improvement associated with anti-VEGF treatment.

Design, Setting, And Participants: This economic evaluation study used data from the published literature to simulate vision outcomes for a cohort of 168 820 patients with wAMD aged 65 years or older and to translate them into economic variables. Data were collected and analyzed from March 2018 to November 2018.

Main Outcomes And Measures: Main outcomes included patient benefits, costs, and societal value. Each outcome was estimated for a newly diagnosed cohort and the full population across 5 years, with a focus on year 3 as the primary outcome because data beyond that point may be less representative of the general population. Drug costs were the weighted mean across anti-VEGF therapies. Two current treatment scenarios were considered: less frequent injections (mean [SD], 8.2 [1.6] injections annually) and more frequent injections (mean [range], 10.5 [6.8-13.1] injections annually). The 2 treatment innovation scenarios, improved adherence and best case, had the same vision outcomes as the current treatment scenarios had but included more patients treated from higher initiation and lower discontinuation.

Results: The study population included 168 820 patients aged 65 years at the time of diagnosis with wAMD. The underlying clinical trials that were used to parameterize the model did not stratify visual acuity outcomes or treatment frequency by sex; therefore, the model parameters could not be stratified by sex. The current treatment scenario of less frequent injections generated $1.1 billion for the full population in year 1 and $5.1 billion in year 3, whereas the scenario of more frequent injections generated $1.6 billion (year 1) and $8.2 billion (year 3). Three-year benefits ranged from $7.3 billion to $11.4 billion in the improved adherence scenario and from $9.7 billion to $15.0 billion if 100% of the patients initiated anti-VEGF treatment and the discontinuation rates were 6% per year or equivalent to clinical trial discontinuation (best-case scenario). Societal value (patient benefits net of treatment cost) ranged from $0.9 billion to $3.0 billion across 3 years in the current treatment scenarios and from $0.9 billion to $4.3 billion in the treatment innovation scenarios.

Conclusions And Relevance: This study's findings suggest that improved vision associated with anti-VEGF treatment may provide economic value to patients and society if the outcomes match published outcomes data used in these analyses; however, future innovations that increase treatment utilization may result in added economic benefit.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.4557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865322PMC
January 2020

Dual Energy X-ray Absorptiometry Scanning and Bone Health: The Pressing Need to Raise Awareness Amongst Pakistani Women.

Cureus 2019 Sep 22;11(9):e5724. Epub 2019 Sep 22.

Internal Medicine, Dow University of Health Sciences, Karachi, PAK.

Introduction The use of dual-energy x-ray absorptiometry (DEXA) scanning is instrumental in better management of osteoporosis. This study aimed to assess the level of knowledge about DEXA scanning and bone health in the women of Karachi, as well as to analyze their practices concerning the scan and increase their knowledge and awareness regarding the same. Methodology  The sample size for this cross-sectional study was 384. Data were collected using a self-devised and validated questionnaire, consisting of four sections: social demographics, general knowledge about DEXA scanning, practices regarding DEXA, and knowledge about bone health. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 23 and associations between multiple variables calculated, using independent sample t-test and Pearson's chi-squared test. Results Only one-third of our sample population had heard about DEXA scanning and amongst them, nobody had complete knowledge about it. The mean score of general knowledge of DEXA (5.3±2.0) was higher than that of knowledge about the conditions in which DEXA scanning is recommended (2.7±2.1). The knowledge score showed a significant correlation with education (p=0.007) and employment (p=0.001). Only 7.6% of the sample population had taken a DEXA scan and knowledge and employment status were found to have significant associations with practices (p value=0.000 and 0.001, respectively). Conclusions The awareness levels regarding DEXA scans and bone health should be evaluated amongst similar and other groups of people and effective measures be put into application to educate the public and to guide them towards better prevention and management of osteoporosis.
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http://dx.doi.org/10.7759/cureus.5724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823075PMC
September 2019

Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures.

Invest Ophthalmol Vis Sci 2019 10;60(13):4303-4309

USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina.

Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation.

Results: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-α levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency.

Conclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye.
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http://dx.doi.org/10.1167/iovs.18-25613DOI Listing
October 2019

Flexible piezoelectric ultrasonic energy harvester array for bio-implantable wireless generator.

