Now showing items 8550-8569 of 12955

    • P -wave π π scattering and the ρ resonance from lattice QCD

      Alexandrou, Constantia; Leskovec, Luka; Meinel, Stefan; Negele, John; Paul, Srijit; Petschlies, Marcus; Pochinsky, Andrew; Rendon, Gumaro; Syritsyn, Sergey; Univ Arizona, Dept Phys (AMER PHYSICAL SOC, 2017-08-31)
      We calculate the parameters describing elastic I = 1, P-wave pp scattering using lattice QCD with 2 + 1 flavors of clover fermions. Our calculation is performed with a pion mass of m(pi) approximate to 320 MeV and a lattice size of L approximate to 3.6 fm. We construct the two-point correlation matrices with both quark-antiquark and two-hadron interpolating fields using a combination of smeared forward, sequential and stochastic propagators. The spectra in all relevant irreducible representations for total momenta vertical bar(P) over right arrow vertical bar <= root 32 pi/L are extracted with two alternative methods: a variational analysis as well as multiexponential matrix fits. We perform an analysis using Luscher's formalism for the energies below the inelastic thresholds, and investigate several phase shift models, including possible nonresonant contributions. We find that our data are well described by the minimal Breit-Wigner form, with no statistically significant nonresonant component. In determining the rho resonance mass and coupling we compare two different approaches: fitting the individually extracted phase shifts versus fitting the t-matrix model directly to the energy spectrum. We find that both methods give consistent results, and at a pion mass of am(pi) = 0.18295(36)(stat) obtain g(rho pi pi) = 5.69(13)(stat)(16)(sys), am(rho) = 0.4609(16)(stat)(14)(sys), and am(rho)/am(N) = 0.7476(38)(stat)(23)(sys), where the first uncertainty is statistical and the second is the systematic uncertainty due to the choice of fit ranges.
    • P-wave nucleon-pion scattering amplitude in the Δ(1232) channel from lattice QCD

      Silvi, G.; Paul, S.; Alexandrou, C.; Krieg, S.; Leskovec, L.; Meinel, S.; Negele, J.; Petschlies, M.; Pochinsky, A.; Rendon, G.; et al. (American Physical Society, 2021)
      We determine the Δ(1232) resonance parameters using lattice QCD and the Lüscher method. The resonance occurs in elastic pion-nucleon scattering with JP= 3/2+in the isospin I = 3/2, P-wave channel. Our calculation is performed with Nf= 2 + 1 flavors of clover fermions on a lattice with L ≈ 2.8 fm. The pion and nucleon masses are mπ= 255.4 (1.6) MeV and mN= 1073 (5) MeV, espectively, and the strong decay channel Δ πNis found to be above the threshold. To thoroughly map out the energy dependence of the nucleon-pion scattering amplitude, we compute the spectra in all relevant irreducible representations of the lattice symmetry groups for total momenta up to P→= 2π/L (1, 1, 1), including irreps that mix S and P waves. We perform global fits of the amplitude parameters to up to 21 energy levels, using a Breit-Wigner model for the P-wave phase shift and the effective-range expansion for the S-wave phase shift. From the location of the pole in the P-wave scattering amplitude, we obtain the resonance mass mΔ= 1378(7)(9) MeV and the coupling gΔ-πN= 23.8(2.7)(0.9).
    • P2RX7 Deletion in T Cells Promotes Autoimmune Arthritis by Unleashing the Tfh Cell Response

