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Open Access Publications from the University of California

Scholarly Works (18 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2021)
    Cover page: The Virtual House Call-Providing High-Quality and Safe Pediatric Primary Care Through Video Visits During COVID-19.
    • Thesis
    • Peer Reviewed
    UC Riverside Electronic Theses and Dissertations (2020)

    Oxygenic photosynthesis produces nearly all the O2 on Earth and sustains nearly all of its biomass. This process is catalyzed by Photosystem II (PSII), a large, transmembrane protein embedded in the thylakoid membranes of plants, algae, and cyanobacteria. PSII is catalyzed by a Mn4CaO5 cluster. As light energy is absorbed by the reaction centers of PSII, the Mn4CaO5 cluster accumulates oxidizing equivalents through a discreet and precisely choreographed light-induced electron transfer. The light induced oxidations cause the catalytic cluster to cycle through five oxidation states, Sn (n=0-4) where ‘n’ refers to the number of oxidizing equivalents. After formation of the S4 state, the cluster oxidizes two water molecules, releases O2 and returns to the S0 state, the lowest oxidation state of its catalytic cycle. The oxidation of water is a thermodynamically and kinetically demanding reaction. This is managed by PSII through the careful choreography of proton and electron transfers to the Mn4CaO5 cluster throughout the catalytic cycle. The Mn4CaO5’s reactivity in each catalytic step is carefully controlled by its protein environment. Identifying key amino acid residues, determining their responsibility in the reaction, and characterizing the proton egress pathways during the individual S-state transitions are paramount in understanding the oxygen evolution mechanism.

    This study interrogates and identifies the amino acid residues responsible for controlling the Mn¬4CaO5 cluster’s reactivity and determines the role of each residue through Fourier transform infrared (FTIR) difference spectroscopy. FTIR difference spectroscopy is capable of characterizing the dynamic structural rearrangements during PSII’s catalytic cycle. A combination of site-directed mutagenesis (D1-V185N, D1-S169A, D1-E189G, D1-E189S, D1-E329A), isotopic substitutions, and the substitution of Sr2+ for Ca2+ in PSII’s catalytic center were used to further delineate the dominant water access and proton egress pathways that link the catalytic cluster with the thylakoid lumen, characterize the influence of specific protein residues on substrate water molecules and on the network of hydrogen bonds in these pathways, and elucidate the potential substrates and mechanisms of the S2 to S3 transition.

      Cover page: Light-Induced Fourier Transform Infrared Difference Spectroscopy Study of the Molecular Mechanism of Photosynthetic Oxygen Evolution
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2019)

      Background

      Reliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.

      Methods

      Data were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.

      Results

      At baseline, 125 of 170 patients (73.5%) had potassium level 5.5-< 6.0, 39 (22.9%) had potassium level 6.0-6.5, and 6 (3.5%) had potassium level > 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1-2.0) and 21.6 (4.1-22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.

      Conclusions

      SZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.