Nano Energy 2019 Feb 22;56:216-224. Epub 2018 Nov 22.

Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 USA.

Ultrasonic driven wireless charging technology has recently attracted much attention in the next generation bio-implantable systems; however, most developed ultrasonic energy harvesters are bulky and rigid and cannot be applied to general complex surfaces. Here, a flexible piezoelectric ultrasonic energy harvester (PUEH) array was designed and fabricated by integrating a large number of piezoelectric active elements with multilayered flexible electrodes in an elastomer membrane. The developed flexible PUEH device can be driven by the ultrasonic wave to produce continuous voltage and current outputs on both planar and curved surfaces, reaching output signals of more than 2 Vpp and 4 μA, respectively. Potential applications of using the flexible PUEH to charge energy-storage devices and power commercial electronics were demonstrated. Its low attenuation performance was also evaluated using the test of transmitting power through pork tissue, demonstrating its potential use in the next generation of wirelessly powered bio-implantable micro-devices.
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http://dx.doi.org/10.1016/j.nanoen.2018.11.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717511PMC
February 2019

Antisynthetase syndrome presenting as interstitial lung disease: a case report.

J Med Case Rep 2019 Aug 4;13(1):241. Epub 2019 Aug 4.

Department of Medicine, Khyber Teaching Hospital, Peshawar, Pakistan.

Background: Antisynthetase syndrome is a relatively uncommon entity, and can be easily missed if not specifically looked for in adults whose initial presentation is with interstitial lung disease. Its presentation with interstitial lung disease alters its prognosis.

Case Presentation: This case report describes a 27-year-old Pakistani, Asian man, a medical student, with no previous comorbidities or significant family history who presented with a 3 months' history of low grade fever and lower respiratory tract infections, associated with exertional dyspnea, arthralgias, and gradual weight loss. During these 3 months, he had received multiple orally administered antibiotics for suspected community-acquired pneumonia. When he presented to us, he was pale and febrile. A chest examination was significant for bi-basal end-inspiratory crackles. Preliminary investigations revealed raised erythrocyte sedimentation rate. High resolution computed tomography of his chest showed fine ground-glass attenuation in posterior basal segments of both lower lobes suggestive of interstitial lung disease. He was started on dexamethasone, to which he responded and showed improvement. However, during the course of events, he developed progressive proximal muscle weakness. Further investigations revealed raised creatinine phosphokinase and lactate dehydrogenase. A thorough autoimmune profile was carried out which showed positive anti-Jo-1 antibodies in high titers. A muscle biopsy was consistent with inflammatory myopathy. Clinical, radiological, serological, and histopathological markers aided in making the definitive diagnosis of antisynthetase syndrome. Antisynthetase syndrome is a variant of polymyositis but with visceral involvement, that is, interstitial lung disease and positive anti-Jo-1 antibodies. Our patient responded very well to glucocorticoids and azathioprine.

Conclusion: Antisynthetase syndrome is a rare clinical entity which apart from clinical presentation requires specific serological investigations for diagnosis. Concomitant association of interstitial lung disease gives it a guarded prognosis.
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http://dx.doi.org/10.1186/s13256-019-2146-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679997PMC
August 2019

SPECTRUM - A MATLAB Toolbox for Proteoform Identification from Top-Down Proteomics Data.

Sci Rep 2019 08 2;9(1):11267. Epub 2019 Aug 2.

Biomedical Informatics Research Laboratory, Department of Biology, Lahore University of Management Sciences, Lahore, Pakistan.

Top-Down Proteomics (TDP) is an emerging proteomics protocol that involves identification, characterization, and quantitation of intact proteins using high-resolution mass spectrometry. TDP has an edge over other proteomics protocols in that it allows for: (i) accurate measurement of intact protein mass, (ii) high sequence coverage, and (iii) enhanced identification of post-translational modifications (PTMs). However, the complexity of TDP spectra poses a significant impediment to protein search and PTM characterization. Furthermore, limited software support is currently available in the form of search algorithms and pipelines. To address this need, we propose 'SPECTRUM', an open-architecture and open-source toolbox for TDP data analysis. Its salient features include: (i) MS2-based intact protein mass tuning, (ii) de novo peptide sequence tag analysis, (iii) propensity-driven PTM characterization, (iv) blind PTM search, (v) spectral comparison, (vi) identification of truncated proteins, (vii) multifactorial coefficient-weighted scoring, and (viii) intuitive graphical user interfaces to access the aforementioned functionalities and visualization of results. We have validated SPECTRUM using published datasets and benchmarked it against salient TDP tools. SPECTRUM provides significantly enhanced protein identification rates (91% to 177%) over its contemporaries. SPECTRUM has been implemented in MATLAB, and is freely available along with its source code and documentation at https://github.com/BIRL/SPECTRUM/.
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http://dx.doi.org/10.1038/s41598-019-47724-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677810PMC
August 2019

