Drug law enforcement : a review of the evaluation literature

This article describes the results of a systematic review of drug law enforcement evaluations. The authors describe the search procedures and document the results in five main categories: international/national interventions (e.g., interdiction and drug seizure), reactive/ directed interventions (e.g., crackdowns, raids, buy-busts, saturation patrol, etc.), proactive/ partnership interventions (e.g., third-party policing, problem-oriented policing, community policing, drug nuisance abatement, etc.), individualized interventions (e.g., arrest referral and diversion), or interventions that used a combination of reactive/directed and proactive/ partnership strategies. Results indicate that proactive interventions involving partnerships between the police and third parties and/or community entities appear to be more effective at reducing both drug and nondrug problems in drug problem places than are reactive/ directed approaches. But the general quality of research in drug law enforcement is poor, the range of interventions that have been evaluated is limited, and more high-quality research is needed across a greater variety of drug interventions.

Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

Street-level drug law enforcement : a meta-analytical review

Our paper presents the results of a meta-analytical review of street level drug law enforcement. We conducted a series of meta-analyses to compare and contrast the effectiveness of four types of drug law enforcement approaches, including community-wide policing, problem-oriented/ partnership approaches that were geographically focused, hotspots policing and standard, unfocused law enforcement efforts. We examined the relative impact of these different crime control tactics on streetlevel drug problems as well as associated problems such as property crime, disorder and violent crime. The results of the meta-analyses, together with examination of forest plots, reveal that problem-oriented policing and geographically-focused interventions involving cooperative partnerships between police and third parties tend to be more effective at controlling drug problems than community-wide policing efforts that are unfocused and spread out across a community. But geographically focused and community-wide drug law enforcement interventions that leverage partnerships are more effective at dealing with drug problems than traditional, law enforcement-only interventions. Our results suggest that the key to successful drug law enforcement lies in the capacity of the police to forge productive partnerships with third parties rather than simply increasing police presence or intervention (e.g., arrests) at drug hotspots.

Mussel-inspired porous SiO2 scaffolds with improved mineralization and cytocompatibility for drug delivery and bone tissue engineering

Porous SiO2 scaffolds with mesopore structure (named as MS scaffolds) have been proposed as suitable for bone tissue engineering due to their excellent drug-delivery ability; however, the mineralization and cytocompatibility of MS scaffolds are far from optimal for bone tissue engineering, and it is also unclear how the delivery of drugs from MS scaffolds affects osteoblastic cells. The aims of the present study were to improve the mineralization and cytocompatibility of MS scaffolds by coating mussel-inspired polydopamine on the pore walls of scaffolds. The effects of polydopamine modification on MS scaffolds was investigated with respect to apatite mineralization and the attachment, proliferation and differentiation of bone marrow stromal cells (BMSCs), as was the release profile of the drug dexamethasone (DEX). Our results show that polydopamine can readily coat the pore walls of MS scaffolds and that polydopamine-modified MS scaffolds have a significantly improved apatite-mineralization ability as well as better attachment and proliferation of BMSCs in the scaffolds, compared to controls. Polydopamine modification did not alter the release profile of DEX from MS scaffolds but the sustained delivery of DEX significantly improved alkaline phosphatase (ALP) activity of BMSCs in the scaffolds. These results suggest that polydopamine modification is a viable option to enhance the bioactivity of bone tissue engineering scaffolds and, further, that DEX-loaded polydopamine MS scaffolds have potential uses as a release system to enhance the osteogenic properties of bone tissue engineering applications.