      Felix, Krysta M.; Teng, Fei; Bates, Nicholas A.; Ma, Heqing; Jaimez, Ivan A.; Sleiman, Kiah C.; Tran, Nhan L.; Wu, Hsin-Jung Joyce; Univ Arizona, Dept Immunobiol; Univ Arizona, Coll Med, Arizona Arthrit Ctr (FRONTIERS MEDIA SA, 2019-03-19)
      Rheumatoid arthritis (RA) is an autoimmune disease that affects similar to 1% of the world's population. B cells and autoantibodies play an important role in the pathogenesis of RA. The P2RX7 receptor is an ATP-gated cation channel and its activation results in the release of pro-inflammatory molecules. Thus, antagonists of P2RX7 have been considered to have potential as novel anti-inflammatory therapies. Although originally identified for its role in innate immunity, P2RX7 has recently been found to negatively control Peyer's patches (PP) T follicular helper cells (Tfh), which specialize in helping B cells, under homeostatic conditions. We have previously demonstrated that PP Tfh cells are required for the augmentation of autoimmune arthritis mediated by gut commensal segmented filamentous bacteria (SFB). Thus, we hypothesized that P2RX7 is required to control autoimmune disease by keeping the Tfh cell response in check. To test our hypothesis, we analyzed the impact of P2RX7 deficiency in vivo using both the original K/BxN autoimmune arthritis model and T cell transfers in the K/BxN system. We also examined the impact of P2RX7 ablation on autoimmune development in the presence of the gut microbiota SFB. Our data illustrate that contrary to exerting an anti-inflammatory effect, P2RX7 deficiency actually enhances autoimmune arthritis. Interestingly, SFB colonization can negate the difference in disease severity between WT and P2RX7-deficient mice. We further demonstrated that P2RX7 ablation in the absence of SFB caused reduced apoptotic Tfh cells and enhanced the Tfh response, leading to an increase in autoantibody production. It has been shown that activation of TIGIT, a well-known T cell exhaustion marker, up-regulates anti-apoptotic molecules and promotes T cell survival. We demonstrated that the reduced apoptotic phenotype of P2rx7(-/-) Tfh cells is associated with their increased expression of TIGIT. This suggested that while P2RX7 was regulating the Tfh population by promoting cell death, TIGIT may have been opposing P2RX7 by inhibiting cell death. Together, these results demonstrated that systemic administration of general P2RX7 antagonists may have detrimental effects in autoimmune therapies, especially in Tfh cell-dependent autoimmune diseases, and cell-specific targeting of P2RX7 should be considered in order to achieve efficacy for P2RX7-related therapy.
    • P2X7 receptor antagonism prevents IL-1β release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy

      Khalafalla, Mahmoud G.; Woods, Lucas T.; Camden, Jean M.; Khan, Aslam A.; Limesand, Kirsten H.; Petris, Michael J.; Erb, Laurie; Weisman, Gary A.; Univ Arizona, Dept Nutr Sci (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-10-06)
      Salivary gland inflammation is a hallmark of Sjogren's syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated nonselective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1 beta and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome. Here, our results show that in primary mouse submandibular gland (SMG) epithelial cells, P2X7R activation also induces the assembly of the NLRP3 inflammasome and the maturation and release of IL-1 beta, a response that is absent in SMG cells isolated from mice deficient in P2X7Rs (P2X7R(-/-)). P2X7R-mediated IL-1 beta release in SMG epithelial cells is dependent on transmembrane Na+ and/or K+ flux and the activation of heat shock protein 90 (HSP90), a protein required for the activation and stabilization of the NLRP3 inflammasome. Also, using the reactive oxygen species (ROS) scavengers N-acetyl cysteine and Mito-TEMPO, we determined that mitochondrial reactive oxygen species are required for P2X7R-mediated IL-1 beta release. Lastly, in vivo administration of the P2X7R antagonist A438079 in the CD28(-/-), IFN gamma(-/-), NOD.H-2(h4) mouse model of salivary gland exocrinopathy ameliorated salivary gland inflammation and enhanced carbachol-induced saliva secretion. These findings demonstrate that P2X7R antagonism in vivo represents a promising therapeutic strategy to limit salivary gland inflammation and improve secretory function.
    • P53 suppresses expression of the 14-3-3gamma oncogene

      Radhakrishnan, Vijayababu; Putnam, Charles; Qi, Wenqing; Martinez, Jesse; Arizona Cancer Center, Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona 85724, USA; Department of Pediatrics, Steele Research Center, 1501 N Campbell Ave, Tucson, Arizona 85724, USA; Department of Surgery, 1501 N Campbell ave, Tucson, Arizona 85724, USA; Department of Medicine, 1515 N. Campbell Ave., Tucson, Arizona 85724, USA (BioMed Central, 2011)
      BACKGROUND:14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.METHODS:qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter.RESULTS:Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression.CONCLUSION:Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.
    • P5CS expression level and proline accumulation in the sensitive and tolerant wheat cultivars under control and drought stress conditions in the presence/absence of silicon and salicylic acid

