Sequential intracorneal ring segment implantation followed by transepithelial phototherapeutic keratectomy and corneal cross-linking.

PURPOSE: To evaluate the safety and visual outcomes of intrastromal corneal ring segment (ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and corneal cross-linking (CXL) in patients with mild keratoconus. METHODS: Patients with mild keratoconus and contact lens intolerance who underwent sequential ICRS implantation followed by phototherapeutic keratectomy and corneal CXL between April 2015 and July 2018 were retrospectively included in the study. Refractive and visual outcomes, satisfaction questionnaire and complications were recorded at the last follow-up (mean 9.5 months postoperatively). RESULTS: Twenty eyes of 17 patients were enrolled, including 5 women and 15 men. The mean time between the two procedures was 16 months. Based on values before the first procedure and 9.5 months after the second procedure, significant improvements were noted in uncorrected distance visual acuity (UDVA) (0.80±0.35 logMAR vs. 0.46±0.38 logMAR), corrected distance visual acuity (CDVA) (0.38±0.23 logMAR vs. 0.13±0.16 logMAR), maximal K (56.11±4 diopters [D] vs. 50.6±3.56 D), mean K (51.87±3.43 D vs. 48.45±2.91 D), cylinder (7.99±3.94 D vs. 4.23±3.49 D), and spherical equivalent (-3.84±3.36 D vs. -0.99±2.15 D) (P<0.01). Among the outcomes, we noted 5 (25%) superficial corneal scarring (haze); 75% of eyes gained>=1 logMAR line of CDVA. In all, 94.5% of patients reported that they were satisfied with their outcomes. CONCLUSION: Combining ICRS implantation followed by te-PTK and corneal CXL appears to be a safe and effective approach for improving visual outcomes and quality of life in keratoconus patients.

Lignocellulose-derived inhibitors improve lipid extraction from wet Rhodococcus opacus cells.

Extracting lipids from oleaginous microbial cells in a cost effective and environmentally compatible manner remains a critical challenge in developing manufacturing paradigms for advanced liquid biofuels. In this study, a new approach using microbial growth inhibitors from lignocellulose-derived feedstocks was used to extract lipids efficiently from wet cell mass of the oleaginous bacterium Rhodococcus opacus MITXM-61. Nine common lignocellulose-derived inhibitors for treatment of cells prior to solvent extraction were used and evaluated for their efficiency of lipid extraction from the cells. When the inhibitors were individually examined, formic acid and furfural showed the highest extraction efficiency of lipids from wet cell mass. Multiple extractions of lipids with methanol from wet cell mass pretreated with combined common inhibitors or hardwood hydrolysate comprising lignocellulose-derived inhibitors resulted in lipid recovery of greater than 85% of total lipids, a 1.7-fold increase of lipid extraction as compared to those in the absence of the inhibitors.

Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis.

To measure molecular changes underlying pathogen adaptation, we generated a searchable dataset of more than 12,000 mass spectrometry events, corresponding to lipids and small molecules that constitute a lipidome for Mycobacterium tuberculosis. Iron is essential for M. tuberculosis survival, and the organism imports this metal using mycobactin and carboxymycobactin siderophores. Detection of an unexpected siderophore variant and deletions of genes for iron scavenging has led to a revised mycobactin biosynthesis model. An organism-wide search of the M. tuberculosis database for hypothetical compounds predicted by this model led to the discovery of two families of previously unknown lipids, designated monodeoxymycobactins and monodeoxycarboxymycobactins. These molecules suggest a revised biosynthetic model that alters the substrates and order of action of enzymes through the mycobactin biosynthetic pathway. We tested this model genetically by solving M. tuberculosis lipidomes after deletion of the iron-dependent regulator (ideR), mycobactin synthase B (mbtB), or mycobactin synthase G (mbtG). These studies show that deoxymycobactins are actively regulated during iron starvation, and also define essential roles of MbtG in converting deoxymycobactins to mycobactin and in promoting M. tuberculosis growth. Thus, lipidomics is an efficient discovery tool that informs genetic relationships, leading to a revised general model for the biosynthesis of these virulence-conferring siderophores.

A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis.

The lipidic envelope of Mycobacterium tuberculosis promotes virulence in many ways, so we developed a lipidomics platform for a broad survey of cell walls. Here we report two new databases (MycoMass, MycoMap), 30 lipid fine maps, and mass spectrometry datasets that comprise a static lipidome. Further, by rapidly regenerating lipidomic datasets during biological processes, comparative lipidomics provides statistically valid, organism-wide comparisons that broadly assess lipid changes during infection or among clinical strains of mycobacteria. Using stringent data filters, we tracked more than 5,000 molecular features in parallel with few or no false-positive molecular discoveries. The low error rates allowed chemotaxonomic analyses of mycobacteria, which describe the extent of chemical change in each strain and identified particular strain-specific molecules for use as biomarkers.

Loss of the acyl-CoA binding protein (Acbp) results in fatty acid metabolism abnormalities in mouse hair and skin.

Proper fatty acid metabolism is critical for hair and skin development and maintenance. The acyl-CoA binding protein (Acbp) is a widely expressed protein that binds long-chain fatty acyl-CoA esters and plays a role in fatty acyl-CoA transport and pool formation. However, loss of function of Acbp in the whole animal has not been investigated. Here, we show that deletion of Acbp in mouse results in sebocyte hyperplasia and sparse, matted hair with a greasy appearance. Consistent with these gross abnormalities, Acbp is highly expressed in the pilosebaceous units of mouse skin as determined by Northern analysis and in situ hybridization. Loss of Acbp also results in fatty acid metabolism abnormalities, with hair lipid profiles showing altered levels of triacylglycerols and nearly co-migrating lipids. These data suggest that Acbp plays a role in triacylglycerol biosynthesis, and that regulation of this process is important for proper hair and skin development and maintenance in the mouse.