Problem drug use the public health imperative: what some of the literature says

<p>Abstract</p> <p>Background</p> <p>With more than 200,000 problem drug users is contact with structured treatment services in England the public health imperative behind drug treatment is great. Problem drug use for many is a chronic and relapsing condition, where "cure" is often neither a reasonable or appropriate expectation and it can further be argued that in these circumstances problem drug use is no different from any number of chronic and enduring health conditions that are managed in the health care system and therefore should be conceptualised as such.</p> <p>Discussion</p> <p>A public health approach to drug treatment emphasises the need for drug users in or accessing treatment, to reduce their harmful drug use, reduce drug use related risks such as sepsis and overdose and stay alive for longer. However a public health perspective in relation to problem drug use isn't always either apparent or readily understood and to that end there is still a significant need to continue the arguments and debate that treatment and interventions for problem and dependent drug users need to extend beyond an individualistic approach. For the purposes of discussion in this article public and population health will be used interchangeably.</p> <p>Summary</p> <p>A recognition and acceptance that a public and population health approach to the management of problem drug users is sound public health policy also then requires a long term commitment in terms of staffing and resources where service delivery mirrors that of chronic condition management.</p

Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin

Trithorax-group genes and mammalian homologues, including BAF (mSWI/SNF) complexes, have been known for nearly 30 years to oppose Polycomb repressive activity(1–5). This opposition underlies the tumor-suppression role of BAF(3,5–7) and is expected to contribute to neurodevelopmental disorders, as evidenced by frequent driving mutations(8,9). However, the mechanisms underlying opposition to Polycomb silencing are poorly understood. Here we report that recurrent disease mutations of BAF subunits induce genome-wide increases in Polycomb complex deposition and activity. We show that point mutations of the Smarca4 (Brg) ATPase domain cause loss of direct binding between BAF and PRC1 that occurs independently of chromatin. Release of this direct interaction occurs via an ATP-dependent mechanism, consistent with a role as a transient intermediate of eviction. Using a new in vivo assay, we find that BAF directly evicts Polycomb factors within minutes of its occupancy, together establishing a new mechanism for the widespread opposition underlying development and disease