• A 1200+year reconstruction of temperature extremes for the northeastern Mediterranean region

      Klippel, Lara; Krusic, Paul J.; Konter, Oliver; St George, Scott; Trouet, Valerie; Esper, Jan; Univ Arizona, Tree Ring Res Lab (WILEY, 2019-03-30)
      Proxy evidence is necessary to place current temperature and hydroclimatic changes in a long-term context and to assess the full range of natural and anthropogenic climate forcings. Here, we present the first millennium-length reconstruction of late summer (August-September) temperature variability for the Mediterranean region. We compiled 132 maximum latewood density (MXD) tree-ring series of living and relict Pinus heldreichii trees from a network of four high-elevation sites in the Pindus Mountains of Greece. Forty series reach back into the first millennium and the oldest sample dates to 575 CE. At annual to decadal scales, the record correlates significantly with August-September temperatures over the Balkan Peninsula and northeastern Mediterranean (r1950-2014 = 0.71, p < 0.001). We produce two reconstructions emphasizing interannual and decadal scale variance over the past millennium. Analysis of temperature extremes reveals the coldest summers occurred in 1035, 1117, 1217, 1884 and 1959 and the coldest decades were 1061-1070 and 1811-1820. The warmest summers occurred in 1240 and 1474, and the warmest decades were 1141-1150 and 1481-1490. Comparison of this new reconstruction with MXD-based summer temperature reconstructions across Europe reveals synchronized occurrences of extreme cool summers in the northeastern Mediterranean, and an antiphase-relationship with warm summer temperatures over the British Isles and Scandinavia. This temperature dipole is related to anomalies in the latitudinal position of the North Atlantic Jet. Despite the representation of common atmospheric forcing patterns, the occurrence of warm extremes is limited to few events, suggesting potential weaknesses of MXD to record warm temperature anomalies. In addition, we acknowledge problems in the observational data to capture local temperature variability due to small scale topographic differences in this high-elevation landscape. At a broader geographical scale, the occurrence of common cold summer extremes is restricted to years with volcanically induced changes in radiative forcing.
    • 16S rRNA gene sequencing on a benchtop sequencer: accuracy for identification of clinically important bacteria.

      Watts, G S; Youens-Clark, K; Slepian, M J; Wolk, D M; Oshiro, M M; Metzger, G S; Dhingra, D; Cranmer, L D; Hurwitz, B L; Univ Arizona, Ctr Canc; et al. (WILEY, 2017-12-01)
      Test the choice of 16S rRNA gene amplicon and data analysis method on the accuracy of identification of clinically important bacteria utilizing a benchtop sequencer. Nine 16S rRNA amplicons were tested on an Ion Torrent PGM to identify 41 strains of clinical importance. The V1-V2 region identified 40 of 41 isolates to the species level. Three data analysis methods were tested, finding that the Ribosomal Database Project's SequenceMatch outperformed BLAST and the Ion Reporter Metagenomics analysis pipeline. Lastly, 16S rRNA gene sequencing mixtures of four species through a six log range of dilution showed species were identifiable even when present as 0·1% of the mixture. Sequencing the V1-V2 16S rRNA gene region, made possible by the increased read length Ion Torrent PGM sequencer's 400 base pair chemistry, may be a better choice over other commonly used regions for identifying clinically important bacteria. In addition, the SequenceMatch algorithm, freely available from the Ribosomal Database Project, is a good choice for matching filtered reads to organisms. Lastly, 16S rRNA gene sequencing's sensitivity to the presence of a bacterial species at 0·1% of a mixture suggests it has sufficient sensitivity for samples in which important bacteria may be rare. We have validated 16S rRNA gene sequencing on a benchtop sequencer including simple mixtures of organisms; however, our results highlight deficits for clinical application in place of current identification methods.
    • 5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of Parkinson's disease

