Quantitative trait locus on distal chromosome 1 regulates the occurrence of spontaneous spike-wave discharges in DBA/2 mice.

PURPOSE: Most common forms of human epilepsy result from a complex combination of polygenetic and environmental factors. Quantitative trait locus (QTL) mapping is a first step toward the nonbiased discovery of epilepsy-related candidate genes. QTL studies of susceptibility to induced seizures in mouse strains have consistently converged on a distal region of chromosome 1 as a major phenotypic determinant; however, its influence on spontaneous epilepsy remains unclear. In the present study we characterized the influence of allelic variations within this QTL, termed Szs1, on the occurrence of spontaneous spike-wave discharges (SWDs) characteristic of absence seizures in DBA/2 (D2) mice. METHODS: We analyzed SWD occurrence and patterns in freely behaving D2, C57BL/6 (B6) and the congenic strains D2.B6-Szs1 and B6.D2-Szs1. KEY FINDINGS: We showed that congenic manipulation of the Szs1 locus drastically reduced the number and the duration of SWDs in D2.B6-Szs1 mice, which are homozygous for Szs1 from B6 strain on a D2 strain background. However, it failed to induce the full expression of SWDs in the reverse congenic animals B6.D2-Szs1. SIGNIFICANCE: Our results demonstrate that the occurrence of SWDs in D2 animals is under polygenic control and, therefore, the D2 and B6 strains might be a useful model to dissect the genetic determinants of polygenic SWDs characteristic of typical absence seizures. Furthermore, we point to the existence of epistatic interactions between at least one modifier gene within Szs1 and genes within unlinked QTLs in regulating the occurrence of spontaneous nonconvulsive forms of epilepsies.

Incorporating 3D Printing Into Your Practice: Lessons Learned.

Three-dimensional (3D) printing has greatly benefited medicine, manufacturing vital organs like skin, hearts, kidneys, and livers. Early studies on 3D printing in surgery have consistently reported decreased operative time and improved precision. This technology has gained popularity with orthopaedic surgeons in knee, hip, and shoulder surgeries because 3D printing is associated with enhancing osseointegration. However, this innovation is still not commonly used among foot and ankle surgeons; one reason is that whereas the literature on 3D printing-assisted surgery is populated with studies on operative techniques and clinical outcomes, there exists an ambiguity on how to incorporate this feature into the clinic. Thus, the aim of this technology column is to consolidate and standardize a workflow to guide foot and ankle surgeons on integrating 3D printing into one's practice. We describe a model developed by a single surgeon at one institution who directs a large caseload of 3D-printed foot and ankle surgeries. From the initial patient visit to the interaction between the surgeon and the implant engineering team, to documentation of data adding to the preliminary literature, this work has great implications on streamlining the assimilation of a highly successful technology to improve foot and ankle surgery for both surgeons and patients.Level of Evidence: Level V.

Outcome of Intravitreal Dexamethasone Implant Use in Uveitic Eyes Undergoing Pars Plana Vitrectomy Surgery.

Purpose: To report the outcomes in eyes with noninfectious uveitis receiving dexamethasone implant at the time of pars plana vitrectomy (PPV).Methods: Retrospective analysis of visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), and central subfield thickness (CST) at baseline and follow-up visits.Results: Fourteen eyes received dexamethasone implant at the time of PPV. The CST was improved from 469 ± 182 µm at baseline to 320 ± 60 at 6 months (p = .0112) and 295 ± 46 at 12 months (p = .0728). Vitritis only recurred in 2 eyes at 6 months (18.2%) and 1 eye at 12 months (14.3%). The probability of VA improvement of ≥0.3 logMAR was 57% at 6 months and 66% at 12 months. Therapy for IOP rise was initiated in 6 eyes (42.9%).Conclusions: Local delivery of dexamethasone implant with PPV is a feasible method to counteract postoperative inflammation and macular thickening.

Intraoperative Complications and Visual Outcomes of Cataract Surgery in Diabetes Mellitus: A Multicenter Database Study.

PURPOSE: To compare the visual outcome and the rate of intraoperative complications in eyes of diabetic and nondiabetic patients undergoing phacoemulsification over 15 years. DESIGN: Retrospective clinical cohort study. METHODS: Data of 179,159 eyes that underwent phacoemulsification at 8 centers were classified based on the presence or absence of diabetes mellitus. Visual acuity (VA) was defined as the best value of uncorrected or corrected distance measure available. For the VA analysis, eyes with co-pathologies or combined surgical procedures were further excluded, leaving a subset of 90,729 eyes. Main outcome measures were logarithm of the minimum angle of resolution (logMAR) VA at 4-12 weeks postoperatively, and rate of intraoperative complications. RESULTS: Cataract surgery in eyes of diabetic patients was associated with an improvement in mean VA of 0.48 logMAR (5 Snellen lines). Mean postoperative VA was slightly worse in diabetic compared to nondiabetic group (logMAR 0.23 vs 0.13; Snellen 20/30 vs 20/25; P < .0001) and the proportions of eyes achieving a visual gain of ≥3 Snellen lines (≥0.3 logMAR) was lower in the diabetic group (56.6% vs 63.5%; P < .0001). There was a linear relationship between diabetic retinopathy severity and worse postoperative visual acuity (ß coefficient 0.098 to 0.288; P < .0001). We observed higher rates of posterior capsule rupture (2.3% vs 1.6%; P < .001) and dropped nuclear fragments (0.3% vs 0.2%; P < .001) in the diabetic group. CONCLUSIONS: Postoperative VA negatively correlated with diabetes and diabetic retinopathy severity. Eyes of diabetic subjects had higher risks of posterior capsule rupture.

A Review of Antimicrobial Therapy for Infectious Uveitis of the Posterior Segment.

Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers, which limits penetration of systemic antimicrobials into the posterior segment. In addition, topical and subconjunctival therapies are incapable of producing sufficient drug concentrations, intraocularly. Posterior infectious uveitis can be caused by bacteria, virus, fungi, or protozoa. Mode of treatment varies greatly based on the infectious etiology. Certain drugs have advantages over others in the treatment of infectious uveitis. Topical and systemic therapies are often employed in the treatment of ocular infection, yet the route of treatment can have limitations based on penetration, concentration, and duration. The introduction of intravitreal antimicrobial therapy has advanced the management of intraocular infections. Being able to bypass blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, because the difference between the therapeutic and the toxic doses of some antimicrobial drugs falls within a narrow concentration range, intravitreal therapy could be associated with ocular toxicity risks. In many cases of infectious uveitis, combination of intravitreal and systemic therapies are necessary. In this comprehensive review, the authors aimed at reviewing clinically relevant data regarding intraocular and systemic antimicrobial therapy for posterior segment infectious uveitis. The review also discussed the evolving trends in intraocular treatment, and elaborated on antibiotic pharmacokinetics and pharmacodynamics, efficacy, and adverse effects.

A Pruritic Eyelid Lesion Followed by Conjunctival Swelling.

A 54-year-old woman presented with an erythematous right lower eyelid lesion with a vermiform appearance, accompanied by pruritus and pain. She recently had exposure to farm animals, including dogs and cats. What would you do next?

High-tech brains: a history of technology-based analogies and models of nerve and brain function.

This article reviews some of the technological devices and ideas which have been used over the years to answer the question, how does the brain work? It describes some of the early technology-based analogies and models of nerve fibers, and then discusses other analogies and models of the brain based on mechanical and electrical technologies. There are also short sections on cybernetics, telephone exchanges, and computers. Although all of these ideas are flawed to some extent, this article offers a brief argument on the usefulness of analogy and abstraction in brain science.