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Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics
No full textOropharyngeal cancer (OPC) incidence is increasing significantly among men and often requires intensive therapy causing significant morbidity. Early detection of OPC is needed, when monotherapy can be safely delivered with less treatment-associated morbidity, while maintaining high cure rates. We conducted a study of 101 pretreatment male OPC cases matched 1:1 to 101 disease-free controls for age and smoking history. Oral gargles were collected from cases and controls with additional biopsies or aspirates from cases. The HPV SPF10-LiPA25 PCR assay was utilized for HPV genotyping. Methylation of three CpG sites (438, 427 and 425) in the EPB41L3 gene and methylation status of the L1 (6,367, 6,389), L2 (4,257, 4,262, 4,266, 4,269, 4,275, 4,282) and E2 (3,412, 3,415, 3,417, 3,433, 3,436) CpG sites of HPV 16 positive specimens was assessed by pyrosequencing. Significant correlations were observed between tumor and oral specimens for all methylation biomarkers (p \u3c 0.01). EPB41L3 and HPV 16 L1, L2 and E2 methylation were significantly (p \u3c 0.0001) higher among cases than controls, regardless of early vs. late disease. When HPV 16 genes and EPB41L3 methylation status were combined in a logistic regression analysis, a sensitivity of 70.3% and a specificity of 90.9% were observed for the detection of OPC from an oral gargle. Our data suggest that methylation biomarkers measured in oral gargles may have utility in identifying OPC early. Future studies are needed to replicate these findings and to inform additional biomarkers that can maximize specificity and sensitivity for early OPC detection
Multi-targeted management of upland game birds at the agroecosystem interface in midwestern North America
No full textDespite its imperative, biodiversity conservation is chronically underfunded, a deficiency that often forces management agencies to prioritize. Single-species recovery thus becomes a focus (often with socio-political implications), whereas a more economical approach would be the transition to multi-targeted management (= MTM). This challenge is best represented in Midwestern North America where biodiversity has been impacted by 300+ years of chronic anthropogenic disturbance such that native tall-grass prairie is now supplanted by an agroecosystem. Here, we develop an MTM with a population genetic metric to collaboratively manage three Illinois upland gamebirds: common pheasant (Phasianus colchicus; pheasant), northern bobwhite quail (Colinus virginianus; quail), and threatened-endangered (T&E) greater prairie chicken (Tympanuchus cupido pinnatus; prairie chicken). We first genotyped our study pheasant at 19 microsatellite DNA loci and identified three captive breeding stocks (N = 143; IL Department of Natural Resources) as being significantly bottlenecked, with relatedness \u3e1st-cousin (μR = 0.158). \u27Wild\u27 (non-stocked) pheasant [N = 543; 14 Pheasant-Habitat-Areas (PHAs)] were also bottlenecked, significantly interrelated (μR = 0.150) and differentiated (μFST = 0.047), yet distinct from propagation stock. PHAs that encompassed significantly with larger areas also reflected greater effective population sizes (μNE = 43; P\u3c0.007). We juxtaposed these data against previously published results for prairie chicken and quail, and found population genetic structure driven by drift, habitat/climate impacts, and gender-biased selection via hunter-harvest. Each species (hunter-harvested or T&E) is independently managed, yet their composite population genetic baseline provides the quantitative criteria needed for an upland game bird MTM. Its implementation would require agricultural plots to be rehabilitated/reclaimed using a land-sharing/sparing portfolio that differs markedly from the Conservation Reserve Program (CRP), where sequestered land decreases as agricultural prices escalate. Cost-savings for an MTM would accrue by synchronizing single-species management with a dwindling hunter-harvest program, and by eliminating propagation/stocking programs. This would sustain not only native grasslands and their resident species, but also accelerate conservation at the wildlife-agroecosystem interface
Perspectives of patients on outpatient parenteral antimicrobial therapy: Experiences and adherence
No full textBackground. Nonadherence to medication is a burden to the US health care system and is associated with poor clinical outcomes. Data on outpatient parenteral antimicrobial therapy (OPAT) treatment plan adherence are lacking. The purpose of this study is to determine the rate of nonadherence and factors associated with it. Methods. We surveyed patients discharged from a tertiary hospital on OPAT between February and August 2019 about their baseline characteristics, OPAT regimen, adherence, and experience with OPAT. Results. Sixty-five patients responded to the survey. The median age was 62 years, and 56% were male. The rate of reported nonadherence to intravenous (IV) antibiotics was 10%. Factors associated with nonadherence to IV antibiotics included younger age, household income of \u3c$20 000, and lack of time for administering IV antibiotics (30 vs 64 years, P \u3c .01; 83% vs 20%, P \u3c .01, and 33% vs 4%, P = .04, in the nonadherent vs adherent groups, respectively), while less frequent administration (once or twice daily) and having friend or family support during IV antibiotic administration were associated with better adherence (17% vs 76%, P \u3c .01, and 17% vs 66%, P = .03, in the nonadherent vs adherent groups, respectively). Most patients attended their infectious diseases clinic visits (n = 44, 71%), and the most commonly cited reasons for missing an appointment were lacking transportation (n = 12, 60%), not feeling well (n = 8, 40%), and being unaware of the appointment (n = 6, 30%). Conclusions. Less frequent antibiotic dosing and better social support were associated with improved adherence to OPAT. In contrast, younger age, lower income, and lack of time were associated with nonadherence
