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Background:. Kidney transplant (KT) recipients who are not actively engaged in their care and lack self-management skills have poor transplant outcomes, which are disproportionately observed among Black KT recipients. This pilot study aimed to determine whether the MyKidneyCoach app, an mHealth intervention that provides self-management monitoring and coaching, improved patient activation, engagement, and nutritional behaviors in a diverse KT population. Methods:. This was a randomized, age-stratified, parallel-group, attention-control, pilot study in post-KT patients. Participants were randomized into the attention-control with access to MyKidneyCoach for education and self-management (n = 9) or the intervention with additional tailored nurse coaching (n = 7). Feasibility, acceptability, and clinical outcomes were assessed. Results:. The acceptability of MyKidneyCoach by System Usability Scale was 67.5 (95% confidence interval [CI], 59.1-75.9). Completion rates based on actively using MyKidneyCoach were 81% (95% CI, 57%-93%) and study retention rate of 73%. Patient activation measure significantly increased overall by a mean of 11 points (95% CI, 3.2-18.8). Additionally, Black patients (n = 7) had higher nutrition self-efficacy scores of 80.5 (95% CI, 74.4-86.7) compared with 75.6 (95% CI, 71.1-80.1) in non-Black patients (n = 9) but lower patient activation measure scores of 69.3 (95% CI, 56.3-82.3) compared with 71.8 (95% CI, 62.5-81) in non-Black patients after 3 mo. Conclusions:. MyKidneyCoach was easy to use and readily accepted with low attrition, and improvements were demonstrated in patient-reported outcomes. Both Black and non-Black participants using MyKidneyCoach showed improvement in self-management competencies; thus, this intervention may help reduce healthcare inequities in KT.

“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.

Objective: Novel therapeutic angiogenic concepts for critical limb ischemia are still needed for limb salvage. E-selectin, a cell-adhesion molecule, is vital for recruitment of the stem/progenitor cells necessary for neovascularization in ischemic tissues. We hypothesized that priming ischemic limb tissue with E-selectin/adeno-associated virus (AAV) gene therapy, in a murine hindlimb ischemia and gangrene model, would increase therapeutic angiogenesis and improve gangrene. Methods: FVB/NJ mice were given intramuscular hindlimb injections of either E-selectin/AAV or LacZ/AAV and then underwent induction of gangrene via femoral artery ligation and concomitant systemic injections of the nitric oxide synthesis inhibitor L-NAME (L-NG-Nitro arginine methyl ester; 40 mg/kg). Gangrene was evaluated via the Faber hindlimb appearance score. The rate of ischemic limb reperfusion and ischemic tissue angiogenesis were evaluated using laser Doppler perfusion imaging and DiI perfusion with confocal laser scanning microscopy of the ischemic footpads, respectively. The treadmill exhaustion test was performed on postoperative day (POD) 8 to determine hindlimb functionality. Results: The E-selectin/AAV–treated mice (n = 10) had decreased Faber ischemia scores compared with those of the LacZ/AAV–treated mice (n = 7) at both PODs 7 and 14 (P < .05 and P < .01, respectively), improved laser Doppler perfusion imaging reperfusion indexes by POD 14 (P < .01), and greater gangrene footpad capillary density (P < .001). E-selectin/AAV–treated mice also had improved exercise tolerance (P < .05) and lower relative muscular atrophy (P < .01). Conclusion: We surmised that E-selectin/AAV gene therapy would significantly promote hindlimb angiogenesis, reperfusion, and limb functionality in mice with hindlimb ischemia and gangrene. Our findings highlight the reported novel gene therapy approach to critical limb ischemia as a potential therapeutic option for future clinical studies. : Clinical Relevance: In the United States, >150,000 limb amputations are performed annually for critical limb ischemia (CLI) despite the use of medical and surgical therapy. Thus, novel therapeutic angiogenic concepts for CLI are still needed for limb salvage. We used a novel gene therapy approach in a mouse model of gangrene, the most severe form of CLI, to demonstrate the efficacy of our gene therapy with E-selectin. Preclinical studies such as ours are a vital step in the development of new therapies for CLI patients with threatened limbs and no further medical or surgical options.

