Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial.

BACKGROUND: Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation. METHODS: We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student's t test. Wilcoxon's rank sum test was used to test individual symptom scores and clinician's global evaluation of treatment grades. RESULTS: Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer's tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician's global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration. CONCLUSION: The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

Investigating the thermal stability of metallic and non-metallic nanoparticles using a novel graphene oxide-based transmission electron microscopy heating-membrane.

In recent years, graphene has been explored as a heating membrane for studying high-temperature dynamics inside the transmission electron microscope (TEM) due to several limitations with the existing silicon nitride-based membrane. However, the transfer of monolayer graphene films for TEM experiments is challenging and requires many complicated steps with a minimum success rate. This work developed a novelin situheating platform by combining the graphene oxide (GO) flakes in the pre-patterned chips. The isolated GO flake was self-suspended between the metal electrodes by a simple drop-casting process. The GO was reduced and characterized using Raman and electron energy-loss spectroscopy. Furthermore, a GO-based heater was used to investigate the thermal stability of gold and silica nanoparticles. The gold nanoparticles evaporated non-uniformly and left an empty carbon shell, while silica disappeared uniformly by etching carbon support. We successfully demonstrated a GO flake as a heating membrane to study high temperature thermal dynamic reactions: melting/evaporation, agglomeration, Rayleigh instability, and formation/or removal of carbon in the nanoparticles.

Elemental Quantification and Residues Characterization of Wet Digested Certified and Commercial Carbon Materials.

Inductively coupled plasma optical emission spectroscopy (ICP-OES) is a common, relatively low cost, and straightforward analytical technique for the study of trace quantities of metals in solid materials, but its applicability to nanocarbons (e.g., graphene and nanotubes) has suffered from the lack of efficient digestion steps and certified reference materials (CRM). Here, various commercial and certified graphitic carbon materials were subjected to a "two-step" microwave-assisted acid digestion procedure, and the concentrations of up to 18 elements were analyzed by ICP-OES. With one exception (Sm), successful quantification of all certified elements in the two reference nanocarbons studied was achieved, hence validating the sample preparation approach used. The applicability of our "two-step" protocol was further confirmed for a commercial single-walled carbon nanotube sample. However, the digestion was markedly incomplete for all other commercial materials tested. Where possible, the digestion residues of the carbon materials analyzed (CRM included) were characterized to understand the structural changes that take place and how this may explain the challenge of disintegrating graphitic carbon. In this respect, it was found that solid state nuclear magnetic resonance holds considerable promise as a nonlocalized, easily interpretable, and reliable tool to access the efficient disintegration of these materials.

Structural changes of electron and ion beam-deposited contacts in annealed carbon-based electrical devices.

The use of electron and ion beam deposition to make devices containing discrete nanostructures as interconnectors is a well-known nanofabrication process. Classically, one-dimensional materials such as carbon nanotubes (CNTs) have been electrically characterized by resorting to these beam deposition methods. While much attention has been given to the interconnectors, less is known about the contacting electrodes (or leads). In particular, the structure and chemistry of the electrode-interconnector interface is a topic that deserves more attention, as it is critical to understand the device behavior. Here, the structure and chemistry of Pt electrodes, deposited either with electron or ion beams and contacted to a CNT, are analyzed before and after thermally annealing the device in a vacuum. Free-standing Pt nanorods, acting as beam-deposited electrode models, are also characterized pre- and post-annealing. Overall, the as-deposited leads contain a non-negligible amount of amorphous carbon that is consolidated, upon heating, as a partially graphitized outer shell enveloping a Pt core. This observation raises pertinent questions regarding the definition of electrode-nanostructure interfaces in electrical devices, in particular long-standing assumptions of metal-CNT contacts fabricated by direct beam deposition methods.

Carboxymethyl Cellulose versus Hydroxypropyl Methylcellulose Tear Substitutes for Dry Eye Due to Computer Vision Syndrome: Comparison of Efficacy and Safety.