Increased Prevalence in Alzheimer Disease in the Northeast Tennessee Region of the United States
No full textThis study describes the changes in prevalence odds ratios (PORs) for Alzheimer disease (AD) in the northeast Tennessee region (NTR) during a 3-year period, describes the statistical assessment process, and critically assesses the database from which the statistical association was derived. The article also examines several beliefs pertinent to the clinical management of AD in the NTR from the perspective of professionals delivering services. Methods We extracted prevalence data for NTR counties for 2013, 2014, and 2015 from the Centers for Medicare & Medicaid Services Geographic Variation Public Use File. We used the crude prevalence and the 2010 US Census Data fixed population for each county to compute the POR. The 2013 Economic Research Service Rural-Urban Continuum Codes were used to identify rural and urban counties in the NTR. We collected primary data on the perceived observation of the increasing prevalence in the NTR during the last 3 years and barriers to early diagnosis through an online survey from 44 experts and professionals working in AD-related fields within the NTR. Results The PORs of AD in rural counties in NTR increased by 18.3%, 4.7%, and 19% compared with urban counties for 2013, 2014, and 2015, respectively. The POR of AD for the entire NTR region increased by 22.7%, 22.5%, and 21.2% compared with other regions in Tennessee for 2013, 2014, and 2015, respectively. Compared with 2012, 68.4% of respondents currently work with more individuals with AD; 71.8% reported that the NTR has a higher number of late-stage diagnoses of AD. A total of 92.3% strongly agreed that early detection of AD is important, and 95% agreed that early diagnosis could prolong the lives of patients with AD; 51.2% were unaware of existing AD screening services. Reported barriers were denial, lack of patient awareness, inefficient screening methods, communication, and lack of community resources. Conclusions Increased prevalence of AD among inhabitants in the NTR and identified barriers to early screening or diagnosis in the management of AD were identified. Access to early screening techniques must be prioritized in deprived areas within the NTR. Healthcare providers and medical professionals in the NTR must be well equipped with the required training and resources to respond adequately to the increasing prevalence of AD
Identifying priority student leadership and professionalism attributes among faculty, preceptors, and students via modified delphi
No full textObjective. To identify and build consensus on priority leadership and professionalism attributes for pharmacy student development among faculty, preceptors, and students. Methods. One hundred individuals (27 faculty members, 30 preceptors, 43 students) were invited to participate in a three-round, modified Delphi. Published literature on leadership and professionalism informed the initial attribute list. In the first round, participants reviewed and provided feedback on this list. In the second round, participants prioritized attributes as highly important, important, or less important for pharmacy student development. Leadership and professionalism attributes that achieved an overall consensus (a priori set to ≥80.0%) of being highly important or important for pharmacy student development were retained. In the third round, participants rank ordered priorities for leadership and professionalism attributes. Results. Fifteen leadership and 20 professionalism attributes were included in round one while 21 leadership and 21 professionalism attributes were included in round two. Eleven leadership and 13 professionalism attributes advanced to round three. Consensus was reached on the top four leadership attributes (adaptability, collaboration, communication, integrity) and five professionalism attributes (accountability, communication, honor and integrity, respect for others, trust). Differences were observed for certain attributes between faculty members, preceptors, and/or students. Conclusion. The modified Delphi technique effectively identified and prioritized leadership and professionalism attributes for pharmacy student development. This process facilitated consensus building and identified gaps among stakeholders (ie, faculty, preceptors, students). Identified gaps may represent varying priorities among stakeholders and/or different opportunities for emphasis and development across classroom, experiential, and/or cocurricular settings
A user-centered, learning asthma smartphone application for patients and providers
