Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

Analysis of physical activity in emmetropic and myopic university students during semester and holiday periods: A pilot study

Background Previous studies (mostly questionnaire-based in children) suggest that outdoor activity is protective against myopia. There are few studies on young adults investigating both the impact of simply being outdoors versus performing physical activity. The aim was to study the relationship between the refractive error of young adults and their physical activity patterns. Methods Twenty-seven university students, aged 18 to 25 years, wore a pedometer (Omron HJ720ITE) for seven days both during the semester and holiday periods. They simultaneously recorded the type of activity performed, its duration, the number of steps taken (from the pedometer) and their location (indoors/outdoors) in a logbook. Mean spherical refractive error was used to divide participants into three groups (emmetropes: +1.00 to -0.50 D, low myopes: -0.62 to -3.00 D, higher myopes: -3.12 D or greater myopia). Results There were no significant differences between the refractive groups during the semester or holiday periods; the average daily times spent outdoors, the duration of physical activity, the ratio of physical activity performed outdoors to indoors and amount of near work performed were similar. The peak exercise intensity was similar across all groups: approximately 100 steps perminute, a brisk walk. Up to one-third of all physical activity was performed outdoors. There were some significant differences in activities performed during semester and holiday times. For example, lowmyopes spent significantly less time outside (49 ± 47 versus 74 ± 41 minutes, p = 0.005) and performed less physical activity (6,388 ± 1,747 versus 6,779 ± 2,746 steps per day; p = 0.03) during the holidays compared to during semester. Conclusions The fact that all groups had similar low exercise intensity butmany were notmyopic suggests that physical activity levels are not critical. There were differences in the activity patterns of lowmyopes during semester and holiday periods. This study highlights the need for a larger longitudinal-based study with particular emphasis on how discretionary time is spent.

Miniscleral lens wear influences corneal curvature and optics

Purpose Transient changes in corneal topography associated with soft and conventional or reverse geometry rigid contact lens wear have been well documented; however, only a few studies have examined the influence of scleral contact lens wear upon the cornea. Therefore, in this study, we examined the influence of modern miniscleral contact lenses, which land entirely on the sclera and overlying tissues, upon anterior corneal curvature and optics. Methods Anterior corneal topography and elevation data were acquired using Scheimpflug imaging (Pentacam HR, Oculus) immediately prior to and following 8 hours of miniscleral contact lens wear in 15 young healthy adults (mean age 22 ± 3 years, 8 East Asian, 7 Caucasian) with normal corneae. Corneal diurnal variations were accounted for using data collected on a dedicated measurement day without contact lens wear. Corneal clearance was quantified using an optical coherence tomographer (RS-3000, Nidek) following lens insertion and after 8 hours of lens wear. Results Although corneal clearance was maintained throughout the 8 hour lens wear period, significant corneal flattening (up to 0.08 ± 0.04 mm) was observed, primarily in the superior mid-peripheral cornea, which resulted in a slight increase in against-the-rule corneal astigmatism (mean +0.02/-0.15 x 94 for an 8 mm diameter). Higher order aberration terms of horizontal coma, vertical coma and spherical aberration all underwent significant changes for an 8 mm corneal diameter (p ≤ 0.01), which typically resulted in a decrease in RMS error values (mean change in total higher order RMS -0.035 ± 0.046 µm for an 8 mm diameter). There was no association between the magnitude of change in central or mid-peripheral corneal clearance during lens wear and the observed changes in corneal curvature (p > 0.05). However, Asian participants displayed a significantly greater reduction in corneal clearance (p = 0.04) and greater superior-nasal corneal flattening compared to Caucasians (p = 0.048). Conclusions Miniscleral contact lenses that vault the cornea induce significant changes in anterior corneal surface topography and higher order aberrations following 8 hours of lens wear. The region of greatest corneal flattening was observed in the superior-nasal mid-periphery, more so in Asian participants. Practitioners should be aware that corneal measurements obtained following miniscleral lens removal may mask underlying corneal steepening.

