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Objective: Oxaloacetate (OAA) is a long-known potent inhibitor of succinate dehydrogenase (SDH), a phenomenon that has, however, received only limited attention. We previously found that skeletal muscle mitochondria incubated at low membrane potential (Δψ) or interscapular brown adipose tissue (IBAT) mitochondria, wherein Δψ is intrinsically low, accumulate OAA in amounts sufficient to inhibit SDH (complex II) respiration. We proposed a mechanism wherein low Δψ reduces reverse electron transport (RET) to complex I causing a low NADH/NAD+ ratio favoring malate conversion to OAA. To further assess the mechanism and its physiologic relevance we carried out studies of mice with inherently different levels of IBAT mitochodnrial inner membrane potential. Hypothesis: Mice with differential expression of UCP1 would manifest Δψ-dependent differences in OAA-regulated mitochondrial respiration. Methodology: We examined several parameters in complex II and complex I energized IBAT mitochondria isolated from obesity prone C57BL/6J compared to obesity resistant 129SVE mice and from UCP1 knock-out (UCP1KO) compared to wildtype (WT) mice. Data were analyzed by unpaired, 2-tailed t-test and expressed as mean ± SE. Data: Isolated complex II (succinate)-energized IBAT mitochondria from 129SVE mice versus C57BL/6J displayed greater UCP1 expression, similar O2 flux despite lower Δψ, similar OAA concentrations, and similar NADH/NAD+. When GDP was added to inhibit UCP1, 129SVE IBAT mitochondria, despite their lower Δψ, exhibited much lower respiration (AUC of respiration versus time, 19963 ± 1764 vs 36015 ± 2527, p = 0.0004, n = 6), greater OAA concentrations (22.9 ± 1.8 vs 12.1 ± 3.3, p = 0.016, n = 6), much lower RET (as marked by ROS), and much lower NADH and NADH/NAD+ ratios compared to the C57BL/6J IBAT mitochondria. UCP1 knock-out abolished OAA accumulation by succinate-energized mitochondria associated with markedly greater Δψ, ROS, and NADH, but equal or greater O2 flux compared to WT mitochondria. GDP addition, compared to no GDP, increased Δψ and complex II respiration in WT mice associated with much less OAA. Respiration on complex I substrates for mitochondria of both strains of mice and for WT and UCP1KO mice followed the more classical dynamics of greater O2 flux at lower Δψ. Summary: These findings support the above-mentioned mechanism for OAA- and Δψ-dependent complex II respiration and support its physiologically relevance. Conclusions: Oxaloacetate regulates mitochondrial complex II dynamics in a manner dependent on inner membrane potential as intrinsically determined by mouse strain or genetic manipulation. NIH award, 1 R01 DK123043-01A1, VA Merit Review Award 2 I01 BX000285-06, and the Iowa Fraternal Order of the Eagles This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Supplementary Tables 1-3, Figure Legends 1-6 from Antitumor and Antiangiogenic Activities of BMS-690514, an Inhibitor of Human EGF and VEGF Receptor Kinase Families

Purpose: The extensive involvement of the HER kinases in epithelial cancer suggests that kinase inhibitors targeting this receptor family have the potential for broad spectrum antitumor activity. BMS-690514 potently inhibits all three HER kinases, and the VEGF receptor kinases. This report summarizes data from biochemical and cellular pharmacology studies, as well as antitumor activity of BMS-690514.Experimental Design: The potency and selectivity of BMS-690514 was evaluated by using an extensive array of enzymatic and binding assays, as well as cellular assays that measure proliferation and receptor signaling. Antitumor activity was evaluated by using multiple xenograft models that depend on HER kinase signaling. The antiangiogenic properties of BMS-690514 were assessed in a matrigel plug assay, and effect on tumor blood flow was measured by dynamic contrast-enhanced MRI.Results: BMS-690514 is a potent and selective inhibitor of epidermal growth factor receptor (EGFR), HER2, and HER4, as well as the VEGF receptor kinases. It inhibits proliferation of tumor cells with potency that correlates with inhibition of receptor signaling, and induces apoptosis in lung tumor cells that have an activating mutation in EGFR. Antitumor activity was observed with BMS-690514 at multiple doses that are well tolerated in mice. There was evidence of suppression of tumor angiogenesis and endothelial function by BMS-690514, which may contribute to its efficacy.Conclusions: By combining inhibition of two receptor kinase families, BMS-690524 is a novel targeted agent that disrupts signaling in the tumor and its vasculature. Clin Cancer Res; 17(12); 4031–41. ©2011 AACR.

