Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136447/1/ijc30618-sup-0001-supptables.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136447/2/ijc30618_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136447/3/ijc30618.pd

Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

<p>Abstract</p> <p>Background</p> <p>Myeloid derived suppressor cells (MDSCs) are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines) and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11b^low/CADO48^low) cell population that is increased in the peripheral blood of tumor-bearing dogs.</p> <p>Results</p> <p>Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11b^low/CADO48A^low cells (7.9%) as compared to the control dogs (3.6%). Additionally, sorted CD11b^low/CADO48A^low generated <it>in vitro</it> suppressed the proliferation of canine lymphocytes.</p> <p>Conclusions</p> <p>The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11b^low/CADO48A^low cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice) and utilizes commercially available canine-specific antibodies. Importantly, CD11b^low/CADO48A^low from a tumor environment suppress the proliferation of lymphocytes. These results provide a useful phenotype of cells increased in canine cancer patients that may serve as a useful prognostic marker for assessing immune status and functional response to cancer immunotherapies in dogs. Understanding MDSCs in dogs will allow for increased effectiveness of cancer immunotherapy in both dogs and humans.</p

Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse azoxymethane (AOM) model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group) after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), adipokines, proliferation, apoptosis, and expression of microRNAs (miRs) were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat), while CR induced a lean phenotype (∼14% body fat); controls were intermediate (∼26% body fat). Relative to controls, DIO increased (and CR decreased) the number of colon tumors (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation (p<0.001). DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs

Association of Burnout with Workforce-Reducing Factors among EMS Professionals

<p><b>Objectives</b>: Emergency medical services (EMS) professionals often work long hours at multiple jobs and endure frequent exposure to traumatic events. The stressors inherent to the prehospital setting may increase the likelihood of experiencing burnout and lead providers to exit the profession, representing a serious workforce and public health concern. Our objectives were to estimate the prevalence of burnout, identify characteristics associated with experiencing burnout, and quantify its relationship with factors that negatively impact EMS workforce stability, namely sickness absence and turnover intentions. <b>Methods</b>: A random sample of 10,620 emergency medical technicians (EMTs) and 10,540 paramedics was selected from the National EMS Certification database to receive an electronic questionnaire between October, 2015 and November, 2015. Using the validated Copenhagen Burnout Inventory (CBI), we assessed burnout across three dimensions: personal, work-related, and patient-related. We used multivariable logistic regression modeling to identify burnout predictors and quantify the association between burnout and our workforce-related outcomes: reporting ten or more days of work absence due to personal illness in the past 12 months, and intending to leave an EMS job or the profession within the next 12 months. <b>Results</b>: Burnout was more prevalent among paramedics than EMTs (personal: 38.3% vs. 24.9%, work-related: 30.1% vs. 19.1%, and patient-related: 14.4% vs. 5.5%). Variables associated with increased burnout in all dimensions included certification at the paramedic level, having between five and 15 years of EMS experience, and increased weekly call volume. After adjustment, burnout was associated with over a two-fold increase in odds of reporting ten or more days of sickness absence in the past year. Burnout was associated with greater odds of intending to leave an EMS job (personal OR:2.45, 95% CI:1.95–3.06, work-related OR:3.37, 95% CI:2.67–4.26, patient-related OR: 2.38, 95% CI:1.74–3.26) or the EMS profession (personal OR:2.70, 95% CI:1.94–3.74, work-related OR:3.43, 95% CI:2.47–4.75, patient-related OR:3.69, 95% CI:2.42–5.63). <b>Conclusions</b>: The high estimated prevalence of burnout among EMS professionals represents a significant concern for the physical and mental well-being of this critical healthcare workforce. Further, the strong association between burnout and variables that negatively impact the number of available EMS professionals signals an important workforce concern that warrants further prospective investigation.</p

Real time PCR of microRNAs to validate microarray.

<p>Ten miRs were validated using real-time PCR. They included miR-425, miR-196a, miR-155, miR-150, miR-351, miR-16, let-7f, miR-34c, miR-138a, and miR-21. Results were analyzed using the comparative C_T method and reported as fold differences compared to the control group. Each bar represents the mean of six animals.</p

A. Bodyweights in calorie restricted (CR), control, and diet-induced obesity (DIO) FVB mice.

<p>Bodyweight was measured weekly in all three dietary interventions. Each data point represents the mean of all the mice in that dietary group. B. Body fat in CR, control, and DIO dietary treatments. Dual-energy X-ray absorptiometer (DEXA) scans were conducted at the beginning of the study and after ten weeks of dietary treatment. Each bar represents the mean of ten mice per group. One-way analysis of variance (ANOVA) at the beginning of the study, p = 0.78. One-way ANOVA at ten weeks, p<0.001. <i>a</i>, <i>b</i>, and <i>c</i> represent dietary treatments that are significantly different from one another (p<0.05) as determined by Bonferroni test.</p

Adipokine, IGF-1, IGFBP-3, and insulin levels among CR, control, and DIO mice.

<p>Levels of <b>A</b>) IGF-1, <b>B</b>) IGFBP-3, <b>C</b>) insulin, <b>D</b>) leptin, <b>E</b>) resistin, and <b>F</b>) adiponectin were measured in the serum of the mice ten weeks after the last injection of AOM. Each boxplot represent the mean and range (n = 20). Overall differences among groups were determined using a one-way ANOVA. For <b>A</b>) IGF-1, p = 0.002; <b>B</b>) IGFBP-3, p<0.001; <b>C</b>) insulin, p = 0.002; <b>D</b>) leptin, p<0.0001; <b>E</b>) resistin, p = 0.001; and <b>F</b>) adiponectin, p = 0.14. <i>a</i>,<i>b</i>, and <i>c</i> represent dietary treatments that are significantly different (p<0.05) from one another as determined by a Bonferroni test.</p

Diet composition.

<p>Diet composition.</p

Cellular proliferation and apoptosis in CR, control, and DIO mice 20 weeks after the last AOM injection.

<p><b>A</b>) Proliferation was assessed via immunohistochemistry for proliferating cell nuclear antigen (PCNA). A field of 1000 cells was counted for each animal and the proliferative index represents the percentage of cells that stained positive for PCNA. The bars represent the average proliferative index for each dietary group (n = 20). <b>B</b>) Apoptosis in the tumors of LID versus wildtype mice 20 weeks after the last AOM injection. Apoptosis was assessed via TUNEL staining. A field of 1000 cells was counted for each animal and the apoptotic index represents the percentage of cells that stained positive and also appeared apoptotic based on cell morphology. The bars represent the average apoptotic index for each dietary group (n = 20). <i>a</i>,<i>b</i>, and <i>c</i> represent dietary treatments that are significantly different (p<0.05) from one another as determined by a Bonferroni test.</p