Now showing items 1-20 of 13619

    • Discovery of New Catalytic Topoisomerase II Inhibitors for Anticancer Therapeutics

      Matias-Barrios, Victor M; Radaeva, Mariia; Song, Yi; Alperstein, Zaccary; Lee, Ahn R; Schmitt, Veronika; Lee, Joseph; Ban, Fuqiang; Xie, Ning; Qi, Jianfei; et al. (Frontiers Media S.A., 2021-02-01)
    • The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons

      Hossain Saad, Md Zubayer; Xiang, Liuruimin; Liao, Yan-Shin; Reznikov, Leah R; Du, Jianyang (Frontiers Media S.A., 2021-02-02)
      Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH50 of 5.5. whereas internal protons inhibit TRPM3 with an inhibitory pH50 of 6.9. We identified three titratable residues, D1059, D1062, and D1073, at the vestibule of the channel pore that contributes to pH sensitivity. The mutation of D1073Q reduced TRPM3 current by low external pH 5.5 from 62 ± 3% in wildtype to 25 ± 6.0% in D1073Q mutant. These results indicate that D1073 is essential for pH sensitivity. In addition, we found that a single mutation of D1059 or D1062 enhanced pH sensitivity. In summary, our findings identify molecular determinants respionsible for the pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/pathological functions.
    • Physicochemical Effects of Niobic Acid Addition Into Dental Adhesives

      Garcia, Isadora Martini; Leitune, Vicente Castelo Branco; Balbinot, Gabrielade Souza; Balhaddad, Abdul Rahman A.; Melo, Mary Anne S.; Samuel, Susana Maria Werner; Collares, Fabrício Mezzomo (Frontiers Media S.A., 2021-02-02)
      The incorporation of metallic oxides in dental adhesives has been a strategy to confer improved radiopacity and physicochemical properties for polymers. Tailoring the structure of these fillers could contribute to their application in therapeutic strategies for dental restorations. The aim of this study was to evaluate the incorporation of niobic acid into experimental dental adhesives, and compare these adhesives to niobium pentoxide containing adhesives. A control group without Nb2O5·n H2O or Nb2O5 was also used for comparison. Niobium-based particles have been used as a feasible approach, mainly because of their bioactivity. In this study, hydrated niobium pentoxide, also called niobic acid (Nb2O5·n H2O), was incorporated into an experimental dental adhesive as a potential catalyst for monomer conversion. A base resin for dental adhesive was formulated with methacrylate monomers and photoinitiators. Two types of oxides were tested as filler for this adhesive: Nb2O5·n H2O or niobium pentoxide (Nb2O5). Both fillers were added separately into the experimental adhesive at 0, 2.5, 5, and 10 wt.%. One group without Nb2O5·n H2O or Nb2O5 (0 wt.% of filler addition) was used as a control group. The formulated materials were analyzed for radiopacity according to the ISO 4049 and used FTIR analysis to assess the degree of conversion (DC) and the maximum polymerization rate (RPmax). Mechanical properties were analyzed by ultimate tensile strength (UTS) in a testing machine. Softening in solvent was conducted by measuring Knoop microhardness before and after immersion of samples in ethanol. Normality of data was assessed with Shapiro-Wilk, and comparisons between factors were conducted with two-way ANOVA and Tukey at 5% of significance. Both fillers, Nb2O5 or Nb2O5·n H2O, increased the radiopacity of dental adhesives in comparison to the unfilled adhesive (p < 0.05). There were no differences among groups for the ultimate tensile strength (p > 0.05), and all groups containing Nb2O5 or Nb2O5·n H2O improved the resistance against softening in solvent (p < 0.05). The groups with 5 and 10 wt% addition of Nb2O5 showed decreased DC compared to the control group (p < 0.05), while the addition of Nb2O5·nH2O up to 10 wt% did not alter the DC (p > 0.05). The polymerization rate did not change among groups (p > 0.05). In conclusion, Nb2O5·n H2O is a promising filler to be incorporated into dental adhesives providing proper mechanical properties, improved resistance against solvents, and increased radiopacity, without changing the DC. © Copyright © 2021 Garcia, Leitune, Balbinot, Balhaddad, Melo, Samuel and Collares.
    • Non-cannabinoid metabolites of cannabis sativa l. With therapeutic potential

      Lowe, Henry; Steele, Blair; Bryant, Joseph; Toyang, Ngeh; Ngwa, Wilfred (MDPI AG, 2021-02-20)
      The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD). Both ∆9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed. © 2021 by the authors.
    • A Brief Update on the Effect of the COVID-19 Pandemic on Hip and Knee Arthroplasty Patients in the United States: A Multicenter Update to a Previous Survey Study of Patients Postponed by the Pandemic

      Brown, Timothy S; Bedard, Nicholas A; Rojas, Edward O; Anthony, Christopher A; Schwarzkopf, Ran; Stambough, Jeffrey B; Nandi, Sumon; Prieto, Hernan; Parvizi, Javad; Bini, Stefano A; et al. (Elsevier Inc., 2020-12-03)
      Background: In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States. Methods: Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA or TKA but canceled due to the COVID-19 elective surgery stoppage (3/2020-5/2020) were included in the study. Descriptive statistics along with subgroup analysis with Wilcoxon rank were performed. Results: In total, surveys were distributed to 2135 patients and completed by 848 patients (40%) from 15 institutions. Most patients (728/848, 86%) had their surgery postponed or canceled by the surgeon or hospital. Unknown length of surgical delay remained the highest source of anxiety among survey participants. Male patients were more likely to be willing to proceed with surgery in spite of COVID-19. There were minimal regional differences in responses. Only 61 patients (7%) stated they will continue to delay surgery for fear of contracting COVID-19 while in the hospital. Conclusion: Similar to the previous study, the most anxiety-provoking thought was the uncertainty, over if and when the canceled joint replacement surgery could be rescheduled. Patients suffering from the daily pain of hip and knee arthritis who have been scheduled for elective arthroplasty remain eager to have their operation as soon as elective surgery is allowed to resume.
    • Characterization and implications of the initial estimated glomerular filtration rate 'dip' upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial

