Testing an Innovative Approach to Improve Hypertension Management at a Federally Qualified Health Center.

Despite the availability of effective treatments, hypertension control rates remain inadequate in the United States and locally in Los Angeles County. To address this health condition, QueensCare Health Centers developed and launched a team-based hypertension management program that was led by clinical pharmacists and designed to mitigate treatment barriers encountered at the system, provider, and patient levels. System- and provider-focused strategies included incorporating self-monitored blood pressure values into the electronic health record and retraining clinicians to regularly review these values; adding a community health worker to the disease management team; and utilizing clinical pharmacists to assess and titrate medications. Patient-focused strategies included tailoring education materials to reduce literacy and linguistic barriers; providing tailored one-on-one education and support; and providing blood pressure cuffs and pedometers. This multilevel intervention serves as a practical example of how team-based care can be optimized at a Federally Qualified Health Center.

Celecoxib enhances the inhibitory effect of 5-FU on human squamous cell carcinoma proliferation by ROS production.

OBJECTIVES: The role of celecoxib in preventing and treating tumors has attracted broad attention in recent years because of its selective and specific inhibition of COX-2 activity. We investigated the inhibitory effects and mechanisms of celecoxib combined with 5-fluorouracil (5-FU) on proliferation of squamous cell carcinoma cells in vivo and in vitro. STUDY DESIGN: Animal study and basic research. METHODS: SNU-1041 and SNU-1076 squamous cell lines and an orthotopic tongue cancer mouse model were used to study growth inhibition with 5-FU enhanced by celecoxib. Sensitivity of cells to drug treatment was analyzed by the MTT assay, and generation of reactive oxygen species (ROS) was measured using dichlorofluorescein diacetate. Phosphorylation of AKT was detected by Western blotting. Survival analysis in the mouse model was assessed according to combination treatment with 5-FU and celecoxib. RESULTS: Reactive oxygen species production in vitro was highest when celecoxib was administered 48 hours after 5-FU treatment. 5-FU-induced inhibition of cell proliferation was enhanced when combined with celecoxib, which was positively correlated with ROS production. Antioxidant treatment reversed 5-FU-inhibited cell proliferation by up to 60%. Cotreatment with celecoxib and 5-FU partially blocked AKT phosphorylation, although no significant changes in total AKT protein levels were detected. An increased survival time was observed in an orthotopic mouse model treated with a combination of celecoxib and 5-FU compared to treatment with either agent alone. CONCLUSION: Celecoxib may have an enhanced anticancer effect in combination with 5-FU. Reactive oxygen species production may be a key mechanism in this combination therapy by inhibiting the AKT pathway. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:E117-E123, 2017.

5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

BACKGROUND: Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. METHODS AND RESULTS: DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. CONCLUSIONS: From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.

Study protocol of "Worth the Walk": a randomized controlled trial of a stroke risk reduction walking intervention among racial/ethnic minority older adults with hypertension in community senior centers.

BACKGROUND: Stroke disproportionately kills and disables ethnic minority seniors. Up to 30 % of ischemic strokes in the U.S. can be attributed to physical inactivity, yet most Americans, especially older racial/ethnic minorities, fail to participate in regular physical activity. We are conducting a randomized controlled trial (RCT) to test a culturally-tailored community-based walking intervention designed to reduce stroke risk by increasing physical activity among African American, Latino, Chinese, and Korean seniors with hypertension. We hypothesize that the intervention will yield meaningful changes in seniors' walking levels and stroke risk with feasibility to sustain and scale up across the aging services network. METHODS/DESIGN: In this randomized single-blind wait-list control study, high-risk ethnic minority seniors are enrolled at senior centers, complete baseline data collection, and are randomly assigned to receive the intervention "Worth the Walk" immediately (N = 120, intervention group) or in 90 days upon completion of follow-up data collection (N = 120, control group). Trained case managers employed by the senior centers implement hour-long intervention sessions twice weekly for four consecutive weeks to the intervention group. Research staff blinded to participants' group assignment collect outcome data from both intervention and wait-list control participants 1 and 3-months after baseline data collection. Primary outcome measures are mean steps/day over 7 days, stroke knowledge, and self-efficacy for reducing stroke risk. Secondary and exploratory outcome measures include selected biological markers of health, healthcare seeking, and health-related quality of life. Outcomes will be compared between the two groups using standard analytic methods for randomized trials. We will conduct a formal process evaluation to assess barriers and facilitators to successful integration of Worth the Walk into the aging services network and to calculate estimated costs to sustain and scale up the intervention. Data collection is scheduled to be completed in December 2016. DISCUSSION: If this RCT demonstrates superior improvements in physical activity and stroke knowledge in the intervention group compared to the control group and is found to be sustainable and scalable, Worth the Walk could serve as a primary stroke prevention model for racial/ethnic communities across the nation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02181062 ; registered on June 30, 2014.

Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species.

BACKGROUND: The endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2-AG in head and neck squamous cell carcinoma (HNSCC) cell lines. METHODS AND RESULTS: Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2-AG did not. The anticancer effect of AEA seemed to be mediated by a receptor-independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA-dependent inhibition of cell proliferation. We found that cyclooxygenase-2 (COX-2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA-dependent inhibition of cell proliferation. CONCLUSION: These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor-independent mechanism.

Novel histopathological and molecular effects of natural compound pellitorine on larval midgut epithelium and anal gills of Aedes aegypti.

The yellow fever mosquito, Aedes aegypti, is a vector for transmitting dengue fever and yellow fever. In this study, we assessed the histopathological and molecular effects of pellitorine, an isobutylamide alkaloid, on the third instar of Ae. aegypti larvae. At 5 mg/l concentration of pellitorine, the whole body of the treated larvae became dark in color, particularly damaged thorax and abdominal regions. Pellitorine was targeted mainly on midgut epithelium and anal gills, indicating variably dramatic degenerative responses of the midgut through a sequential epithelial disorganization. The anterior and posterior midgut was entirely necrosed, bearing only gut lumen residues inside the peritrophic membranes. Pellitorine caused comprehensive damage of anal gill cells and branches of tracheole and debris was found in hemolymph of the anal gills. RT-PCR analysis indicates that the compound inhibited gene expression encoding V-type H(+)-ATPase and aquaporine 4 after treatment with 2.21 mg/l pellitorine. These results verify that pellitorine merits further study as a potential larvicide with a specific target site and a lead molecule for the control of mosquito populations.

Sensitive quantitation of minimal residual disease in chronic myeloid leukemia using nanofluidic digital polymerase chain reaction assay.

Undetectable BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) should not be regarded as indicative of a cure, due to the sensitivity limit of current real-time quantitative polymerase chain reaction (RQ-PCR) technology. To demonstrate the feasibility of more sensitive approaches, 62 samples from 43 patients with CML were screened by conventional RQ-PCR, replicate RQ-PCR (rRQ-PCR), and/or nanofluidic digital PCR (dPCR). First, we confirmed the correlation of dPCR to conventional RQ-PCR using 30 patient samples with various minimal residual disease (MRD) levels. When the sensitivity limits were determined using cell line and patient sample dilutions, rRQ-PCR and dPCR with pre-amplification showed 2-3 log improvement compared to conventional RQ-PCR, and 24 of 32 PCR negative samples as assayed by conventional RQ-PCR showed detectable BCR-ABL in rRQ-PCR and/or dPCR. More important, using dPCR in conjunction with a pre-amplification step, a continuous decline in MRD level could be precisely monitored even after it became undetectable by conventional RQ-PCR. In this study, both rRQ-PCR and dPCR demonstrated successful detection of BCR-ABL transcripts not detectable in conventional RQ-PCR, and these data show the potential feasibility of highly sensitive PCR approaches for molecular monitoring and clinical relevance in future CML management by allowing further characterization of patients who achieve PCR negativity in a conventional RQ-PCR assay.

Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells.

Induction of differentiation is a new and promising approach to cancer therapy, well illustrated by the treatment of acute myeloid leukemia with all-trans retinoic acid (ATRA). Using combination of ATRA and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. In this study, we demonstrated that the indeno[1,2-c]isoquinolines markedly enhanced differentiation of human myeloid leukemia HL-60 and NB4 cells when simultaneously combined with a low dose of ATRA. Of the tested compounds, 6-(4-methoxybenzyl)-2,11-dimethyl-6H,11H-indeno[1,2-c]isoquinolin-5-one (IIQ-16), an indeno[1,2-c]isoquinoline derivative, showed the highest differentiation-enhancing activity via a pathway involved with protein kinase C, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. The ability to enhance the differentiation potential of ATRA by IIQ-16 may improve outcomes in the therapy of acute promyelocytic leukemia.