Enhanced Depth Navigation Through Augmented Reality Depth Mapping in Patients with Low Vision.

Sci Rep 2019 08 2;9(1):11230. Epub 2019 Aug 2.

University of Southern California, USC Ginsburg Institute for Biomedical Therapeutics, Los Angeles, 90033, USA.

Patients diagnosed with Retinitis Pigmentosa (RP) show, in the advanced stage of the disease, severely restricted peripheral vision causing poor mobility and decline in quality of life. This vision loss causes difficulty identifying obstacles and their relative distances. Thus, RP patients use mobility aids such as canes to navigate, especially in dark environments. A number of high-tech visual aids using virtual reality (VR) and sensory substitution have been developed to support or supplant traditional visual aids. These have not achieved widespread use because they are difficult to use or block off residual vision. This paper presents a unique depth to high-contrast pseudocolor mapping overlay developed and tested on a Microsoft Hololens 1 as a low vision aid for RP patients. A single-masked and randomized trial of the AR pseudocolor low vision aid to evaluate real world mobility and near obstacle avoidance was conducted consisting of 10 RP subjects. An FDA-validated functional obstacle course and a custom-made grasping setup were used. The use of the AR visual aid reduced collisions by 50% in mobility testing (p = 0.02), and by 70% in grasp testing (p = 0.03). This paper introduces a new technique, the pseudocolor wireframe, and reports the first significant statistics showing improvements for the population of RP patients with mobility and grasp.
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http://dx.doi.org/10.1038/s41598-019-47397-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677879PMC
August 2019

Histopathologic Assessment of Optic Nerves and Retina From a Patient With Chronically Implanted Argus II Retinal Prosthesis System.

Transl Vis Sci Technol 2019 May 30;8(3):31. Epub 2019 May 30.

Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, USA.

Purpose: To characterize histologic changes in the optic nerve and the retina of an end-stage retinitis pigmentosa (RP) patient after long-term implantation with the Argus II retinal prosthesis system.

Methods: Serial cross sections from the patient's both eyes were collected postmortem 6 years after implantation. Optic nerve from both eyes were morphometrically analyzed and compared. Retina underneath and outside the array was analyzed and compared with corresponding regions in the fellow eye.

Results: Although the optic nerve of the implant eye demonstrated significantly more overall atrophy than the fellow eye ( < 0.01), the temporal quadrant that retinotopically corresponded to the location of the array did not show additional damage. The total neuron count of the macular area was not significantly different between the two eyes, but the tack locations and their adjacent areas showed significantly fewer neurons than other perimacular areas. There was an increased expression of glial fibrillary acidic protein (GFAP) throughout the retina in the implant eye versus the fellow eye, but there was no significant difference in the cellular retinaldehyde-binding protein (CRALBP) expression. Except for the revision tack site, no significant increase of inflammatory reaction was detected in the implant eye.

Conclusion: Long-term implantation and electrical stimulation with an Argus II retinal prosthesis system did not result in significant tissue damage that could be detected by a morphometric analysis.

Translational Relevance: This study supports the long-term safety of the Argus II device and encourages further development of bioelectronics devices at the retina-machine interface.
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http://dx.doi.org/10.1167/tvst.8.3.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543856PMC
May 2019

Evaluating New Ophthalmic Digital Devices for Safety and Effectiveness in the Context of Rapid Technological Development.

JAMA Ophthalmol 2019 Aug;137(8):939-944

Center for Devices and Radiological Health, Division of Ophthalmic and ENT Devices, US Food and Drug Administration, Silver Spring, Maryland.

Importance: The US Food and Drug Administration's medical device regulatory pathway was initially conceived with hardware devices in mind. The emerging market for ophthalmic digital devices necessitates an evolution of this paradigm.

