1997 research outputs found
Sort by
Coxiella burnetii infection upregulates enzyme cycloxygenase-2 gene expression in alveolar macrophages
No full textCoxiella burnetii is an obligate intracellular Gram-negative bacterium that causes Q fever in humans. While acute infection manifests as self-limiting flu-like illness, chronic Q fever presents as non-culturable endocarditis, which is fatal if untreated. Although Coxiella spreads via inhalation and initially infects alveolar macrophages, it survives in the host long-term and may spread to the heart and cause endocarditis. The occurrence of Coxiella endocarditis up to 20 years after initial infection suggests that the bacterium persists in the host and subverts several host cell processes to promote infection. Our overall goal is to identify specific host cell pathways that Coxiella manipulates to achieve long-term intracellular survival. Previous studies in Coxiella endocarditis patients reported increased production of the lipid immune mediator prostaglandin E2 (PGE2), which subsequently promoted Coxiella growth. Our preliminary studies in infected alveolar macrophages reveal an increase in PGE2 production, suggesting its importance during Coxiella infection. Hence, we hypothesize that targeting PGE2 production in Coxiella-infected cells prevents bacterial intracellular growth. Since PGE2 production is directly proportional to the expression and activity of the enzyme cyclooxygenases (Cox), we first determined the gene expression of constitutively expressed Cox-1 and infection-induced Cox-2. Our studies show that Coxiella infection increases Cox-2 gene expression and not Cox-1, suggesting the importance of Cox-2-derived PGE2 production in Coxiella-infected cells. Ongoing studies are determining Cox-2 enzymatic activity in infected cells. Future studies will deter-mine the potential of Cox-2 as a therapeutic target to prevent Coxiella\u27s long-term survival and thus treat endocarditis
Catholic Medical Conscience App
No full textIntroduction: The Catholic medical ethic is supported by a rich intellectual tradition and remains foundational to the practice of medicine, especially within Catholic hospitals. In the US, the United States Conference of Catholic Bishops’ Ethical and Religious Directives for Catholic Health Care Services (ERDs) is the cornerstone for practical application of ethical principles in a healthcare setting. A major barrier to said application remains, due to a lack of education regarding the ERDs and formal ethical reasoning. Objective: The purpose of this project is to create and maintain an application that presents common ethical dilemmas and walks the user through them by asking pertinent questions to elicit the central ethical questions. The goal is to inform the medical conscience and teach ethical reasoning. Methods: The application is organized in like manner to the ERDs with three distinct parts: Beginning of Life, During Life, and End of Life. Within each part are various relevant scenarios. Selecting a scenario begins a series of ‘yes or no’ questions aimed at guiding the provider through the unfamiliar waters of ethical decision making while they steer the ship with their medical knowledge. With the specific medical details relevant to the case, the provider ‘fills in the blanks’ and the application is able to make a moral recommendation based on scenario and the ethical tradition of the Church. Each question contains relevant citations/links and comments that provide further reasoning regarding the question and why it is important in getting to the crux of the matter at hand. Results: The application is currently available as Catholic Medical Conscience App on iOS and Android platforms. It features an easy to use interface that includes the ability to search by topic. This tool is free to use and capable of being updated and expanded upon by medical ethics experts. It has received a nihil obstat by Fr. C. Ryan McCarthy, censor liborum of the Archdiocese of Indianapolis. Conclusions: The application is a robust and adaptable tool for guiding physicians in ethical decision making for real-world scenarios. Backed by the immense moral tradition of the Catholic Church, it provides easy to follow logic and supplementary re-sources to not only parse particular questions, but also delve deeper into medical ethics in general
What is OMT’s Effect on the Autonomic Nervous System?