      Scholpa, Natalie E.; Lynn, Mary K.; Corum, Daniel; Boger, Heather A.; Schnellmann, Rick G.; Univ Arizona, Dept Pharmacol & Toxicol, Coll Pharm (WILEY, 2018-01)
      Background and PurposeParkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioural abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5-HT1F receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), we investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron loss in a mouse model of Parkinson's disease. Experimental ApproachMale C57BL/6 mice underwent bilateral intrastriatal 6-hydroxydopamine or saline injections and daily treatment with 2mgkg(-1) LY344864 or vehicle for 14days beginning 7days post-lesion. Tyrosine hydroxylase immunoreactivity (TH-ir) and MB were assessed in the brains of all groups following treatment, and locomotor activity was evaluated prior to lesioning, 7days post-lesion and after treatment. Key ResultsIncreased mitochondrial DNA content and nuclear- and mitochondrial-encoded mRNA and protein expression was observed in specific brain regions of LY344864-treated naive and lesioned mice, indicating augmented MB. LY344864 attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle-treated lesioned animals. LY344864 treatment also increased locomotor activity in 6-hydroxydopamine lesioned mice, while vehicle treatment had no effect. Conclusions and ImplicationsThese data revealed that LY344864-induced MB attenuates dopaminergic neuron loss and improves behavioural endpoints in this model. We suggest that stimulating MB may be beneficial for the treatment of Parkinson's disease and that the 5-HT1F receptor may be an effective therapeutic target.
    • Accelerated MR parameter mapping with a union of local subspaces constraint

      Mandava, Sagar; Keerthivasan, Mahesh B.; Li, Zhitao; Martin, Diego R.; Altbach, Maria I.; Bilgin, Ali; Univ Arizona, Dept Elect & Comp Engn; Univ Arizona, Dept Med Imaging; Univ Arizona, Dept Biomed Engn (WILEY, 2018-12)
      Purpose: A new reconstruction method for multi-contrast imaging and parameter mapping based on a union of local subspaces constraint is presented. Theory: Subspace constrained reconstructions use a predetermined subspace to explicitly constrain the relaxation signals. The choice of subspace size (K) impacts the approximation error vs noise-amplification tradeoff associated with these methods. A different approach is used in the model consistency constraint (MOCCO) framework to leverage the subspace model to enforce a softer penalty. Our proposed method, MOCCO-LS, augments the MOCCO model with a union of local subspaces (LS) approach. The union of local subspaces model is coupled with spatial support constraints and incorporated into the MOCCO framework to regularize the contrast signals in the scene. Methods: The performance of the MOCCO-LS method was evaluated in vivo on T-1 and T-2 mapping of the human brain and with Monte-Carlo simulations and compared against MOCCO and the explicit subspace constrained models. Results: The results demonstrate a clear improvement in the multi-contrast images and parameter maps. We sweep across the model order space (K) to compare the different reconstructions and demonstrate that the reconstructions have different preferential operating points. Experiments on T-2 mapping show that the proposed method yields substantial improvements in performance even when operating at very high acceleration rates. Conclusions: The use of a union of local subspace constraints coupled with a sparsity promoting penalty leads to improved reconstruction quality of multi-contrast images and parameter maps.
    • Acute and 1-Year Hospitalization Costs for Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention: Results From the TRANSLATE-ACS Registry

      Cowper, Patricia A; Knight, J David; Davidson-Ray, Linda; Peterson, Eric D; Wang, Tracy Y; Mark, Daniel B; Univ Arizona, Univ Phys Healthcare Hosp (WILEY, 2019-04-12)
      Background-Hospitalization for acute myocardial infarction (MI) in the United States is both common and expensive, but those features alone provide little insight into cost-saving opportunities. Methods and Results-To understand the cost drivers during hospitalization for acute MI and in the following year, we prospectively studied 11 969 patients with acute MI undergoing percutaneous coronary intervention at 233 US hospitals (2010-2013) from the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) registry. Baseline costs were collected in a random subset (n=4619 patients, 54% ST-segment-elevation MI [STEMID, while follow-up costs out to 1 year were collected for all patients. The mean index length of stay was 3.1 days (for both STEMI and non-STEMI) and mean intensive care unit length of stay was 1.2 days (1.4 days for STEMI and 1.0 days for non-STEMI). Index hospital costs averaged $18 931 ($19 327 for STEMI, $18 465 for non-STEMI), with 45% catheterization laboratory-related and 20% attributable to postprocedure hospital stay. Patient factors, including severity of illness and extent of coronary disease, and hospital characteristics, including for profit status and geographic region, identified significant variations in cost. Intensive care was used for 53% of non-STEMI and increased costs by $3282. Postdischarge 1-year costs averaged $8037, and 48% of patients were rehospitalized (half within 2 months and 57% with a cardiovascular diagnosis). Conclusions-While much of the cost of patients with acute MI treated with percutaneous coronary intervention is probably not modifiable by the care team, cost reductions are still possible through quality-preserving practice efficiencies, such as need-based use rather than routine use of intensive care unit for patients with stable non-STEMI.
    • An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia

      Wilson, Stephen M.; Yen, Melodie; Eriksson, Dana K.; Univ Arizona, Dept Speech Language & Hearing Sci (WILEY, 2018-08)
      Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia.
    • Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury

      Shin, Eric Y.; Wang, Lanfang; Zemskova, Marina; Deppen, Juline; Xu, Kai; Strobel, Frederick; García, Andrés J.; Tirouvanziam, Rabindra; Levit, Rebecca D.; Univ Arizona, Coll Med, Dept Otolaryngol, Tucson, AZ USA (WILEY, 2018-01-23)
      BackgroundDuring myocardial ischemia/reperfusion (MI/R) injury, there is extensive release of immunogenic metabolites that activate cells of the innate immune system. These include ATP and AMP, which upregulate chemotaxis, migration, and effector function of early infiltrating inflammatory cells. These cells subsequently drive further tissue devitalization. Mesenchymal stromal cells (MSCs) are a potential treatment modality for MI/R because of their powerful anti-inflammatory capabilities; however, the manner in which they regulate the acute inflammatory milieu requires further elucidation. CD73, an ecto-5-nucleotidase, may be critical in regulating inflammation by converting pro-inflammatory AMP to anti-inflammatory adenosine. We hypothesized that MSC-mediated conversion of AMP into adenosine reduces inflammation in early MI/R, favoring a micro-environment that attenuates excessive innate immune cell activation and facilitates earlier cardiac recovery. Methods and ResultsAdult rats were subjected to 30minutes of MI/R injury. MSCs were encapsulated within a hydrogel vehicle and implanted onto the myocardium. A subset of MSCs were pretreated with the CD73 inhibitor, ,-methylene adenosine diphosphate, before implantation. Using liquid chromatography/mass spectrometry, we found that MSCs increase myocardial adenosine availability following injury via CD73 activity. MSCs also reduce innate immune cell infiltration as measured by flow cytometry, and hydrogen peroxide formation as measured by Amplex Red assay. These effects were dependent on MSC-mediated CD73 activity. Finally, through echocardiography we found that CD73 activity on MSCs was critical to optimal protection of cardiac function following MI/R injury. ConclusionsMSC-mediated conversion of AMP to adenosine by CD73 exerts a powerful anti-inflammatory effect critical for cardiac recovery following MI/R injury.
    • Affordable remote monitoring of plant growth in facilities using Raspberry Pi computers

      Grindstaff, Brandin; Mabry, Makenzie E; Blischak, Paul D; Quinn, Micheal; Chris Pires, J; Univ Arizona, Dept Ecol & Evolutionary Biol (WILEY, 2019-08-01)
      Using a Raspberry Pi computer, open-source software, environmental sensors, and a camera, we developed Growth Monitor pi (GMpi), a cost-effective system for monitoring growth chamber conditions. Coupled with our software, GMPi_Pack, our setup automates sensor readings, photography, and alerts when conditions fall out of range.
    • Agriculture creates subtle genetic structure among migratory and nonmigratory populations of burrowing owls throughout North America

      Macias-Duarte, Alberto; Conway, Courtney J.; Culver, Melanie; Univ Arizona, Sch Nat Resources, Arizona Cooperat Fish & Wildlife Res Unit (WILEY, 2020)
      Population structure across a species distribution primarily reflects historical, ecological, and evolutionary processes. However, large-scale contemporaneous changes in land use have the potential to create changes in habitat quality and thereby cause changes in gene flow, population structure, and distributions. As such, land-use changes in one portion of a species range may explain declines in other portions of their range. For example, many burrowing owl populations have declined or become extirpated near the northern edge of the species' breeding distribution during the second half of the 20th century. In the same period, large extensions of thornscrub were converted to irrigated agriculture in northwestern Mexico. These irrigated areas may now support the highest densities of burrowing owls in North America. We tested the hypothesis that burrowing owls that colonized this recently created owl habitat in northwestern Mexico originated from declining migratory populations from the northern portion of the species' range (migration-driven breeding dispersal whereby long-distance migrants from Canada and the United States became year-round residents in the newly created irrigated agriculture areas in Mexico). We used 10 novel microsatellite markers to genotype 1,560 owls from 36 study locations in Canada, Mexico, and the United States. We found that burrowing owl populations are practically panmictic throughout the entire North American breeding range. However, an analysis of molecular variance provided some evidence that burrowing owl populations in northwestern Mexico and Canada together are more genetically differentiated from the rest of the populations in the breeding range, lending some support to our migration-driven breeding dispersal hypothesis. We found evidence of subtle genetic differentiation associated with irrigated agricultural areas in southern Sonora and Sinaloa in northwestern Mexico. Our results suggest that land use can produce location-specific population dynamics leading to subtle genetic structure even in the absence of dispersal barriers.
    • Alignment of stakeholder agendas to facilitate the adoption of school-supervised asthma therapy