No full textProblem: Smartphone applications are an increasingly useful part of patients\u27 self-management of chronic health conditions. Asthma is a common chronic health condition for which good self-management by patients is very helpful in maintaining stability. User-centered design and intelligent systems that learn are steps forward in building applications that are more effective in providing quality care that is scalable and tailored to each patient. Methods: A literature and application store search to review historic and current asthma smart phone applications. User-centered design is a methodology that involves all stakeholders of a proposed system from the beginning of the design phase to the end of installation. One aspect of this user-centered approach involved conducting focus groups with patients and health care providers to determine what features they desire for use in applications and create a model to build smart infrastructure for a learning health care system. A simple prototype for an asthma smartphone application is designed and built with basic functionality. Outcomes: Only one publication in the literature review of asthma smartphone applications describes both user-centered design and intelligent learning systems. The authors have presented a set of user-desired attributes for a smart health care application and a possible data flow diagram of information for a learning system. A prototype simple user-centered designed asthma smartphone application that better assists patients in their care illustrates the value of the proposed architecture. Discussion: Our user-centered approach helped design and implement a learning prototype smart phone application to help patients better manage their asthma and provide information to clinical care providers. While popular in other industries, user-centered design has had slow adoption in the health care area. However, the popularity of this approach is increasing and will hopefully result in mobile application that better meets the needs of both patients and their care providers
The analgesic potential of glycosides derived from medicinal plants
No full textPain represents an unpleasant sensation linked to actual or potential tissue damage. In the early phase, the sensation of pain is caused due to direct stimulation of the sensory nerve fibers. On the other hand, the pain in the late phase is attributed to inflammatory mediators. Current medicines used to treat inflammation and pain are effective; however, they cause severe side effects, such as ulcer, anemia, osteoporosis, and endocrine disruption. Increased attention is recently being focused on the examination of the analgesic potential of phytoconstituents, such as glycosides of traditional medicinal plants, because they often have suitable biological activities with fewer side effects as compared to synthetic drugs. The purpose of this article is to review for the first time the current state of knowledge on the use of glycosides from medicinal plants to induce analgesia and anti-inflammatory effect. Various databases and search engines, including PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar, were used to search and collect relevant studies on glycosides with antinociceptive activities. The results led to the identification of several glycosides that exhibited marked inhibition of various pain mediators based on different well-established assays. Additionally, these glycosides were found to induce most of the analgesic effects through cyclooxygenase and lipoxygenase pathways. These findings can be useful to identify new candidates which can be clinically developed as analgesics with better bioavailability and reduced side effects. [Figure not available: see fulltext.]
Targeting CD47 as a novel immunotherapy for multiple myeloma
No full textMultiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me” signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients
Is it time for a quality rating system for colleges of pharmacy?
No full textThe quality of educational programs, including Doctor of Pharmacy (PharmD) programs, has largely escaped the societal trend towards public reporting. Recent criticisms of pharmacy academia by practitioners should prompt us to reexamine how the quality of pharmacy education is measured and reported to the public. In supporting greater transparency related to quality, important questions that should be addressed include: Is the current public reporting of quality indicators for pharmacy schools sufficient for determining the quality of education provided by a school? Can a quality rating system be developed that will not only provide a valid assessment of quality, but also be easy to interpret by potential applicants and employers? The intent of this commentary is to initiate a discussion centered around this issue and to encourage the development of a new measure of pharmacy school quality
Pharmacy practice faculty and preceptor development
No full textFaculty development is a priority for colleges and schools of pharmacy for both corporate and individual success. Recommendations in the 2008 American College of Clinical Pharmacy (ACCP) position statement and white paper on faculty development remain relevant today. However, changes in educational standards, delivery of pharmacy education, and faculty and learners have prompted an update of the 2008 documents. This 2020 white paper focuses on three components: preceptor development, updates in pharmacy practice faculty development, and program formation and implementation. The paper provides evidence and recommendations for preceptor development and summarizes the literature updates related to pharmacy practice faculty development in several areas, including teaching, practice, and research. This update explores additional topics not emphasized in the previous paper, including faculty well-being, holistic career-long development, and challenges with implementing and assessing development programs