Teaching Tradition: Diverse Perspectives on the Pilot Urban American Indian Traditional Spirituality Program.

Many urban American Indian community members lack access to knowledgeable participation in indigenous spiritual practices. And yet, these sacred traditional activities remain vitally important to their reservation-based kin. In response, our research team partnered with an urban American Indian health center in Detroit for purposes of developing a structured program to facilitate more ready access to participation in indigenous spiritual knowledge and practices centered on the sweat lodge ceremony. Following years of preparation and consultation, we implemented a pilot version of the Urban American Indian Traditional Spirituality Program in the spring of 2016 for 10 urban AI community participants. Drawing on six first-person accounts about this program, we reflect on its success as a function of participant meaningfulness, staff support, mitigated sensitivities, and program structure. We believe that these observations will enable other community psychologists to undertake similar program development in service to innovative and beneficial impacts on behalf of their community partners.

Comparison of butterfly volumetric modulated arc therapy to full arc with or without deep inspiration breath hold for the treatment of mediastinal lymphoma.

PURPOSE: Radiotherapy is an effective treatment for mediastinal lymphoma but induces late effects including cardiac toxicity and secondary breast and lung cancer. Therefore reducing the dose to these organs is vital. We compared full arc volumetric modulated arc therapy (F-VMAT) against limited angle 'Butterfly' VMAT (B-VMAT) on free breathing (FB) and deep inspiration breath-hold (DIBH) computed tomography scans. The aim was to assess the benefits of B-VMAT over F-VMAT and to establish if the addition of DIBH results is a cumulative benefit. MATERIALS AND METHODS: F-VMAT and B-VMAT plans were calculated for 20 consecutive patients (15 females) with mediastinal lymphoma on both FB and DIBH scans. The planning target volume V95% was kept comparable between all plans while reducing organ doses as much as possible. RESULTS: B-VMAT significantly reduced low lung doses (V5-10), while F-VMAT was better for higher lung doses (V20-30). DIBH further improved lung doses for both types of plans. DIBH B-VMAT produced the lowest mean lung dose. With FB, heart doses were slightly higher for B-VMAT but the maximum difference was small (0.8% for V20) and only statistically significant for V10-20. The mean heart dose increased by only 0.1 Gy. The addition of DIBH however significantly reduced heart doses. While DIBH F-VMAT had the lowest heart doses, the difference was small compared with DIBH B-VMAT. B-VMAT significantly reduced breast V4 while DIBH reduced the V10. CONCLUSION: B-VMAT and DIBH are both effective in reducing organ doses and the dosimetric benefit is additive for some parameters and complementary for others.

Relative gene-silencing efficiencies of small interfering RNAs targeting sense and antisense transcripts from the same genetic locus.

Short interfering RNAs (siRNAs) directed against different regions of genes display marked variation in their potency in mediating mRNA degradation. Various factors have been proposed to affect the efficacy of siRNA. We explored some of the factors by evaluating in cultured human cells 28 randomly selected siRNAs targeting the GPR39 and MGC29643 transcripts derived from the same genetic locus but transcribed in opposite directions. Twenty of the 24 siRNAs targeting the overlapping regions of the transcripts simultaneously reduced the levels of both transcripts. Single nucleotide changes in either of the siRNA strands significantly reduced the gene-silencing efficiency of the siRNA on targeted sense transcript without affecting the antisense transcript. Overall, we observed a greater gene-silencing efficiency on the MGC29643 transcript than on the GPR39 transcript in HeLa cells. Since MGC29643 transcript is more abundant than the GPR39 transcript [0.24 versus 0.008% relative to 100% for glyceraldehyde-3-phosphate dehydrogenase (GAPDH)], the results suggest that the abundance of the mRNA affects the efficiency of silencing. Two additional observations supported this hypothesis. First, GAPDH whose intracellular level is the highest of the three was the most efficiently silenced. Second, a reversal of gene-silencing efficiency was observed in U-138 MG cells in which the relative abundance of the GPR39 and MGC29643 transcripts is also reversed. Our study suggests that low-abundant transcripts are less susceptible to siRNA-mediated degradation than medium- and high-abundant transcripts.

A new inducible RNAi xenograft model for assessing the staged tumor response to mTOR silencing.

Human xenograft tumor models are widely used for efficacy evaluation of potential cancer targets. siRNA is usually stably introduced into tumor cells prior to transplantation. However, silencing of the cancer therapeutic target usually results in reduced cell growth/survival in vitro and/or failure to establish tumors in vivo, thus hindering tumor response-based efficacy evaluation. The present study explored a new tumor response model based on regulated RNAi, which is more relevant from a clinical standpoint. As a proof of principle, an inducible lentiviral RNAi vector was used to silence the known cancer therapeutic target mTOR upon induction with Doxycycline (DOX). The responses to DOX-induced mTOR silencing were tested both in vitro and in vivo for prostate cancer PC3 models. Significant reduction in cancer cell survival was observed due to cell cycle arrest and apoptosis when mTOR silencing was induced in vitro. mTOR silencing also caused tumor regression for the early-staged PC3 tumors (100% tumor regressed and 45% became tumor-free). The advanced-staged tumors also demonstrated significant responses (100% regressed). Therefore, our results demonstrate the powerful utility of this new inducible xenograft tumor model for efficacy evaluation of cancer targets, and it provides a direct in vivo efficacy validation of mTOR as a cancer therapeutic target.