Supplementary Figures 1-6 from Antitumor and Antiangiogenic Activities of BMS-690514, an Inhibitor of Human EGF and VEGF Receptor Kinase Families

"Run-Hide-Fight" is the summative life-saving mantra taught by governmental and private agencies in active shooter training. Initial research focused on patient expectations of health care provider responses in life-threatening situations suggests patients believe health care providers will take significant action to protect patient well-being. The potential disparity between expectations of the public and health care practitioner training must be examined, as conflict, confusion, and delays may have mortal consequences in active shooter situations.Public perceptions of the extent of health care practitioners' duties and responsibilities to themselves and their patients during an active shooter event were investigated.A survey that queried perceived expectations of health care provider response efforts in 4 emergency department patient case scenarios interrupted by an active shooter event was developed and implemented to patients and retinue of the University of Toledo Emergency Department. Responses were grouped into provider-centric or patient-centric actions.One hundred twenty-seven participants responded to the survey and were included in the analysis: 82 patients and 45 guests. In all 4 scenarios, a mean of 87.4% responses was patient-centric. Frequency of patient-centric responses differed significantly by scenario, and women were more likely to have patient-centric expectations.The public has significant expectations that the health care provider will assist them during active shooter situations. Providing for the security of the health care provider and patient simultaneously is in conflict with common hospital crisis training. Efforts must be taken to bring patient expectations and provider training into greater alignment.

This study was a retrospective analysis of inpatient and emergency department (ED) data on respiratory pathogen panel (RPP) testing between December 16, 2013, and December 15, 2015, at a mid-sized children’s hospital. We assessed whether RPP decreases antibiotic days of therapy and length of hospital stay for pediatric patients with acute respiratory infections. In the inpatient population, patients testing positive with RPP were given fewer antibiotic days of therapy (2.99 vs 4.30 days; P = .032) and had shorter hospital stays (2.84 vs 3.80 days; P = .055) than patients testing negative. In the ED population, patients testing positive with RPP received fewer discharge prescriptions for antibiotics than patients not tested (8.8% vs 41.1%; P < .001). RPP use was more prevalent in admitted patients than in ED patients (78.9% vs 7.3%; P < .001). Our results suggest that RPP testing curbs antibiotic use and decreases length of hospital stay.

Introduction:Herd immunity, a concept normally applied in vaccinated populations, is a preventative measure to determine if a significant portion of a population can protect vulnerable individuals against a certain disease. Like vaccines, tourniquet education can be a form of herd immunity to protect vulnerable individuals in a population and prevent the loss of life from a peripheral hemorrhage. The authors have identified a deficiency in simple, quick, and effective hemorrhage control education. Therefore, to maximize herd immunity, the novel educational platform evaluates the efficacy of “Just-in-Time” (JiT) tourniquet application training.Hypothesis/Problem:The authors hypothesize that the utilization of JiT training will be effective in promoting both competence and confidence for individuals to utilize tourniquets in response to a disaster environment.Methods:This Institutional Review Board-approved study recruited medical students who were trained in hemorrhage control measures at a Level 1 Trauma Center. Tourniquet training sessions were held, and naïve civilians received tourniquet education. The subjects received a five- to ten-minute lesson on indications, contraindications, and application techniques of commercial and improvisational tourniquets. Participants subsequently applied a tourniquet to an instructor’s arm to demonstrate proper tourniquet application for a brachial artery hemorrhage. Pre- and post-educational surveys were completed to test participant competency and confidence.Results:Of the 104 subjects who completed the course, 97 had no prior training in hemorrhage control techniques, including commercial and improvisational tourniquet application. The mean pre-test score was 2.27/5.00 and the mean post-test score was 4.38/5.00, P Conclusion:Just-in-Time training is an effective method in teaching naïve civilians proper tourniquet application. This platform could serve as an alternative to more extensive training programs and requires less time, costs, and resources. If a significant number of individuals in a local community can effectively apply a tourniquet in a disaster scenario, a “herd immunity” effect could be achieved to control peripheral hemorrhages.

