However, re-differentiation effects (expression level of thyroid-specific genes) were modest compared to PT. We are currently seeking the better method enabling more efficient differentiation. In addition, these cells do not have unlimited proliferative capacity: all targets the cells will stop growing until 3�C4 months, due to cellular senescence. Conversion of differentiated cells into multipotent progenitor or different lineage has been reported by several groups. Adult hepatocytes were converted into insulin-producing cells by transgenes, Pdx-1 and Ngn-3 [26]; retinal pigment epithelium into retinal neurons by Sox-2 [27]; and interfollicular epidermal basal keratinocytes into the cells capable of differentiating into neuronal cells by Oct-4 [28].

The aforementioned studies used exogenous trangenes, some of which are key transcription factors for generating iPS cells. To our knowledge, there is only one report describing conversion from differentiated cells into multilineage progenitor cells without any gene delivery. Adult intestinal epithelial cells were dedifferentiated into nestin-positive cells that have multilineage differentiation capacity into neuronal, pancreatic and hepatic lineages [29]. The authors cultured intestinal epithelial cells on mouse embryonic fibroblasts (feeder layer) in medium supplemented with leukemia inhibitory factor, EGF and bFGF. For generating iPS cells, two key transcription factors Klf-4 and Sox-2 could be replaced by chemical compounds [30], [31]. SAGM contains EGF, insulin, other growth factors and chemicals.

These findings suggest that a particular combination of growth factors/chemicals probably changes transcriptional profiling, leading to dedifferentiation of thyrocytes. Microarray analysis revealed that the expression of ABCG2, Oct-4 and CD133 which have been used to identify stem cells in a number of tissues, were not up-regulated in the SAGM-grown cells, suggesting that the cells were a bit far from genuine pluripotent stem cells. Rather, they seem to be more committed stem/progenitor cells. In fact, mesenchymal stem cell markers CD106, CD105 and CD90 but not CD73 were highly up-regulated. Taken together with down-regulation of E-cadherin, these results suggest that the SAGM-grown cells acquired properties prior to cells committed to thyroid epithelial lineage. GO enrichment analysis was performed and revealed differentially regulated cellular processes.

Embryo implantation had the lowest p value among the up-regulated GO processes. Other up-regulated processes were endoplasmic reticulum, sterol/steroid/lipid biosynthesis/metabolic processes, cell cycle and oxidoreductase activity. These processes are generally related to protein/membrane synthesis presumably linked Carfilzomib to cell proliferation. Regarding down-regulated GO processes, protein binding and cell adhesion processes were impacted.

Thus, the growth kinetics of wild-type MHV-A59 and MHV-N1348A in macrophages and DCs were indistinguishable. FIG. 3. MHV-N1348A replication in macrophages and DCs. (a) Peritoneal macrophages, a Kupffer cell line, and bone marrow-derived cDCs and pDCs were infected with wild-type MHV-A59 or MHV-N1348A (MOI = 1). Viral titers in supernatants were measured at the … MHV-N1348 meanwhile infection results in elevated IFN-�� expression in pDCs. The control of MHV-A59 in mice is strongly dependent on swift IFN-�� expression by pDCs during the early phase of infection (5). We found no difference in the ability of MHV-N1348A to replicate in pDCs (Fig. (Fig.3);3); however, compared to that for wild-type MHV-A59 infection, IFN-�� production was significantly increased following MHV-N1348A infection (Fig. (Fig.

4a).4a). Notably, neither macrophages nor cDCs produced elevated IFN-�� levels upon MHV-N1348A infection, suggesting that, similar to that for wild-type MHV-A59, immediate IFN-�� expression upon MHV-N1348A infection is still restricted to pDCs. We also assessed if MHV-N1348A replication is more vulnerable to IFN-�� pretreatment than wild-type MHV-A59 replication. Macrophages and cDCs were pretreated with different dosages of IFN-�� and, 4 h later, were infected with wild-type MHV-A59 or MHV-N1348A. As shown in Fig. Fig.4b,4b, the viral titers determined at 18 h p.i. were indistinguishable between wild-type MHV-A59 and MHV-N1348A infections, irrespective of whether the infections were done at low (0.01) or high (1) MOIs. FIG. 4. MHV-N1348A and type I IFNs.

