Alternatives to prison for drug offenders in Belgium during the past decade

Objective: Imprisonment has a more pronounced criminogenic effect on drug offenders than on other types of offenders. Additionally, little research has been conducted on the practical application of drug-related alternatives to prison. Therefore, this study describes drug-related alternatives to prison in Belgium over a ten years' period since 2005. Methods: The applied drug-related alternatives to prison ('probation', 'conditional release', 'mediation in criminal cases', 'community service' and 'electronic monitoring') were subject to a secondary data analysis of the database of the Houses of Justice. Results: Men, the age group of 16-24 years old and Belgians are most sentenced to alternatives to prison. Nevertheless, 38% of women are guided towards 'probation' while 8% is 'mediated in criminal cases' compared to 30% and 5% of males respectively (p < .001). 26% of non-Belgians are involved in 'conditional release' and 'electronic monitoring' compared to 22% and 16% among Belgians (p < .001) respectively. With regards to age, 21% of the offenders older than 24 years are involved in 'electronic monitoring' compared to 6% among the offenders younger than 25 years (p < .001). Conclusions: The results highlight differences in punishment judgments by age, gender and nationality that continues to be indicative for perceived threat, danger and culpability of the offenders

Use of health care services by people with substance use disorders in Belgium: a register-based cohort study

Abstract Background The objective of the study was to describe the frequencies of health-care utilization by people with substance use disorder (SUD), including contacts with general practitioners (GP), psychiatrists, emergency departments (ED) and hospital admissions and to compare this frequency to the general population. Methods Data from the national register of people who were in treatment for SUD between 2011 and 2014 was linked to health care data from the Belgian health insurance (N = 30,905). Four comparators were matched on age, sex and place of residence to each subject in treatment for SUD (N = 123,620). Cases were further divided in five mutually exclusive categories based on the main SUD (opiates, crack/cocaine, stimulants, cannabis and alcohol). We calculated the average number of contacts with GP, psychiatrists and ED, and hospital admissions per person over a ten year period (2008–2017), computed descriptive statistics for each of the SUD and used negative binomial regression models to compare cases and comparators. Results Over the ten-year period, people in treatment for SUD overall had on average 60 GP contacts, 3.9 psychiatrist contacts, 7.8 visits to the ED, and 16 hospital admissions. Rate ratios, comparing cases and corresponding comparators, showed that people in treatment for SUD had on average 1.9 more contacts with a GP (95 % CI 1.9-2.0), 7.4 more contacts with a psychiatrist (95 % CI 7.0-7.7), 4.2 more ED visits (95 % CI 4.2–4.3), and 6.4 more hospital admissions (95 % CI 6.3–6.5). Conclusions The use of health services for people with SUD is between almost two (GP) and seven times (psychiatrist) higher than for comparators. People in treatment for alcohol use disorders use health care services more frequently than people in treatment for other SUD. The use of health services remained stable in the five years before and after the moment people with SUD entered into treatment for SUD. The higher use of primary health care services by people with SUD might indicate that they have higher health care needs than comparators. </jats:sec

Pituitary tumors contain a side population with tumor stem cell-associated characteristics

Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.Fil: Mertens, Freya. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Gremeaux, Lies. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica; BélgicaFil: Chen, Jianghai. Huazhong University of Science and Technology. Tongji Medical College Union Hospital; China. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Fu, Qiuli. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica. Zhejiang Provincial Key Laboratory of Ophthalmology; China. Medical College of Zhejiang University. Eye Center of the 2nd Affiliated Hospital; ChinaFil: Willems, Christophe. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Roose, Heleen. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Govaere, Olivier. KU Leuven. Department of Imaging and Pathology; BélgicaFil: Roskams, Tania. KU Leuven. Department of Imaging and Pathology; BélgicaFil: Cristina, Silvia Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Becu Villalobos, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Joriseen, Mark. University Hospitals Leuven. Unit Head and Neck Oncology; BélgicaFil: Vander Poorten, Vincent. University Hospitals Leuven. Research Group Experimental Oto-Rhino-Laryngology, ; BélgicaFil: Bex, Marie. University Hospitals Leuven. Unit Clinical and Experimental Endocrinology; BélgicaFil: Van Loon, Johannes. University Hospitals Leuven. Research Group Experimental Neurosurgery and Neuroanatomy; BélgicaFil: Vankelecom, Hugo. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgic

Stem cells in the pituitary gland and candidate cancer stem cells in pituitary tumors