[Image: see text] C-terminal Src kinase (CSK) functions as a negative regulator of T cell activation through inhibitory phosphorylation of LCK, so inhibitors of CSK are of interest as potential immuno-oncology agents. Screening of an internal kinase inhibitor collection identified pyridazinone lead 1, and a series of modifications led to optimized compound 13. Compound 13 showed potent activity in biochemical and cellular assays in vitro and demonstrated the ability to increase T cell proliferation induced by T cell receptor signaling. Compound 13 gave extended exposure in mice upon oral dosing and produced a functional response (decrease in LCK phosphorylation) in mouse spleens at 6 h post dose.

BackgroundOpen-book pelvic fractures are associated with significant mortality. Emergency management may require a commercial pelvic circumferential compression device to reduce the fracture and compress haemorrhaging pelvic vasculature. Standard, commercial, twin-sized bedsheets are acceptable should commercial devices be unavailable. However, obese victims or personnel with insufficient body strength may impede successful reduction.ObjectiveTo demonstrate the value of an improvisational windlass (intravenous pole) in improving the ability to reduce an open-book pelvic fracture.MethodsThe Institutional Review Board-approved study involved 28 diverse healthcare students and emergency medicine residents. Each participant’s demographic information and physical characteristics were recorded. A METIman was prepared with knee and ankle binding and a sphygmomanometer set at 40 mm Hg placed over the symphysis pubis. Two-person teams were randomly selected to place a bedsheet at greater trochanter level and atop the sphygmomanometer. The bedsheet was secured with maximum effort by the pairs and the pressure recorded. Following this, the pairs inserted an intravenous pole in the knot and torqued the pole to maximum effort and a repeat pressure recorded.ResultsThe mean increase in pressure using only the bedsheet was 106.43 mm Hg per team. With bedsheet and intravenous pole, the mean pressure increase was 351.79 mm Hg per team. The difference was statistically significant (independent samples t-test: t = 17.177, p < 0.001, 95% CI (216.65 to 274.07 mm Hg). There was no correlation between pressure increases and the individual physical characteristics of the subjects (r = − 0.183, p = 0.352).ConclusionsRegardless of personnel’s physical attributes, the addition of an improvisational windlass to a pelvic circumferential compression bedsheet can improve the ability to reduce an open-book fracture, especially in obese victims.

IntroductionWhile the art and science of disaster triage continue to evolve, the education of the US health care student in matters pertaining to disaster preparedness and response remains stifled. Unfortunately, these students will be assuming major decision-making responsibilities regarding catastrophes that will be complicated by climate change, nuclear threats, global terrorism, and pandemics. Meanwhile, Sort, Assess, Life-Saving Interventions, Treatment, and/or Transport (SALT) triage is being advocated over the globally popular Simple Triage and Rapid Treatment (START) algorithm for multiple reasons: (1) it’s an all-hazard approach; (2) it has four medical interventions; and (3) it has an additional triage color for victims with non-survivable injuries.Hypothesis/ProblemAs present-day threats become more ominous and health care education emphasizes the needs of vulnerable populations and palliative care, the authors hypothesize that, when given a choice, health care students will prefer SALT triage.MethodsA convenience sample of 218 interprofessional, disaster-naïve health care students received just-in-time, unbiased education on both START and SALT triage systems. Students then completed a survey asking them to decide which triage system they believe would be most effective in their community.ResultsA total of 123 health care students (56.4%) preferred SALT while 95 (43.6%) preferred START; however, only the physician assistant students showed a statistically significantly preference (28 versus six, respectively; P=.042). Interestingly, there was also a statistically significant difference in preference by gender (Chi-square=5.02; P=.025) of the observed distribution versus expected distribution in SALT and START. The females preferred SALT (61.0%) while the males preferred START (55.9%).Among those who preferred START, START being easier to learn was the most important reason cited. Among those who preferred SALT, the most important reason cited was that the number of patient triage categories seemed more logical, comprehensible, and consistent with traditional medical care.Conclusion:While SALT’s preference among females and physician assistant students was based on the addition of medical interventions and the provision of palliative care, START’s preference was related to expediency. Based on this research, incorporating disaster concepts into US health care students’ curricula encourages thoughtful consideration among the future health care leaders about the most effective approach to triage care. It is critical that further research be completed to determine, without reservation, which triage system will not only save the most lives but provide the most humane care to victims.Fink BN, Rega PP, Sexton ME, Wishner C. START versus SALT triage: which is preferred by the 21st century health care student? Prehosp Disaster Med. 2018;33(4):381–386