      Maghsoudi, Kobra; Emam, Yahya; Niazi, Ali; Pessarakli, Mohammad; Arvin, Mohammad Javad; Univ Arizona, Dept Plant Sci (TAYLOR & FRANCIS LTD, 2018-08-09)
      The effects of silicon (Si) and salicylic acid (SA) applications on proline content and expression of (1)-pyrrolin-5-carboxylate synthetase (P5CS) were examined under different drought levels and different drought exposure times. Two wheat cultivars, a drought tolerant and a drought sensitive were used. The experiment was a factorial based on completely randomized design with three replicates. Expression analysis by the quantitative real time PCR showed that the tolerant cultivar had significantly higher P5CS expressions compared to the sensitive one under drought stress. In sampling time points, the maximum level of mRNA was observed at 48h after stress was applied. At 48h after stress induction, the expression of P5CS was almost 3.1 fold higher in the tolerant cultivar compared to the sensitive one. In both cultivars, gene expression decreased from 48 to 72h. The stressed plants treated with Si+SA showed a higher expression. Proline content started to increase by Si and SA treatments and the maximum proline content was obtained at simultaneous application of Si+SA. Drought stress significantly reduced chlorophyll content, relative water content and leaf water potential of both cultivars, while increased electrolyte leakage (EL) of the leaves. In contrast, foliar-applied Si and SA significantly increased these parameters and reduced EL, and the effect of simultaneous application of Si and SA was greater. The results suggest that the P5CS is a stress inducible gene. This gene has the potential to be used for improvement of drought stress tolerance in wheat. Network analysis highlighted positive interaction of osmotic stress, drought and cold stress on P5CS1 and the regulatory role of MYB2, ERF-1, and EIN3 transcription factors. In conclusion, alleviation of drought stress by application of Si and SA was associated partially with enhanced expression of P5CS gene and following proline accumulation.
    • p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex

      Tao, Shasha; Liu, Pengfei; Luo, Gang; Rojo de la Vega, Montserrat; Chen, Heping; Wu, Tongde; Tillotson, Joseph; Chapman, Eli; Zhang, Donna D.; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (AMER SOC MICROBIOLOGY, 2017-04-15)
      Activation of the stress-responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and is targeted to the proteasome for degradation ( the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation was previously unknown. p97 is a ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system ( UPS). In this study, we show that p97 negatively regulates NRF2 through the canonical pathway by extracting ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex, with the aid of the heterodimeric cofactor UFD1/NPL4 and the UBA-UBX containing protein UBXN7, for efficient proteasomal degradation. Given the role of NRF2 in chemoresistance and the surging interest in p97 inhibitors to treat cancers, our results indicate that dual p97/NRF2 inhibitors may offer a more potent and long-term avenue of p97-targeted treatment.
    • PA program characteristics and diversity in the profession

      Coplan, Bettie; Bautista, Tara G.; Dehn, Richard W.; Univ Arizona, Coll Med, Dept Biomed Informat (LIPPINCOTT WILLIAMS & WILKINS, 2018-03)
      Objectives: The primary objective of this study was to identify PA program characteristics that may be associated with higher or lower percentages of underrepresented minority students in PA programs. Methods: Data from the Physician Assistant Education Association (PAEA) 2002-2003 and 2012-2013 annual surveys were analyzed. Bivariate correlation coefficients and multiple regression modeling were used to identify relationships between program characteristics and percentages of black and Hispanic students. Results: The percentage of white matriculants in PA programs increased from 76.5% in 2002-2003 to 81.8% in 2012-2013; the percentage of black students decreased from 6.2% to 4.4%. Multiple linear regression revealed a modest negative relationship between master's degree and percentage of underrepresented minority students and a modest positive relationship between percentages of underrepresented minority employees and underrepresented minority students. Conclusions: Further research is needed to identify strategies to increase underrepresented minority participation in healthcare professions programs.
    • Pacific sea level rise patterns and global surface temperature variability

      Peyser, Cheryl E.; Yin, Jianjun; Landerer, Felix W.; Cole, Julia E.; Univ Arizona, Dept Geosci; Department of Geosciences; University of Arizona; Tucson Arizona USA; Department of Geosciences; University of Arizona; Tucson Arizona USA; Jet Propulsion Laboratory/NASA; California Institute of Technology; Pasadena California USA; Department of Geosciences; University of Arizona; Tucson Arizona USA (AMER GEOPHYSICAL UNION, 2016-08-28)
      During 1998-2012, climate change and sea level rise (SLR) exhibit two notable features: a slowdown of global surface warming (hiatus) and a rapid SLR in the tropical western Pacific. To quantify their relationship, we analyze the long-term control simulations of 38 climate models. We find a significant and robust correlation between the east-west contrast of dynamic sea level (DSL) in the Pacific and global mean surface temperature (GST) variability on both interannual and decadal time scales. Based on linear regression of the multimodel ensemble mean, the anomalously fast SLR in the western tropical Pacific observed during 1998-2012 indicates suppression of a potential global surface warming of 0.16 degrees 0.06 degrees C. In contrast, the Pacific contributed 0.29 degrees 0.10 degrees C to the significant interannual GST increase in 1997/1998. The Pacific DSL anomalies observed in 2015 suggest that the strong El Nino in 2015/2016 could lead to a 0.21 degrees 0.07 degrees C GST jump.
    • Pacific sea surface temperatures, midlatitude atmospheric circulation, and widespread interannual anomalies in western U.S. streamflow