(a) Bone marrow-derived pDCs and cDCs, as well as peritoneal macrophages, were infected with wild-type MHV-A59 (MHV wt) or MHV-N1348A (MOI = 1). The levels of IFN-�� in the supernatants were measured at the indicated … MHV-N1348A is attenuated in livers of IFNAR?/? mice. The phenotypic analysis of MHV-N1348A revealed a profound impact of this mutant virus on the induction of viral hepatitis in mice, and we observed elevated IFN-�� expression in MHV-N1348A-infected pDCs. To clarify if the lack of acute viral hepatitis is related to elevated IFN-�� expression, we infected type I IFN receptor-deficient mice (IFNAR?/? mice) that cannot respond to type I IFNs. MHV-A59 can replicate essentially uncontrolled in IFNAR?/? mice, and these mice succumb to the infection at day 2 p.i. (4). Therefore, at day 2 p.i.

we assessed the viral titers in the spleens and livers and the serum ALT values of IFNAR?/? mice (on the B6 or 129Sv background) that were infected with 5 PFU (i.p.) of wild-type MHV-A59 or MHV-N1348A. As shown in Fig. Fig.4c,4c, wild-type MHV-A59 and MHV-N1348A titers were increased by several orders of magnitude in mice lacking the IFNAR compared Brefeldin_A to those for wild-type mice. However, MHV-N1348A titers did not fully reach those of wild-type MHV-A59 in B6-IFNAR?/? and A129 (IFNAR?/? on the 129Sv background) mice.

12,15,41�C45 Interestingly, expression of some of these genes is regulated by DNA methylation at their promoters. In general, selleckchem promoter hypermethylation is associated with the loss of expression of these genes. A spectrum of methods is available for DNA methylation. These include cytosine deamination PCR, semi-quantitative and quantitative methylation-specific PCR (MSP), differential methylation hybridization (DMH), restriction landmark genomic scanning (RLGS), single-nucleotide primer extension (SNuPE), pyrosequencing, and methylation microarray for large-scale genome analysis.15,46 However, MSP is a simple and sensitive method, and is the most commonly employed method for methylation analysis.15 Table 1 shows some common genes that are hypermethylated in the prostate cancer and are tested for the development of early detection.

These genes participate in DNA damage repair (GSTP1, MGMT), cell adhesion (CD44, EDNRB, ECADHERIN, APC, LGALS3), cell growth, invasion and metastasis (TIMP2, TIMP3, LGALS3), apoptosis (DAPK), cell cycle control (CDKN2A, CDKN1A), signal transduction (RASSF1A), and hormonal responses (AR, ER, RAR��2).12,15,41�C45 Table 1. Summary of genes whose promoters are frequently methylated in prostate cancer. The glutathione S transferases (GSTs) are a family of enzymes involved in protecting cells from DNA damage, and thence cancer initiation. GSTs carry out intracellular detoxification of xenobiotics and carcinogens by covalent bonding to glutathione via a thiol link.

47 In humans, six cytosolic isoforms of GST (alpha, mu, pi, sigma, theta, and omega) and one membrane isoform of GST have been described- of which the pi isoform (GSTP1) has been extensively studied.48,49 In prostate cancer, GSTP1 is observed to be silenced by promoter methylation.17,39,50,51GSTP1 promoter methylation has been detected in cancerous as well as prostatic intraepithelial neoplasia (PIN) lesions, whereas it has been rarely detected in normal prostate or BPH tissues.40,52,53 Hypermethylation of GSTP1 was also found in a subset of proliferative inflammatory atrophy (PIA) lesions, which are believed to be tumors precursors.53 Another DNA repair gene O6-Methylguanine-DNA-Methyltransferase (MGMT) was found to be hypermethylated (moderate to high levels) in many cancers including prostate cancer.54,55MGMT removes mutagenic and cytotoxic alkyl adducts from O6-guanine in DNA.

56 However, hypermethylation of this gene promoter results in a loss of function in various cancers including prostate cancer.55,57 CD44, an integral membrane glycoprotein, plays a role in cell adhesion and cell-matrix interactions as a receptor for hyaluronic Dacomitinib acid and osteopontin.58 In prostate cancer, CD44, acts as a metastasis suppressor gene, and its down-regulation is associated with tumor progression and metastasis. Hypermethylation of CpG islands in the promoter region of CD44 results in decreased expression.

