Stigma as a fundamental hindrance to the United States opioid overdose crisis response.

Alexander Tsai and co-authors discuss the role of stigma in responses to the US opioid crisis

HIV-2 diagnosis and quantification in high-risk patients

Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States

Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

<p>Abstract</p> <p>Background</p> <p>Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.</p> <p>Methods</p> <p>Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-<it>trans </it>retinoic acid (RA) or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes.</p> <p>Results</p> <p>Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B), receptors (FZD5, FZD6, FZD10), secreted inhibitors (SFRP4, SFRP1), and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine). Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi) inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines tested including NT2/D1, NT2/D1-R1, Tera-1 and 833K cells.</p> <p>Conclusion</p> <p>During induced differentiation of human EC cells, the Wnt signalling pathway is reprogrammed and canonical Wnt signalling induced. Specific species regulating non-canonical Wnt signalling conferred growth inhibition when targeted for repression in these EC cells. Notably, FZD7 repression significantly inhibited growth of human EC cells and is a promising therapeutic target for TGCTs.</p

Substance use disorders and avoidable mortality after prison

Worldwide, more than 30 million people spend time in prison every year.1 The USA incarcerates 25 % of these people and one in 31 Americans is currently under correctional control, either in jail, prison, or on probation or parole.2 Most prisoners will eventually be released, and the 2 weeks after release have been shown to be associated with a substantial increase in mortality, especially from overdose.3 Substance use disorders are highly prevalent among incarcerated populations, with more than half of prisoners in some countries being imprisoned for drug-related convictions.4 In the USA, 85 % of people in prisons or jails are substance involved, with 1·5 million individuals meeting DSM criteria for a substance use disorder and an additional 458 000 either with a history of substance use, under the influence at the time of arrest, or convicted of a crime committed to obtain money to buy drugs.5 Addiction is a treatable disease and decades of scientific evidence support the efficacy of treatment to improve clinical outcomes, save lives, and reduce societal costs. Treatment for opioid use disorder during incarceration with agonists such as buprenorphine or methadone has been shown to reduce recidivism, improve treatment retention, reduce illicit drug use

Language, substance use disorders, and policy: the need to reach consensus on an “addiction-ary”.

The language used to describe health conditions reflects and influences our attitudes and approaches to addressing them, even to the extent of suggesting that a health condition is a moral, social, or criminal issue. The language and terminology we use is particularly important when it comes to highly stigmatized and life-threatening conditions, such as those relating to alcohol and other drugs. Scientific research has demonstrated that, whether we are aware of it, the use of certain terms implicitly generates biases that can influence the formation and effectiveness of our social and public health policies in addressing them. Such research has made it difficult to trivialize or dismiss the terminology debate as merely “semantics” or a linguistic preference for “political correctness.” Furthermore, given that alcohol and other drug-related conditions are among the top public health concerns in the United States and in most English speaking countries globally (e.g., United Kingdom, Australia, Ireland), this is no trivial matter. In this article, the authors detail the conceptual and empirical basis for the need to avoid using certain terms and to reach consensus on an “addiction-ary.” The authors conclude that consistent use of agreed-upon terminology will aid precise and unambiguous clinical and scientific communication and help reduce stigmatizing and discriminatory public health and social policies