Background: Iontophoresis utilizes a transcutaneous process to deliver charged medication to a localized area of injury via an electrical current to remedy pain symptoms. Although this practice is largely used in the physical and occupational therapy settings, there is little evidence showing its use and efficacy in the emergency department as a therapeutic modality. Methods: Through the voluntary enrollment of 39-participants, 21 in the treatment group and 18 serving as controls, subjects were treated via iontophoresis using lidocaine-HCl and dexamethasone or oral NSAID therapy alone. Measurements of pain were numerated in person on the visual-analogue scale (VAS) using a 0-10 range immediately prior to treatment, 30 minutes after treatment, and via phone at 24 and 72-hours after treatment for both groups. Results: At the initiation of treatment, average pain scores for the treatment and control groups were 7.29 and 6.50, respectively. Greater reduction in pain was seen in the iontophoresis group compared to the control group; 62% pain reduction in the iontophoresis group and only 8% reduction in the control group at 30-minutes post-treatment (p

Introduction:The use of tourniquets by the civilian population has been deemed a critical aspect of the initial response during an active shooter situation. Tourniquet deployment in public-access must be accompanied by education. Studies indicate that the act itself is not an intuitive process and enclosed instructions may be inadequate. However, civilians for diverse reasons may not avail themselves of accepted training programs.Aim:To develop an alternative means of “Just-In-Time” education to enable a naïve responder to apply a commercial tourniquet efficaciously.Methods:A video (~40 seconds long) was created highlighting the actual application of a C-A-T® (Combat Application Tourniquet) on a human model. It was uploaded to YouTube on a public channel. A QR® code was generated using https://www.qr-code-generator.com, embedding the link for the YouTube® video. An appropriately-sized QR® code was printed and applied with packaging tape (Scotch®) to the exterior wrapping of a C-A-T® device. The C-A-T® with code was then accessed with the iPhone®.Results:With the iPhone® camera app activated and focused on the C-A-T’s QR® code, a request popped-up to open “YouTube.com” in Safari. When pressed, the full-screen video appeared immediately with audio of excellent quality.Discussion:The use of a QR® code and its video link is a feasible option to provide “Just-In-Time” training to a naïve civilian population who are responding to an active shooter situation. This offers the naïve responder two options of immediate education: the enclosed instructions and the QR® code. Redundancy in communications is essential in any emergency response. An important limitation of this innovation is the inability to obtain Internet® access and therefore, the availability of the enclosed instructions is still critical. Research to prove that this innovation will allow the application of a tourniquet to proceed expeditiously with few errors is currently underway.

Introduction:According to the Federal Bureau of Investigation (FBI), there were fifty active shooter incidents in 2016 and 2017. In the first five months of 2018, there have been 23 school shootings where someone was injured or killed. Hemorrhage-control tourniquets have proven their life-saving capability in the military and civilian EMS. Now, they are being advocated for use by civilians – the true “first responders.” Since Combat Application Tourniquets (CATs) are strap-and-windlass devices, the question remains whether a naïve population can intuitively apply them efficaciously.Aim:To determine the efficacy (speed, correct placement) of a CAT by an interprofessional group of healthcare students naïve to tourniquet hemorrhage control.Methods:Consenting students attempted to apply a CAT to a standardized patient with a simulated hemorrhaging brachial artery. No instruction was given except for the directions included in the package. Timing began upon removal of the tourniquet from the package and ended when the participants stated they completed their attempt. Errors in application were documented. Afterward, students received education and an opportunity to properly re-apply the tourniquet. The completion times of the students were compared to ten emergency medical technicians (EMT-P), serving as subject matter experts. Errors in application were categorized.Results:50 students from the following professions participated: Medicine, Nursing, Public Health, and Respiratory Therapy. The mean time of tourniquet application was 96.16 seconds (range: 25.12-226.31). This was statistically different from the EMT-Ps’ time of 42.83 seconds (range: 23.89-82.94). Additionally, only five (10%) placed the tourniquet correctly. Errors included improper location and windlass misuse or non-use. The instructions were frequently critiqued for being difficult to read and containing confusing graphics.Discussion:Provision of commercial tourniquets in public access areas must be accompanied by civilian education and the creation of CAT instructions that are simplistic, comprehensible, and suitably graphic.