Recent studies showed that the HH pathway is Seliciclib frequently activated in HCC (1-3). The increased expression of GLI1 protein in breast tumor and hepatoblastoma is also reportedly correlated with significantly poor prognosis (24-26). The HH pathway mediates the progression of breast cancer from non-invasive to invasive and serves as a significant independent prognostic indicator in gastric and bladder cancers (27,28). In our previous studies, we found an association with poor clinical prognosis of the HH pathway in human HCC (29) as well as the simultaneous expression of GLI1 in HCC and liver tissues adjacent to the tumor. These findings prompted us to expand our sample size to 46 HCC patients and extend their follow ups to confirm whether the expression of HH pathway components is associated with HCC progression and clinical outcome.

Materials and methods Patients and tumor samples This study included 46 HCC patients consisting of 40 (86.96%) males and 6 (13.04%) females with ages ranging from 35 years to 79 years (median age =49 years). All patients underwent surgical treatment from April 2002 to July 2005 in Beijing Cancer Hospital. The clinical and pathologic data included patients�� demographics (age, gender), tumor size, degree of histological differentiation, and complete follow-up record. The exclusion criterion was preoperative therapy. The study was approved by the Ethics Committee of Human Experimentation of Beijing Cancer Hospital. All samples of tumor and adjacent normal liver tissues were freshly obtained immediately after surgery.

The samples of tumor tissue were collected from the luminal aspect of the malignancy, whereas those of paired adjacent normal tissue were from the luminal aspect of the liver tissues 2 cm away from the tumor margin. All tissue samples were snap-frozen in liquid nitrogen for 30 min after resection and stored at �C80 ��C. RNA extraction and complementary DNA (cDNA) preparation The total RNA was isolated from 100 mg of each tissue sample using TRIzol reagent (Invitrogen, Carlsbad, CA, USA) following the manufacturer��s instructions, and stored at -80 ��C for further use. The reverse transcription (RT) of the total RNA (1 ��L) was performed using SuperScript First-Strand Synthesis System (Invitrogen). The internal control was glyceraldehyde-3-phosphate dehydrogenase (GAPDH; forward primer: 5′-TCA ACG GAT TTG GTC GTA TT-3′, reverse primer: 5′-AGT CTT CTG GGT GGG AGT GAT-3′, 540 bp).

Polymerase chain reaction (PCR) amplification To analyze the expression of individual HH gene, 1 ��L of cDNA was amplified with 6.25 units of AmpliTaq Gold (Roche, Basel, Switzerland) in 25 ��L reaction solution containing 0.5 mmol/L dNTPs and 1.5 mmol/L MgCl2. Anacetrapib The primer sequences for PCR of each gene were designed according to a previous study (9) or using Genbank sequences (Table 1).

4 pmol of siRNA for 20 min at room temperature and the mixture was added drop-wise to wells. Reduced expression of target proteins was confirmed by western blot analysis of cell read me lysates. Preparation of cell lysates Cells (1��107) were harvested, washed three times in 20 mM iodoacetamide (with centrifugation for 5 min at 450 x g each time), and resuspended in cell lysis buffer (150 mM NaCl, 5 mM EDTA, 20 mM Tris-HCl pH 7.5, 0.5% Triton X-100). Resuspended cells were incubated on ice for 1 h with occasional mixing, and then stored at ?80��C overnight. The following day, the cell lysates were thawed on ice, and then centrifuged at top speed in a desktop microcentrifuge for 30 min at 4��C. The supernatants were transferred to new tubes and stored at ?80��C.

Aliquots of lysates were mixed with 5X sodium dodecyl sulfate loading dye (250 mM Tris-HCl pH 6.8, 10% w/v sodium dodecyl sulfate, 30% v/v glycerol, 5% v/v ��-mercaptoethanol, 0.02% w/v bromophenol blue) and boiled for 5 min prior to gel loading. Western blot analysis Cell lysate samples were boiled for 5 min and then loaded on 4�C20% Tris-glycine pre-cast gels (Invitrogen). Electrophoresis was performed at 125 V at room temperature. The proteins were transferred at 30 V for 2 h at room temperature to polyvinylidene difluoride Immobilon-P membranes (Millipore, Billerica, MA, USA). After overnight blocking in a 5% w/v solution of nonfat dry milk, the membranes were incubated with primary antibodies (diluted with 5% nonfat dry milk).