No full textParaspinal inhibition is an osteopathic manipulative treatment (OMT) purported to work via the sympathetic nervous system and aid in restoring autonomic homeostasis. Despite clinical anecdotal evidence, the mechanism of action has not been robustly evaluated. This study tested the hypothesis that OMT acutely alters the autonomic nervous system (ANS) and that the effects of OMT would be more pronounced in excited states. Because direct measures of ANS are difficult to assess in human in vivo studies, static and dynamic measures of ANS-mediated end-organ responses were quantified. These included beat-by-beat heart rate, arterial blood pressure, arm and forehead skin blood flow, and stroke volume as well as calculations of systemic and cutaneous vascular resistance/conductance and cardiac output. To determine if the excited state modulates ANS effects or restores autonomic homeostasis, participants were tested in a resting supine position and a 60° head-up tilt. Head-up tilt was performed via a tilt table to reduce physiological adjustments associated with volitional standing. Nineteen apparently healthy (health history and vital sign assessment) individuals participated in this randomly assigned cross-over designed study. The protocol consisted of supine baseline, OMT, and recovery for one session then supine baseline, tilt baseline, tilt OMT, and supine recovery for the other. Each data segment was recorded for 6 minutes to allow for fast Fourier and transfer function analysis of beat-by-beat data. No differences were noted between variables when comparing the supine baselines, indicating baselines were similar for both trials. During neutral conditions OMT decreased the heart rate and increased stroke volume but did not alter the cardiac output or any other measured variable. Excitation was observed with head-up tilt as identified by a) increases in arterial blood pressure and heart rate, b) decreases in stroke volume and cutaneous vascular conductance, and c) no change in systemic vascular resistance and cardiac output. During sympathoexcitatory conditions no static differences were observed during OMT. Dynamic analysis of systolic blood pressure, R-to-R, and skin blood flow interval yielded some condition and treatment trends and effects in both the low and high frequency ranges. Low frequency ranges are often linked to sympathetic nervous system, while high frequency changes are often linked to the parasympathetic nervous system, or a combination of the two branches of the ANS. This may indicate that the ANS is being altered by OMT, but these control system changes are complex and not always manifested in static averages. Thus, studies involving OMT influences on the ANS and associated variables need to account for these complexities, especially with regard to background sympathetic tone, hemostasis, and neural reflexes when evaluating mechanisms of action and associated physiological effects
TILT Your Assignments – Transparency in Learning & Teaching
Get PDFTransparency in Teaching and Learning (TILT) is an easy, practical way to start creating transparent assignments for students. The framework is a part of a national study that has shown making your assignments transparent using the TILT method increases a sense of belonging, academic confidence, higher quality of student work, as well as many other factors that impact learning. For more, go to https://tilthighered.com
Dysfunctional Stem and Progenitor Cells Impair Fracture Healing with Age
Get PDFSuccessful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly
Individualized exercise and the health of the AYA cancer survivor population
No full textObjective Adolescent and young adult cancer survivors (AYACS: ages 15-39) have an 84.5% five -year survival rate. AYACS have a 10 times greater risk to develop cardiac disease compared to healthy peers. This is in part due to their lower physical activity. Structured exercise in adult cancer survivors improves strength, fatigue, VO2, and antioxidant levels and it decreases markers of cellular damage. AYACS could benefit similarly, reducing long-term health effects. Although evidence suggests exercise is beneficial in older cancer survivors, this has not been demonstrated in AYACS. We hypothesized that a 12-week one-on-one multi-modal, community-based exercise program would improve AYACS outcomes compared to baseline or inactive AYACS. The current study hopes to demonstrate the feasibility of an exercise intervention in a community setting within Indianapolis. Methods Six individuals were included in a feasibility trial for a larger pilot study of 374 participants. On day 1, baseline assessments were performed for experimental outcomes: body composition, strength, flexibility, VO2peak, balance, plasma biomarkers, PA, psychological health, health-related quality of life, and fatigue. Mini reassessments were performed at week 5, measuring strength and VO2peak with an estimated 1-rep maximum and 6-minute Walk Test respectively; in the larger pilot study participants will be reassessed at weeks 12 and 24. Participants train for 60 minutes (20 cardio, 30 weights, 10 stretching) 3 times a week for 12 weeks, one-on-one with a cancer exercise specialist. Results The average change in VO2peak was +25.3% and in strength was +17.5% (no statistical analysis). Adherence was 90.9%. Conclusions This trial suggests the feasibility of a pilot larger study. The greatest limitation was that the population sample was not within the AYACS age range. However, as the goal was to show feasibility rather than to prove efficacy, the sample gave useful information
Autocrine Notch receptor 3 signaling stimulates the proliferation and enhances the osteoclastogenic potential of multiple myeloma cells
