Criminal Code reform of HIV non-disclosure is urgently needed: Social science perspectives on the harms of HIV criminalization in Canada.

The criminalization of HIV non-disclosure represents a significant issue of concern among people living with HIV, those working across the HIV sector, public health practitioners, and health and human rights advocates around the world. Recently, the government of Canada began a review of the criminal law regarding HIV non-disclosure and invited feedback from the public about potential reforms to the Criminal Code. In light of this public consultation, this commentary examines social science research from Canadian scholars that documents the intersecting damaging effects of HIV criminalization.

When biographical disruption meets HIV exceptionalism: Reshaping illness identities in the shadow of criminalization.

Drawing on interviews with civil society actors in the AIDS Service Organization (ASO) sector in Canada, this article explores how these actors contribute to shaping the illness identities of people living with HIV/AIDS in the shadow of efforts to criminalize exposure to HIV. While the biographically disruptive qualities associated with an HIV diagnosis have been addressed in the medical sociology literature, we turn our attention to the key role played by ASOs as interlocutors in this process. Paying specific attention to the intersection of processes of medicalization and criminalization, we ask how they are re-stigmatizing a condition that has shifted in the public consciousness from its earlier association with deviance and moral culpability.

Governing COVID-19 without government in Brazil: Ignorance, neoliberal authoritarianism, and the collapse of public health leadership.

Brazil's governance of the COVID-19 pandemic has been described as nothing short of tragic by several commentators. President Jair Bolsonaro's dangerous brew of neoliberal authoritarianism, science denialism and ableism has plunged this country into catastrophe. In this article we argue that this form (or lack) of public health governance can best be described as governance without (central) government.

"We write as little as we have to": charting practices and documenting disclosure in response to HIV criminalization in Canada.

The criminalization of HIV nondisclosure is reshaping the landscape of support and care for people living with HIV/AIDS (PLWHA). Focusing on Canada, this article examines how criminalization is reshaping the relationships between frontline AIDS Service Organization (ASO) workers and their HIV-positive service users. Using data gleaned through semi-structured interviews with  = 62 frontline ASO staff members across Canada that were coded using thematic analysis, we describe how ASO workers are rethinking and altering their notetaking practices in light of fears about criminalization and how their charts may be used by legal actors.

High-Throughput Screening Strategy Identifies Allosteric, Covalent Human D-Amino Acid Oxidase Inhibitor.

Genome-wide association studies have linked polymorphisms in the gene G72 to schizophrenia risk in several human populations. Although controversial, biochemical experiments have suggested that the mechanistic link of G72 to schizophrenia is due to the G72 protein product, pLG72, exerting a regulatory effect on human D-amino acid oxidase (hDAAO) activity. In an effort to identify hDAAO inhibitors of novel mechanism of action, we designed a pLG72-directed hDAAO activity assay suitable for high-throughput screening (HTS).

Globalization and the health of Canadians: 'Having a job is the most important thing'.

Background: Globalization describes processes of greater integration of the world economy through increased flows of goods, services, capital and people. Globalization has undergone significant transformation since the 1970s, entrenching neoliberal economics as the dominant model of global market integration. Although this transformation has generated some health gains, since the 1990s it has also increased health disparities.

A selective small molecule NOP (ORL-1 receptor) partial agonist for the treatment of anxiety.

Small molecule (1) has been identified as a selective partial agonist of Opioid Receptor Like-1 (ORL-1) with potential utility for the treatment of anxiety and other disorders. Nociceptin (orphanin FQ) is an endogenous peptide ligand that binds to ORL-1, however it does not bind the classical δ, μ and κ opioid receptors with high affinity. The synthesis of 1 involved using a molecular diversity approach, to rapidly advance a library of compounds for biological testing.

Novel human D-amino acid oxidase inhibitors stabilize an active-site lid-open conformation.

The NMDAR (N-methyl-D-aspartate receptor) is a central regulator of synaptic plasticity and learning and memory. hDAAO (human D-amino acid oxidase) indirectly reduces NMDAR activity by degrading the NMDAR co-agonist D-serine. Since NMDAR hypofunction is thought to be a foundational defect in schizophrenia, hDAAO inhibitors have potential as treatments for schizophrenia and other nervous system disorders.

Structural, kinetic, and pharmacodynamic mechanisms of D-amino acid oxidase inhibition by small molecules.

We characterized the mechanism and pharmacodynamics of five structurally distinct inhibitors of d-amino acid oxidase. All inhibitors bound the oxidized form of human enzyme with affinity slightly higher than that of benzoate (Kd ≈ 2-4 μM). Stopped-flow experiments showed that pyrrole-based inhibitors possessed high affinity (Kd ≈ 100-200 nM) and slow release kinetics (k < 0.

