Angiotensin II in the Treatment of Distributive Shock, an Old Theory Revitalized

Objective: To assess whether or not angiotensin II in combination with current treatment has a favorable outcome in the treatment of distributive shock in terms of decreasing duration of vasopressor usage, increasing mean arterial pressure (MAP) above 65 mmHg, and improving mortality. Design: Systematic Literature Review Methods: Searches were conducted in PubMed, Google Scholar, and the James Madison University Library Database for the key terms angiotensin II, shock, septic shock, vasodilatory shock, distributive shock, blood pressure, double-blind, humans, and vasoconstrictor agents. Search results were filtered by year, for animal trials, irrelevant therapies, meta-analysis, retrospective studies, and case studies. Only original studies published within the last ten years that used angiotensin II for human trials in the treatment of distributive shock were included in the review. Results: Two of three studies showed statistically significant data supporting the ability of angiotensin II to increase MAP above 65 mmHg; however, statistical significance was not found in the reduction of mortality. Conclusion: The addition of angiotensin II to current standard therapy for the treatment of distributive shock decreases the requirement for vasopressors and increases MAP. Further studies are needed to address the long-term effects of angiotensin II and to investigate outcomes in specific types of shock such as sepsis-induced and anaphylaxis

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

Clinical care for obesity:a preliminary survey of sixty-eight countries

Obesity is a chronic relapsing condition affecting a rapidly increasing number of people worldwide. The United Nations has stated that universal health coverage is an essential element of the globally‐agreed sustainable development goals. This article provides a preliminary report of a survey of relevant health professionals and other interest groups on the readiness of health systems to provide obesity treatment services. Interviews and questionnaires were completed by 274 respondents from a total of 68 low, middle and high income countries. Respondents in the majority of countries stated that there were professional guidelines for obesity treatment, but that there was a lack of adequate services, especially in lower income countries, and in rural areas of most countries. Lack of treatment was attributed to a broad range of issues including: no clear care pathways from primary care to secondary services; absent or limited secondary services in some regions; lack of trained multi‐disciplinary support professionals; potentially high costs to patients; long waiting times for surgery; and stigma experienced by patients within the health care services. Defining obesity as a disease may help to overcome stigma and may also help to secure better funding streams for treatment services. However, the survey found that few countries were ready to accept this definition. Furthermore, until countries fully adopt and implement obesity prevention policies the need for treatment will continue to rise while the necessary conditions for treatment will remain inadequate

Inflationary perturbations from a potential with a step

We use a numerical code to compute the density perturbations generated during an inflationary epoch which includes a spontaneous symmetry breaking phase transition. A sharp step in the inflaton potential generates $k$ dependent oscillations in the spectrum of primordial density perturbations. The amplitude and extent in wavenumber of these oscillations depends on both the magnitude and gradient of the step in the inflaton potential. We show that observations of the cosmic microwave background anisotropy place strong constraints on the step parameters.Comment: 6 pages, Revtex - v2. reference adde

Novel methods of targeting IL-1 signalling for the treatment of breast cancer bone metastasis

Breast cancer bone metastasis is currently incurable. Evidence suggests that inhibiting IL-1 signalling with the IL1R antagonist, Anakinra, or the IL1β antibody, Canakinumab, prevents metastasis and almost eliminates breast cancer growth in the bone. However, these drugs increase primary tumour growth. We, therefore, investigated whether targeting other members of the IL-1 pathway (Caspase-1, IL1β or IRAK1) could reduce bone metastases without increasing tumour growth outside of the bone. Inhibition of IL-1 via MLX01 (IL1β secretion inhibitor), VRT043198/VX765 (Caspase-1 inhibitor), Pacritinib (IRAK1 inhibitor) or Anakinra (IL1R antagonist) on tumour cell viability, migration and invasion were assessed in mouse mammary E0771 and Py8119 cells in vitro and on primary tumour growth, spontaneous metastasis and metastatic outgrowth in vivo. In vitro, Inhibition of IL-1 signalling by MLX01, VRT043198 and Anakinra reduced migration of E0771 and Py8119 cells and reversed tumour-derived IL1β induced-increased invasion and migration towards bone cells. In vivo, VX765 and Anakinra significantly reduced spontaneous metastasis and metastatic outgrowth in the bone, whereas MLX01 reduced primary tumour growth and bone metastasis. Pacritinib had no effect on metastasis in vitro or in vivo. Targeting IL-1 signalling with small molecule inhibitors may provide a new therapeutic strategy for breast cancer bone metastasis

Repeatability of the Six-Minute Walk Test and Relation to Physical Function in Survivors of a Critical Illness