Stewart and Khan’s overview on the clinical connection between a life-threatening pelvic fracture and the obesity pandemic highlights an important issue that is seldom considered in US emergency departments.[1][1] While the application of a commercial pelvic circumferential compression device may

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we utilized interview data from a population-based sample of 1,463 breast cancer cases and 1,500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was employed to account for biologically plausible nutrient pathways (one-carbon metabolism, oxidative stress, glycemic control and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the one-carbon metabolism, oxidative stress and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer.

Determine the safety experience of adult obstructive sleep apnea patients undergoing airway surgery.A retrospective cohort study.The experience of members of a large Medicaid managed care organization between January 10, 2009, and June 30, 2011.Four hundred fifty-two adult Medicaid obstructive sleep apnea (OSA) patients (404 ambulatory, 48 inpatient) receiving head and neck airway surgery form the basis of this report. Four safety indicators were reported from administrative data for 30 days: emergency room visit, inpatient admission, observation day, and 3 or more primary care physician visits. The occurrence of myocardial infarction, deep venous thrombosis, stroke, pulmonary embolism, tracheostomy, or transfusion was noted.Ninety-four percent of the nasal, 86% of the palatal, and 79% of the nasal/palatal surgeries (89% overall) were ambulatory. The observed catastrophic complication rate among ambulatory patients was zero (95% confidence interval, 0.0%-1.1%). Emergency room visits for pain-related diagnoses were the most common adverse outcome (51%). Administrative data sets can be used to provide insight into practice safety questions.Contrary to guidelines, most OSA patients underwent ambulatory head and neck airway surgery. The observed catastrophic complication rate was zero. Administrative data sets can be used to provide insight into practice safety questions. Further study is warranted of ambulatory surgery management of adult sleep apnea patients.

Background: Superintendents' perceptions regarding the effect of health insurance status on academics, the role schools should play in the process of obtaining health insurance, and the benefits/barriers to assisting students in enrolling in health insurance were surveyed. Superintendents' basic knowledge of health insurance, the link between health and learning, and specific school system practices for assisting students were also examined. Methods: A 4-page questionnaire was sent to a national random sample of public school superintendents using a 4-wave postal mailing. Results: Only 19% of school districts assessed the health insurance status of students. School districts' assistance in helping enroll students in health insurance was assessed using Stages of Change theory; 36% of superintendents' school districts were in the action or maintenance stages. The schools most often made health insurance materials available to parents (53%). The perceived benefits identified by more than 80% of superintendents were to keep students healthier, reduce the number of students with untreated health problems, reduce school absenteeism, and improvement of students' attention/concentration during school. The 2 most common perceived barriers identified by at least 50% of superintendents were not having enough staff or financial resources. Conclusions: Most superintendents believed schools should play a role in helping students obtain health insurance, but the specific role was unclear. Three fourths of superintendents indicated overwhelmingly positive beliefs regarding the effects of health insurance status on students' health and academic outcomes. School personnel and public policy makers can use the results to support collaboration in getting students enrolled in health insurance.

The use of highly active antiretroviral therapy (HAART) has decreased morbidity and mortality for people living with HIV/AIDS, but adherence to HAART is a critical factor in successful treatment. Adherence to medication is a complex and poorly understood behavior. A survey was undertaken to evaluate subjective correlates of adherence and non-adherence based on previously distilled themes from a qualitative study of adherence. A 60-question survey was completed by patients in the outpatient clinic setting regarding demographics, CD4 cell count, viral load, adherence, and screening questions about medication usage and attitudes toward HIV. Ninety-eight adherent and 34 non-adherent patients completed the survey. After logistic regression analysis, several questions appeared to be the main predictors of non-adherence: Have you ever thought of having HIV as a "punishment?" Do you feel that your medicines are hard to take? Do you believe the medicines for HIV that you take are working for you? These questions may be helpful in the development of a clinically useful screening tool to assess patients at risk for non-adherence.

Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival.Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n = 1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n = 173 deaths) and breast cancer–specific mortality (n = 113 deaths) were determined through the National Death Index.Results: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer–specific mortality only.Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2285–92)

Background Acute respiratory infection (ARI) is a leading cause of pediatric hospitalizations in the US and are generally caused by viruses, thus antibiotics are prescribed more often than needed. Identifying viral agents using the respiratory pathogen panel (RPP) can help with judicious use of antibiotics in hospitalized patients. ProMedica Toledo Children’s Hospital, a mid-sized pediatric hospital, began offering the RPP to patients in Dec 2014. This study was conducted to assess if the use of RPP would decrease the antibiotic days of therapy (DOT) and length of hospital stay for patients admitted for uncomplicated ARI and for those seen in the ED. Methods This was a retrospective analysis of pediatric hospital inpatient and ED data collected between December 16, 2013 and December 15, 2015. Patients before and after implementation of the RPP were compared. 299 and 263 pediatric patients between 1 month to 18 years of age with uncomplicated ARIs in the pre-RPP and post-RPP periods, respectively, were included for analysis. Similarly, 472 and 461 patients were included from the ED. Clinical data were collected by chart review. Analysis was performed using descriptive and inferential statistics. Results Out of 299 admitted patients in the post-RPP period, 63 (21.1%) patients did not receive the RPP (RPP-NT). 201 (67.2%) received it and tested positive (RPP-P), and 35 (11.7%) patients tested negative (RPP-N). RPP-N had an increased length of hospital stay (P = 0.055, borderline significance) and increased number of antibiotic DOT (P = 0.032) than RPP-P. Furthermore, we discovered that older patients (mean = 6.21 years) tested negative with RPP, while younger patients either did not receive the test (mean = 2.43 years) or tested positive (mean = 2.40 years). In the ED, RPP-P received fewer discharge prescriptions for antibiotics than RPP-N and RPP-NT (P < 0.01). The use of RPP was more prevalent in admitted patients than in ED patients (P = 0.01). Conclusion Our results suggest that the use of RPP effectively curbs unnecessary antibiotic use for pediatric patients with viral ARIs. Furthermore, age discrepancies among RPP-P, RPP-N, and RPP-NT warrant further study. Lastly, the results suggest that use of RPP in ED should be encouraged. Disclosures C. Zhu, IDSA Foundations Medical Scholars Program 2015–2016: Member, Educational scholarship.

Pandemic management involves strategic and tactical concepts rarely experienced with other disasters. To comprehend the enormity of these tasks and experience the critical decision-making required, local public health and other stakeholders participate in tabletop and functional exercises. Students in Master of Public Health (MPH) programs not only rarely experience this educational format, but also are seldom afforded substantive time to appreciate the critical decision making that is unique to pandemics. An immersive semester-long simulation exercise was created to educate graduate public health students about pandemics. Students in a MPH course were divided into groups representing county health departments. During the semester, students collaborated and completed incident command training, received audio lectures, and materials concerning an imminent pandemic. The students then participated in the 2.5-hr facilitated tabletop exercises in the classroom. A survey was developed to assess their perceptions of the experience. Most students felt more knowledgeable afterward and thought that this training style was innovative, entertaining, educational, and recommended it to fellow students and colleagues. The students believed that delivering a tabletop exercise in this fashion was educational and entertaining. It gave the students a better appreciation of the role of public health in managing the complexities associated with pandemics.

We previously reported an inverse association between flavonoid intake and breast cancer incidence, which has been confirmed by others, but no studies have considered simultaneously potential interactions of flavonoids with multiple genetic polymorphisms involved in biologically relevant pathways (oxidative stress, carcinogen metabolism, DNA repair, and one-carbon metabolism). To estimate interaction effects between flavonoids and 13 polymorphisms in these four pathways on breast cancer risk, we used population-based data (n = 875 cases and 903 controls) and several statistical approaches, including conventional logistic regression and semi-Bayesian hierarchical modeling (incorporating prior information on the possible biologic functions of genes), which also provides biologic pathway-specific effect estimates. Compared to the standard multivariate model, the results from the hierarchical model indicate that gene-by-flavonoid interaction estimates are attenuated, but more precise. In the hierarchical model, the average effect of the deleterious versus beneficial gene, controlling for average flavonoid intake in the DNA repair pathway, and adjusted for the three other biologically relevant pathways (oxidative stress, carcinogen metabolism, and one-carbon metabolism), resulted in a 27 % increase risk for breast cancer [odds ratio = 1.27; 95 % confidence interval (CI) = 0.70, 2.29]. However, the CI was wide. Based on results from the semi-Bayesian model, breast cancer risk may be influenced jointly by flavonoid intake and genes involved in DNA repair, but our findings require confirmation.

e18201Background: In April 2012, the American Society of Clinical Oncology (ASCO) published the first guidelines for dosing chemotherapy in obese patients. The guidelines recommend full weight-base...

