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Since the introduction of femtosecond laser (FS) systems for corneal flap creation in laser-assisted in-situ keratomileusis there have been numerous applications for FS laser in corneal surgery. This manuscript details the utility of FS lasers in corneal surgical procedures including refractive laser surgeries, intracorneal ring segment tunnels, presbyopic treatments, and FS-assisted keratoplasty. We also review the role of FS lasers in diagnostic procedures such as two photon excitation fluorescence and second harmonic generation.
To compare the three-dimensional (3D) morphology of the deep load-bearing structures of the human optic nerve head (ONH) as revealed in vivo by spectral domain optical coherence tomography (SDOCT) with ex vivo quantitative 3D histology.
SDOCT imaging of the ONH was performed in six eyes from three brain-dead organ donors on life-support equipment awaiting organ procurement (in vivo conditions). Following organ procurement (ex vivo conditions), the eyes were enucleated and underwent a pars plana vitrectomy followed by pressurization to physiologic IOP and immersion fixation. learn more Ex vivo ONH morphology was obtained from high-fidelity episcopic fluorescent 3D reconstruction. Morphologic parameters of the observed ONH canal geometry and peripapillary choroid, as well as the shape, visibility and depth of the lamina cribrosa were compared between ex vivo and in vivo measurements using custom software to align, scale, and manually delineate the different regions of the ONH.
There was significant correspondence being models and biomarkers based on ex vivo imaging of fixed tissue. Lack of visibly of most of the lamina surface in SDOCT images is an important limitation to metrics and biomarkers based on in vivo images of the ONH deep tissues.
Morphologic parameters by SDOCT imaging of the deep ONH showed promising correspondence to histology metrics. Small but significant shrinkage artifact, along with large effects of exsanguination of the choroid, was seen in the ex vivo reconstructions of fixed tissues that may impact the quantification of ex vivo histoarchitecture, and this should be considered when developing models and biomarkers based on ex vivo imaging of fixed tissue. Lack of visibly of most of the lamina surface in SDOCT images is an important limitation to metrics and biomarkers based on in vivo images of the ONH deep tissues.
Fibrillin-1 and -2 are major components of tissue microfibrils that compose the ciliary zonule and cornea. While mutations in human fibrillin-1 lead to ectopia lentis, a major manifestation of Marfan syndrome (MFS), in mice fibrillin-2 can compensate for reduced/lack of fibrillin-1 and maintain the integrity of ocular structures. Here we examine the consequences of a heterozygous dominant-negative mutation in the Fbn1 gene in the ocular system of the mgΔ
mouse model for MFS.
Eyes from mgΔ
and wild-type mice at 3 and 6 months of age were analyzed by histology. The ciliary zonule was analyzed by scanning electron microscopy (SEM) and immunofluorescence.
Mutant mice presented a significantly larger distance of the ciliary body to the lens at 3 and 6 months of age when compared to wild-type, and ectopia lentis. Immunofluorescence and SEM corroborated those findings in MFS mice, revealing a disorganized mesh of microfibrils on the floor of the ciliary body. Moreover, mutant mice also had a larger volume of the anterior chamber, possibly due to excess aqueous humor. Finally, losartan treatment had limited efficacy in improving ocular phenotypes.
In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔ
mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease.
In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔlpn mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease.In recent time, gene therapy has proven to be a promising remedial approach for treating visual disorders either by replacement of nonfunctioning gene(s) or by introduction of light sensitive proteins (opsins) as artificial photoreceptors in retinal cells. Conventional viral vector-based gene delivery method is often confronted with limitations due to immunogenetic reaction, unintended non-targeted delivery, non-feasibility of repeated re-dosing due to immunorejection, and complicated manufacturing process, leading to significant roadblock in translational success. In this regard, non-viral delivery provides a safer, simpler and cost-effective alternative. However, most of the non-viral approaches lack spatial and/or cellular specificity and limited by low transfection efficacy and cytotoxicity. Here, we present a minimally invasive, non-viral and clinically translatable safe targeted gene delivery method utilizing functionalized plasmonic gold nanorods (fGNRs, targeted to attach to specific cell types of the organ of interest) and spatially targeted controlled light irradiation. Targeted in-vivo delivery and expression of opsin-encoding gene in bipolar and ganglion cell layers were achieved by use of cell specific fGNRs concurrent with light irradiation. Evaluation of safety and toxicity associated with the transduction of opsin-encoding genes by use of fGNRs and light irradiation were examined by electrophysiology, Optical coherence tomography, intra-ocular pressure and other analytical methods (confocal microscopy, immunohistochemistry). The non-viral light-based opsin-gene delivery provides a safe and effective alternative to viral-vector based gene delivery and holds promise for