Objectives: To facilitate innovation in ophthalmic digital health with attention to safety and effectiveness.

Evidence Review: This article presents a summary of the presentations, discussions, and literature review that occurred during a joint Ophthalmic Digital Health workshop of the American Academy of Ophthalmology, the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Cataract and Refractive Surgery, the American Society of Retina Specialists, the Byers Eye Institute at Stanford and the US Food and Drug Administration.

Findings: Criterion standards and expert graders are critically important in the evaluation of automated systems and telemedicine platforms. Training at all levels is important for the safe and effective operation of digital health devices. The risks associated with automation are substantially increased in rapidly progressive diseases. Cybersecurity and patient privacy warrant meticulous attention.

Conclusions And Relevance: With appropriate attention to safety and effectiveness, digital health technology could improve screening and treatment of ophthalmic diseases and improve access to care.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.1576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196315PMC
August 2019

Biallelic mutations in the LPAR6 gene causing autosomal recessive wooly hair/hypotrichosis phenotype in five Pakistani families.

Int J Dermatol 2019 Aug 11;58(8):946-952. Epub 2019 May 11.

Institute of Biochemistry, University of Balochistan, Quetta, Pakistan.

Background: Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes.

Methods: To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis. Direct Sanger sequencing of LIPH and LPAR6 genes was carried out using BigDye chain termination chemistry. P2RY5 protein homology models were developed to study the effect of mutation on protein structure in a family having novel mutation.

Results: Sanger sequencing revealed a novel homozygous missense mutation (c.47A>T) in the LPAR6 gene in family A, while recurrent mutation (c.436G>A) was detected in the rest of the four families (B-E). Protein homology models for both native and mutant P2RY5 protein were developed to study the difference in subtle structural features because of Lys16Met (K16M) mutation. We observed that P2RY5 mutation results decrease in the number of ionic interactions detrimental to the protein stability. Protein modeling studies revealed that the novel mutation identified here decreased the number of ionic interactions by affecting physicochemical parameters of the protein, leading to an overall decrease in protein stability with no major secondary structural changes.

Conclusion: The molecular analysis further confirms the frequent involvement of LPAR6 in autosomal recessive wooly hair/hypotrichosis, while the bioinformatic study revealed that the missense mutation destabilizes the overall structure of P2RY5 protein.
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http://dx.doi.org/10.1111/ijd.14480DOI Listing
August 2019

Photodegradation of 2,4-dichlorophenol and rhodamine B over n-type ZnO/p-type BiFeO heterojunctions: detailed reaction pathway and mechanism.

Environ Sci Pollut Res Int 2019 Jun 27;26(17):17696-17706. Epub 2019 Apr 27.

China-EU Institute for Clean and Renewable Energy, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.

The development of new technologies for efficient degradation of pollutant has been an increasing demand in the globe due to the serious environmental issues. Herein, we report n-type ZnO/p-type BiFeO composites as highly efficient visible light nanophotocatalysts prepared via a wet chemical solution method. Based on the measurements of OH-related fluorescence (FL) spectra, photoluminescence (PL) spectra, photoelectrochemical I-V curves, and electrochemical impedance spectra (EIS), it is demonstrated that the photo-induced charge carrier (electron-hole pairs) in the as-prepared n-type ZnO/p-type BiFeO composites with proper amount of the coupled ZnO (10% by mass) exhibits high separation compared with the bare BiFeO (BFO) nanoparticles. This is well responsible for the superior visible light photocatalytic performance of the composites for 2,4-dichlorophenol (2,4-DCP) and rhodamine B (RhB) degradation. It is confirmed by means of scavenger test and liquid chromatography-tandem mass spectrometry (LC/MS) analysis of the intermediate products that OH is the pre-dominant oxidant involved in the degradation of 2,4-DCP. A detailed reaction pathway for 2,4-dichlorophenol degradation over the amount-optimized ZnO/BFO composite is proposed mainly based on the LC/MS product ions. This work will provide a feasible route to design and develop BFO-based highly efficient visible light-active photocatalysts for environmental purification and could be extended to other visible light-active semiconductor materials.
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http://dx.doi.org/10.1007/s11356-019-05079-0DOI Listing
June 2019
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