Successful Implementation of the ABCDEF Bundle in the MICU through Interprofessional Collaboration and Teamwork

Earlier this year, members of the medical intensive care unit (MICU) attended an interprofessional workshop that utilized Awakening/Breathing/Choice of Sedation/Delirium/Early Mobility (ABCDE) bundle simulation combined with TeamSTEPPS training to empower care givers to advocate for patient safety while optimizing patient care. The ABCDE bundle is an evidence-based tool designed to implement pain, agitation, and delirium guideline recommendations into routine practice. To further improve patient safety and outcomes and build upon the ABCDE concept, the MICU team developed an interprofession-al practice project by adding routine assessment of need for indwelling Foley catheters to their daily work list, creating the “ABCDEF” bundle

Performance of a BGO PET/CT with Higher Resolution PET Detectors

A new PET detector block has been designed to replace the standard detector of the Discovery ST PET/CT system. The new detector block is the same size as the original, but consists of an 8/spl times/6 (tangential× axial) matrix of crystals rather than the original 6/spl times/6. The new crystal dimensions are 4.7× 6.3× 30 mm/sup 3/ (tangential× axial× radial). Full PET/CT systems have been built with these detectors (Discovery STE). Most other aspects of the system are identical to the standard Discovery ST, with differences including the low energy threshold for 3D imaging (now 425 keV) and front-end electronics. Initial performance evaluation has been done, including NEMA NU2-2001 tests and imaging of the 3D Hoffman brain phantom and a neck phantom with small lesions. The system sensitivity was 1.90 counts/s/kBq in 2D, and 9.35 counts/s/kBq in 3D. Scatter fractions measured for 2D and 3D, respectively, were 18.6% and 34.5%. In 2D, the peak NEC of 89.9 kcps occurred at 47.0 kBq/cc. In 3D, the peak NEC of 74.3 kcps occurred at 8.5 kBq/cc. Spatial resolution (all expressed in mm FWHM) measured in 2D for 1 cm off-axis source 5.06 transaxial, 5.14 axial and for 10 cm source 5.45 radial, 5.86 tangential, and 6.23 axial. In 3D for 1 cm off-axis source 5.13 transaxial, 5.74 axial, and for 10 cm source 5.92 radial, 5.54 tangential, and 6.16 axial. Images of the brain and neck phantom demonstrate some improvement, compared to measurements on a standard Discovery ST

Mastering tricyclic ring systems for desirable functional cannabinoid activity

There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain and other indications. In continuation of our ongoing program aiming for the development of new small molecule cannabinoid ligands, we have synthesized a novel series of carbazole and γ-carboline derivatives. The affinities of the newly synthesized compounds were determined by a competitive radioligand displacement assay for human CB2 cannabinoid receptor and rat CB1 cannabinoid receptor. Functional activity and selectivity at human CB1 and CB2 receptors were characterized using receptor internalization and [35S]GTP-γ-S assays. The structure–activity relationship and optimization studies of the carbazole series have led to the discovery of a non-selective CB1 and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2 selectivity of this lead compound have led to the discovery of CB2 selective compound 64, which robustly internalized CB2 receptors. Compound 64 had potent inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain. Other potent and CB2 receptor–selective compounds, including compounds 63 and 68, and a selective CB1 agonist, compound 74 were also discovered. In addition, we identified the CB2 ligand 35 which failed to promote CB2 receptor internalization and inhibited compound CP55,940-induced CB2 internalization despite a high CB2 receptor affinity. The present study provides novel tricyclic series as a starting point for further investigations of CB2 pharmacology and pain treatment.Fil: Petrov, Ravil R.. University Of Montana; Estados UnidosFil: Knight, Lindsay. Indiana University; Estados UnidosFil: Chen, Shao Rui. University Of Texas; Estados UnidosFil: Wager Miller, Jim. Indiana University; Estados UnidosFil: McDaniel, Steven W.. University Of Montana; Estados UnidosFil: Diaz, Fanny. University Of Montana; Estados UnidosFil: Barth, Francis. Sanofi-aventis R&D; FranciaFil: Pan, Hui Lin. University Of Texas; Estados UnidosFil: Mackie, Ken. Indiana University; Estados UnidosFil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Diaz, Philippe. University Of Montana; Estados Unido

Telomere length, antioxidant status and incidence of ischaemic heart disease in type 2 diabetes

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of ischaemic heart disease (IHD). An accelerated process of vascular ageing induced by an increased oxidative stress exposure is suggested as potential pathway accounting for this association. However, no studies have explored the relationship between markers of vascular ageing, measures of oxidative stress and risk of IHD in T2D. OBJECTIVES: To explore the association between plasma antioxidant status, marker of cellular ageing (leukocyte telomere length, LTL) and 10years risk of IHD in patients with T2D. METHODS: Between 2001 and 2002, 489 Caucasians subjects with T2D were enrolled at the diabetic clinic, University College London Hospital. Plasma total anti-oxidant status (TAOS) and LTL were measured by photometric microassay and RT-PCR, respectively. The incidence of IHD over 10years was determined through linkage with the national clinical audit of acute coronary syndrome in UK. RESULTS: At baseline, TAOS was associated with LTL (age adjusted: r=0.106, p=0.024). After 10years, 61 patients developed IHD. Lower TAOS and shorter LTL at baseline predicted an increased IHD risk at follow-up (age adjusted: p=0.033 and p=0.040, respectively). These associations were independent of age, gender, cardiovascular risk factors, circulating levels of CRP and medication differences. CONCLUSIONS: Reduced TAOS and short LTL are interrelated pathways which predict risk of IHD in patients with T2D. Our findings suggest that antioxidant defences are important to maintain telomere integrity, potentially reducing the progression of vascular ageing in patients with T2D

Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage

Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Single-leg cycling to maintain and improve function in healthy and clinical populations

Exercise with reduced muscle mass facilitates greater muscle-specific adaptations than training with larger muscle mass. The smaller active muscle mass can demand a greater portion of cardiac output which allows muscle(s) to perform greater work and subsequently elicit robust physiological adaptations that improve health and fitness. One reduced active muscle mass exercise that can promote greater positive physiological adaptations is single-leg cycling (SLC). Specifically, SLC confines the cycling exercise to a smaller muscle mass resulting in greater limb specific blood flow (i.e., blood flow is no longer “shared” by both legs) which allows the individual to exercise at a greater limb specific intensity or for a longer duration. Numerous reports describing the use of SLC have established cardiovascular and/or metabolic benefits of this exercise modality for healthy adults, athletes, and individuals living with chronic diseases. SLC has served as a valuable research tool for understanding central and peripheral factors to phenomena such as oxygen uptake and exercise tolerance (i.e., V̇O2peak and V̇O2 slow component). Together, these examples highlight the breadth of applications of SLC to promote, maintain, and study health. Accordingly, the purpose of this review was to describe: 1) acute physiological responses to SLC, 2) long-term adaptations to SLC in populations ranging from endurance athletes to middle aged adults, to individuals living with chronic disease (COPD, heart failure, organ transplant), and 3) various methods utilized to safely perform SLC. A discussion is also included on clinical application and exercise prescription of SLC for the maintenance and/or improvement of health