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Scholarly Works (10 results)

  • Article
  • Peer Reviewed
Journal of Education and Teaching in Emergency Medicine, Volume 3, Issue 3 (2018)

ABSTRACT: History of present illness: A 40-year-old male presented to the emergency department with report of being shot in the right eye by a foam dart gun just prior to arrival. He was unable to see out of the affected eye. He initially had some pain in the eye, but it had subsided prior to arrival.

Significant findings: Upon initial evaluation, the patient had an obvious hyphema in the right eye with associated conjunctival injection. Initially, the bleeding in the anterior chamber was cloudy just above the level of the pupil (yellow arrow), appearing to possibly be a grade II hyphema. There were no other signs of trauma to the eye under Wood’s lamp examination with fluorescein staining. The globe was intact. Intraocular pressure in the affected eye was 19 mmHg and 15 mmHg in the unaffected eye. Extraocular movements were full and intact. The pupil was 4 mm round and reactive to direct and consensual light. Visual acuity was greater than 20/200 in the affected eye compared to 20/25 in the unaffected eye. After an observation period of two hours, with the patient remaining upright, the hyphema had settled down to a rim in the lower anterior chamber (green arrow), a grade I hyphema.

Discussion: A hyphema is a collection of blood in the anterior chamber of the eye. Most cases are the result of direct trauma and subsequent bleeding from the ciliary vessels. The incidence of traumatic hyphema is estimated to be 12 per 100,000 with males composing nearly eighty percent of cases.1 Rare atraumatic causes can be attributed to intraocular malignancy, bleeding disorders or antiplatelet and anticoagulant medications.2,3 A hyphema is graded based on the depth of blood in the anterior chamber. A grade I hyphema involves less than one-third of the anterior chamber, grade II is defined as one-third to one-half of the anterior chamber, grade III is greater than one-half of the anterior chamber, and grade IV is a total or “8 ball” hyphema. A microphyphema is only visible on slit lamp examination as floating red blood cells. Visual prognosis is related to the degree of hyphema, with a grade I hyphema having a 10 percent chance of vision worse than 20/50 compared to a grade III hyphema having a 50 to 75 percent chance of vision worse than 20/50.4,5

This case illustrates that on initial presentation a hyphema may appear to be graded higher and that a short observation period with the patient seated upright is required to provide an accurate diagnosis and prognosis. The second image also demonstrates the subtleness of a grade I hyphema. Recognition of a smaller hyphema is important because while the lower grade implies better prognosis, complications such as re-bleeding or uncontrolled intraocular pressure may still occur.5 The patient in this case had improvement of his vision throughout observation. He was discharged home with atropine ophthalmic drops and close ophthalmologic follow up.

Topics: Traumatic hyphema, ophthalmology.

    Cover page: Traumatic HyphemaCreative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Santa Barbara Previously Published Works (2015)
    The paper contains a new proof that a complete, non-compact hyperbolic 3–manifold with finite volume contains an immersed, closed, quasi-Fuchsian surface.
      • Article
      • Peer Reviewed
      Journal of Education and Teaching in Emergency Medicine, Volume 4, Issue 4 (2019)
        Cover page: A Low-Cost, Reusable Ultrasound Pericardiocentesis Simulation ModelCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2022)

        Aim

        To characterize cabotegravir population pharmacokinetics using data from phase 1, 2 and 3 studies and evaluate the association of intrinsic and extrinsic factors with pharmacokinetic variability.

        Methods

        Analyses were implemented in NONMEM and R. Concentrations below the quantitation limit were modelled with likelihood-based approaches. Covariate relationships were evaluated using forward addition (P < .01) and backward elimination (P < .001) approaches. The impact of each covariate on trough and peak concentrations was evaluated through simulations. External validation was performed using prediction-corrected visual predictive checks.

        Results

        The model-building dataset included 23 926 plasma concentrations from 1647 adult HIV-1-infected (72%) and uninfected (28%) subjects in 16 studies at seven dose levels (oral 10-60 mg, long-acting [LA] intramuscular injection 200-800 mg). A two-compartment model with first-order oral and LA absorption and elimination adequately described the data. Clearances and volumes were scaled to body weight. Estimated relative bioavailability of oral to LA was 75.6%. Race and age were not significant covariates. LA absorption rate constant (KALA ) was 50.9% lower in females and 47.8% higher if the LA dose was given as two split injections. KALA decreased with increasing BMI and decreasing needle length. Clearance was 17.4% higher in current smokers. The impact of any covariate was ≤32% on trough and peak concentrations following LA administration. The final model adequately predicted 5097 plasma concentrations from 647 subjects who were not included in the model-building dataset.