      Malevich, S. B.; Woodhouse, C. A.; Univ Arizona, Dept Geosci; Univ Arizona, Sch Geog & Dev; Department of Geosciences; University of Arizona; Tucson Arizona USA; School of Geography and Development; University of Arizona; Tucson Arizona USA (AMER GEOPHYSICAL UNION, 2017-05-28)
      Widespread droughts can have considerable impact on western United States (U.S.) streamflow but causes related to moisture delivery processes are not yet fully understood. Here we examine western U.S. streamflow records to identify robust leading modes of interannual variability and their links to patterns of ocean and atmospheric circulation. The leading mode of streamflow variability, a pattern of west-wide streamflow anomalies, accounts for approximately 50% of variability and is associated with persistent high-pressure anomalies related to ridges off the Pacific North American coast. The second mode of variability accounts for approximately 25% of variability and is associated with ocean and atmospheric conditions in the tropical Pacific. Our results suggest that the leading mode of streamflow variability in the western U.S. is more strongly associated with internally driven midlatitude atmospheric variability than equatorial Pacific sea surface temperatures.
    • Pacific-Atlantic Ocean influence on wildfires in northeast China (1774 to 2010)

      Yao, Qichao; Brown, Peter M.; Liu, Shirong; Rocca, Monique E.; Trouet, Valerie; Zheng, Ben; Chen, Haonan; Li, Yinchao; Liu, Duanyang; Wang, Xiaochun; et al. (AMER GEOPHYSICAL UNION, 2017-01-28)
      Identification of effects that climate teleconnections, such as El Nino-Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and North Atlantic Oscillation (NAO), have on wildfires is difficult because of short and incomplete records in many areas of the world. We developed the first multicentury wildfire chronologies for northeast China from fire-scarred trees. Regional wildfires occurred every 7years from the 1700s to 1947, after which fire suppression policies were implemented. Regional wildfires occurred predominately during drought years and were associated with positive phases of ENSO and PDO and negative NAO. Twentieth century meteorological records show that this contingent combination of +ENSO/+PDO/-NAO is linked to low humidity, low precipitation, and high temperature during or before late spring fire seasons. Climate and wildfires in northeast China may be predictable based on teleconnection phases, although future wildfires may be more severe due to effects of climate change and the legacy of fire suppression.
    • Packing trees into 1-planar graphs

      De Luca, F.; Di Giacomo, E.; Hong, S.-H.; Kobourov, S.; Lenhart, W.; Liotta, G.; Meijer, H.; Tappini, A.; Wismath, S.; Department of Computer Science, University of Arizona (Brown University, 2021)
      We introduce and study the 1-planar packing problem: Given k graphs with n vertices G1, …, Gk, find a 1-planar graph that contains the given graphs as edge-disjoint spanning subgraphs. We mainly focus on the case when each Gi is a tree and k = 3. We prove that a triple consisting of three caterpillars or of two caterpillars and a path may not admit a 1-planar packing, while two paths and a special type of caterpillar always have one. We then study 1-planar packings with few crossings and prove that three paths (resp. cycles) admit a 1-planar packing with at most seven (resp. fourteen) crossings. We finally show that a quadruple consisting of three paths and a perfect matching with n ≥ 12 vertices admits a 1-planar packing, while such a packing does not exist if n ≤ 10. © 2021, Brown University. All rights reserved.
    • 'PACLIMS': A component LIM system for high-throughput functional genomic analysis