      Trial registration

      ClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.
        Cover page: Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥ 5.5 mmol/L: pooled analysis from two phase 3 trials
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2021)
        The molecular oxygen we breathe is produced from water-derived oxygen species bound to the Mn4CaO5 cluster in photosystem II (PSII). Present research points to the central oxo-bridge O5 as the 'slow exchanging substrate water (Ws)', while, in the S2 state, the terminal water ligands W2 and W3 are both discussed as the 'fast exchanging substrate water (Wf)'. A critical point for the assignment of Wf is whether or not its exchange with bulk water is limited by barriers in the channels leading to the Mn4CaO5 cluster. In this study, we measured the rates of H2 16O/H2 18O substrate water exchange in the S2 and S3 states of PSII core complexes from wild-type (WT) Synechocystis sp. PCC 6803, and from two mutants, D1-D61A and D1-E189Q, that are expected to alter water access via the Cl1/O4 channels and the O1 channel, respectively. We found that the exchange rates of Wf and Ws were unaffected by the E189Q mutation (O1 channel), but strongly perturbed by the D61A mutation (Cl1/O4 channel). It is concluded that all channels have restrictions limiting the isotopic equilibration of the inner water pool near the Mn4CaO5 cluster, and that D61 participates in one such barrier. In the D61A mutant this barrier is lowered so that Wf exchange occurs more rapidly. This finding removes the main argument against Ca-bound W3 as fast substrate water in the S2 state, namely the indifference of the rate of Wf exchange towards Ca/Sr substitution.
          Cover page: The exchange of the fast substrate water in the S 2 state of photosystem II is limited by diffusion of bulk water through channels – implications for the water oxidation mechanism
          • Article
          • Peer Reviewed
          UC Riverside Previously Published Works (2018)
          Photoinduced water oxidation at the O2-evolving complex (OEC) of photosystem II (PSII) is a complex process involving a tetramanganese-calcium cluster that is surrounded by a hydrogen-bonded network of water molecules, chloride ions, and amino acid residues. Although the structure of the OEC has remained conserved over eons of evolution, significant differences in the chloride-binding characteristics exist between cyanobacteria and higher plants. An analysis of amino acid residues in and around the OEC has identified residue 87 in the D1 subunit as the only significant difference between PSII in cyanobacteria and higher plants. We substituted the D1-Asn87 residue in the cyanobacterium Synechocystis sp. PCC 6803 (wildtype) with alanine, present in higher plants, or with aspartic acid. We studied PSII core complexes purified from D1-N87A and D1-N87D variant strains to probe the function of the D1-Asn87 residue in the water-oxidation mechanism. EPR spectra of the S2 state and flash-induced FTIR spectra of both D1-N87A and D1-N87D PSII core complexes exhibited characteristics similar to those of wildtype Synechocystis PSII core complexes. However, flash-induced O2-evolution studies revealed a decreased cycling efficiency of the D1-N87D variant, whereas the cycling efficiency of the D1-N87A PSII variant was similar to that of wildtype PSII. Steady-state O2-evolution activity assays revealed that substitution of the D1 residue at position 87 with alanine perturbs the chloride-binding site in the proton-exit channel. These findings provide new insight into the role of the D1-Asn87 site in the water-oxidation mechanism and explain the difference in the chloride-binding properties of cyanobacterial and higher-plant PSII.
            Cover page: Substitution of the D1-Asn87 site in photosystem II of cyanobacteria mimics the chloride-binding characteristics of spinach photosystem II
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2020)

            Background

            School health systems are increasingly investing in telemedicine platforms to address acute and chronic illnesses. Asthma, the most common chronic illness in childhood, is of particular interest given its high burden on school absenteeism.

            Objective

            Conduct a systematic review evaluating impact of school-based telemedicine programs on improving asthma-related outcomes.

            Data sources

            PubMed, Cochrane CENTRAL, CINAHL, ERIC, PsycINFO, Embase, and Google Scholar.

            Study eligibility criteria

            Original research, including quasi-experimental studies, without restriction on the type of telemedicine.

            Participants

            School-aged pediatric patients with asthma and their families.

            Interventions

            School-based telemedicine.

            Study appraisal and synthesis methods

            Two authors independently screened each abstract, conducted full-text review, assessed study quality, and extracted information. A third author resolved disagreements.

            Results

            Of 371 articles identified, 7 were included for the review. Outcomes of interest were asthma symptom-free days, asthma symptom frequency, quality of life, health care utilization, school absences, and spirometry. Four of 7 studies reported significant increases in symptom-free days and/or decrease in symptom frequency. Five of 6 reported increases in at least one quality-of-life metric, 2 of 7 reported a decrease in at least 1 health care utilization metric, 1 of 3 showed reductions in school absences, and 1 of 2 reported improvements in spirometry measures.

            Limitations

            Variability in intervention designs and outcome measures make comparisons and quantitative analyses across studies difficult. Only 2 of 7 studies were randomized controlled trials.