Incubation with anti-actin antibody (1:2,000) was for 1 h and incubation with anti-full-length APLP2 antibody (1:1,000), anti-APLP2 C-terminus antibody (1:1,000) or anti-APP C-terminus antibody (1:1,000) was for 1.5 h. After primary antibody incubation, 3 washes with 0.05% Tween-20 in phosphate-buffered saline (PBS) for 10 min were performed. The membranes were subsequently incubated for 1 h in secondary antibodies, diluted 1:10,000 in 0.05% Tween-20 in PBS, and washed 3 times for 10 min with 0.3% Tween-20 in PBS. For protein visualization, the membranes were incubated for 1 min in Pierce ECL Western Blotting Substrate, or (for anti-APLP2 C-terminus) in Pierce SuperSignal West Pico Chemiluminescent Substrate (Thermo Scientific, Rockford, IL, USA) and exposed to Kodak BioMax MR film (Rochester, NY, USA).

For densitometry of protein bands, quantification was done with the Molecular Imager ChemiDoc XRS system with Quantity One 1-D analysis software (BioRad, Hercules, CA, USA). Assessment of cellular growth Growth of cells was assessed using thiazol blue (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium Dacomitinib bromide, MTT) purchased from Sigma (St. Louis, MO, USA), by the MTT assay. Briefly, cells were seeded in 6-well plates at 1��105 cells per well 24 h prior to the start of any cell culture treatments. The addition of ��-secretase inhibitors to S2-013 or hTERT-HPNE cells signified the start of the time course.

Alexa 488 and Alexa 594-conjugated secondary antibodies (Molecular Probes, Carlsbad, CA) were used. VX-770 Each specimen was visualized using a Zeiss LSM 510 META microscope (Carl Zeiss, Gottingen, Germany). siRNA-expressing constructs and the generation of stable cell lines The methods used were as previously reported [4]. We used a pSUPERgfp vector (OligoEngine, Seattle, WA) for expression of siRNA. The target sequences for the scrambled negative control and for BART were 5��-TTCTCCGAACGTGTCACGT-3�� and 5��-CATGGCAGCCTTCACCACA-3��, respectively. S2-013 and PANC-1 cells were transfected with either empty Neo-pSUPERgfp, a scrambled oligo-pSUPERgfp negative control, or a plasmid designed to express siRNA to BART, using FuGENE6 (Roche), according to the manufacturer’s instructions.

Cells were selected in medium containing 500 ��g/mL of geneticin to generate stable pSUPERgfp cell lines. Western blotting was performed to analyze the protein levels of the single clones. siRNA treatment RNAi targeting ANX7 and scrambled negative control siRNA oligonucleotides were purchased from Santa Cruz Biotechnology (29690 and 37007). For assays to examine the effect of siRNAs on ANX7 expression, S2-013 and PANC-1 cells that express ANX7 were plated in six-well plates. After 20 h, the cells were transfected with 80 pmols of siRNA in siRNA transfection reagent (Santa Cruz), following the manufacturer’s instructions. Transwell motility assay Cells (3.0��104) were plated in the upper chamber of BD BioCoat Control Culture Inserts (24-well plates, 8 ��m pore size; Becton Dickinson, San Jose, CA).

Serum-free culture medium was added to the upper chamber, and medium containing 5% FCS was added to the lower chamber. Cells were incubated on the membranes for 12 h, and motility was quantified. Matrigel invasion assay The two-chamber invasion assay was used to assess cell invasion (24-well plates, 8 ��m pore size, membrane coated with a layer of Matrigel extracellular matrix proteins; Becton Dickinson). Cells (4.0��104) were seeded in serum-free medium into the upper chamber and allowed to invade toward 5% FCS (the chemoattractant) in the lower chamber. After 20 h incubation, the number of invading cells at the bottom of the membrane was estimated under microscopic observation by counting three independent visual fields.

BART or ANX7 RNAi S2-013 cells were preincubated for 30 min in serum-free medium containing 250 nM Ro-32-0432, 10 mM safingol, 5.0 ��M rottlerin, or 5.0 ��M myristoylated PKC�� pseudosubstrate inhibitor. These preincubated cells were used Carfilzomib in the two-chamber invasion assay to assess cell invasion. Wound healing immunostaining assay A wound in the form of a cross was made through a confluent cell monolayer with a plastic pipette tip and cells were then allowed to polarize and migrate toward the wound. After 4 h, cells were immunostained with primary antibody and then incubated with fluorophore-conjugated secondary antibodies as described above.