      Donofrio, Nicole; Rajagopalon, Ravi; Brown, Douglas, 1955-; Diener, Stephen; Windham, Donald; Nolin, Shelly; Floyd, Anna; Mitchell, Thomas; Galadima, Natalia; Tucker, Sara; et al. (BioMed Central, 2005)
      BACKGROUND:Recent advances in sequencing techniques leading to cost reduction have resulted in the generation of a growing number of sequenced eukaryotic genomes. Computational tools greatly assist in defining open reading frames and assigning tentative annotations. However, gene functions cannot be asserted without biological support through, among other things, mutational analysis. In taking a genome-wide approach to functionally annotate an entire organism, in this application the ~11,000 predicted genes in the rice blast fungus (Magnaporthe grisea), an effective platform for tracking and storing both the biological materials created and the data produced across several participating institutions was required.RESULTS:The platform designed, named PACLIMS, was built to support our high throughput pipeline for generating 50,000 random insertion mutants of Magnaporthe grisea. To be a useful tool for materials and data tracking and storage, PACLIMS was designed to be simple to use, modifiable to accommodate refinement of research protocols, and cost-efficient. Data entry into PACLIMS was simplified through the use of barcodes and scanners, thus reducing the potential human error, time constraints, and labor. This platform was designed in concert with our experimental protocol so that it leads the researchers through each step of the process from mutant generation through phenotypic assays, thus ensuring that every mutant produced is handled in an identical manner and all necessary data is captured.CONCLUSION:Many sequenced eukaryotes have reached the point where computational analyses are no longer sufficient and require biological support for their predicted genes. Consequently, there is an increasing need for platforms that support high throughput genome-wide mutational analyses. While PACLIMS was designed specifically for this project, the source and ideas present in its implementation can be used as a model for other high throughput mutational endeavors.
    • PaCTS 1.0: A Crowdsourced Reporting Standard for Paleoclimate Data

      Thirumalai, K.; Univ Arizona, Dept Geosci (AMER GEOPHYSICAL UNION, 2019)
      The progress of science is tied to the standardization of measurements, instruments, and data. This is especially true in the Big Data age, where analyzing large data volumes critically hinges on the data being standardized. Accordingly, the lack of community-sanctioned data standards in paleoclimatology has largely precluded the benefits of Big Data advances in the field. Building upon recent efforts to standardize the format and terminology of paleoclimate data, this article describes the Paleoclimate Community reporTing Standard (PaCTS), a crowdsourced reporting standard for such data. PaCTS captures which information should be included when reporting paleoclimate data, with the goal of maximizing the reuse value of paleoclimate data sets, particularly for synthesis work and comparison to climate model simulations. Initiated by the LinkedEarth project, the process to elicit a reporting standard involved an international workshop in 2016, various forms of digital community engagement over the next few years, and grassroots working groups. Participants in this process identified important properties across paleoclimate archives, in addition to the reporting of uncertainties and chronologies; they also identified archive-specific properties and distinguished reporting standards for new versus legacy data sets. This work shows that at least 135 respondents overwhelmingly support a drastic increase in the amount of metadata accompanying paleoclimate data sets. Since such goals are at odds with present practices, we discuss a transparent path toward implementing or revising these recommendations in the near future, using both bottom-up and top-down approaches.
    • Pain Catastrophizing and Arthritis Self-Efficacy as Mediators of Sleep Disturbance and Osteoarthritis Symptom Severity

      Tighe, Caitlan A; Youk, Ada; Ibrahim, Said A; Weiner, Debra K; Vina, Ernest R; Kwoh, C Kent; Gallagher, Rollin M; Bramoweth, Adam D; Hausmann, Leslie R M; Univ Arizona, Coll Med (OXFORD UNIV PRESS, 2019-08-22)
      Objective. Sleep and pain-related experiences are consistently associated, but the pathways linking these experiences are not well understood. We evaluated whether pain catastrophizing and arthritis self-efficacy mediate the association between sleep disturbance and osteoarthritis (OA) symptom severity in patients with knee OA. Methods. We analyzed cross-sectional baseline data collected from Veterans Affairs (VA) patients enrolled in a clinical trial examining the effectiveness of a positive psychology intervention in managing pain from knee OA. Participants indicated how often in the past two weeks they were bothered by trouble falling asleep, staying asleep, or sleeping too much. We used validated scales to assess the primary outcome (OA symptom severity) and potential mediators (arthritis self-efficacy and pain catastrophizing). To test the proposed mediation model, we used parallel multiple mediation analyses with bootstrapping, controlling for sociodemographic and clinical characteristics with bivariate associations with OA symptom severity. Results. The sample included 517 patients (M-age = 64 years, 72.9% male, 52.2% African American). On average, participants reported experiencing sleep disturbance at least several days in the past two weeks (M = 1.41, SD = 1.18) and reported moderate OA symptom severity (M = 48.22, SD = 16.36). More frequent sleep disturbance was associated with higher OA symptom severity directly (b= 3.08, P <0.001) and indirectly, through higher pain catastrophizing (b = 0.60, 95% confidence interval [CI] = 0.20 to 1.11) and lower arthritis self-efficacy (b = 0.84, 95% CI = 0.42 to 1.42). Conclusions. Pain catastrophizing and arthritis self-efficacy partially mediated the association between sleep disturbance and OA symptom severity. Behavioral interventions that address pain catastrophizing and/or self-efficacy may buffer the association between sleep disturbance and OA symptom severity.
    • Pain Management and Risks Associated With Substance Use: Practice Recommendations