Inroduction: The purpose of this study was to explore factors associated with willingness of African Americans and Latinos to participate in biomedical and public health research and to delineate factors that influence the decision to become a human subject. Methods: We present results from a 2010 random digit-dial telephone survey of 2,455 African American (N = 1191) and Latino (N = 1264) adults. We used standard measures to assess knowledge of research, terminology, informed consent procedures, previous participation in research, health care experiences, social support, risk perception, religiousness, and trust. Results: Over 60% of both African Americans and Latinos reported they believed people in medical research are pressured into participating. Over 50% said that it was not at all important to have someone of the same race/ethnicity ask them to participate. In a sub-sample of 322 African Americans and 190 Latinos who had previously been asked to participate in a research study, 63% of African Americans and 65% of Latinos consented to participate in a study. Finally, both African Americans (57%) and Latinos (68%) reported willingness to participate in future research. Overall, the multivariate analysis explained 29% of the variability in willingness to participate in future research. Conclusions: Results suggest that African Americans and Latinos have no automatic predisposition to decline participation in research studies. These results can inform culturally tailored interventions for ethical recruitment of minorities into research and clinical trials.

Introduction: Rectal cancer ranks as the eighth in cancer-related morbidity and the tenth in the cancer-related mortality. A few studies have explored several biomarkers for colorectal cancer. However, there is still a great need for us to excavate novel biomarkers with effective and efficient diagnostic and prognostic values to discover the etiology and pathogenesis of rectal cancer separately. Therefore, we aimed to identify more novel candidate genes that were significantly associated with rectal cancer through integrated bioinformatics analysis. Methods: We analyzed the gene expression profiles of GSE15781 and GSE20842 from Gene Expression Omnibus database to identify differentially expressed genes between normal rectal tissue and rectal cancer tissue. Results: We searched for core genes, carried out survival analysis and analyzed the expressions of core genes. We found that 142 genes were significantly upregulated, and 229 genes were significantly downregulated in all 3 independent studies. In KEGG analysis, the upregulated genes were significantly enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway, cell cycle, etc. The downregulated genes were primarily enriched in nitrogen metabolism, mineral absorption and pentose and glucuronate interconversions. Inhibin subunit beta B (INHBB) expressed markedly higher in rectal cancer tissues compared with normal tissues, and claudins (CLDN) 23 expressed significantly lower in rectal cancer tissues. Conclusion: In conclusion, we discovered that INHBB could provide a great significant diagnostic and prognostic values for rectal cancer.

Background: This study was to assess the risk of venous thromboembolism (VTE) in patients with peritoneal carcinomatosis (PC) and to evaluate the safety and feasibility of physiotherapy program to prevent VTE during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: For VTE prevention, we developed a systematic physiotherapy program consisting of active exercises of both arms and legs, and intermittent pneumatic compression device to massage both legs. This physiotherapy was applied to all patients, and the VTE-related events were recorded and analyzed. Results: Cytoreductive surgery + HIPEC was performed on 466 patients with PC. All patients had highest VTE risk, with the median Caprini risk factor score being 11. During the 3-month observation period, 8 patients had 9 (1.9%) clinically symptomatic VTE events, including 8 (1.7%) deep vein thrombosis and 1 (0.2%) pulmonary embolism. Among those, 5 patients received pharmacological treatments with low-molecular-weight heparin, and the other 3 received physical exercises only. All these patients recovered well, and there was no mortality about VTE perioperatively. Conclusions: Patients with PC treated by CRS + HIPEC are at highest risk for VTE. The systematic physiotherapy program is safe and feasible to prevent VTE post CRS + HIPEC.

Background: Olmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricemic agent for the treatment of hyperuricemia and gout. Objective: The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers. Methods: In a randomized, open-label, 2-way crossover study, 12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus probenecid) separated by 4 days. Blood samples were obtained for a 48-hour pharmacokinetic evaluation after drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests before and after administration of the study drug. Results: Pharmacokinetic parameters were evaluated in 6 male and 6 female healthy volunteers (mean age, 22 [range, 20–25] years]; weight, 56.0 [range, 51.0–60.0] kg). Probenecid coadministration increased olmesartan Css-av, AUC0→∞, and AUC0–48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000, 0.000, respectively), but there was no statistical significance for Tmax, t1/2, Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P = 0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was reported during the study. The proportion of volunteers with AEs in the olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus probenecid period were abnormal routine urine test results. The AE in olmesartan-alone period was dizziness. All AEs were classified as mild and considered to be at least possibly related to treatment. All volunteers recovered from the AEs by 2 weeks after the end of the study. Conclusions: Probenecid increases the exposure speed of olmesartan by increasing the AUC0–48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid may increase the occurrence of genitourinary side effects. ClinicalTrials.gov identifier: NCT01907373.