Durable antibody production after vaccination or infection is mediated by long-lived plasma cells. Pathways that specifically allow long-lived plasma cells to persist remain unknown. Through bioenergetic profiling, we demonstrate that human and mouse long-lived plasma cells possess much greater mitochondrial spare respiratory capacity than do short-lived plasma cells. Inhibition of mitochondrial pyruvate import in long-lived plasma cells attenuates spare, but not basal respiration. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, leads to a progressive loss of long-lived plasma cells and vaccine-specific antibodies in vivo. Long-lived plasma cells uptake more glucose than do their short-lived counterparts, and subsequent catabolism to pyruvate is essential for spare respiratory capacity. IL-4 or IFNg treatment of activated B lymphocyte precursors to plasma cells promotes glucose uptake. Thus, signals provided to precursors, glucose uptake, and mitochondrial pyruvate transport allow long-lived plasma cells to provide enduring antibody-mediated immunity.

Introduction Studies have shown that a diet high in fruit and vegetable intake, as well as a routine including daily exercise or physical activity, can independently affect relapse rates and survivorship in breast cancer patients. Fruits and vegetables contain powerful anti-oxidant molecules, capable of preventing tumor formation and proliferation. Exercise can lower circulating levels of estrogen, the female hormone responsible for tumor proliferation in the estrogen-sensitive form of the disease. The most beneficial results have been shown in women who exercise and consume a diet rich in fruits and vegetables. We studied the attitudes towards and behaviors related to fruit and vegetable intake and exercise in a cohort of breast cancer survivors in northwest Ohio. Materials and Methods Data were gathered from a survey sent out by the Northwest Ohio Branch of the Susan G. Komen For the Cure Foundation. We assessed and evaluated survivors’ self-reported beliefs, attitudes, and behaviors regarding exercise and fruit and vegetable intake. Results Nearly half of the survivors (46.5%) reported being unsure or in disagreement with the statement “Eating at least 5 servings of fruits and/or vegetables per day will reduce the risk of breast cancer recurrence.” Only 46.8% of those in agreement with the previous statement actually report eating at least 5 fruits and/or vegetables per day. With respect to exercise, 32.9% reported being unsure or in disagreement with the statement “Engaging in regular physical activity will reduce the risk of breast cancer recurrence.” Only 68.5% of those in agreement with the previous statement report any physical activity in the past 30 days. Conclusions Many breast cancer survivors do not appear to be aware of the benefits of diet and exercise. Further, a large proportion of those who are aware of the benefits do not adapt a healthy diet and exercise as part of their lifestyle. A majority of these survivors see a primary care physician, which we believe is the best venue to bridge this education gap. It is apparent by the pattern our data shows that more needs to be done to educate breast cancer survivors about the benefits of exercise and fruit and vegetable intake. Steps need to be taken to ensure that those who are educated also remain motivated to engage in a healthy lifestyle with the hopes of avoiding breast cancer recurrence.

This chapter describes the development and use of a geographic information system (GIS) in an environmental health investigation of the application of Class B biosolids (sewage sludge) on agricultural fields. The research project is broad-based including field observations and modeling to investigate the presence of microorganisms, metals, and pharmaceutical and personal care products (PPCPs) in biosolids applied agricultural fields and the associated runoff. These data has been linked with remote sensing imagery and added to GIS layers for Wood, Lucas and Greene Counties in Ohio. Specifically, this project describes the way in which a GIS was developed and utilized with a mailed, epidemiological health survey to investigate the potential impact of biosolids application to agricultural fields in relation to self-reported human health symptoms, acute diseases and chronic diseases among groups of individuals living specified distances from fields where biosolids were permitted and applied. For Wood County, of the 24 symptoms in the survey, six were statistically higher near biosolids permitted fields and of the 29 diseases in the survey, five were statistically higher near biosolids permitted fields. The Lucas and Greene County surveys are still being analyzed. Our future work includes refinement of the spatial analysis and health survey to include the application of biosolids and the constituents of the biosolids to fields, distances to any farm field and to other potential relationships to health effects.