No full textIntroduction. Multiple myeloma (MM) is a hematological cancer characterized by the expansion and accumulation of monoclonal malignant plasma cells in the bone marrow (BM). Interactions between MM cells and cells of the bone/BM niche play a critical role in MM onset and progression by promoting tumor growth, bone destruction, and resistance to therapy. We found that, upon contact with osteocytes, MM cells exhibit increased Notch signaling, a rapid upregulation of Notch receptor (NR) 3 expression, and increased proliferation rates. However, whether NR3 signaling contributes to MM cell proliferation, communication with osteocytes, and resistance to therapy is unknown. Objective. The goal of this study was to characterize the effects of the genetic deletion of NR3 in 5TGM1 MM cells on MM cell proliferation, viability, and response to anti-MM agents. Methods. Murine 5TGM1 MM cells were transduced with lentiviral particles containing shRNA-scramble (control) or shRNAs targeting NR3 and were selected with puromycin. 5TGM1 cells transduced with shRNA-NR3 clone 1 exhibited a 50-60% decrease in NR3 mRNA expression and were selected for follow up studies. To study the consequences of NR3 silencing in MM cell function we used MTT and Trypan Blue exclusion assays, and RT-qPCR. Results. NR3 expression was undetectable in MM cells transduced with shRNA-NR3, whereas the expression of NR1 and NR2 remained unchanged compared to control cells. In addition, NR3 silencing significantly decreased the mRNA expression of Notch target genes and the pro-osteoclastogenic cytokine Rankl. NR3-silenced cells displayed a 15%, 25%, and 35% reduction in cell proliferation/number after 24h, 48h, and 72h of culture compared to control cells. These effects were associated with modest increases in the number of NR3-silenced dead cells (2% vs 10%, control vs shNR3, respectively). Next, we evaluated the response to treatment with a gamma-secretase inhibitor (GSI) and bortezomib (BTZ), anti-MM agents, in both control and NR3- silenced cells. 72h treatment with GSI induced a 20-25% decrease in cell number and a 2-fold increase in cell death in both control and NR3-silenced cells. Treatment with GSI reduced the expression of Notch target genes, cyclin D1, and Rankl similarly in both control and NR3-silenced cells. In contrast, GSI did not affect the expression of NR1, 2 and 3. BTZ equally decreased (20-25%) the number/proliferation of control and NR3-silenced cells, an effect accompanied by a 2-fold increase in cell death in both cell lines. Conclusions. Our findings support that autocrine NR3 signaling in MM cells drives proliferation, favors survival, and enhances their osteoclastogenic potential by increasing Rankl expression. NR3 silencing did not alter the anti-MM efficacy of BTZ, suggesting that other NRs may contribute to Notch-mediated drug resistance in MM. Future studies will analyze the role of NR3 signaling in the communication between MM cells and osteocytes
3D Modeling of a Kidney Transplant: Pre-Operative Patient Education
No full textKidney transplantation is a major surgical intervention and patients undergoing counseling for this procedure do not always fully understand the essentials of this procedure. We present an improved way to facilitate patient education by creating a visual aid that can be used to supplement physician counseling in patients considering kidney transplantation. We used anonymized CT scans and image analysis software to compute anatomical renderings of normal kidney anatomy as well as the anatomical differences in a patient before and after a kidney transplant. These 3D renderings were animated to create a basic educational video explaining the procedure to candidate patients
The Use of Direct-to-Consumer Genetic Testing in Evaluation of Genetic Disease Risk Perception
No full textIntroduction: 23andMe provides consumers the opportunity to receive genetic information without involvement of a healthcare provider. As 23andMe continues to increase the number of variants and genetic diseases included in their health predisposition and carrier status reports, it is becoming apparent that direct-to-consumer genetic testing will play a role in the future of preventative medicine. Objective: The goal of this study is to gain knowledge of how participants interpret their own genetic information, their perceived risk of developing a genetic disease, and their perceived risk of passing a genetic disease to offspring. Methods: Thirty-two participants were sought to participate in the study. Participants were divided into four categories based on their experience in the biomedical sciences. A “gold standard” group composed of genetic counselors was used as a control. Partic-ipants were asked to complete 23andMe’s Health + Ancestry package. After reviewing their genetic results, participants completed a questionnaire analyzing how they interpreted their results and how they might use their results in the future. Results: Preliminary results demonstrate that most participants have a basic under-standing of genetic concepts and inheritance patterns of genetic disease. However, less comprehension of genetic reports was observed when participants were asked about specific genetic diseases and/or tested variants. Participants did not report a high level of concern for developing a genetic disease or passing a genetic disease to offspring and reported they do not plan to consult a genetic counselor about their results at this time. Further, participants reported high self-efficacy with interpreting their results. Conclusions: Preliminary findings demonstrate that while most participants under-stand basic genetic concepts and inheritance patterns, their comprehension of more detailed genetic concepts is lower when compared to genetic counselors. When combined with a high reported self-efficacy with the presented genetic information, participants may feel falsely-reassured by their results
Intramuscular versus Subcutaneous Injections of Testosterone in Transgender Men
No full textHormone replacement therapy (HRT) is a common treatment for gender dysphoria, a condition where a person’s gender assigned at birth does not match their gender identify. For transgender men seeking to achieve virilization, HRT is included in the standard of care as set forward by the World Professional Association for Transgender Health (WPATH). There are several routes of HRT administration including injection, pellet, gel, and patch. Many transgender men opt for the injectable testosterone for a variety of reasons including cost, insurance coverage, and impact on lifestyle. While the WPATH standards of care do include injectable testosterone as one of the HRT options, only intramuscular injections are mentioned in the most recent edition of standards published in 2012. Research has been put forth within the last several years exploring the effectiveness of not only intramuscular injections, but also subcutaneous injections. Though intramuscular injections continue to be the standard route by which testosterone is administered, there is substantial research that subcutaneous injections are equally, if not more, effective with a much higher patient preference. This primary literature review focuses primarily on the injectable methods of HRT and directly com-paring the effectiveness of intramuscular and subcutaneous testosterone for transgender men