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The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled "trafficking (...) the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal.
Establishing Trafficking in Human Beings for the Purpose of Organ Removal and Improving Cross-Border Collaboration in Criminal Cases: Recommendations In this short summary report on the legal definition of trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases, challenges, and recommendations in the areas of defining the crime, criminal investigation and prosecution, and cross-border cooperation are made. These are the outcomes (...) of a working group discussion during the writers' conference of the HOTT project, a European Union-funded project against trafficking in human beings for the purpose of organ removal.
Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded (...) in the view that an individual who parts with an organ for money within an illegal scheme is ipso facto a victim and that the crime of trafficking in human beings for the purpose of organ removal (THBOR) intersects with the crime of trafficking in organs. Consequently, the protection of victims should be a priority for all actors involved in antitrafficking activities: those combating organ-related crimes, such as health organizations and survivor support services, and those combating trafficking in human
Trafficking in Human Beings for the Purpose of Organ Removal and the Ethical and Legal Obligations of Healthcare Providers Physicians and other health care professionals seem well placed to play a role in the monitoring and, perhaps, in the curtailment of the trafficking in human beings for the purpose of organ removal. They serve as important sources of information for patients and may have access to information that can be used to gain a greater understanding of organ trafficking networks
Indicators to Identify Trafficking in Human Beings for the Purpose of Organ Removal This article presents indicators to support transplant professionals, judicial and law enforcement authorities and victim support workers with the identification of trafficking in persons for the purpose of organ removal. It outlines the legal and illegal service providers that facilitate trafficking in human beings for the purpose of organ removal and guides the reader through the following criminal process (...) : recruitment, transport, entrance, documents, housing, transplant, aftercare, and finance. Identification of illegal transplant activities by transplant professionals can support police and judiciary with the investigation, disruption, and prosecuting of trafficking networks.
Disrupted ERâ€toâ€Golgi trafficking underlies antiâ€HIV drugs and alcoholâ€induced cellular stress and hepatic injury Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two (...) dislocation and ER stress. Moreover, the coat protein complex II (COPII) complexes that mediate ER-to-Golgi trafficking accumulated in the RL-treated liver cells; this was not due to interference of RL with the initial assembly of the COPII complexes. RL also inhibited Golgi fragmentation and reassembly induced by short treatment and removal of brefeldin A.Our study indicates that ER-to-Golgi trafficking is disrupted by anti-HIV drugs and/or alcohol, and this contributes to subsequent ER stress
of individuals from five services in Vietnam were invited to be interviewed within the first 2 weeks of admission. It is part of a wider dataset for research on the health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam, the largest study to date on humantrafficking and health. We calculated proportions for all variables and conducted bivariate analyses using Fisher Exact Tests for their associations with mental health disorders symptoms.Before leaving home, 31 (...) Trafficking of Vietnamese women and girls for marriage in China Bride-trafficking has been a growing phenomenon in Southeast Asia, particularly in China, where one-child policies have resulted in demographic imbalances favoring males. Yet, empirical evidence about women and girls sold into marriage in China remains sparse.This study describes the experiences of 51 Vietnamese women and girls as young as 14 in post-trafficking services who were sold into marriage in China. A consecutive sample
A specialized pathway for erythroid iron delivery through lysosomal trafficking of transferrin receptor 2 Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released (...) in mitochondrial maintenance. Human TFR2 shares a lineage- and stage-specific expression pattern with MCOLN1, encoding a lysosomal iron channel, and MFN2, encoding a protein mediating organelle contacts. Functional studies reveal these latter factors to be involved in mitochondrial regulation and erythroid differentiation, with Mfn2 required for mitochondrial-lysosomal contacts. These findings identify a new pathway for erythroid iron trafficking involving TfR2-mediated lysosomal delivery followed
Immune Cell Trafficking to the Liver. The human liver is an organ with a diverse array of immunologic functions. Its unique anatomic position that leads to it receiving all the mesenteric venous blood, combined with its unique micro anatomy, allows it to serve as a sentinel for the body's immune system. Hepatocytes, biliary epithelial cells, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells express key molecules that recruit and activate innate and adaptive immunity (...) . Additionally, a diverse array of lymphoid and myeloid immune cells resides within and traffics to the liver in specific circumstances. Derangement of these trafficking mechanisms underlie the pathophysiology of autoimmune liver diseases, NASH, and liver transplantation. Here, we review these pathways and interactions along with potential targets that have been identified to be exploited for therapeutic purposes.
