Manual vs. Mechanical Chest Compressions in Out-of-Hospital Cardiac Arrest

Objective: The objective was to conduct an analysis of literature that examined whether the use of mechanical vs. manual chest compressions results in outcomes (e.g. quality of CPR, return of spontaneous circulation (ROSC), neurologic outcome, survival) that are significantly increased or decreased in adults that experienced out of hospital cardiac arrest (OHCA). Methods: Systematic searches were conducted through the James Madison University Library. The inclusion criteria included human adults that experienced out of hospital cardiac arrest that were treated by Emergency Medical Services (EMS) with and/or without a mechanical chest compression device. Results: A statistically significant difference was not found between the manual chest compression study arm and the automated chest compression study arm. Conclusion: Because P-values were not statistically significant, when comparing manual to automated chest compressions, the researchers were unable to confidently state recommendations. However, there was moderate clinical significance for improved outcome with manual chest compressions

Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

<p>Abstract</p> <p>Background</p> <p>Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor.</p> <p>Methods</p> <p>The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry.</p> <p>Results</p> <p>Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm³vs. 1195 ± 84 mm³, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg.</p> <p>Conclusions</p> <p>CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis.</p

Yeast Bxi1p/Ybh3p is a pH-sensitive calcium channel in Escherichia coli.

Amanda Raffa ’21 Major: Biology John Kalhorn ’21 Major: Biology Faculty Mentor: Fr. Nicanor Austriaco, Biolog

Rationale for Stereotactic Body Radiation Therapy in Treating Patients with Oligometastatic Hormone-Naïve Prostate Cancer

Despite advances in treatment for metastatic prostate cancer, patients eventually progress to castrate-resistant disease and ultimately succumb to their cancer. Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer and has been shown to improve median time to progression and median survival time. Research suggests that castrate-resistant clones may be present early in the disease process prior to the initiation of ADT. These clones are not susceptible to ADT and may even flourish when androgen-responsive clones are depleted. Stereotactic body radiation therapy (SBRT) is a safe and efficacious method of treating clinically localized prostate cancer and metastases. In patients with a limited number of metastatic sites, SBRT may have a role in eliminating castrate-resistant clones and possibly delaying progression to castrate-resistant disease

CyberKnife® enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

<p>Abstract</p> <p>Introduction</p> <p>With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma.</p> <p>Methods</p> <p>Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife^®image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide.</p> <p>Results</p> <p>During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients.</p> <p>Conclusion</p> <p>We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.</p

A Francisella Mutant in Lipid A Carbohydrate Modification Elicits Protective Immunity

Francisella tularensis (Ft) is a highly infectious Gram-negative bacterium and the causative agent of the human disease tularemia. Ft is designated a class A select agent by the Centers for Disease Control and Prevention. Human clinical isolates of Ft produce lipid A of similar structure to Ft subspecies novicida (Fn), a pathogen of mice. We identified three enzymes required for Fn lipid A carbohydrate modifications, specifically the presence of mannose (flmF1), galactosamine (flmF2), or both carbohydrates (flmK). Mutants lacking either galactosamine (flmF2) or galactosamine/mannose (flmK) addition to their lipid A were attenuated in mice by both pulmonary and subcutaneous routes of infection. In addition, aerosolization of the mutants (flmF2 and flmK) provided protection against challenge with wild-type (WT) Fn, whereas subcutaneous administration of only the flmK mutant provided protection from challenge with WT Fn. Furthermore, infection of an alveolar macrophage cell line by the flmK mutant induced higher levels of tumor necrosis factor-α (TNF-α) and macrophage inhibitory protein-2 (MIP-2) when compared to infection with WT Fn. Bone marrow–derived macrophages (BMMø) from Toll-like receptor 4 (TLR4) and TLR2/4 knockout mice infected with the flmK mutant also produced significantly higher amounts of interleukin-6 (IL-6) and MIP-2 than BMMø infected with WT Fn. However, production of IL-6 and MIP-2 was undetectable in BMMø from MyD88−/− mice infected with either strain. MyD88−/− mice were also susceptible to flmK mutant infection. We hypothesize that the ability of the flmK mutant to activate pro-inflammatory cytokine/chemokine production and innate immune responses mediated by the MyD88 signaling pathway may be responsible for its attenuation, leading to the induction of protective immunity by this mutant

Simultaneous pharmacokinetic and pharmacodynamic analysis of 5α-reductase inhibitors and androgens by liquid chromatography tandem mass spectrometry