BACKGROUND: Prolonged use of visual display terminal images on electronic devices such as computers frequently leads to symptoms of dry eye. Tear substitutes form the mainstay of treatment for mild-to-moderate dry eye. AIM: The study aimed to evaluate the efficacy and safety of carboxymethyl cellulose (CMC) versus hydroxypropyl methylcellulose (HPMC) tear substitutes for dry eye due to computer vision syndrome (CVS). MATERIALS AND METHODS: This was a prospective, randomized, comparative, and open-labeled study. The efficacy of CMC 0.5% and HPMC 0.3% tear substitutes was compared in 180 participants (90 in each group) with dry eye. Change in Ocular Surface Disease Index (OSDI) score, Schirmer I test score, and tear film break up time (TF-BUT) were used as efficacy parameters. Safety was monitored on all visits. RESULTS: The baseline OSDI score? 23.48 and 23.32 in Group A and B, respectively, decreased with treatment in both groups on all follow-up visits as compared to the baseline (day 90: 13.9 ± 3 vs. 14.81 ± 3.17, P: 0.01). The scores of Schirmer I test increased in both groups, with a greater improvement in Group A (at day 90: 22.75 ± 3.04 mm vs. 21.78 ± 3.36 mm, P: 0.04). The values of TF-BUT improved in both groups, the difference being statistically insignificant. An initial stinging was reported by one participant, each in both groups. CONCLUSION: CMC and HPMC tear substitutes were equally efficacious and safe in reducing symptoms of dry eye due to CVS.

Can a Procedure for the Growth of Single-layer Graphene on Copper be used in Different Chemical Vapor Deposition Reactors?

In the last decade, catalytic chemical vapor deposition (CVD) has been intensively explored for the growth of single-layer graphene (SLG). Despite the scattering of guidelines and procedures, variables such as the surface texture/chemistry of catalyst metal foils, carbon feedstock, and growth process parameters have been well-scrutinized. Still, questions remain on how best to standardize the growth procedure. The possible correlation of procedures between different CVD setups is an example. Here, two thermal CVD reactors were explored to grow graphene on Cu foil. The design of these setups was entirely distinct, one being a "showerhead" cold-wall type, whereas the other represented the popular "tubular" hot-wall type. Upon standardizing the Cu foil surface, it was possible to develop a procedure for cm2 -scale SLG growth that differed only by the carrier gas flow rate used in the two reactors.

Paper-Based In-Situ Gold Nanoparticle Synthesis for Colorimetric, Non-Enzymatic Glucose Level Determination.

Due to its properties, paper represents an alternative to perform point-of-care tests for colorimetric determination of glucose levels, providing simple, rapid, and inexpensive means of diagnosis. In this work, we report the development of a novel, rapid, disposable, inexpensive, enzyme-free, and colorimetric paper-based assay for glucose level determination. This sensing strategy is based on the synthesis of gold nanoparticles (AuNPs) by reduction of a gold salt precursor, in which glucose acts simultaneously as reducing and capping agent. This leads to a direct measurement of glucose without any enzymes or depending on the detection of intermediate products as in conventional enzymatic colorimetric methods. Firstly, we modelled the synthesis reaction of AuNPs to determine the optical, morphological, and kinetic properties and their manipulation for glucose sensing, by determining the influence of each of the reaction precursors towards the produced AuNPs, providing a guide for the manipulation of nucleation and growth. The adaptation of this synthesis into the developed paper platform was tested and calibrated using different standard solutions with physiological concentrations of glucose. The response of the colorimetric signals obtained with this paper-based platform showed a linear behavior until 20 mM, required for glycemic control in diabetes, using the Red × Value/Grey feature combination as a calibration metric, to describe the variations in color intensity and hue in the spot test zone. The colorimetric sensor revealed a detection limit of 0.65 mM, depending on calibration metric and sensitivity of 0.013 AU/mM for a linear sensitivity range from 1.25 to 20 mM, with high specificity for the determination of glucose in complex standards with other common reducing interferents and human serum.

Current-Induced Helicity Reversal of a Single Skyrmionic Bubble Chain in a Nanostructured Frustrated Magnet.