      Turner, Helen N.; Oliver, June; Compton, Peggy; Matteliano, Deborah; Sowicz, Timothy Joseph; Strobbe, Stephen; St. Marie, Barbara; Wilson, Marian; University of Arizona College of Nursing (Elsevier BV, 2021-12)
      Assessing and managing pain while evaluating risks associated with substance use and substance use disorders continues to be a challenge faced by health care clinicians. The American Society for Pain Management Nursing and the International Nurses Society on Addictions uphold the principle that all persons with co-occurring pain and substance use or substance use disorders have the right to be treated with dignity and respect, and receive evidence-based, high quality assessment, and management for both conditions. The American Society for Pain Management Nursing and International Nurses Society on Addictions have updated their 2012 position statement on this topic supporting an integrated, holistic, multidimensional approach, which includes nonopioid and nonpharmacological modalities. Opioid use disorder is used as an exemplar for substance use disorders and clinical recommendations are included with expanded attention to risk assessment and mitigation with interventions targeted to minimize the risk for relapse or escalation of substance use. Opioids should not be excluded for anyone when indicated for pain management. A team-based approach is critical, promotes the active involvement of the person with pain and their support systems, and includes pain and addiction specialists whenever possible. Health care systems should establish policies and procedures that facilitate and support the principles and recommendations put forth in this article.
    • Pain management modalities for hidradenitis suppurativa: a patient survey

      Fernandez, Jennifer M; Thompson, Alyssa M; Borgstrom, Mark; Orenstein, Lauren A V; Hsiao, Jennifer L; Shi, Vivian Y; Univ Arizona, Coll Med; Univ Arizona, Univ Informat Technol Serv (TAYLOR & FRANCIS LTD, 2020-09-20)
      Background Pain is one of the most common and debilitating symptoms of hidradenitis suppurativa (HS). Objective We sought to identify pain management therapies used in HS and assess patient-perceived effectiveness. Methods An anonymous online survey was posted to Facebook HS support groups. Participants selected all that applied from a list of 20 therapies to indicate which ones they have tried for HS pain. For each therapy used, participants were asked to rate effectiveness on a 5-point scale: not successful (1), mildly successful (2), moderately successful (3), very successful (4), and extremely successful (5). Mean effectiveness ratings were calculated by averaging the corresponding numbers. Results Of the 438 participants, 93.8% were female. Participants classified themselves as Hurley stage I (8.2%), II (53.4%), and III (38.4%). Warm compresses were the most commonly used therapy (82.4%), followed by ibuprofen/naproxen (74.7%), Epsom salt baths (57.8%), cold compresses (45.4%), and acetaminophen (44.7%). Marijuana smoking received the highest mean effectiveness rating (2.92 +/- 1.10), followed by marijuana edibles (2.87 +/- 1.10), and opioids (2.83 +/- 0.98). Mean effectiveness ratings were lowest for bleach baths (1.52 +/- 0.80), sitz baths (1.53 +/- 0.56), massage (1.61 +/- 0.92), gabapentin (1.64 +/- 0.73), and acetaminophen (1.71 +/- 0.75). Conclusions and relevance Even the highest-rated pain management modalities are considered only moderately effective by HS patients.
    • Pak2 regulates myeloid-derived suppressor cell development in mice