      Trivedi, Michelle; Patel, Janki; Hoque, Shushmita; Mizrahi, Raphael; Biebel, Kathleen; Phipatanakul, Wanda; Lemon, Stephenie C; Byatt, Nancy; Gerald, Lynn B; Rosal, Milagros; et al. (WILEY, 2019-12-19)
      Background School-supervised inhaled corticosteroid (ICS) therapy improves pediatric asthma medication adherence, outcomes, and morbidity. However, school-supervised ICS therapy has not been widely adopted into practice. We developed Asthma Link (TM) as a sustainable, low-cost model of school-supervised asthma therapy, designed for real-world adoption. Initial outcomes of Asthma Link (TM) demonstrated a significant improvement in health outcomes. Objective In this study, we examined the perspectives of Asthma Link (TM) participants to identify systems-level barriers and facilitators to refine the Asthma Link (TM) protocol and facilitate real-world uptake of school-supervised asthma therapy. Methods Using qualitative research methods, we interviewed 29 participants in Asthma Link (TM) from 2016 to 2018. Semi-structured interviews were conducted over the phone. Interviews were transcribed and the transcripts were coded to identify major themes within and across stakeholder groups. Results Stakeholders agreed on many facilitators for successful Asthma Link (TM) execution including the brief and easy to follow procedures and the perceived beneficial health impacts for children involved. Some of the barriers identified were deviations from the protocol and insurance companies denying coverage for two inhalers. However, the participants did propose solutions to address these barriers. Conclusion Asthma Link (TM) is a low-cost, sustainable model of school-supervised asthma therapy that leverages the established infrastructure and collaboration of medical providers, school staff, and families. In this study, we elicited the perspectives from these stakeholder groups and identified an agreement in several facilitators, barriers, and proposed solutions that will ultimately inform refinement of the program protocol and support real-world adoption of Asthma Link (TM) and other similar models.
    • Alleviating and exacerbating foods in hidradenitis suppurativa

      Fernandez, Jennifer M; Marr, Kendra D; Hendricks, Aleksi J; Price, Kyla N; Ludwig, Catherine M; Maarouf, Melody; Hsiao, Jennifer L; Shi, Vivian Y; Univ Arizona, Coll Med; Univ Arizona, Dept Med, Div Dermatol (WILEY, 2020-08-29)
      While dietary triggers have been investigated in acne and other inflammatory follicular dermatoses, there is a paucity of data on diet and hidradenitis suppurativa (HS). We sought to identify exacerbating and alleviating foods in HS patients. An anonymous survey was distributed via HS Facebook support groups and in person at HS specialty clinics. Participants were asked to select all that apply from a list to indicate foods that worsen and make HS better including sweet foods, breads and pasta, red meat, chicken, fish, canned foods, fruits, vegetables, dairy, high-fat foods, I do not know, and no. Only 12.0% (n = 89/744) identified alleviating foods while 32.6% (n = 237/728) identified HS-symptom-exacerbating foods. The most commonly reported exacerbating foods were sweets (67.9%), bread/pasta/rice (51.1%), dairy (50.6%), and high-fat foods (44.2%). The most commonly reported alleviating foods included vegetables (78.7%), fruit (56.2%), chicken (51.7%), and fish (42.7%). Further studies are required to evaluate the mechanistic links between diet and HS. HS patients may benefit from receiving dietary counseling as part of a comprehensive HS management plan.
    • Analysis, Simulation, and Optimization of Stochastic Vesicle Dynamics in Synaptic Transmission