Helicity indicates the in-plane magnetic-moment swirling direction of a skyrmionic configuration. The ability to reverse the helicity of a skyrmionic bubble via purely electrical means has been predicted in frustrated magnetic systems; however, it has been challenging to observe this experimentally. The current-driven helicity reversal of the skyrmionic bubble in a nanostructured frustrated Fe3 Sn2 magnet is experimentally demonstrated. The critical current density required to trigger the helicity reversal is 109 -1010 A m-2 , with a corresponding pulse-width varying from 1 µs to 100 ns. Computational simulations reveal that both the pinning effect and dipole-dipole interaction play a crucial role in the helicity reversal process.

Current-induced restructuring in bent silver nanowires.

A number of metallic one-dimensional nanostructures have been proposed as interconnects for next-generation electronic devices. Generally, reports on charge transport properties consider low current density regimes in nanowires (or nanotubes) with intrinsically straight configurations. In these circumstances, direct observations of the interconnecting nanofilament electrical failure are scarce, particularly for initially crooked structures. Here, the electrical and structural responses of suspended silver nanowires exposed to increasing current densities were analysed using in situ transmission electron microscopy. At low rates of bias application, initially straight nanowires showed trivial behaviour up to their breakdown, with electromigration and gradual necking taking place. By contrast, these nanowires with an initially crooked configuration exhibit a mixed set of responses which included string-like resonance and structural rearrangements. Remarkably, it was observed that restructuring does not necessarily compromise the transport function of these interconnectors. Hence, initially crooked nanowires could import higher resilience to future nanoelectronic devices by delaying catastrophic breakdown of interconnectors subjected to unexpected current surges.

Cobalt ferrite supported on reduced graphene oxide as a T 2 contrast agent for magnetic resonance imaging.

Nanoscaled spinel-structured ferrites bear promise as next-generation contrast agents for magnetic resonance imaging. However, the small size of the particles commonly leads to colloidal instability under physiological conditions. To circumvent this problem, supports onto which the dispersed nanoparticles can be anchored have been proposed. Amongst these, flakes of graphene have shown interesting performance but it remains unknown if and how their surface texture and chemistry affect the magnetic properties and relaxation time (T 2) of the ferrite nanoparticles. Here, it is shown that the type of graphene oxide (GO) precursor, used to make composites of cobalt ferrite (CoFe2O4) and reduced GO, influences greatly not just the T 2 but also the average size, dispersion and magnetic behaviour of the grafted nanoparticles. Accordingly, and without compromising biocompatibility, a judicious choice of the initial GO precursor can result in the doubling of the proton relaxivity rate in this system.

Chemical and Structural Analysis of Carbon Materials Subjected to Alkaline Oxidation.

Redox species such as transition metals may, unknowingly, integrate carbon materials that are produced (or supplied) for the assembling of electrodes in batteries, supercapacitors, and fuel cells. The extent to which these species alter the electrochemical profile of carbons and affect the performance and/or degradation of energy storage systems is still not fully appreciated. Alkaline oxidation (or fusion) is a promising approach to disintegrate nanocarbons for the subsequent study of their chemical composition by routine analytical tools. In this work, three commercial carbon powders, relevant for electrochemical applications and bearing varied textural orientation (point, radial, and planar), were selected to evaluate the versatility of fusion as a pretreatment process for elemental analysis. Additionally, the interaction of the flux, a lithium borate salt, with the carbons was elucidated by examining their post-fusion residues. The degree of structural degradation varied and, generally, the doping with Li and/or B (whether substitutional or interstitial) was low to nonexistent. With future developments, fusion could become a relevant pretreatment method to analyze the composition of carbon materials, even when complex mixtures (e.g., cycled battery electrodes) and larger batch scales are considered.

Pattern of Ocular Morbidity in the Elderly Population of Northern India.