AbstractBenign prostatic hyperplasia and prostate cancer can be treated with the 5α-reductase inhibitors, finasteride and dutasteride, when pharmacodynamic biomarkers are useful in assessing response. A novel method was developed to measure the substrates and products of 5α-reductases (testosterone, 5α-dihydrotestosterone (DHT), androstenedione) and finasteride and dutasteride simultaneously by liquid chromatography tandem mass spectrometry, using an ABSciex QTRAP® 5500, with a Waters Acquity™ UPLC. Analytes were extracted from serum (500µL) via solid-phase extraction (Oasis® HLB), with 13C3-labelled androgens and d9-finasteride included as internal standards. Analytes were separated on a Kinetex C18 column (150×3mm, 2.6µm), using a gradient run of 19min. Temporal resolution of analytes from naturally occurring isomers and mass +2 isotopomers was ensured. Protonated molecular ions were detected in atmospheric pressure chemical ionisation mode and source conditions optimised for DHT, the least abundant analyte. Multiple reaction monitoring was performed as follows: testosterone (m/z 289→97), DHT (m/z 291→255), androstenedione (m/z 287→97), dutasteride (m/z 529→461), finasteride (m/z 373→317). Validation parameters (intra- and inter-assay precision and accuracy, linearity, limits of quantitation) were within acceptable ranges and biological extracts were stable for 28 days. Finally the method was employed in men treated with finasteride or dutasteride; levels of DHT were lowered by both drugs and furthermore the substrate concentrations increased

Analysis and Interpretation of Factors Leading to Increased AIDS Prevalence in Sub-Saharan Africa

My thesis research project focuses on the major factors that are contributing to the worst disease epidemic on the planet today. I have aimed to determine what may be some of the most important factors contributing to highly variable difference in HIV/AIDS prevalence rates are among the regions of East, West, and South Africa. The HIV/AIDS epidemic has been growing and expanding to new areas of the world since the first case arose in 1959 in what is now called Kinshasa, Congo (Avert, 2011). The AIDS/HIV epidemic is believed to have originated on the African continent, and this is where the disease is currently causing the most problems (Avert, 2011). In particular, Sub-Saharan Africa is experiencing disease prevalence rates unlike anywhere else in the world (Avert, 2011). In order for the countries being most impacted by HIV to begin reversing the effects of this disease on their country, it is important to know which factors could be potentially the most important to do so. For comparison, this project focuses on three Sub-Saharan countries that are currently experiencing varying rates of HIV/AIDS disease prevalence. The country of Zimbabwe, located in Southern Africa, has one of the highest HIV/AIDS prevalence rates in the world. By comparing Zimbabwe with the East African country of Kenya, as well as the West African country of Ghana, I will be able to establish what some clear differences are between these three distinct regions of Africa

Preserving Pastoralism: Exploring the Role of Ecotourism in Kenya's Pastoral Rangelands

Pastoralism is one of the oldest sociocultural and economic practices of humankind. It has endured for hundreds of years against all odds, but is now diminishing as a livelihood possibility given the current social, political, economic, and literal climate.  This paper seeks to analyze the potential role of ecotourism in addressing the challenges facing pastoral livelihoods and wildlife in Sub-Saharan Africa, with a focus on northern Kenya. This question is addressed primarily through an examination of existing literature, supplemented with empirical examinations of existing models and their insights through my own on site interviews with pastoralists, different level employees in conservancies, tourism operators, as well as government officials across three counties in northern Kenya: Laikipia, Isiolo, and Samburu. The paper begins by laying out the framework of pastoralism, its synergies with wildlife, and the current challenges threatening the traditional livelihood in Sub-Saharan Africa. The following chapter explores this similar framework, with the focus being on the pastoralists and wildlife in Kenya. This chapter introduces two of the largest styles of conservation: national parks and game reserves, and explains their limitations in integrating pastoralists. Chapter 3 introduces the more community-centric conservation option that has gained traction in northern Kenya: the conservancy model, colloquially known as ‘ecotourism'. The different types of conservancy models are laid out, followed by examples of existing models and their respective evaluations on criteria examining commercial viability, conservation efficacy, community integration, as well as additional lessons. Finally, Chapter 4 discusses the potential role for ecotourism for preserving the pastoral livelihood in addition to wildlife populations, and the best practices of potential conservancy models moving forward.