Sleep and Economic Status are Linked to Daily Life Stress in African-born Blacks Living in America.

To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 ± 10 years (mean ± SD), range 22-65 years) who came to the United States as adults (age ≥ 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (≥16) and low-stress as PSS \u3c 16. Poor sleep quality required PSQI \u3e 5. Low income was defined as groups, PSS were: 21 ± 4 versus 9 ± 4, p \u3c 0.001 and PSQI were: 6 ± 3 versus 4 ± 3, p \u3c 0.001, respectively. PSS and PSQI were correlated (r = 0.38, p \u3c 0.001). The odds of high-stress were higher among those with poor sleep quality (OR 5.11, 95% CI: 2.07, 12.62), low income (OR 5.03, 95% CI: 1.75, 14.47), and no health insurance (OR 3.01, 95% CI: 1.19, 8.56). Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance

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

Sleep and Economic Status Are Linked to Daily Life Stress in African-Born Blacks Living in America

To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 &plusmn; 10 years (mean &plusmn; SD), range 22&ndash;65 years) who came to the United States as adults (age &ge; 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (&ge;16) and low-stress as PSS &lt; 16. Poor sleep quality required PSQI &gt; 5. Low income was defined as &lt;40 k yearly. In the high and low-stress groups, PSS were: 21 &plusmn; 4 versus 9 &plusmn; 4, p &lt; 0.001 and PSQI were: 6 &plusmn; 3 versus 4 &plusmn; 3, p &lt; 0.001, respectively. PSS and PSQI were correlated (r = 0.38, p &lt; 0.001). The odds of high-stress were higher among those with poor sleep quality (OR 5.11, 95% CI: 2.07, 12.62), low income (OR 5.03, 95% CI: 1.75, 14.47), and no health insurance (OR 3.01, 95% CI: 1.19, 8.56). Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance

Data_Sheet_1_Non-invasive type 2 diabetes risk scores do not identify diabetes when the cause is β-cell failure: The Africans in America study.docx

BackgroundEmerging data suggests that in sub-Saharan Africa β-cell-failure in the absence of obesity is a frequent cause of type 2 diabetes (diabetes). Traditional diabetes risk scores assume that obesity-linked insulin resistance is the primary cause of diabetes. Hence, it is unknown whether diabetes risk scores detect undiagnosed diabetes when the cause is β-cell-failure.AimsIn 528 African-born Blacks living in the United States [age 38 ± 10 (Mean ± SE); 64% male; BMI 28 ± 5 kg/m2] we determined the: (1) prevalence of previously undiagnosed diabetes, (2) prevalence of diabetes due to β-cell-failure vs. insulin resistance; and (3) the ability of six diabetes risk scores [Cambridge, Finnish Diabetes Risk Score (FINDRISC), Kuwaiti, Omani, Rotterdam, and SUNSET] to detect previously undiagnosed diabetes due to either β-cell-failure or insulin resistance.MethodsDiabetes was diagnosed by glucose criteria of the OGTT and/or HbA1c ≥ 6.5%. Insulin resistance was defined by the lowest quartile of the Matsuda index (≤ 2.04). Diabetes due to β-cell-failure required diagnosis of diabetes in the absence of insulin resistance. Demographics, body mass index (BMI), waist circumference, visceral adipose tissue (VAT), family medical history, smoking status, blood pressure, antihypertensive medication, and blood lipid profiles were obtained. Area under the Receiver Operator Characteristics Curve (AROC) estimated sensitivity and specificity of each continuous score. AROC criteria were: Outstanding: >0.90; Excellent: 0.80–0.89; Acceptable: 0.70–0.79; Poor: 0.50–0.69; and No Discrimination: 0.50.ResultsPrevalence of diabetes was 9% (46/528). Of the diabetes cases, β-cell-failure occurred in 43% (20/46) and insulin resistance in 57% (26/46). The β-cell-failure group had lower BMI (27 ± 4 vs. 31 ± 5 kg/m2P 3, P ConclusionsAt a prevalence of 43%, β-cell-failure accounted for nearly half of the cases of diabetes. All six diabetes risk scores failed to detect previously undiagnosed diabetes due to β-cell-failure while effectively identifying diabetes when the etiology was insulin resistance. Diabetes risk scores which correctly classify diabetes due to β-cell-failure are urgently needed.</p