INTRODUCTION: The frequency of eye diseases has been suggested to start increasing around 40 years of age, with an even steeper increase beginning around 60 years of age. Health promotions and curative and rehabilitative services for the visually impaired elderly population should therefore be a priority in the coming years especially in low and middle income countries. AIM: To examine the changing pattern of ocular morbidity in the elderly population of Northern India and to determine the socioeconomic status in relation to ocular morbidities. MATERIALS AND METHODS: A team from the Department of Ophthalmology and Department of Community Medicine, conducted house visits and did a complete eye examination of 450 elderly subjects. They were selected by systematic random sampling from the data base available in the Department of Community Medicine. RESULTS: A total of 900 eyes were examined. Visual impairment and blindness was seen in 135 (30%) and 36 (8%) individuals respectively. The most common cause of blindness was cataract, followed by corneal opacity, glaucoma, refractive error, diabetic retinopathy, macular scar, age related macular degeneration, retinal detachment, retinitis pigmentosa. Visual impairment was more in individuals with low socioeconomic status. CONCLUSION: The results of this study suggest that though cataract remains the main cause of blindness, there is an increase in blindness and visual impairment due to corneal diseases and glaucoma which was not seen earlier. The availability and accessibility to eye care facilities particularly for corneal diseases and glaucoma should be increased to reduce blindness in Northern India.

Structural and chemical analysis of gadolinium halides encapsulated within WS2 nanotubes.

The hollow cavities of nanotubes serve as templates for the growth of size- and shape-confined functional nanostructures, giving rise to novel materials and properties. In this work, considering their potential application as MRI contrast agents, gadolinium halides are encapsulated within the hollow cavities of WS2 nanotubes by capillary filling to obtain GdX3@WS2 nanotubes (where X = Cl, Br or I and @ means encapsulated in). Aberration corrected scanning/transmission electron microscopy (S/TEM) and spectroscopy is employed to understand the morphology and composition of the GdI3@WS2 nanotubes. The three dimensional morphology is studied with STEM tomography but understanding the compositional information is non-trivial due to the presence of multiple high atomic number elements. Therefore, energy dispersive X-ray spectroscopy (EDS) tomography was employed revealing the three dimensional chemical composition. Molecular dynamics simulations of the filling procedure shed light into the mechanics behind the formation of the confined gadolinium halide crystals. The quasi-1D system employed here serves as an example of a TEM-based chemical nanotomography method that could be extended to other materials, including beam-sensitive soft materials.

Ophthalmic manifestations of acute and chronic leukemias presenting to a tertiary care center in India.

CONTEXT: Screening for ocular manifestations of leukemia, although not a routine practice, is important as they may antedate systemic disease or form an isolated focus of its relapse. AIMS: This study evaluates the spectrum of ocular manifestations in acute and chronic leukemias presenting to a tertiary care center in India. SETTINGS AND DESIGN: Subjects of leukemia presenting to a tertiary care center in India. SUBJECTS AND METHODS: A prospective, cross-sectional study looking at the spectrum of ocular manifestations in all inpatients of acute or chronic leukemia. STATISTICAL ANALYSIS USED: The collected data were analyzed using the Statistical Package for Social Sciences for Windows software, version 16 (SPSS Inc., Chicago, Illinois, USA). RESULTS: The study subjects (n = 96) comprised 61 males and 35 females whose age ranged from 18 months to 91 years (mean = 39.73, ±22.1). There were 79 adults and 17 children, 53 new and 43 existing patients, 68 acute and 28 chronic, 61 myeloid and 35 lymphoid patients. Ocular lesions were found in 42 patients (43.8%). The ocular manifestations of leukemia were significantly (P = 0.01467) more frequent in acute 35/68 (51.9%) than chronic 7/28 (25%) leukemias. Primary or direct leukemic infiltration was seen in 8 (8.3%) subjects while secondary or indirect involvement due to anemia, thrombocytopenia, hyperviscosity, total body irradiation, and immunosuppression were seen in 42 (43.8%) subjects. Ocular changes were present in 37/79 (46.8%) adults and 5/17 (29.4%) children (P = 0.09460). Twenty-eight males (28/61) 45.9% and 14/35 (40%) females had ocular manifestations (P = 0.2874). The ocular manifestations were significantly (P = 0.01158) more frequent in myeloid leukemias 32/61 (52.9%) than lymphoid leukemias 10/35 (28.6%). CONCLUSIONS: Leukemic ophthalmic lesions were found in 42/96 (43.8%) patients. Ocular involvement is more often seen in adults, acute and myeloid leukemias. All the primary leukemic manifestations were seen in males. A periodic ophthalmic examination should be mandatory for all leukemic patients, as ocular changes are often picked up in asymptomatic patients.