The influence of a novel simulated learning environment upon student clinical subjective refraction performance: A pilot study

Background: Optometry students are taught the process of subjective refraction through lectures and laboratory based practicals before progressing to supervised clinical practice. Simulated learning environments (SLEs) are an emerging technology that are used in a range of health disciplines, however, there is limited evidence regarding the effectiveness of clinical simulators as an educational tool. Methods: Forty optometry students (20 fourth year and 20 fifth year) were assessed twice by a qualified optometrist (two examinations separated by 4-8 weeks) while completing a monocular non-cycloplegic subjective refraction on the same patient with an unknown refractive error simulated using contact lenses. Half of the students were granted access to an online SLE, The Brien Holden Vision Institute (BHVI®) Virtual Refractor, and the remaining students formed a control group. The primary outcome measures at each visit were; accuracy of the clinical refraction compared to a qualified optometrist and relative to the Optometry Council of Australia and New Zealand (OCANZ) subjective refraction examination criteria. Secondary measures of interest included descriptors of student SLE engagement, student self-reported confidence levels and correlations between performance in the simulated and real world clinical environment. Results: Eighty percent of students in the intervention group interacted with the SLE (for an average of 100 minutes); however, there was no correlation between measures of student engagement with the BHVI® Virtual Refractor and speed or accuracy of clinical subjective refractions. Fifth year students were typically more confident and refracted more accurately and quickly than fourth year students. A year group by experimental group interaction (p = 0.03) was observed for accuracy of the spherical component of refraction, and post hoc analysis revealed that less experienced students exhibited greater gains in clinical accuracy following exposure to the SLE intervention. Conclusions: Short-term exposure to a SLE can positively influence clinical subjective refraction outcomes for less experienced optometry students and may be of benefit in increasing the skills of novice refractionists to levels appropriate for commencing supervised clinical interactions.

Distribution of ocular biometry in 7- and 14-year-old Chinese children

Purpose: To describe distributions of ocular biometry and their associations with refraction in 7- and 14-year-old children in urban areas of Anyang, central China. Methods: A total of 2271 grade 1 students aged 7.1 ± 0.4 years and 1786 grade 8 students aged 13.7 ± 0.5 years were measured with ocular biometry and cycloplegic refraction. A parental myopia questionnaire was administered to parents. Results: Mean axial length, anterior chamber depth, lens thickness, central corneal thickness, corneal diameter, corneal radius of curvature, axial length/corneal radius of curvature ratio, and spherical equivalent refraction were 22.72 ± 0.76 mm, 2.89 ± 0.24 mm, 3.61 ± 0.19 mm, 540.5 ± 31 μm, 12.06 ± 0.44 mm, 7.80 ± 0.25 mm, 2.91 ± 0.08, and +0.95 ± 1.05 diopters (D), respectively, in 7-year-old children. They were 24.39 ± 1.13 mm, 3.42 ± 0.41 mm, 3.18 ± 0.24 mm, 548.9 ± 33 μm, 12.03 ± 0.43 mm, 7.80 ± 0.26 mm, 3.13 ± 0.14, and −2.06 ± 2.20 D, respectively, in 14-year-old children. Compared with 7-year-old children, the older group had significantly more myopia (−3.0 D), longer axial length (1.7 mm), deeper anterior chamber depth (0.3 mm), thinner lens thickness (−0.2 mm), thicker central corneal thickness (10 μm), and greater axial length/corneal radius of curvature ratio (0.22) (all p < 0.001), as well as smaller corneal diameter (−0.03 mm, p = 0.02) and similar corneal radius of curvature. Sex differences were similar in both age groups, with boys having longer axial length (0.5 mm), deeper anterior chamber depth (0.1 mm), shorter lens thickness (0.03 mm), greater central corneal thickness (5 μm), greater corneal diameter (0.15 mm), and greater corneal radius of curvature (0.14 mm) than girls (all p < 0.01). The most important variables related to spherical equivalent refraction were vitreous length, corneal radius of curvature, and lens thickness. Conclusions: The 14-year-old group had larger parameter dimensions than the 7-year-old group except for corneal radius of curvature (unchanged) and lens thickness and corneal diameter (both smaller). Boys had large parameter dimensions than girls except for lens thickness (smaller). Axial length, corneal radius of curvature, and lens thickness were the most important determinants of refraction.