      Zeng, Yi; Hahn, Seongmin; Stokes, Jessica; Hoffman, Emely A.; Schmelz, Monika; Proytcheva, Maria; Chernoff, Jonathan; Katsanis, Emmanuel; Univ Arizona, Dept Pediat, Steele Childrens Res Ctr; Univ Arizona, Ctr Canc; et al. (AMER SOC HEMATOLOGY, 2017-10-10)
      Myeloid-derived suppressor cells (MDSCs) are CD11b(+)Gr1(+) cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11b(high)Gr1(high) cells in mice. In this study, we confirmed that Pak2-KO CD11b(high)Gr1(high) cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4(+) T cells that produced more interferon gamma, tumor necrosis factor alpha, and GM-CSF. Pak2 disruption activated STAT5 while downregulating the expression of IRF8, a well-described myeloid transcription factor. Together, our data reveal a previously unrecognized role of Pak2 in regulating MDSC development via both cell-intrinsic and extrinsic mechanisms. Our findings have potential translational implications, as the efficacy of targeting Paks in cancer therapeutics may be undermined by tumor escape from immune control and/or acceleration of tumorigenesis through MDSC expansion.
    • Paleo-Asian oceanic slab under the North China craton revealed by carbonatites derived from subducted limestones

      Chen, Chunfei; Liu, Yongsheng; Foley, Stephen F.; Ducea, Mihai N.; He, Detao; Hu, Zhaochu; Chen, Wei; Zong, Keqing; Department of Geosciences, University of Arizona (GEOLOGICAL SOC AMER, INC, 2016-12)
      It is widely accepted that the lithospheric mantle under the North China craton (NCC) has undergone comprehensive refertilization due to input from surrounding subducted slabs. However, the possible contribution from the Paleo-Asian oceanic slab to the north is poorly constrained, largely because of the lack of convincing evidence for the existence of this slab under the NCC. We report here carbonatite intruding Neogene alkali basalts in the Hannuoba region, close to the northern margin of the NCC. Trace element patterns with positive Sr and U anomalies, negative high field strength elements (Nb, Ta, Zr, Hf, and Ti) and Ce anomalies, high Sr-87/Sr-86 ratios (0.70522-0.70796), and high delta O-18(SMOW) (standard mean ocean water) values (22.2%-23%) indicate that this carbonatite had a limestone precursor. However, the presence of coarse-grained mantle-derived clinopyroxene, orthopyroxene, and olivine, and chemical features of the carbonates suggest that the carbonate melts were derived from the mantle. The carbonates have high Nd-143/Nd-144 ratios (0.51282-0.51298) and show negative correlation between CaO and Ni contents, resulting from reaction between carbonate melt and peridotite. Considering the regional tectonic setting, the carbonatite probably formed by melting of subducted sedimentary carbonate rocks that formed part of the Paleo-Asian oceanic slab, and thus could provide the first direct evidence for the presence of the Paleo-Asian oceanic slab beneath the NCC.
    • Paleohydrological context for recent floods and droughts in the Fraser River Basin, British Columbia, Canada

      Brice, B.L.; Coulthard, B.L.; Homfeld, I.K.; Dye, L.A.; Anchukaitis, K.J.; School of Geography Development and Environment, University of Arizona; Laboratory of Tree-Ring Research, University of Arizona (IOP Publishing Ltd, 2021)
      The recent intensification of floods and droughts in the Fraser River Basin (FRB) of British Columbia has had profound cultural, ecological, and economic impacts that are expected to be exacerbated further by anthropogenic climate change. In part due to short instrumental runoff records, the long-Term stationarity of hydroclimatic extremes in this major North American watershed remains poorly understood, highlighting the need to use high-resolution paleoenvironmental proxies to inform on past streamflow. Here we use a network of tree-ring proxy records to develop 11 subbasin-scale, complementary flood-and drought-season reconstructions, the first of their kind. The reconstructions explicitly target management-relevant flood and drought seasons within each basin, and are examined in tandem to provide an expanded assessment of extreme events across the FRB with immediate implications for water management. We find that past high flood-season flows have been of greater magnitude and occurred in more consecutive years than during the observational record alone. Early 20th century low flows in the drought season were especially severe in both duration and magnitude in some subbasins relative to recent dry periods. Our Fraser subbasin-scale reconstructions provide long-Term benchmarks for the natural flood and drought variability prior to anthropogenic forcing. These reconstructions demonstrate that the instrumental streamflow records upon which current management is based likely underestimate the full natural magnitude, duration, and frequency of extreme seasonal flows in the FRB, as well as the potential severity of future anthropogenically forced events. © 2021 The Author(s). Published by IOP Publishing Ltd.