      Zhang, Calvin; Peskin, Charles S.; Univ Arizona, Dept Math (WILEY, 2020-01)
      Synaptic transmission is the mechanism of information transfer from one neuron to another (or from a neuron to a muscle or to an endocrine cell). An important step in this physiological process is the stochastic release of neurotransmitter from vesicles that fuse with the presynaptic membrane and spill their contents into the synaptic cleft. We are concerned here with the formulation, analysis, and simulation of a mathematical model that describes the stochastic docking, undocking, and release of synaptic vesicles and their effect on synaptic signal transmission. The focus of this paper is on the parameter p(0), the probability of release for each docked vesicle when an action potential arrives. We study the influence of this parameter on the statistics of the release process and on the theoretical capability of the model synapse in reconstructing various desired outputs based on the timing and amount of neurotransmitter release. This theoretical capability is assessed by formulating and solving an optimal filtering problem. Methods for parameter identification are proposed and applied to simulated data. (c) 2019 Wiley Periodicals, Inc.
    • Approach to High Volume Enrollment in Clinical Research: Experiences from an All of Us Research Program Site

      Ilori, Titilayo O; Viera, Emma; Wilson, Jillian; Moreno, Francisco; Menon, Usha; Ehiri, John; Peterson, Rachele; Vemulapalli, Tejo; StimsonRiahi, Sara C; Rosales, Cecilia; et al. (WILEY, 2020-01-31)
      Clinical trials and cohort studies are required to meet target recruitment of study participants within stipulated timelines, especially when the priority is to include populations traditionally unrepresented in biomedical research. By the third quarter of 2019, the University of Arizona-Banner Health Provider Organization (UA-Banner HPO) has enrolled > 30,000 core participants into theAll of UsResearch Program (AoURP), the research cohort of the Precision Medicine Initiative. The majority of enrolled participants meet the criteria for individuals under-represented in biomedical research. The enrollment goals were calculated based on a target of 20,000 as set by the National Institutes of Health and our health provider organization achieved enrollment numbers between 17% and 86% above the targeted daily enrollment. We evaluated enrollment methods and challenges to enrollments encountered by the UA-Banner Health Provider Organization into theAoURP. Challenges to enrollment centered around the need for high-touch engagement methods, time investment necessary for stakeholder inclusion, and the use of purely digital enrollment methods especially in populations under-represented in biomedical research. These challenges occurred at the level of the individual, provider, institutions, and community, and cumulatively impacted participant enrollment. Successful strategies for engagement and enrollment leveraged provider partners as advocates for the program. For high-volume enrollment in clinical research, it is important to engage leaders in the healthcare setting, patient providers, and tailor engagement and enrollment to potential participant needs. We emphasize the need for precision engagement and enrollment methods tailored to individual needs.
    • Arsenic remediation by formation of arsenic sulfide minerals in a continuous anaerobic bioreactor

      Rodriguez-Freire, Lucia; Moore, Sarah E; Sierra-Alvarez, Reyes; Root, Robert A; Chorover, Jon; Field, James A; Univ Arizona, Dept Chem & Environm Engn; Univ Arizona, Dept Soil Water & Environm Sci (WILEY, 2016-03-01)
      Arsenic (As) is a highly toxic metalloid that has been identified at high concentrations in groundwater in certain locations around the world. Concurrent microbial reduction of arsenate (AsV) and sulfate (SO42-) can result in the formation of poorly soluble arsenic sulfide minerals (ASM). The objective of this research was to study As biomineralization in a minimal iron environment for the bioremediation of As-contaminated groundwater using simultaneous AsV and SO42- reduction. A continuous-flow anaerobic bioreactor was maintained at slightly acidic pH (6.25-6.50) and fed with AsV and SO42-, utilizing ethanol as an electron donor for over 250 d. A second bioreactor running under the same conditions but lacking SO42- was operated as a control to study the fate of As (without S). The reactor fed with SO42- removed an average 91.2% of the total soluble As at volumetric rates up to 2.9 mg As/(L∙h), while less than 5% removal was observed in the control bioreactor. Soluble S removal occurred with an S to As molar ratio of 1.2, suggesting the formation of a mixture of orpiment- (As2S3) and realgar-like (AsS) solid phases. Solid phase characterization using K-edge X-Ray absorption spectroscopy confirmed the formation of a mixture of As2S3 and AsS. These results indicate that a bioremediation process relying on the addition of a simple, low-cost electron donor offers potential to promote the removal of As from groundwater with naturally occurring or added sulfate by precipitation of ASM.
    • Asleep Deep Brain Stimulation of the Nucleus Ventralis Intermedius for Essential Tremor Using Indirect Targeting and Interventional Magnetic Resonance Imaging: Single‐Institution Case Series