We have demonstrated breast milk transmitted MoMuLV-ts1 retrovirus infection and subsequent lymphoma development in offspring of uninfected mothers suckled by infected surrogate mothers. Additionally, we have shown that the lymphoma development occurs as a result of viral gene integration into host genome. A total of 146 pups from Balb/C mice were divided into 5 groups; one control and 4 experimental. All offspring suckled from surrogate infected or control mothers, except one group of infected pups left with their biological mothers. Thirteen of 91 infected pups developed lymphoma. Inverse-PCR, DNA cloning, and quantitative real-time PCR (qRT-PCR) were used to study the virus integration sites (VIS) and alterations in gene expression. VIS were randomly distributed throughout the genome. The majority of insertion sites were found in chromosomes 10, 12 and 13. A total of 209 proviral genomic insertion sites were located with 52 intragenic and 157 intergenic sites. We have identified 29 target genes. Four genes including Tacc3, Aurka, Gfi1 and Ahi1 showed the maximum upregulation of mRNA expression. These four genes can be considered as candidate genes based on their association with cancer. Upregulation of these genes may be involved in this type of lymphoma development. This model provides an important opportunity to gain insight into the relationship of viral gene insertion into host genome and development of lymphoma via natural transmission route such as breast milk.

Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological studies conducted to evaluate this hypothesis have not assessed all flavonoids, including classes that could contribute to intake among Americans, which would result in an underestimation of intake. This misclassification could mask variability among individuals, resulting in attenuated effect estimates for the association between flavonoids and cancer. To augment flavonoid and lignan intake estimates, we developed a database that can be used in conjunction with a food-frequency questionnaire (FFQ). Coupling information derived from the available literature with the U.S. Department of Agriculture databases, we estimated content of 6 flavonoid classes and lignans for 50 food group items. We combined these estimates with responses from a modified Block FFQ that was self-completed in 1996-1997 by a population-based sample of women without breast cancer on Long Island, New York (n = 1,500). Total flavonoid and lignan content of food items ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and grapefruit. Individual intake estimates, from highest to lowest, were flavan-3-ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones. Each class of flavonoids and lignans exhibited a wide range of intake levels. This database is useful to quantify flavonoid and lignan intake for other observational studies conducted in the United States that utilize the Block FFQ.

Flavonoids are found in a variety of foods and have anticarcinogenic properties in experimental models. Few epidemiologic studies have examined whether flavonoid intake is associated with breast cancer in humans. In this study, the authors investigated whether dietary flavonoid intake was associated with reduced risk of breast cancer in a population-based sample of US women. They conducted a case-control study among women who resided in Nassau and Suffolk counties on Long Island, New York. Cases and controls were interviewed about known and suspected risk factors and asked to complete a food frequency questionnaire regarding their average intake in the prior 12 months. A total of 1,434 breast cancer cases and 1,440 controls provided adequate responses. A decrease in breast cancer risk was associated with flavonoid intake; the decrease was most pronounced among postmenopausal women for flavonols (odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.40, 0.73), flavones (OR = 0.61, 95% CI: 0.45, 0.83), flavan-3-ols (OR = 0.74, 95% CI: 0.55, 0.99), and lignans (OR = 0.69, 95% CI: 0.51, 0.94). The authors conclude that intake of flavonols, flavones, flavan-3-ols, and lignans is associated with reduced risk of incident postmenopausal breast cancer among Long Island women. These results suggest that US women can consume sufficient levels of flavonoids to benefit from their potential chemopreventive effects.

To determine whether fruit, vegetable, and micronutrient intake 1 year prior to breast cancer diagnosis is associated with a reduction in the subsequent risk of all-cause or breast cancer-specific mortality.Follow-up data from 1,235 invasive breast cancer cases age 25-98 years from the Long Island Breast Cancer Study Project were analyzed. At the 1996-1997 case-control interview, respondents completed a food frequency questionnaire, which assessed dietary intake of fruits, vegetables, and vitamin supplement use in the previous 12 months. All-cause mortality (n=186 deaths) and breast cancer-specific mortality status (n=125 deaths, 67.2%) were determined through December 31, 2002.Hazard ratios (HRs) for all-cause mortality were insignificantly reduced for intake of any fruits, fruit juices, and vegetables (HR=0.68, 95% CI: 0.42-1.09) and leafy vegetables (HR=0.72, 95% CI: 0.41-1.24) among post-menopausal women only. Both of these associations were more pronounced among those with ER+PR+ tumors (HR=0.54, 95% CI: 0.27-1.10, and HR=0.66, 95% CI: 0.33-1.31, respectively). Similar associations were observed for breast cancer-specific mortality.In a cohort of women diagnosed with breast cancer, higher intake of fruits, vegetables, and micronutrients was associated with a non-significant survival advantage in post-menopausal women only.