      Kraus, Bettina J; Weir, Matthew R; Bakris, George L; Mattheus, Michaela; Cherney, David Z I; Sattar, Naveed; Heerspink, Hiddo J L; Ritter, Ivana; von Eynatten, Maximilian; Zinman, Bernard; et al. (Elsevier B.V., 2020-11-10)
      Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3-5 ml/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin and largely reversible, this 'eGFR dip' may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with eGFR available at baseline and week four were categorized by initial eGFR change into three groups; over 10% decline ('eGFR dipper'), over 0 and up to 10% decline ('eGFR intermediate'), no eGFR decline ('eGFR non-dipper'). Baseline characteristics of 'eGFR intermediate' and 'eGFR non-dipper' were generally comparable. An initial 'eGFR dip' was observed in 28.3% of empagliflozin versus 13.4% of placebo-treated participants; odds ratio 2.7 [95% Confidence Interval 2.3-3.0]. In multivariate logistic regression, diuretic use and higher KDIGO risk category at baseline were independently predictive of an 'eGFR dip' in empagliflozin versus placebo. Safety and beneficial treatment effects with empagliflozin on cardiovascular and kidney outcomes were consistent across subgroups based on these predictive factors. The initial 'eGFR dip' did not have a major impact on the treatment effect of empagliflozin on subsequent cardiovascular death, hospitalization for heart failure, and incident or worsening kidney disease. Thus, patients with type 2 diabetes with more advanced kidney disease and/or on diuretic therapy were more likely to experience an 'eGFR dip' of over 10% with empagliflozin, but reduction in cardiovascular and kidney outcomes was not relevantly modified by such 'eGFR dip.'
    • Providing Ancillary Care in Clinical Research: A Case of Diffuse Large B-Cell Lymphoma during a Malaria Vaccine Trial in Equatorial Guinea

      Manock, Stephen R; Mtoro, Ali; Urbano Nsue Ndong, Vicente; Olotu, Ally; Chemba, Mwajuma; Sama Roca, Antonio E; Eburi, Esther; García, Guillermo A; Cortes Falla, Carlos; Niemczura de Carvalho, Julie; et al. (American Society of Tropical Medicine and Hygiene, 2020-11-23)
      Providing medical care for participants in clinical trials in resource-limited settings can be challenging and costly. Evaluation and treatment of a young man who developed cervical lymphadenopathy during a malaria vaccine trial in Equatorial Guinea required concerted efforts of a multinational, multidisciplinary team. Once a diagnosis of diffuse large B-cell lymphoma was made, the patient was taken to India to receive immunochemotherapy. This case demonstrates how high-quality medical care was provided for a serious illness that occurred during a trial that was conducted in a setting in which positron emission tomography for diagnostic staging, an oncologist for supervision of treatment, and an optimal therapeutic intervention were not available. Clinical researchers should anticipate the occurrence of medical conditions among study subjects, clearly delineate the extent to which health care will be provided, and set aside funds commensurate with those commitments.
    • Effect of SARS-CoV-2 infection in pregnancy on maternal and neonatal outcomes in Africa: An AFREhealth call for evidence through multicountry research collaboration

      Nachega, Jean B.; Sam-Agudu, Nadia A.; Budhram, Samantha; Taha, Taha E.; Vannevel, Valerie; Somapillay, Priya; Ishoso, Daniel Katuashi; Pipo, Michel Tshiasuma; Nswe, Christian Bongo Pasi; Ditekemena, John; et al. (American Society of Tropical Medicine and Hygiene, 2021-02-01)
      In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health's COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.
    • Delayed stroke after hospitalization for coronavirus disease 2019 pneumonia from common and internal carotid artery thrombosis

      Hosseini, Motahar; Sahajwani, Sunny; Zhang, Jackie; Toursavadkohi, Shahab; Ucuzian, Areck A (Society for Vascular Surgery, 2020-11-10)
      Large vessel arterial thrombosis has been reported to complicate a subset of cases of coronavirus disease 2019 (COVID-19). Thrombosis of the extracranial carotid arterial system can lead to devastating stroke in some patients with COVID-19. We have presented the case of a patient previously hospitalized with COVID-19 for oxygen supplementation who had presented after discharge with delayed stroke from a right common carotid artery and internal carotid artery thrombosis. The thrombotic occlusion resolved with antithrombotic medications and no invasive intervention. The present report highlights the complicated and heterogeneous nature of COVID-19 and provides one approach to managing the devastating complication of stroke from carotid arterial thrombosis. © 2020 The Authors
    • Virtual Face to Face with Dr. Bruce Jarrell: Town Hall Addresses Telework, Return to Campus

      Jarrell, Bruce E.; Fenwick, Christina; Bratt, Jonathan; Dickerson, Juliet; Rhodes, Dawn M.; Likowski, Alex (2021-02-25)
    • Vaccine Doses Now Available For UMB

      UMB Recovery Task Force (2021-02-26)
    • Council on Accreditation for Children and Family Services: Employee Assistance Program Accreditation

      Stockert, Timothy (Council on Accreditation, 2002)
      These slides present a variety of information regarding the process of becoming an accredited EAP from the Council on Accreditation. Beginning with the history of the COA and EASNA, it then explores the development of standards and the process of accreditation. The benefits and costs of accreditation are also covered, and, finally, the slides explore peer reviewer's and team leader's tasks.