Information Communication Technology as Instrumental Activities of Daily Living for Aging-in-Place in Chinese Older Adults With and Without Cognitive Impairment: The Validation Study of Advanced Instrumental Activities of Daily Living Scale

Background: The capability in applying information communication technology (ICT) is crucial to the functional independence of older peoples of community living nowadays. The proper assessment of individuals' capability of ICT application is the corner stone for the future development of telemedicine in our aging population. Methods: With the recruitment of 300 participants of different functional and social background in home-living, hostel-living, and care-and-attention home living; and through assessing the ability of individuals in instrumental activities of daily living and cognitive assessments, this study aimed at capturing the content validity and construct validity of the Advanced Instrumental Activities of Daily Living (AIADL scale). In addition, this study assess the ability of older peoples in applying ICT and how the functional and social background affects their independence in aging-in-place. Results: The AIADL scale showed good test-retest reliability and good-to-excellent internal consistency. To determine if items of the AIADL scale measure various aspects of community living, exploratory factor analysis revealed a two-factor structure with “home living and management” and “community living”. Validity analysis with the known-groups method showed a high overall accuracy of prediction of individuals' capability of independent living in the community. Conclusions: The AIADL scale is a valid and reliable instrument to assess the ability of older adults in handling ICT as part of their instrumental activities in daily living. The scale can reflect capability of older peoples in applying ICT. This instrument can serve as a reference in measuring readiness of individuals in receiving telemedicine and their ability of aging-in-place

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

The Rational Design of Highly Potent and Selective Covalent MAP2K7 Inhibitors

The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes from yeast to humans, where it plays a central role regulating activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, allowing external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads situated immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T-cell acute lymphoblastic leukemia. Herein, we describe the rational design, synthesis, evaluation, and optimization of a novel class of irre-versible MAP2K7 inhibitors. With a streamlined one-pot synthesis, favorable in vitro potency and selectivity, as well as promising cellular activity, this novel class of compounds wields promise as a powerful tool in the study of pediatric T-AL

Wireless Home Blood Pressure Monitoring System With Automatic Outcome-Based Feedback and Financial Incentives to Improve Blood Pressure in People With Hypertension: Protocol for a Randomized Controlled Trial

BackgroundHypertension is prevalent in Singapore and is a major risk factor for cardiovascular morbidity and mortality and increased health care costs. Strategies to lower blood pressure include lifestyle modifications and home blood pressure monitoring. Nonetheless, adherence to home blood pressure monitoring remains low. This protocol details an algorithm for remote management of primary care patients with hypertension. ObjectiveThe objective of this study was to determine whether wireless home blood pressure monitoring with or without financial incentives is more effective at reducing systolic blood pressure than nonwireless home blood pressure monitoring (usual care). MethodsThis study was designed as a randomized controlled open-label superiority study. A sample size of 224 was required to detect differences of 10 mmHg in average systolic blood pressure. Participants were to be randomized, in the ratio of 2:3:3, into 1 of 3 parallel study arms :(1) usual care, (2) wireless home blood pressure monitoring, and (3) wireless home blood pressure monitoring with financial incentives. The primary outcome was the mean change in systolic blood pressure at month 6. The secondary outcomes were the mean reduction in diastolic blood pressure, cost of financial incentives, time taken for the intervention, adherence to home blood pressure monitoring, effectiveness of the framing of financial incentives in decreasing nonadherence to blood pressure self-monitoring and the adherence to antihypertensive medication at month 6. ResultsThis study was approved by SingHealth Centralised Institutional Review Board and registered. Between January 24, 2018 and July 10, 2018, 42 participants (18.75% of the required sample size) were enrolled, and 33 participants completed the month 6 assessment by January 31, 2019. ConclusionsDue to unforeseen events, the study was stopped prematurely; therefore, no results are available. Depending on the blood pressure information received from the patients, the algorithm can trigger immediate blood pressure advice (eg, Accident and Emergency department visit advice for extremely high blood pressure), weekly feedback on blood pressure monitoring, medication titration, or skipping of routine follow-ups. The inclusion of financial incentives framed as health capital provides a novel idea on how to promote adherence to remote monitoring, and ultimately, improve chronic disease management. Trial RegistrationClinicalTrials.gov NCT 03368417; https://clinicaltrials.gov/ct2/show/NCT03368417 International Registered Report Identifier (IRRID)DERR1-10.2196/2749

The performance characteristics of prostate-specific antigen and prostate-specific antigen density in Chinese men

We investigated the performance characteristics of prostate-specific antigen (PSA) and PSA density (PSAD) in Chinese men. All Chinese men who underwent transrectal ultrasound-guided prostate biopsy (TRUS-PB) from year 2000 to 2013 were included. The receiver operating characteristic (ROC) curves for both PSA and PSAD were analyzed. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at different cut-off levels were calculated. A total of 2606 Chinese men were included. For the ROC, the area under curve was 0.770 for PSA (P < 0.001) and 0.823 for PSAD (P < 0.001). PSA of 4.5 ng ml−1 had sensitivity of 94.4%, specificity of 14.1%, PPV of 29.5%, and NPV of 86.9%; PSAD of 0.12 ng ml−1 cc−1 had sensitivity of 94.5%, specificity of 26.6%, PPV of 32.8%, and NPV of 92.7%. On multivariate logistic regression analyses, PSA cut-off at 4.5 ng ml−1 (OR 1.61, 95% CI 1.05-2.45, P= 0.029) and PSAD cut-off at 0.12 ng ml−1 cc−1 (OR 6.22, 95% CI 4.20-9.22, P< 0.001) were significant predictors for prostate cancer detection on TRUS-PB. In conclusion, the performances of PSA and PSAD at different cut-off levels in Chinese men were very different from those in Caucasians. PSA of 4.5 ng ml−1 and PSAD of 0.12 ng ml−1 cc−1 had near 95% sensitivity and were significant predictors of prostate cancer detection in Chinese men

Anterior perineal hernia after anterior exenteration

Perineal hernia is a rare complication of anterior exenteration. We reported this complication after an anterior exenteration for bladder cancer with bleeding complication requiring packing and second-look laparotomy. Perineal approach is a simple and effective method for repair of perineal hernia