      Gravbrot, Nicholas; Burket, Aaron; Saranathan, Manojkumar; Kasoff, Willard S.; Univ Arizona, Coll Med, Dept Neurosurg; Univ Arizona, Coll Med, Dept Med Imaging (WILEY, 2020-04-27)
      Background Literature on asleep deep brain stimulation (DBS) of the ventralis intermedius (Vim) nucleus in essential tremor is relatively sparse. Furthermore, controversy exists as to whether indirect ("consensus" or "atlas-based") targeting of the Vim requires physiologic adjustment for effective clinical outcomes in DBS surgery. Objectives The objective of this study was to evaluate the clinical results of asleep Vim DBS using indirect coordinates and real-time interventional magnetic resonance imaging guidance. Methods Retrospective review of a prospectively collected database was performed to identify patients with essential tremor undergoing asleep Vim DBS using interventional magnetic resonance imaging guidance. Stereotactic and clinical outcomes were abstracted and analyzed using descriptive statistics. Results A total of 12 consecutive patients were identified, all of whom were available for 6-month clinical follow-up. Stereotactic (radial) error was 0.5 +/- 0.2 mm on the left and 0.5 +/- 0.3 mm on the right. Fahn-Tolosa-Marin tremor scores in the treated limb(s) decreased by 71.2% +/- 31.0% (P = 0.0088), The Essential Tremor Rating Assessment Scale activities of daily living improved by 74.9% +/- 23.7% (P < 0.0001), and The Essential Tremor Rating Assessment Scale performance improved by 64.3 +/- 16.2% (P = 0.0004). Surgical complications were mild and generally transient. Stimulation-related side effects were similar to those reported in historical series of awake Vim DBS. Conclusions Asleep Vim DBS using indirect targeting and interventional magnetic resonance imaging-guided placement is safe and effective, with 6-month clinical results similar to those achieved with awake placement. These data support the use of asleep surgery in essential tremor and represent a baseline for comparison with future studies using more advanced targeting techniques.
    • Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices

      Melmed, Kara R; Schlick, Konrad H; Rinsky, Brenda; Dumitrascu, Oana M; Volod, Oksana; Nezhad, Mani; Padrick, Matthew M; Runyan, Carmelita; Arabia, Francisco A; Moriguchi, Jaime D; et al. (WILEY, 2020-05)
      BACKGROUND AND PURPOSE Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). METHODS From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. RESULTS We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (+/- SD) PI of .43 (+/-.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (+/-.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (+/-.24). In intra-arterial balloon pump patients, mean PI was 1.01 (+/-.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (+/- 32.33) cm/seconds and PI of .74 (+/-.14) approached normal values. CONCLUSION TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.
    • Assessing precipitation, evapotranspiration, and NDVI as controls of U.S. Great Plains plant production

      Chen, Maosi; Parton, William J.; Hartman, Melannie D.; Del Grosso, Stephen J.; Smith, William K.; Knapp, Alan K.; Lutz, Susan; Derner, Justin D.; Tucker, Compton J.; Ojima, Dennis S.; et al. (WILEY, 2019-10)
      Productivity throughout the North American Great Plains grasslands is generally considered to be water limited, with the strength of this limitation increasing as precipitation decreases. We hypothesize that cumulative actual evapotranspiration water loss (AET) from April to July is the precipitation-related variable most correlated to aboveground net primary production (ANPP) in the U.S. Great Plains (GP). We tested this by evaluating the relationship of ANPP to AET, precipitation, and plant transpiration (Tr). We used multi-year ANPP data from five sites ranging from semiarid grasslands in Colorado and Wyoming to mesic grasslands in Nebraska and Kansas, mean annual NRCS ANPP, and satellite-derived normalized difference vegetation index (NDVI) data. Results from the five sites showed that cumulative April-to-July AET, precipitation, and Tr were well correlated (R-2: 0.54-0.70) to annual changes in ANPP for all but the wettest site. AET and Tr were better correlated to annual changes in ANPP compared to precipitation for the drier sites, and precipitation in August and September had little impact on productivity in drier sites. April-to-July cumulative precipitation was best correlated (R-2 = 0.63) with interannual variability in ANPP in the most mesic site, while AET and Tr were poorly correlated with ANPP at this site. Cumulative growing season (May-to-September) NDVI (iNDVI) was strongly correlated with annual ANPP at the five sites (R-2 = 0.90). Using iNDVI as a surrogate for ANPP, we found that county-level cumulative April-July AET was more strongly correlated to ANPP than precipitation for more than 80% of the GP counties, with precipitation tending to perform better in the eastern more mesic portion of the GP. Including the ratio of AET to potential evapotranspiration (PET) improved the correlation of AET to both iNDVI and mean county-level NRCS ANPP. Accounting for how different precipitation-related variables control ANPP (AET in drier portion, precipitation in wetter portion) provides opportunity to develop spatially explicit forecasting of ANPP across the GP for enhancing decision-making by land managers and use of grassland ANPP for biofuels.
    • Assessment of antioxidant and antidiabetic properties of Agaricus blazei Murill extracts