corrective cell-specific gene therapies for retinal degenerative diseases.Both social networks and social support are important in addressing bio-psycho-social events in older adults. Their associations with health-related quality of life (HRQOL), however, are not well understood. This study aims to examine the associations of diversity of social networks and perceived quality of social support with HRQOL in older adults. We used data from 2012 to 2013 National Epidemiological Survey on Alcohol and Related Conditions Wave III (NESARC-III), and included respondents aged 65 or older (n = 5799 unweighted). We used the Social Network Index (SNI) to measure diversity of social connections and the Interpersonal Support Evaluation List (ISEL-12) to measure perceived quality of social support. We also constructed HRQOL (mental component summary (MCS) and physical component summary (PCS)) and quality-adjusted life years (QALYs). We characterized socio-demographic, behavioral, and clinical factors, and HRQOL and QALYs by type of social support. We also used multivariable-adjusted regression analyses to assess the associations of diversity of social networks and perceived quality of social support with HRQOL and QALYs, respectively. Older adults with greater diversity of social networks, regardless of perceived quality of social support, had higher mean scores in HRQOL domains, although effect sizes were small. In multivariable-adjusted analyses, diversity of social networks was positively associated with HRQOL-MCS (coefficient = 0.59; 95% confidence intervals [CI], 0.08-1.09), HRQOL-PCS (coefficient = 1.00; 95% CI, 0.38-1.61), and QALYs (coefficient = 0.01; 95% CI, 0.00-0.02). Perceived quality of social support was not associated with HRQOL. The diversity of social networks, more than perceived quality of social support, may be protective for HRQOL in older adults.There is still a need for more empirical investigations to better understand the causal pathways by which neighborhood socioeconomic contexts translate into states of health. This study explored the relationship between neighborhood socioeconomic position and health, as well as the role of social cohesion, violence, places to buy healthy food, and sports and leisure spaces in mediating this relationship in a diverse set of neighborhoods in Brazil. We applied a general multiple mediation approach to analyze a cross-sectional survey of 4.046 adults living in 149 neighborhoods in 2008 and 2009. The property value was chosen as an indicator of neighborhood socioeconomic position and self-rated health as the outcome. The four mediators were constructed from the self-perception of the participants. Results We found that people living in economically advantaged neighborhoods were less likely to report their health as being fair/poor/very poor (OR = 0.71; 95% CI = 0.63, 0.76) than people living in disadvantaged neighborhoods, and this effect was mediated by the perception of violence in the neighborhoods. On average, 8.4% of the neighborhood socioeconomic disparity in self-rated health may be explained by violence. We did not ascertain as mediators social cohesion, places to buy healthy food, and sports and leisure spaces. Violence perception mediates the relationship between neighborhood socioeconomic position and self-rated health. Targeted interventions designed to improve the health status of the population could usefully focus on reducing the level of violence in which people live.Flavin adenine dinucleotide synthetase (FADS), a bifunctional prokaryotic enzyme, is involved in the synthesis of two vital cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Here, we investigated the biochemical characteristics of FADS from Staphylococcus aureus (Sa), a pathogenic bacteria causing food-borne diseases. The SaFADS possesses riboflavin kinase (RFK) and FMN adenylyltransferase (FMNAT) activities that transforms riboflavin to FMN and FMN to FAD, respectively. The FMNAT domain also exhibits reversible FAD pyrophosphorylase activity (FADpp). Further, we show that the FMNAT and FADpp activities are dependent on the reducing environment. Mutations of the conserved K289 and F290 residues present on the RFK domain affect the kinetic parameters of both the RFK and FMNAT domains. Additionally, the molecular dynamics analysis of apo and riboflavin ATP Mg2+ ternary complex of SaFADS shows that F290 is involved in stabilizing the active site geometry to hold the enzyme-substrate complex. In addition, the deletion of the αh2 helix that acts as a connecting linker between the FMNAT and RFK domains showed substantial loss of their activities. The helix deletion could have affected the flap motion of L2c, L4c, β4n and L3n present in the close proximity resulting in the distortion of the active site geometry. In conclusion, our study has characterized the RFK and FMNAT activities of SaFADS and shown the importance of conserved K289 and F290 in RFK activity. As FADSs are potential drug targets, understanding their mechanism of action might help in discovering species-specific antibacterial drugs.There is a dire need for innovative solutions to address global health needs. Polymeric systems have been shown to provide substantial benefit to all sectors of healthcare, especially for their ability to extend and control drug delivery. Herein, we review polymeric drug delivery devices for vaccines, tuberculosis, and contraception.
Website: https://www.selleckchem.com/products/AZD6244.html
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