        Conclusions

        A cabotegravir population pharmacokinetic model was developed that can be used to inform dosing strategies and future study design. No dose adjustment based on subject covariates is recommended.
          Cover page: Population pharmacokinetics of cabotegravir following administration of oral tablet and long‐acting intramuscular injection in adult HIV‐1‐infected and uninfected subjects
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2015)
          The interaction of sperm with the egg's extracellular matrix, the zona pellucida (ZP) is the first step of the union between male and female gametes. The molecular mechanisms of this process have been studied for the past six decades with the results obtained being both interesting and confusing. In this article, we describe our recent work, which attempts to address two lines of questions from previous studies. First, because there are numerous ZP binding proteins reported by various researchers, how do these proteins act together in sperm-ZP interaction? Second, why do a number of acrosomal proteins have ZP affinity? Are they involved mainly in the initial sperm-ZP binding or rather in anchoring acrosome reacting/reacted spermatozoa to the ZP? Our studies reveal that a number of ZP binding proteins and chaperones, extracted from the anterior sperm head plasma membrane, coexist as high molecular weight (HMW) complexes, and that these complexes in capacitated spermatozoa have preferential ability to bind to the ZP. Zonadhesin (ZAN), known as an acrosomal protein with ZP affinity, is one of these proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts with other acrosomal proteins, proacrosin/acrosin and sp32 (ACRBP), also present in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on spermatozoa further indicates that both proteins traffic to the sperm head surface during capacitation where the sperm acrosomal matrix is still intact, and therefore they are likely involved in the initial sperm-ZP binding step.
            Cover page: Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2015)
            The interaction of sperm with the egg's extracellular matrix, the zona pellucida (ZP) is the first step of the union between male and female gametes. The molecular mechanisms of this process have been studied for the past six decades with the results obtained being both interesting and confusing. In this article, we describe our recent work, which attempts to address two lines of questions from previous studies. First, because there are numerous ZP binding proteins reported by various researchers, how do these proteins act together in sperm-ZP interaction? Second, why do a number of acrosomal proteins have ZP affinity? Are they involved mainly in the initial sperm-ZP binding or rather in anchoring acrosome reacting/reacted spermatozoa to the ZP? Our studies reveal that a number of ZP binding proteins and chaperones, extracted from the anterior sperm head plasma membrane, coexist as high molecular weight (HMW) complexes, and that these complexes in capacitated spermatozoa have preferential ability to bind to the ZP. Zonadhesin (ZAN), known as an acrosomal protein with ZP affinity, is one of these proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts with other acrosomal proteins, proacrosin/acrosin and sp32 (ACRBP), also present in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on spermatozoa further indicates that both proteins traffic to the sperm head surface during capacitation where the sperm acrosomal matrix is still intact, and therefore they are likely involved in the initial sperm-ZP binding step.
              Cover page: Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2015)
              The gut microbiota plays a key role in host metabolism. Toll-like receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5-deficient (T5KO) mice are prone to develop microbiota-dependent metabolic syndrome. Here we observed that T5KO mice display elevated neutral lipids with a compositional increase of oleate [C18:1 (n9)] relative to wild-type littermates. Increased oleate contribution to hepatic lipids and liver SCD1 expression were both microbiota dependent. Analysis of short-chain fatty acids (SCFAs) and (13)C-acetate label incorporation revealed elevated SCFA in ceca and hepatic portal blood and increased liver de novo lipogenesis in T5KO mice. Dietary SCFAs further aggravated metabolic syndrome in T5KO mice. Deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases.
                Cover page: Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice.
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2023)
                BACKGROUND AND OBJECTIVE: HIV treatment options remain limited in children. Dolutegravir is a potent and well-tolerated, once-daily HIV-1 integrase inhibitor recommended for HIV-1 infection in both adults and children down to 4 weeks of age. To support pediatric dosing of dolutegravir in children, we used a population pharmacokinetic model with dolutegravir data from the P1093 and ODYSSEY clinical trials. The relationship between dolutegravir exposure and selected safety endpoints was also evaluated. METHODS: A population pharmacokinetic model was developed with data from P1093 and ODYSSEY to characterize the pharmacokinetics and associated variability and to evaluate the impact of pharmacokinetic covariates. The final population pharmacokinetic model simulated exposures across weight bands, doses, and formulations that were compared with established adult reference data. Exploratory exposure-safety analyses evaluated the relationship between dolutegravir pharmacokinetic parameters and selected clinical laboratory parameters and adverse events. RESULTS: A total of N = 239 participants were included, baseline age ranged from 0.1 to 17.5 years, weight ranged from 3.9 to 91 kg, 50% were male, and 80% were black. The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination, enabling predictions of dolutegravir concentrations in the pediatric population across weight bands and doses/formulations. The predicted geometric mean trough concentration was comparable to the adult value following a 50-mg daily dose of dolutegravir for all weight bands at recommended doses. Body weight, age, and formulation were significant predictors of dolutegravir pharmacokinetics in pediatrics. Additionally, during an exploratory exposure-safety analysis, no correlation was found between dolutegravir exposure and selected safety endpoints or adverse events. CONCLUSIONS: The dolutegravir dosing in children ≥ 4 weeks of age on an age/weight-band basis provides comparable exposures to those historically observed in adults. Observed pharmacokinetic variability was higher in this pediatric population and no additional safety concerns were observed. These results support the weight-banded dosing of dolutegravir in pediatric participants currently recommended by the World Health Organization.
                  Cover page: Population Pharmacokinetic Modeling of Dolutegravir to Optimize Pediatric Dosing in HIV-1-Infected Infants, Children, and Adolescents.
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2018)
                  Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
                    Cover page: How many human proteoforms are there?
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2016)
                    A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.
                      Cover page: Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
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