Relative peripheral hyperopia does not predict development and progression of myopia in children

Purpose To test the hypothesis that relative peripheral hyperopia predicts development and progression of myopia. Methods Refraction along the horizontal visual field was measured under cycloplegia at visual field angles of 0°, ±15°, and ±30° at baseline, 1 and 2 years in over 1700 initially 7-year-old Chinese children, and at baseline and 1 year in over 1000 initially 14-year olds. One refraction classification for central refraction was “nonmyopia, myopia” (nM, M), consisting of nM greater than −0.50 diopters (D; spherical equivalent) and M less than or equal to −0.50 D. A second classification was “hyperopia, emmetropia, low myopia, and moderate/high myopia” (H, E, LM, MM) with H greater than or equal to +1.00 D, E, −0.49 to +0.99 D, LM, −2.99 to −0.50 D, and MM less than or equal to −3.00 D. Subclassifications were made on the basis of development and progression of myopia over the 2 years. Changes in central refraction over time were determined for different groups, and relative peripheral refraction over time was compared between different subgroups. Results Simple linear regression of central refraction as a function of relative peripheral refraction did not predict myopia progression as relative peripheral refraction became more hyperopic: relative peripheral hyperopia and relative peripheral myopia predicted significant myopia progression for 0% and 35% of group/visual field angle combinations, respectively. Subgroups who developed myopia did not have more initial relative peripheral hyperopia than subgroups who did not develop myopia. Conclusions Relative peripheral hyperopia does not predict development nor progression of myopia in children. This calls into question the efficacy of treatments that aim to slow progression of myopia in children by “treating” relative peripheral hyperopia.

Mechanical testing of internal fixation devices: A theoretical and practical examination of current methods

Successful healing of long bone fractures is dependent on the mechanical environment created within the fracture, which in turn is dependent on the fixation strategy. Recent literature reports have suggested that locked plating devices are too stiff to reliably promote healing. However, in vitro testing of these devices has been inconsistent in both method of constraint and reported outcomes, making comparisons between studies and the assessment of construct stiffness problematic. Each of the methods previously used in the literature were assessed for their effect on the bending of the sample and concordant stiffness. The choice of outcome measures used in in vitro fracture studies was also assessed. Mechanical testing was conducted on seven hole locked plated constructs in each method for comparison. Based on the assessment of each method the use of spherical bearings, ball joints or similar is suggested at both ends of the sample. The use of near and far cortex movement was found to be more comprehensive and more accurate than traditional centrally calculated inter fragmentary movement values; stiffness was found to be highly susceptible to the accuracy of deformation measurements and constraint method, and should only be used as a within study comparison method. The reported stiffness values of locked plate constructs from in vitro mechanical testing is highly susceptible to testing constraints and output measures, with many standard techniques overestimating the stiffness of the construct. This raises the need for further investigation into the actual mechanical behaviour within the fracture gap of these devices.

Diurnal variation of anterior scleral and conjunctival thickness

Purpose To examine whether anterior scleral and conjunctival thickness undergoes significant diurnal variation over a 24-hour period. Methods Nineteen healthy young adults (mean age 22 ± 2 years) with minimal refractive error (mean spherical equivalent refraction -0.08 ± 0.39 D), had measures of anterior scleral and conjunctival thickness collected using anterior segment optical coherence tomography (AS-OCT) at seven measurement sessions over a 24-hour period. The thickness of the temporal anterior sclera and conjunctiva were determined at 6 locations (each separated by 0.5 mm) at varying distances from the scleral spur for each subject at each measurement session. Results Both the anterior sclera and conjunctiva were found to undergo significant diurnal variations in thickness over a 24-hour period (both p <0.01). The sclera and conjunctiva exhibited a similar pattern of diurnal change, with a small magnitude thinning observed close to midday, and a larger magnitude thickening observed in the early morning immediately after waking. The amplitude of diurnal thickness change was larger in the conjunctiva (mean amplitude 69 ± 29 μm) compared to the sclera (21 ± 8 μm). The conjunctiva exhibited its smallest magnitude of change at the scleral spur location (mean amplitude 56 ± 17 μm) whereas the sclera exhibited its largest magnitude of change at this location (52 ± 21 μm). Conclusions This study provides the first evidence of diurnal variations occurring in the thickness of the anterior sclera and conjunctiva. Studies requiring precise measures of these anatomical layers should therefore take time of day into consideration. The majority of the observed changes occurred in the early morning immediately after waking and were of larger magnitude in the conjunctiva compared to the sclera. Thickness changes at other times of the day were of smaller magnitude and generally not statistically significant.