            Conclusions and implications of key findings

            High-quality evidence supporting the use of school-based telemedicine programs to improve patient outcomes is limited. While available evidence suggests benefit, only 2 comparative trials were identified, and the contribution of telemedicine to these studies' results is unclear.
              Cover page: School-Based Telemedicine Interventions for Asthma: A Systematic Review
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2015)
                Cover page: RE: Anesthetic Management for&nbsp;Resection of Hepatic Paraganglioma&nbsp;Metastatic From&nbsp;the&nbsp;Donor Organ in an Orthotopic&nbsp;Liver Transplant Recipient:&nbsp;A Case Report
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2017)

                Context

                - Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas.

                Objectives

                - To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields.

                Data sources

                - Data sources include literature review, authors' research data, and personal practice experience.

                Conclusions

                - Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.
                  Cover page: Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas
                  • Article
                  • Peer Reviewed
                  Dermatology Online Journal, Volume 25, Issue 9 (2019)
                  Introduction: Patients use the internet to search for health-related information. We sought to characterize the information that patients find when searching for dermatologists on Google. Methods: The Centers for Medicare and Medicaid Services (CMS) Physician Comparable Downloadable File was utilized to identify all Medicare-participating dermatologists practicing in Pennsylvania (PA). A custom Google-based search engine was used to search each dermatologist. Up to the top 10 results for each physician were then sorted into: (1) physician, hospital, or healthcare system, (2) third-party, (3) social media, (4) academic journal articles, or (5) other. Results: Within the CMS, 519 health care providers (53.9% male, 46.1% female) self-identified as dermatologists practicing in PA. At least one search result was obtained for each physician (4,963 total search results). About 30.6% (1,519) search results were hospital, health system, or physician-controlled websites, and 26.6% (1,318) were third-party websites (1,318; 26.6%). Social media websites accounted for 601 (12.1%) hits whereas peer-reviewed academic journal websites generated 135 (2.7%) results. One-way chi-square analysis showed domains were not randomly distributed across the five categories (P<0.0001). Conclusion: Dermatologists should be better aware of their digital presence and the strategies to better control their online identity.
                    Cover page: What patients see online: assessing the online identities of Pennsylvania dermatologists
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2016)
                    BACKGROUND: The transition out of the hospital is a vulnerable time for patients, relying heavily on communication and coordination of resources across care settings. Understanding the perspectives of inpatient and outpatient physicians regarding factors contributing to readmission and potential preventive strategies is crucial in designing appropriately targeted readmission prevention efforts. OBJECTIVE: To examine and compare inpatient and outpatient physician opinions regarding reasons for readmission and interventions that might have prevented readmission. DESIGN: Cross-sectional multicenter study. PARTICIPANTS: We identified patients readmitted to general medicine services within 30 days of discharge at 12 US academic medical centers, and surveyed the primary care physician (PCP), discharging physician from the index admission, and admitting physician from the readmission regarding their endorsement of pre-specified factors contributing to the readmission and potential preventive strategies. MAIN MEASURES: We calculated kappa statistics to gauge agreement between physician dyads (PCP-discharging physician, PCP-admitting physician, and admitting-discharging physician). KEY RESULTS: We evaluated 993 readmission events, which generated responses from 356 PCPs (36 % of readmissions), 675 discharging physicians (68 % of readmissions), and 737 admitting physicians (74 % of readmissions). The most commonly endorsed contributing factors by both PCPs and inpatient physicians related to patient understanding and ability to self-manage. The most commonly endorsed preventive strategies involved providing patients with enhanced post-discharge instructions and/or support. Although PCPs and inpatient physicians endorsed contributing factors and potential preventive strategies with similar frequencies, agreement among the three physicians on the specific factors and/or strategies that applied to individual readmission events was poor (maximum kappa 0.30). CONCLUSIONS: Differing opinions among physicians on factors contributing to individual readmissions highlights the importance of communication between inpatient and outpatient providers at discharge to share their different perspectives, and suggests that multi-faceted, broadly applied interventions may be more successful than those that rely on individual providers choosing specific services based on perceived risk factors.
                      Cover page: Physician Perspectives on Factors Contributing to Readmissions and Potential Prevention Strategies: A Multicenter Survey.
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