Constructive activism in the dark web: cryptomarkets and illicit drugs in the digital ‘demimonde’

This paper explores activism enacted through Silk Road, a nowdefunct cryptomarket where illicit drugs were sold in the darkweb. Drawing on a digital ethnography of Silk Road, we developthe notion of constructive activism to extend the lexicon ofconcepts available to discuss forms of online activism. Monitoringof the cryptomarket took place between June 2011 and its closurein October 2013. Just before and after the closure of themarketplace we conducted anonymous online interviews with 17people who reported buying drugs on Silk Road (1.0). Theseinterviews were conducted synchronously and interactivelythrough encrypted instant messaging. Participants discussedharnessing and developing the technological tools needed toaccess Silk Road and engage within the Silk Road community. Forparticipants Silk Road was not just a market for trading drugs: itfacilitated a shared experience of personal freedom within alibertarian philosophical framework, where open discussionsabout stigmatized behaviours were encouraged and supported.Tensions between public activism against drug prohibition andthe need to hide one’s identity as a drug user from public scrutinywere partially resolved through community actions thatinternalized these politics, rather than engaging in forms of onlineactivism that are intended to have real-world political effects.Most aptly described through van de Sande’s (2015) concept ofprefigurative politics, they sought to transform their values intobuilt environments that were designed to socially engineer amore permissive digital reality, which we refer to as constructiveactivism.

Midwives experiences of establishing partnerships: working with pregnant women who use illicit drugs

OBJECTIVE: To present the interpreted experiences of midwives who choose to work with pregnant women who also use illicit drugs. DESIGN: Twelve (n=12) Australian midwives were interviewed. Each interview was audio-taped, de-identified and transcribed. The interviews were analysed using a systematic, thematic analysis approach informed by Heideggarian hermeneutic phenomenology. FINDINGS: Three themes identified from the data that encapsulate the experience were establishing partnerships, making a difference, and letting go and redefining practice. The interpretations of establishing partnerships which includes engagement, genuine regard and compassion, with a subtheme courting the system are presented in this paper. The midwives' experiences were both positive and negative, as they were rewarded and challenged by the needs of women who use illicit drugs and the systems in which they worked. CONCLUSION: The midwives in this study found that establishing partnerships was essential to their work. They appraised their experience of working with pregnant women who used illicit drugs and found strategies that attempted to meet the needs of the women, the system and themselves. The participants revealed that to support women and families who use illicit drugs in their community, partnerships must be based on deep respect and trust. Significant components engagement, genuine regard and compassion that are central to midwifery partnerships require revisiting to address the needs of this vulnerable population of women.

Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity.

Microencapsulation of coupled folate and chitosan nanoparticles for targeted delivery of combination drugs to colon

Folate-chitosan nanoparticles, co-loaded with 5-fluourouacil (5-FU) and leucovorin (LV) and prepared by ionic gelation technology were physically microencapsulated by enteric polymer using a solvent evaporation method. Average particle size of the microencapsulated particles was in the range of 15 to 35 µm. High drug encapsulation efficiency was obtained for both 5-FU and LV in the microencapsulated particles. Both drugs were in amorphous state in the microencapsulated particles. By enteric coating, excellent pH-dependent release profile was achieved and no drug release was observed in simulated gastric and intestinal fluids. However, when the pH value reached the soluble threshold of Eudragit S-100, a constant and slow drug release was observed. The results indicated that these microencapsulated particles are a promising vehicle for selectively targeting drugs to colon in the chemotherapy of colon cancer.