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Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Neuromodulators have been associated with learning but much of our knowledge comes from pharmacological and in vitro studies. Therefore, a mechanistic understanding of how these neuromodulators play a role on learning in vivo is lacking. We used motor learning as a robust learning platform previously established by our lab since the resulting structural and phenotypic changes are known in detail. Using this platform, we studied neuromodulators in high degrees of specificity in learning animals using both a loss and gain of function approach. Our loss of function approach consisted of a series of surgeries, viral injections, and CRISPR. However, with cutting-edge technology, came obstacles. Therefore, the loss of function approach served as a technical side of the project.

In contrast, the gain of function was the experimental side of the project. Our investigation began with neuromodulator acetylcholine, but hope to continue with all the neuromodulators. By using the tools of optogenetics, the acetylcholine system was upregulated in the motor cortex and the resulting behavioral effects were analyzed in mice learning a lever-press task. Since acetylcholine is involved in attention, I hypothesized that excess acetylcholine in the mouse motor cortex would accelerate motor learning. If my hypothesis is correct, then we can investigate exactly how acetylcholine controls plasticity during learning using in vivo two-photon calcium imaging. Successfully using various cutting-edge techniques and gaining a mechanistic understanding of how neuromodulators affect learning will expand our understanding of the brain and contribute to public health as better pharmacological approaches can be created to target these systems.

    Cover page: The Role of Neuromodulators in Learning
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2022)

    Background

    Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad-spectrum intravitreous antibiotics. Due to their anti-inflammatory effects, steroids in conjunction with antibiotics have been proposed as being beneficial in endophthalmitis management.

    Objectives

    To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection.

    Search methods

    We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 8), MEDLINE Ovid (1946 to August 2021), Embase Ovid (1980 to August 2021), LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to August 2021), the ISRCTN registry; searched August 2021, ClinicalTrials.gov; searched August 2021, and the WHO International Clinical Trials Registry Platform; searched August 2021. We did not use any date or language restrictions in the electronic searches for trials.

    Selection criteria

    We included randomized controlled trials (RCTs) comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids.

    Data collection and analysis

    We used standard Cochrane methodology, and graded the certainty of the body of evidence for six outcomes using the GRADE classification.

    Main results

    We included four RCTs with a total of 264 eyes of 264 participants in this review update. The studies were conducted in South Africa, India, and the Netherlands. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged two trials to be at overall low risk of bias, and the other two studies to be at overall unclear risk of bias due to lack of reporting of study methods. Only one study was registered in a clinical trial register.  While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low certainty evidence suggested no difference in combined success when comparing adjunctive steroid to antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low certainty evidence from two studies suggested that adjunctive dexamethasone may result in having a good visual outcome (Snellen visual acuity 6/6 to 6/18) at 3 months compared with antibiotics alone (RR 1.95, 95% CI 1.05 to 3.60; 60 participants); however, the evidence was less conclusive at 12 months (RR 1.12, 95% CI 0.92 to 1.37; 2 studies; 195 participants; low certainty evidence). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide any estimates of precision. Only one study examined intraocular pressure (IOP). The evidence suggests that adjunctive dexamethasone may reduce IOP slightly after 12 months of interventions (mean difference -1.90, 95% CI -3.78 to 0.07; 1 study; 167 participants; low certainty evidence). Three studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, seclusion of pupil, floaters, and pucker). The total numbers of adverse events were 14 out of 111 (12.6%) for those who received dexamethasone versus 12 out of 116 (10.3%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment: any difference between the two treatment groups was uncertain (RR 1.41, 95% CI 0.53 to 3.74; 227 participants; low certainty evidence). No study reported cost-related outcomes.

    Authors' conclusions

    The currently available evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests that use of adjunctive steroids may provide a higher chance of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null, and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use of adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patients' symptoms and clinical examination into account; report outcomes in a uniform and consistent manner; and follow up at short- and long-term intervals.
      Cover page: Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure
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