Background: The Six-Minute Walk Test (6MWT) is widely used as an outcome measure in exercise rehabilitation. However, the repeatability of the 6MWT performed at home in survivors of a critical illness has not been evaluated. Objective: The purpose of this study was to evaluate, in survivors of a critical illness: (1) the repeatability of the 6MWT performed at home, (2) the effect on estimates of change in functional exercise capacity if only one 6MWT was performed at follow-up assessments, and (3) the relationship between the physical functioning (PF) score of the 36-Item Short-Form Health Survey questionnaire (SF-36) and the 6MWT. Design: Repeated measures of the 6MWT and SF-36 were obtained. Methods: Eligible participants had an intensive care unit (ICU) length of stay of ≥48 hours and were mechanically ventilated for ≥24 hours. Two 6MWTs and the SF-36 were conducted in participants' homes at weeks 1, 8, and 26 after hospital discharge. Results: One hundred seventy-three participants completed the study. The participants had a mean age of 57 years (SD=16), a mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission of 19 (SD=10), a mean ICU length of stay of 9 days (SD=8), and a mean mechanical ventilation time of 140 hours (SD=137). Of the 173 participants, 110 performed two 6MWTs at weeks 1, 8, and 26. There were significant mean increases in 6-minute walk distance in the second test of 15 m (P<.0001) at week 1, 13 m (P<.0001) at week 8, and 9 m (P=.04) at week 26. If only one 6MWT was performed at weeks 8 and 26, the estimate of change in 6-minute walk distance from week 1 was 19 m less (P<.001) at both weeks 8 and 26. There was a moderate to strong correlation between SF-36 PF score and 6-minute walk distance at each assessment (week 1: r=.62, P<.001; week 8: r=.55, P<.001; and week 26: r=.47, P<.001).Limitations: Some study participants were unable to perform a second 6MWT, and these participants may have differed in important aspects of function compared with those individuals who completed two 6MWTs. Conclusions: In survivors of a critical illness, the 6MWT in the home environment should be performed twice at each assessment to give an accurate reflection of change in exercise capacity over time. The SF-36 PF score was a strong indicator of 6-minute walk distance in early recovery from a critical illness

Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia

SummaryMany human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation

“Being Guided”: What Oncofertility Patients’ Decisions Can Teach Us About the Efficacy of Autonomy, Agency, and Decision-Making Theory in the Contemporary Critical Encounter

Recent research on patient decision-making reveals a disconnect between theories of autonomy, agency, and decision-making and their practice in contemporary clinical encounters. This study examines these concepts in the context of female patients making oncofertility decisions in the United Kingdom in light of the phenomenon of “being guided.” Patients experience being guided as a way to cope with, understand, and defer difficult treatment decisions. Previous discussions condemn guided decision-making, but this research suggests that patients make an informed, autonomous decision to be guided by doctors. Thus, bioethicists must consider the multifaceted ways that patients enact their autonomy in medical encounters

2016 Wild Blueberry Project Reports

FOOD SCIENCE AND NUTRITION1. Increasing the food safety margin of wild blueberries through improved intervention measures ENTOMOLOGY 2. Control tactics for blueberry pest insects, 2016 3. Pest biology and IPM, 2016 4. Biology of spotted wing drosophila, 2016 5. Biology of blueberry, bees, and blueberry pollination DISEASE MANAGEMENT 6. Research and control of leaf spot diseases 7. Research and control of mummy berry and Botrytis blossom blight 8. Lab and field studies of mummy berry and interactions between the fungus and bees WEED MANAGEMENT 9. Pre-emergence and post-emergence applications of Zeus Prime XC for weed control in wild blueberry fields, 2016 10. Comparisons of Matrix and Callisto in combination with Matrix or Sinbar for weed control in wild blueberry fields, 2016 11. Herbicide combinations with Sinbar WDG to assess efficacy on weed control in wild blueberry 12. Single vs split applications of post-emergent herbicides for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields – crop year results 13. Comparison of multiple post-emergence Callisto applications for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields 14. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields – crop year 2016 (final report, SCRI ancillary study) 15. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields, 2016-17 EXTENSION 16. Wild Blueberry Extension Education Program in 201

2015 Wild Blueberry Project Reports

FOOD SCIENCE AND NUTRITION 1. Increasing the food safety margin of wild blueberries through improved intervention measures ENTOMOLOGY 2. Control tactics for blueberry pest insects, 2015 3. Pest biology and IPM, 2015 4. Biology of spotted wing drosophila, 2015 5. Biology of blueberry bees, and blueberry pollination DISEASE MANAGEMENT 6. Research and control of mummy berry disease 7. Evaluation of fungicides for control of mummy berry on lowbush blueberry (2015) 8. Evaluation of fungicides for control of leafspot on lowbush blueberry (2015) WEED MANAGEMENT 9. Single vs split applications of post-emergent herbicides for spreading dogbane (Apocynum androsaemifolium) control in wild blueberry fields 10. Evaluation of fall applications of herbicides targeting horseweed in wild blueberry fields 11. Herbicide combinations with Sinbar and Grounded to assess efficacy on weed control in wild blueberry EXTENSION 12. Wild Blueberry Extension Education Program in 2015 INPUT SYSTEMS STUDY – SCRI GRANT PAGE 13. Systems approach to improving the sustainability of wild blueberry production, Year Six of a six-year study – experimental design 14. Systems approach to improving the sustainability of wild blueberry production, Year 6 15. Systems approach to improving the sustainability of wild blueberry production, 2015, Year 6 of a six-year study, disease management results 16. Systems approach to improving the sustainability of wild blueberry production, Year Six of a six-year study, weed management results 17. Systems approach to improving the sustainability of wild blueberry production, preliminary economic comparison for 2014-15 18. Ancillary projects in disease research (ancillary study) 19. Evaluation of fall and spring combinations of preemergence herbicides to prevent weed resistance in wild blueberry fields, 2013-15 (ancillary study) 20. Post-harvest control of red sorrel in a non-crop blueberry field, 2013-2015 - crop year evaluation (ancillary study) 21. Evaluation of spring applications of herbicides targeting red sorrel in wild blueberry fields (ancillary study