It has repeatedly been postulated that the pituitary gland contains stem cells, putatively involved in the generation of new hormonal cells during homeostatic turnover as well as during plastic remodelling in response to changing endocrine needs of the body. In previous studies, our group clearly designated a candidate stem cell population in the anterior pituitary (AP) lobe of the adult mouse using the side population (SP) approach. In the first part of this thesis, we followed upon these studies and succeeded in identifying the stem/progenitor cells by fractionating the SP according to stem cell antigen-1 (Sca1) expression level. Detailed analysis of whole-genome expression profile, and of the capacity to form pituispheres and generate hormonal lineages (multipotency), tracked down the pituitary stem/progenitor cells in the non-Sca1high SP fraction. Sox2 emerged as one of the important markers of the cells . In situ examination localized the Sox2+ cells in the marginal zone around the cleft (periluminal layer), but additionally in clusters scattered over the gland, thus suggesting the existence of multiple niches which is considered favorably for swift and/or subtle adaptation of cellular composition. To probe the functional significance of the stem/progenitor cells, we meticulously examined their phenotype during neonatal maturation of the pituitary as a (re-)modelling paradigm. Higher abundance and proliferative activity , swifter differentiation competence and more prominent stemness-expression characteristics all point to an activated state of the stem/progenitor cells during the neonatal maturation phase. Moreover, in situ scrutiny revealed some remarkable topography including accumulation of Sox2+ cells in the wedge region of AP and intermediate lobe, and connection of the Sox2+ cell clusters to the periluminal layer, suggesting the idea that Sox2+ cell groups in the parenchyma originate from the cleft . Also these topographical peculiarities were more pronounced at neonatal than adult age. Together, our observations argue for functional involvement of the pituitary stem/progenitor cells in plastic (re-)modelling of the gland. There is growing evidence that tumors contain a subset of cells that drive their growth, maintenance, progression, therapy resistance and/or recurrence. Because knowledge on pituitary tumor pathogenesis is very limited, we introduced this appealing concept of cancer stem cells (CSC) in the field. In the second part of this thesis, we started to search for CSC(-like) cells by applying SP analysis,in other tumors shown to enrich for tumorigenic (CSC) activity. A SP was identified in all human pituitary adenomas analyzed, and whole-genome expression profiling revealed CSC-associated expression characteristics including EMT (epithelial-mesenchymal transition), a process recently shown to drive the generation and activity of CSC. Because microarray analysis indicated that the adenoma SP still included endothelial and immunecells, we further purified the SP from these cells and reached similar conclusions regarding transcriptomal profile. To assess functional CSC properties, the in vivo xenograft assay was tried but did not work forpituitary adenomas, probably because they are typically benign and slow-growing. Therefore, we set up in vitro tumorigenic (CSC) assays which are currently tested on adenoma SP. Moreover, we implemented complementary pituitary tumor models including (rodent) cell lines and a transgenic mouse model in which pituitary tumor develops de novo in the normal microenvironment of the gland. A SP was identified in all these modelsand is now examined for molecular and functional CSC characteristics. In conclusion, this thesis study essentially contributed to the final identification of stem/progenitor cells in the pituitary gland and strongly argues for the functional implication of these cells in plastic cell (re-)modeling of the gland. Moreover, we identified a SP as candidate CSC in pituitary adenomas. In particular, EMT - in connection with SP/CSC -, may play an important role in pituitary tumor pathogenesis and represent an interesting mechanistic and therapeutic concept to advance the fieldstatus: publishe

Activated phenotype of the pituitary stem/progenitor cell compartment during the early-postnatal maturation phase of the gland

The rodent pituitary gland undergoes prominent maturation during the first weeks after birth, including a well-known increase in hormone-producing cells. In the past, it has frequently been postulated that stem cells are involved in this early-postnatal growth phase. This hypothesis can now be explored, as pituitary stem/progenitor cells were recently identified. Here, we analyzed in detail the mouse pituitary stem/progenitor cell compartment during the first postnatal week and compared its phenotype with that at the end of the first pituitary growth wave and at adult age. Stem/progenitor cells, as assessed by both side population phenotype and Sox2 expression, are most abundant at birth and gradually decline toward adulthood. The neonatal stem/progenitor cell compartment is clearly more active in terms of proliferation, stemness gene expression, and stem cell-related functional activity including sphere formation and multipotent differentiation capacity. In situ examination of pituitary sections reveals peculiar topographical arrangements of Sox2+ cells, again more pronounced at the neonatal age. Sox2+ cells are particularly prominent at the wedge junction of the anterior and intermediate lobe, and clusters of Sox2+ cells appear to sprout from this and other cleft-lining, marginal zone regions. Colocalization of Sox2 and hormones is generally not observed, thus suggesting mutually exclusive expression. Together, the neonatal pituitary stem/progenitor cell compartment displays an activated phenotype, thus supporting its involvement in the early-postnatal maturation process of the gland.status: publishe