      Wei, Qi; Zhan, Yishu; Chen, Bingzhi; Xie, Baogui; Fang, Ting; Ravishankar, Sadhana; Jiang, Yuji; Univ Arizona, Sch Anim & Comparat Biomed Sci (WILEY, 2019-11-04)
      Agaricus blazei Murill (ABM), a medicinal mushroom, has beneficial effects on various human metabolic diseases. The objective of this research was to evaluate the antioxidant and antidiabetic properties of ABM extracts (ethanol extract and ethyl acetate extract). The antioxidant activities of ABM ethanol extract (EE) and ethyl acetate extract (EA) were analyzed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2 '-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radical scavenging assays and the reducing power using K3Fe(CN)(6) in vitro. Moreover, the effects of EE and EA on alpha-glucosidase inhibitory activity and improving glucose uptake by HepG2 cells were investigated in vitro. The EA showed stronger antioxidant activity, as well as inhibition of alpha-glucosidase, compared to EE. The analysis of glucose uptake by HepG2 cells showed that EA had significant glucose-lowering activity and exhibited no difference compared to metformin. The results suggest that ABM extracts could improve the glucose uptake by HepG2 cells and thereby alleviate postprandial hyperglycemia. This investigation provides a strong rationale for further studies on the application of ABM to control type 2 diabetes.
    • Assessment of YAP gene polymorphisms and arsenic interaction in Mexican women with breast cancer

      Michel-Ramirez, Gladis; Recio-Vega, Rogelio; Lantz, R Clark; Gandolfi, A Jay; Olivas-Calderon, Edgar; Chau, Binh T; Amistadi, Mary Kay; Univ Arizona, Dept Cellular & Mol Med; Univ Arizona, Southwest Environm Hlth Sci Ctr; Univ Arizona, Dept Pharmacol & Toxicol; et al. (WILEY, 2019-10-21)
      The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.
    • Association between algal productivity and phycosphere composition in an outdoorChlorella sorokinianareactor based on multiple longitudinal analyses

      Steichen, Seth A.; Gao, Song; Waller, Peter; Brown, Judith K.; Univ Arizona, Sch Plant Sci; Univ Arizona, Biosyst Engn (WILEY, 2020-09)
      Microalgae as a biofuel source are of great interest. Bacterial phycosphere inhabitants of algal cultures are hypothesized to contribute to productivity. In this study, the bacterial composition of theChlorella sorokinianaphycosphere was determined over several production cycles in different growing seasons by 16S rRNA gene sequencing and identification. The diversity of the phycosphere increased with time during each individual reactor run, based on Faith's phylogenetic diversity metricversusdays post-inoculation (R = 0.66,P < 0.001). During summer months,Vampirovibrio chlorellavorus, an obligate predatory bacterium, was prevalent. Bacterial sequences assigned to the Rhizobiales, Betaproteobacteriales and Chitinophagales were positively associated with algal biomass productivity. Applications of the general biocide, benzalkonium chloride, to a subset of experiments intended to abateV. chlorellavorusappeared to temporarily suppress phycosphere bacterial growth, however, there was no relationship between those bacterial taxa suppressed by benzalkonium chloride and their association with algal productivity, based on multinomial model correlations. Algal health was approximated using a model-based metric, or the 'Health Index' that indicated a robust, positive relationship betweenC. sorokinianafitness and presence of members belonging to the Burholderiaceae and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade. Bacterial community composition was linked to the efficiency of microalgal biomass production and algal health.