They do not specialise in any specific industry but provide public access to 3D printing. They provide a fast service (less than 10-day turnaround) and charge based on volume in cm3 and the material used to produce the model. We used a plastic-like material PA 2200, which is printed selleck using the technique of Selective-Laser-Sintering (SLS). SLS uses a high power laser (e.g., a carbon dioxide laser) to fuse small particles of plastic or metal, ceramic, or glass powders into the designated object. PA 2200 is a white nylon, which is strong and flexible. It is also one of their most detailed (minimum detail 0.2mm) materials. Minimum wall thickness of structures printed can be 0.7mm and maximum size of printed structure can be 31 �� 23 �� 18cm (http://www.shapeways.com/materials/white_strong_flexible��accessed 19/09/11).

It is stable up to a temperature of 80��C.4.6. Assessment of the ModelThe models produced were then validated against the 3D CT scan images using digital electronic vernier calipers to take multiple measurements at defined intervals (20mm) along the model bones and at the same points on the CT scan (Figure 8). Two observers measured the same segments independently on three separate occasions.Figure 8Measurements on CT scan.The measurements were analysed for a statistically significant difference with a paired Student’s t-test. The P values showed no statistical difference in dimensions between the printed models and the original CT scans (see Tables Tables11 and and22).Table 1Table 24.7. Model ProductionWe produced a 3D reproduction of malunited forearm bones from standard CT DICOM data using free open-source software.

The models cost a total of ��77 including shipping to the department for both the radius and ulna (Figures (Figures99 and and10)10) and took only 7 days to arrive.Figure 9��Model�� radius and ulna.Figure 10Distal radius showing level of physeal detail.5. DiscussionThe main objective was to establish a simple and cost-effective method to produce accurate and detailed physical 3 dimensional models from standard CT scans. We aimed to do this quickly without specialist expertise. With the use of OsiriX and Meshlab on a standard personal computer and a publicly accessed commercial online 3D printing service, an inexpensive (��77 compared with ��500�C��900) model suitable for preoperative planning can be produced in a short time frame (7 days).

The data from the measurements confirmed the fidelity of the model produced. Other reports have used the technique of Carfilzomib SLS [18]. However, none are known to have used Osirix [22] to manipulate the data for this purpose.The measurements and validation of 3D models can undoubtedly be improved and are the subject of further work. This study focused on simple-shaped long bones with thick periosteum allowing for noncomplex image processing.

4. Experimental DesignThe searches were carried out on the MDL Drug Data Report (MDDR) database. The 102,516 molecules in the MDDR database were converted to Pipeline Pilot ECFC_4 fingerprints and folded to give 1024-element fingerprints [28].For the screening experiments, three data sets (DS1�CDS3) [29] were chosen from the MDDR database. Dataset DS1 contains selleckchem Imatinib 11 MDDR activity classes, with some of the classes involving actives that are structurally homogeneous and others involving actives that are structurally heterogeneous (structurally diverse). The DS2 dataset contains 10 homogeneous MDDR activity classes and the DS3 dataset contains 10 heterogeneous MDDR activity classes. Full details of these datasets are given in Tables Tables11�C3.

Each row in the tables contains an activity class, the number of molecules belonging to the class, and the class’s diversity, which was computed as the mean pair-wise Tanimoto similarity calculated across all pairs of molecules in the class using ECFP6. The pair-wise similarity calculations for all datasets were performed using Pipeline Pilot software [28]. Table 1MDDR activity classes for DS1 dataset.Table 3MDDR activity classes for DS3 dataset.For each dataset (DS1�CDS3), the screening experiments were conducted with 10 reference structures selected randomly from each activity class and the similarity measure used to obtain an activity score for all of its compounds. These activity scores were then sorted in descending order with the recall of the active compounds, meaning the percentage of the desired activity class compounds that are retrieved in the top 1% and 5% of the resultant sorted activity scores, providing a measure of the performance of our similarity method.

3. Results and DiscussionOur goal was to identify different retrieval effectiveness of using different search approaches. In this study, we tested the TAN, BIN, and BINRF models against the MDDR database using three different datasets (DS1�CDS3). The results of the searches of DS1�CDS3 are presented in Tables Tables44–6,6, respectively, using cutoffs at both 1% and 5%.Table 4The recall is calculated using the top 1% and top 5% of the DS1 data sets when ranked using the TAN, BIN, and BINRF.Table 6The recall is calculated using the top 1% and top 5% of the DS3 data sets when ranked using the TAN, BIN, and BINRF.