Induced higher-order aberrations after laser in situ keratomileusis (LASIK) performed with wavefront-guided IntraLase femtosecond laser in moderate to high astigmatism

Background Wavefront-guided Laser-assisted in situ keratomileusis (LASIK) is a widespread and effective surgical treatment for myopia and astigmatic correction but whether it induces higher-order aberrations remains controversial. The study was designed to evaluate the changes in higher-order aberrations after wavefront-guided ablation with IntraLase femtosecond laser in moderate to high astigmatism. Methods Twenty-three eyes of 15 patients with moderate to high astigmatism (mean cylinder, −3.22 ± 0.59 dioptres) aged between 19 and 35 years (mean age, 25.6 ± 4.9 years) were included in this prospective study. Subjects with cylinder ≥ 1.5 and ≤2.75 D were classified as moderate astigmatism while high astigmatism was ≥3.00 D. All patients underwent a femtosecond laser–enabled (150-kHz IntraLase iFS; Abbott Medical Optics Inc) wavefront-guided ablation. Uncorrected (UDVA), corrected (CDVA) distance visual acuity in logMAR, keratometry, central corneal thickness (CCT) and higher-order aberrations (HOAs) over a 6 mm pupil, were assessed before and 6 months, postoperatively. The relationship between postoperative change in HOA and preoperative mean spherical equivalent refraction, mean astigmatism, and postoperative CCT were tested. Results At the last follow-up, the mean UDVA was increased (P < 0.0001) but CDVA remained unchanged (P = 0.48) and no eyes lost ≥2 lines of CDVA. Mean spherical equivalent refraction was reduced (P < 0.0001) and was within ±0.50 D range in 61 % of eyes. The average corneal curvature was flatter by 4 D and CCT was reduced by 83 μm (P < 0.0001, for all), postoperatively. Coma aberrations remained unchanged (P = 0.07) while the change in trefoil (P = 0.047) postoperatively, was not clinically significant. The 4th order HOAs (spherical aberration and secondary astigmatism) and the HOA root mean square (RMS) increased from −0.18 ± 0.07 μm, 0.04 ± 0.03 μm and 0.47 ± 0.11 μm, preoperatively, to 0.33 ± 0.19 μm (P = 0.004), 0.21 ± 0.09 μm (P < 0.0001) and 0.77 ± 0.27 μm (P < 0.0001), six months postoperatively. The change in spherical aberration after the procedure increased with an increase in the degree of preoperative myopia. Conclusions Wavefront-guided IntraLASIK offers a safe and effective option for vision and visual function improvement in astigmatism. Although, reduction of HOA is possible in a few eyes, spherical-like aberrations are increased in majority of the treated eyes.

Influence of biodiesel fuel composition on the morphology and microstructure of particles emitted from diesel engines

This study investigates the morphology, microstructure and surface composition of Diesel engine exhaust particles. The state of agglomeration, the primary particle size and the fractal dimension of exhaust particles from petroleum Diesel (petrodiesel) and biodiesel blends from microalgae, cotton seed and waste cooking oil were investigated by means of high resolution transmission electron microscopy. With primary particle diameters between 12-19 nm, biodiesel blend primary particles are found to be smaller than petrodiesel ones (21±2 nm). Also it was found that soot agglomerates from biodiesels are more compact and spherical, as their fractal dimensions are higher, e.g. 2.2±0.1 for 50% algae biodiesel compared to 1.7±0.1 for petrodiesel. In addition, analysis of the chemical composition by means of x-ray photoelectron spectroscopy revealed an up to a factor of two increased oxygen content on the primary particle surface for biodiesel. The length, curvature and distance of graphene layers were measured showing a greater structural disorder for biodiesel with shorter fringes of higher tortuosity. This change in carbon chemistry may reflect the higher oxygen content of biofuels. Overall, it seems that the oxygen content in the fuels is the underlying reason for the observed morphological change in the resulting soot particles.