Trafficking of women for the purpose of sexual exploitation in Europe

Tens of thousands of women and girls are trafficked from mainly poorer to richer regions of Europe and forced into prostitution. Traffickers abuse the poor socio-economic situation of young women in these poorer regions to exploit them into prostitution. Sex trafficking poses a huge impact on society. Besides the economical side – sanctions for not complying with certain anti-trafficking efforts or health care costs for victims – the political- and social impact is drastic. Social impact for victims is huge: during their trafficking they face extreme violence, coercion, and rape, which leave both psychological as physical marks after their return. Additionally, drug use by victims will eventually place another burden on society. In order to stop sex trafficking the pre-departure state, transit stage, exploitation stage and demand side need to be targeted. The pre-departure state is most important for source countries. The exploitation- and demand stages are tightly intertwined with legislation on prostitution. When prostitution is legalized and demand is high, exploitation is a natural result. Sweden has shown that demand can be strongly decreased by criminalizing the purchase of sex. By not criminalizing sales of sex, victims of sexual exploitation cannot be prosecuted. The European Commission has recently adopted a law prohibiting the purchase of sex, therewith copying this system. Country-specific adaptations might be necessary, as European countries are very different and deal with trafficking in very dissimilar ways. Adopting demand-tackling legislation might not have the desired effect in Eastern European source countries. Additionally, European countries must continue to work together. Sex trafficking seemingly follows basic economics: when there’s no demand, there’s no market, and therefore supplies will drop. Having looked at the different efforts countries make, it can be concluded that – although all stages of sex trafficking need to be targeted – eliminating the demand for sex workers seems to work as a best method

Possibilities and Pitfalls of Social Media for Translational Medicine

We live in an age where the sharing of scientific findings and ideas is no longer confined to people with access to academic libraries or scientific journals. Social media have permitted for knowledge and ideas to be shared with an unprecedented speed and magnitude. This has made it possible for research findings to have a greater impact and to be rapidly implemented in society. However, the spread of unfiltered, unreferenced, and non-peer-reviewed articles through social media comes with dangers as well. In this perspective article, we aim to address both the possibilities and pitfalls of social media for translational medicine. We describe how social media can be used for patient engagement, publicity, transparency, sharing of knowledge, and implementing findings in society. Moreover, we warn about the potential pitfalls of social media, which can cause research to be misinterpreted and false beliefs to be spread. We conclude by giving advice on how social media can be harnessed to combat the pitfalls and provide a new avenue for community engagement in translational medicine

Adaptive Translational Medicine: Towards New Therapeutic Approaches For Metabolic Diseases

Inborn errors of metabolism, also known as metabolic diseases, are caused by monogenetic variants and often follow autosomal recessive inheritance. These variants cause a change in enzyme function, including a partial or total loss of function or gained abnormal function, leading to changes in cellular metabolism, e.g., synthesis, breakdown or change of cellular metabolites. Thousands of enzymes, thus thousands of metabolic diseases exist. There is an urgent need for (curative) treatment options that are applicable to multiple diseases or that can be rapidly adapted for use in different diseases. In this thesis, three levels of possible therapeutic interventions are discussed, developed for patients from our own hospital. First, using the conventional approach for IARS1 deficiency, we utilize characterization of the disease and evaluation of the molecular mechanism to develop and test a substrate therapy. This approach is specific to a single disease. We continue to test similar treatments for patients with other ARS1 deficiencies, and further explore its use in patients with various ARS2 deficiencies. Second, we target the liver, as it has a central role in metabolism. Many metabolic diseases can be treated or cured by liver transplantation, but long-term survival of transplantation recipients has remained suboptimal. With the emergence of alternatives such as bankable liver stem cells, allogenous matched or autologous ex vivo genetically corrected stem cells could be transplanted. Improved donor-recipient compatibility could help improve outcomes. We therefore investigate the effect of HLA matching on liver transplantation outcomes. Third, we explore the use of in vivo genetic correction using prime editing, a precise search-and-replace genetic editing technique, which has the potential to cure almost any metabolic disease by directly targeting the underlying genetic defect. We pave the way towards the first in vivo genetic correction therapy of the brain and liver of patients with POLG-related disease

Possibilities and Pitfalls of Social Media for Translational Medicine

10.3389/fmed.2018.00345Frontiers in Medicine

The role of M3-muscarinic receptor signaling in insulin secretion

Recently, M3-muscarinic receptor (M3R) has been identified as the bona fide receptor responsible for the cholinergic regulation of glucose-induced insulin release. The molecular mechanisms of such regulation have also begun to be unravelled. These include the conventional G protein-dependent pathways involving calcium mobilization and activation of protein kinase C. In addition, recent studies also provided evidence for G protein-independent pathways in the regulation of insulin secretion by M3R. These include phosphorylation/arrestin-dependent activation of protein kinase D1, Src family kinase-dependent activation of the sodium channel NALCN and the involvement of regulator of G protein signaling (RGS)-4. Time has now come to extend these studies which were done mainly in rodents to human and explore the potential for targeting such pathways at different levels for the treatment of diseases with impaired insulin secretion such as type II diabetes

The Effect of Genetic HLA Matching on Liver Transplantation Outcome: A Systematic Review and Meta-Analysis

Objective:. We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation Background:. Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes. Methods:. We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality). Results:. We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, P = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, P = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ. Conclusions:. We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality

Assessment of human leukocyte antigen matching algorithm PIRCHE-II on liver transplantation outcomes

For liver transplantations, human leukocyte antigen (HLA) matching is not routinely performed because observed effects have been inconsistent. Nevertheless, long-term liver transplantation outcomes remain suboptimal. The availability of a more precise HLA-matching algorithm, Predicted Indirectly Recognizable HLA Epitopes II (PIRCHE-II), now enables robust assessment of the association between HLA matching and liver transplantation outcomes. We performed a single-center retrospective cohort study of 736 liver transplantation patients. Associations between PIRCHE-II and HLAMatchmaker scores and mortality, graft loss, acute and chronic rejection, ischemic cholangiopathy, and disease recurrence were evaluated with Cox proportional hazards models. Associations between PIRCHE-II with 1-year, 2-year, and 5-year outcomes and severity of acute rejection were assessed with logistic and linear regression analyses, respectively. Subgroup analyses were performed for autoimmune and nonautoimmune indications, and patients aged 30 years and younger, and older than 30 years. PIRCHE-II and HLAMatchmaker scores were not associated with any of the outcomes. However, patients who received transplants for autoimmune disease showed more acute rejection and graft loss, and these risks negatively associated with age. Rhesus mismatch more than doubled the risk of disease recurrence. Moreover, PIRCHE-II was inversely associated with graft loss in the subgroup of patients aged 30 years and younger with autoimmune indications. The absence of associations between PIRCHE-II and HLAMatchmaker scores and the studied outcomes refutes the need for HLA matching for liver (stem cell) transplantations for nonautoimmune disease. For autoimmune disease, the activated immune system seems to increase risks of acute rejection and graft loss. Our results may suggest the benefits of transplantations with rhesus matched but PIRCHE-II mismatched donor livers

Aminoacyl-tRNA synthetase deficiencies in search of common themes

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