In these tables, the first column from the left contains the results for the TAN, the second column contains the corresponding results when BIN is used, and the last column of each table contains the corresponding results when BINRF is used.Each row in the tables lists the recall for the top 1% and 5% of a sorted ranking when averaged over the ten searches for each activity class; and the penultimate row in each table corresponds to the mean value for that similarity method when averaged over all of the activity Drug_discovery classes for a dataset.

Moreover, abstinence and treatment completion were the sole outcome measures in this study. Finally, the meta-analysis by Lees and colleagues [27] can be regarded as outdated, till as it does not include any published study since 1999. Since sound scientific evidence is needed to inform service users, treatment providers, and policy makers about TCs’ potential to promote recovery, the aim of this paper is to review the effectiveness of TCs for addictions, based on a comprehensive systematic review of available randomized and nonrandomized controlled studies. The paper is limited to studies with a controlled design, as these are robust study designs that generate a high level of evidence. Also, nonrandomized studies were included, since the number of randomized studies was very small (n = 5) and true randomization was compromised in several studies.

Given the focus on recovery, a range of outcome measures��apart from abstinence��will be evaluated and a long-term outcome perspective will be applied, including an assessment of the influence of aftercare or continuing support. 2. MethodsThis narrative review focuses on controlled studies (randomized trials as well as quasi-experimental designs) of therapeutic communities for addictions. We opted for a narrative review instead of a meta-analysis, given the heterogeneity of the study methodologies and the variety in data reporting. Studies were eligible if they met the following inclusion criteria.

Intervention: therapeutic communities for the treatment of drug addiction that are long-term hierarchically structured (residential) educational environments, where former drug users live together and work towards recovery, and which are based on self-help and mutual help principles [12, 21].Target population: adults addicted to illegal drugs (mostly heroin, cocaine, or amphetamines), often in combination with an addiction to other (legal) substances (e.g., alcohol, prescription drugs). Studies including Batimastat persons with comorbid psychiatric disorders were eligible, if all study participants had a drug addiction.Outcome measures: at least one of the following (nonexhaustive) list of outcome measures was reported: substance use (illicit drug use, alcohol use), length of stay in treatment (retention, treatment completion/drop-out), employment status, criminal involvement, health and well being, family relations, quality of life, treatment status, mortality, and so forth. Objective (describing the actual situation) and subjective (indicating individuals’ personal perspective) indicators were considered, as well as self-report measures, biological markers, and administrative data.

However, this does not imply that their goal is abstinence. 15 respondents were still using drugs in the year preceding the interview. Despite their drug use, these respondents identified themselves as desasters; for instance, they were former regular heroin users but since that period they switched to regular cannabis use. We did include these respondents in selleck Volasertib our study when they identified themselves as desisting persons. In the past, lifelong abstinence was seen as the only indicator of recovery. In recent years, however, abstinence is seen as just one indicator of recovery and not the only or ultimate goal; significant reductions in drug use are also seen as important indicators [44].4.3.

The Transtheoretical Theory as an Extension of the Cognitive Transformation TheoryRecovery and desistance are two research traditions originated from a different context, developed parallel to each other, and seldom interconnected. Recovery originated from the mental health discipline; desistance originated from the criminal career tradition and it is predominantly criminological focused. However, theories on recovery and desistance have important similar characteristics. Recovery and desistance are both transformational processes and not linear but dynamic and gradual processes. People in the process of recovery and desistance are active agents. These processes require human agency which in its turn demands individual choice and power. The major difference between recovery and desistance is that has to do with the final ��goal�� of change. Regarding recovery, the people themselves define what recovery entails.

White has described this goal for people living with psychiatric and/or addiction disorders as ��to eliminate or manage their symptoms, increase their capacity to participate in valued relationships and roles, and embrace purpose and meaning in their lives, in other words, experience recovery�� [45]. In desistance, however, the focus is mainly on socially desirable outcomes (e.g., no illegal drug use, no criminal offences, employment) and less on client-reported outcomes and starting from clients’ own expectations and experiences (e.g., quality of life) [46]. As active agents, the respondents in our study challenge some of the socially desirable outcome indicators of change, in particular of no drug use.

Following the drug users’ perspective, when tackling drug-related crime, it is as important to tackle the drug using problem and related problems on other life domains, besides the criminal problem. After all, in most cases, when controlling the drug AV-951 problem, the criminal career will be positively influenced.We are thus convinced that these two traditions can learn from each other and that evidence of one tradition can extend knowledge of the other.