Memory, mood and associated neuroanatomy in individuals with steroid sulphatase deficiency (X-linked ichthyosis).

Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and steroid (sulphate) levels correlate with mood and age-related cognitive decline. In animals, STS inhibition or deletion of the associated gene, enhances memory/neuroprotection and alters hippocampal neurochemistry. Little is known about the consequences of constitutive STS deficiency on memory-related processes in humans. We investigated self-reported memory performance (Multifactorial Memory Questionnaire), word-picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X-linked ichthyosis (XLI; n = 41) and in adult female carriers of XLI-associated genetic variants (n = 79); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, n = 98) or recruited from the general population (n = 250)]. Using the UK Biobank, we compared mood/memory-related neuroanatomy in carriers of genetic deletions encompassing STS (n = 28) and non-carriers (n = 34,522). We found poorer word-picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI-associated variant carriers and individuals with IV reported more adverse mood symptoms, reduced memory contentment and greater use of memory aids, compared with general population controls. Mood and memory findings appeared largely independent. Neuroanatomical analysis only indicated a nominally-significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non-carriers. In humans, constitutive STS deficiency appears associated with mood-independent impairments in memory but not with large effects on underlying brain structure; the mediating psychobiological mechanisms might be explored further in individuals with XLI and in new mammalian models lacking STS developmentally.

Stabilization of Immobilized Enzymes via the Chaperone-Like Activity of Mixed Lipid Bilayers.

Biomimetic lipid bilayers represent intriguing materials for enzyme immobilization, which is critical for many biotechnological applications. Here, through the creation of mixed lipid bilayers, the retention of immobilized enzyme structures and catalytic activity are dramatically enhanced. The enhancement in the retention of enzyme structures, which correlated with an increase in enzyme activity, is observed using dynamic single-molecule (SM) fluorescence methods. The results of SM analysis specifically show that lipid bilayers composed of mixtures of 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DOPG) stabilize the folded state of nitroreductase (NfsB), increasing the rate of refolding relative to unfolding of enzyme molecules on the bilayer surface. Remarkably, for optimal compositions with 15-50% DOPG, over 95% of NfsB remains folded while the activity of the enzyme is increased as much as 2 times over that in solution. Within this range of DOPG, the strength of the interaction of folded and unfolded NfsB with the bilayer surface was also significantly altered, which was evident by the change in the diffusion of folded and unfolded NfsB in the bilayer. Ultimately, these findings provide direct evidence for the chaperone-like activity of mixed DOPG/DOPC lipid bilayers, which can be controlled by tuning the fraction of DOPG in the bilayer.

Long-term visual prognosis in children after corneal transplant surgery for Peters anomaly type I.

PURPOSE: To evaluate the long-term visual prognosis in children with corneal transplant surgery for Peters anomaly type I. DESIGN: Retrospective review of interventional case series. METHODS: Twenty-four children treated in a university-based practice were divided into two groups for analysis: a younger preverbal group and an older group of children three years of age or older. Children underwent corneal transplantation surgery (penetrating keratoplasty [PKP]) for Peters anomaly type I as infants (age range, two to 18 months). Visual acuity using Snellen or Allen charts and glaucoma and other complications were tabulated. RESULTS: Twenty-four patients had Peters anomaly; 16 had unilateral disease, eight had bilateral disease. Thirty eyes underwent PKP. Average age at PKP was five months. The mean follow-up from PKP to the most recent visit was 78.9 months. Fifteen eyes (50%) were treated for glaucoma. Five transplants (17%) had graft rejection episodes; two of these failed and were regrafted. Six eyes (20%) required cataract surgery. One eye had a retinal detachment. Currently, 27 eyes (90%) have clear grafts. In the younger group of children, five of six grafts are clear (83%). In the older group of 24 eyes of verbal children, seven eyes (29%) have visual acuity ranging from 20/20 to 20/50, six (25%) have visual acuity ranging from 20/60 to 20/100, nine (38%) have visual acuity ranging from 20/200 to counting fingers, and two eyes (8%) have visual acuity of hand movements. In this group, nine of 12 eyes without glaucoma had visual acuity better than 20/100; only four of 11 eyes with glaucoma were better than 20/100. CONCLUSIONS: Many children with PKP for Peters anomaly type I can experience good or functional vision in their operated eye. Children with glaucoma have a poorer visual prognosis.

Predictors for success of needle revision of failing filtration blebs.

OBJECTIVE: To assess the factors that can predict the success of external needle revision of failing blebs. DESIGN: Retrospective, nonrandomized, comparative case series. PARTICIPANTS: Forty-nine eyes of 43 patients who underwent a needle revision of a filtration bleb with 5-fluourouracil (5-FU) by one physician (SVLB) between August 1993 and December 1994. INTERVENTION: Needle revision of a failing filtration bleb using 5-FU. MAIN OUTCOMES: The intraocular pressure, glaucoma medications, and any complications. RESULTS: The risk ratio of fornix-based trabeculectomies compared with limbus-based trabeculectomies was 3.781; P = 0.047. The risk ratios for gender, race, type of glaucoma, lens status, previous surgery, antimetabolite used for the initial trabeculectomy, and preoperative bleb characteristics were not statistically different for any one group. CONCLUSIONS: Fornix-based trabeculectomies were more likely to fail the needle revisions compared with limbus-based trabeculectomies. None of the five preneedling bleb characteristics showed a propensity toward success or failure. Other demographics such as gender, race, type of glaucoma, previous surgery, antimetabolite used for the initial trabeculectomy, and lens status were also not predictive for success.