Role of cancer stem cells in pancreatic ductal adenocarcinoma

As our understanding of pancreatic cancer evolves, evidence is growing to support a role for cancer stem cells in this devastating disease. Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis; these cells are thought to be highly resistant to standard treatment modalities. Here we review the current knowledge on pancreatic cancer stem cells and the implementation of cancer stem cell markers as prognostic or predictive biomarkers. We also discuss prospects for the use of cancer stem cells as targets for future therapeutic regimens in pancreatic cancer.status: publishe

Chemometrics and infrared spectroscopy – A winning team for the analysis of illicit drug products

Abstract Spectroscopic techniques such as infrared spectroscopy and Raman spectroscopy are used for a long time in the context of the analysis of illicit drugs, and their use is increasing due to the development of more performant portable devices and easy application in the context of harm reduction through drug checking or onsite forensic analysis. Although these instruments are routinely used with a spectral library, the importance of chemometric techniques to extract relevant information and give a full characterisation of samples, especially in the context of adulteration, is increasing. This review gives an overview of the applications described in the context of the analysis of illicit drug products exploiting the advantages of the combination of spectroscopy with chemometrics. Next to an overview of the literature, the review also tries to emphasize the shortcomings of the presented research papers and to give an incentive to what is needed to include chemometrics as a part of the daily routine of drug checking services and mobile forensic applications.info:eu-repo/semantics/publishe

Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine

ABSTRACT: BACKGROUND: Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC([MINUS SIGN]like) phenotype. METHODS: Human PDAC samples were expanded in immunodeficient mice and first-generation xenografts analyzed for the presence of a Hoechst dye-effluxing SP using flow cytometry (FACS). To investigate chemoresistance of the SP, mice bearing PDAC xenografts were treated with gemcitabine and SP proportion determined. In addition, the SP and the main tumour cell population (MP) were sorted by FACS for RNA extraction to profile gene expression, and for culturing under sphere-forming conditions. RESULTS: A SP was identified in all PDAC samples, analyzed. This SP was more resistant to gemcitabine than the other tumour cells as examined in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the MP as analyzed in vitro by sphere-forming capacity. CONCLUSION: We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer.Trial registrationClinicaltrials.gov NCT00936104.status: publishe

Synthetic cannabinoids and cannabis: how the patterns of use differ: results from the European web survey on drugs.

The aim of the current study is to assess if the patterns of use, socio-demographic characteristics, and use of other drugs differ among people who only use cannabis and those that use synthetic cannabinoids. Data from the second wave of the European Web Survey on Drugs, a web-based cross-sectional survey from 10 different European countries including individuals aged 18 and over (n = 37,109). Participation was anonymous, self-selecting, and voluntary. Cannabinoid exposure was taken as the dependent variable and categorized into the four following variables: (1) neither last year use of cannabis nor of synthetic cannabinoids (SC) independently of lifetime use, (2) cannabis use, (3) synthetic cannabinoids use, and (4) use of both, in the last 12 months. Independent variables included socio-demographic data, other drug use in the last month, and patterns of cannabis use. The use of SC was associated with higher odd of polysubstance use in the last year (OR 2.17; 95%CI 1.27–3.72) and use of other drugs during the last month. Low income (OR 2.34; 95%CI 1.20–4.58) and unemployment (OR 3.02; 95%CI 1.34–6.83) were related to SC use alone and cannabis plus SC use (OR 1.53; 95%CI 1.13–2.05) (OR 4.12; 95%CI 3.45–4.91). Social vulnerabilities were associated with the use of cannabis in the last year, but more markedly with synthetic cannabinoids use. Those who used synthetic cannabinoids reported using other drugs more often than those who used or did not use cannabis. The findings highlight the importance of social vulnerabilities and poly-drug use when assessing the use of new psychoactive substances such as SC and how these differ when compared to&nbsp;cannabis.</p