Antipsychotics Promote Metabolic Disorders Disrupting Cellular Lipid Metabolism and Trafficking. Antipsychotics frequently cause obesity and related metabolic disorders that current psychopharmacological/endocrinological theories do not explain consistently. An integrative/alternative theory implies metabolic alterations happening at the cellular level. Many observations in vitro and in vivo, and pivotal observations in humans, point towards chemical properties of antipsychotics, independent (...) of receptor binding characteristics. Being amphiphilic weak bases, antipsychotics can disrupt lysosomal function, affecting cholesterol trafficking; moreover, by chemical mimicry, antipsychotics can inhibit cholesterol biosynthesis. These two molecular adverse effects may trigger a cascade of transcriptional and biochemical events, ultimately reducing available cholesterol while increasing cholesterol precursors and fatty acids. The macroscopic manifestation of these molecular alterations includes
TBC1D8B Loss-of-Function Mutations Lead to X-Linked Nephrotic Syndrome via Defective Trafficking Pathways. Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glomerular epithelial cell, as major factors in disease pathogenesis. By exome (...) sequencing, we identified missense mutations in TBC1D8B in two families with an X-linked early-onset SRNS with FSGS. TBC1D8B is an uncharacterized Rab-GTPase-activating protein likely involved in endocytic and recycling pathways. Immunofluorescence studies revealed TBC1D8B presence in human glomeruli, and affected individual podocytes displayed architectural changes associated with migration defects commonly found in FSGS. In zebrafish we demonstrated that both knockdown and knockout of the unique
accelerated LCFA uptake, preventing C16 acyl CoA loss post-TAC. Long-chain acyl CoA was similarly reduced in human failing myocardium and restored to control levels by mechanical unloading. ACSL1 trafficked LCFA into ceramides without normalizing the reduced triglyceride storage in TAC. ACSL1 prevented de novo synthesis of cardiotoxic C16- and C24-, and C24:1 ceramides and increased potentially cardioprotective C20- and C22-ceramides post-TAC. ACLS1 overexpression activated AMPK at baseline, but during (...) TAC, prevented the reduced LCFA oxidation in hypertrophic hearts and normalized energy state (phosphocreatine:ATP) and consequently, AMPK activation.This is the first demonstration of reduced acyl CoA in failing hearts of humans and mice, and suggests possible mechanisms for maintaining mitochondrial oxidative energy metabolism by restoring long-chain acyl CoA through ASCL1 activation and mechanical unloading. By mitigating cardiac lipotoxicity, via redirected LCFA trafficking to ceramide
Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs (...) are beneficial in allergic asthma models, the effect on eosinophils has remained elusive.The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma.Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca2+ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time
The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling. The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein (...) mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving
“Substantial” number of NHS hospital staff treat victims of humantrafficking “Substantial” number of NHS hospital staff treat victims of humantrafficking | BMJ Open by Maternity services most likely to do so; but staff across NHS don’t know how best to respond published in the online journal . Although understanding of the sorts of health problems trafficked patients are likely to have, is generally high, few NHS staff feel adequately prepared to respond appropriately, the findings suggest (...) . International law requires that the UK provides victims of humantrafficking with whatever medical treatment they require, which includes psychological help, counselling, and further information on support services. It is thought that around 2.5 million people are trafficked every year, with every country in the world either a source, transit point, or destination. The researchers wanted to know just how likely it is that NHS hospital staff will encounter patients who have been trafficked, and how well
Virus Control of Trafficking from Sorting Endosomes The maintenance of cell surface proteins is critical to the ability of a cell to sense and respond to information in its environment. As such, modulation of cell surface composition and receptor trafficking is a potentially important target of control in virus infection. Sorting endosomes (SEs) are control stations regulating the recycling or degradation of internalized plasma membrane proteins. Here we report that human cytomegalovirus (HCMV (...) that are subject to alternative sorting fates.IMPORTANCE Cells maintain their surface composition, take up nutrients, and respond to their environment through the internalization and recycling of cargo at the cell surface through endocytic trafficking pathways. During infection with human cytomegalovirus (HCMV), host endocytic membranes are reorganized into a juxtanuclear structure associated with viral assembly and egress. Less appreciated is the effect of this reorganization on the trafficking of host
expression, trafficking, and degradation in human dermal fibroblasts from hypertrophic scar [HSF], non-scar fibroblasts, and normal fibroblasts. We also investigated the modulation of these events by propranolol. Catecholamine-stimulated cAMP production was lower in HSFs and non-scar fibroblasts than in normal fibroblasts. β1- and β2-AR cell surface expression was lowest in HSFs, but propranolol increased cell surface expression of these receptors. Basal β2-AR ubiquitination was higher in HSFs than non (...) β-Adrenergic receptor trafficking, degradation, and cell-surface expression are altered in dermal fibroblasts from hypertrophic scars. Burn trauma elevates catecholamines for up to 2 years and causes hypertrophic scarring. Propranolol, a nonspecific β1-, β2-adrenergic receptor (AR) inverse agonist, counters the hypermetabolic response to elevated catecholamines and may decrease hypertrophic scarring by an unknown mechanism. We investigated the effect of burn injury on β1-, β2-, and β3-AR
Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism. Our aim was to evaluate lipid trafficking and inflammatory response of macrophages exposed to lipoproteins from subjects with moderate to severe chronic kidney disease (CKD), and to investigate the potential benefits of activating cellular cholesterol transporters via liver X receptor (LXR) agonism.LDL and HDL were isolated by sequential density gradient (...) ultracentrifugation of plasma from patients with stage 3-4 CKD and individuals without kidney disease (HDLCKD and HDLCont, respectively). Uptake of LDL, cholesterol efflux to HDL, and cellular inflammatory responses were assessed in human THP-1 cells. HDL effects on inflammatory markers (MCP-1, TNF-α, IL-1β), Toll-like receptors-2 (TLR-2) and - 4 (TLR-4), ATP-binding cassette class A transporter (ABCA1), NF-κB, extracellular signal regulated protein kinases 1/2 (ERK1/2) were assessed by RT-PCR and western blot
Crucial Role of Legionella pneumophila TolC in the Inhibition of Cellular Trafficking in the Protistan Host Paramecium tetraurelia Legionella pneumophila is a facultative intracellular Gram-negative bacterium, which is a major causative agent of Legionnaires' disease. In the environment, this bacterium survives in free-living protists such as amoebae and Tetrahymena. The association of L. pneumophila and protists leads to the replication and spread of this bacterium. Thus, from a public health (...) perspective, their association can enhance the risk of L. pneumophila infection for humans. Paramecium spp. are candidates of natural hosts of L. pneumophila, but their detailed relationships remain unclear. In the present study, we used an environmental strain, L. pneumophila Ofk308 (Ofk308) and Paramecium tetraurelia st110-1a to reveal the relationship between L. pneumophila and Paramecium spp. Ofk308 was cytotoxic to P. tetraurelia in an infection-dependent manner. We focused on TolC, a component