Design, synthesis, and structure-activity relationships of novel bicyclic azole-amines as negative allosteric modulators of metabotropic glutamate receptor 5.

A novel series of diaryl bicyclic azole-amines that are potent selective negative modulators of metabotropic glutamate receptor 5 (mGluR5) were identified through rational design. An initial hit compound 5a of modest potency (IC(50) = 1.2 μM) was synthesized.

The unintended consequences of being friendly: a case study.

Baby-friendly certification recognizes hospitals that promote early physical bonding between mother and infant, immediately after birth. Most births can accomplish physical bonding without increased risk to mother or infant. When mother or infant have complications and each have intravenous (i.

Identifying nonselective hits from a homogeneous calcium assay screen.

The authors used a homogeneous calcium dye kit with a cell line transfected using a recombinant protein construct to screen a 50,000 compound library for G-protein coupled receptor (GPCR) agonists. Only 1 of the 365 primary hits activated Gq-coupled GPCRs, as shown using IP-ONE HTRF. Furthermore, an agonist screen against the entire compound library and same heterologous cell line using AequoScreen technology generated no false positives and identified the same positive hit.

Metastin (KiSS-1) mimetics identified from peptide structure-activity relationship-derived pharmacophores and directed small molecule database screening.

Metastin, also known as KiSS-1, the cognate ligand for the metastin receptor GPR54, is a peptide known to dramatically reduce metastasis in experimental models. Despite this, there is no reported structure for metastin nor any small molecule modulators of metastin function that could be used either clinically or experimentally. Here we report the NMR solution structure of a 13-residue metastin peptide in a membrane-like environment (SDS micelles) and find it to have a relatively stable helix conformation from residues 7 to 13.

8-(Heteroaryl)phenalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones as opioid receptor modulators.

A series of N-biarylalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones were prepared and evaluated for biological activity at opioid (mu, delta, kappa) and opioid receptor like-1 (ORL-1) G-protein coupled receptors. Substitution on the biaryl moiety produced enhanced affinity for the mu-opioid receptor.

3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands for the ORL-1 receptor.

A novel series of indoles and 1H-pyrrolo[2,3-b]pyridines having a piperidine ring at the 3-position were synthesized and found to bind with high affinity to the ORL-1 receptor. Structure-activity relationships at the piperidine nitrogen were investigated in each series. Substitution on the phenyl ring and nitrogen atom of the indole and 1H-pyrrolo[2,3-b]pyridine cores generated several selective high-affinity ligands that were agonists of the ORL-1 receptor.

Medication safety--reliability of preference cards.

A CLINICAL ANALYSIS of surgeons' preference cards was initiated in one hospital as part of a comprehensive analysis to reduce medication-error risks by standardizing and simplifying the intraoperative medication-use process specific to the sterile field. THE PREFERENCE CARD ANALYSIS involved two subanalyses: a review of the information as it appeared on the cards and a failure mode and effects analysis of the process involved in using and maintaining the cards. THE ANALYSIS FOUND that the preference card system in use at this hospital is outdated.

Preparation of 3-spirocyclic indolin-2-ones as ligands for the ORL-1 receptor.

A novel series of indolin-2-ones having a spirocyclic piperidine ring at the 3-position was synthesized and found to bind with high affinity to the ORL-1 receptor. Structure-activity relationships at the piperidine nitrogen were investigated. Substitution on the phenyl ring and nitrogen atom of the indolin-2-one core generated several selective high-affinity ligands that were antagonists of the ORL-1 receptor.

The nociceptin pharmacophore site for opioid receptor binding derived from the NMR structure and bioactivity relationships.

Nociceptin, a 17 amino acid opioid-like peptide that has an inhibitory effect on synaptic transmission in the nervous system, is involved in learning, memory, attention, and emotion and is also implicated in the perception of pain and visual, auditory, and olfactory functions. In this study, we investigated the NMR solution structure of nociceptin in membrane-like environments (trifluoroethanol and SDS micelles) and found it to have a relatively stable helix conformation from residues 4-17 with functionally important N-terminal residues being folded aperidoically on top of the helix. In functional assays for receptor binding and calcium flux, alanine-scanning variants of nociceptin indicated that functionally important residues generally followed helix periodicity, consistent with the NMR structural model.

Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.

The major human metabolite of atomoxetine (4-hydroxyatomoxetine) was tested against a panel of receptors and enzymes, and was found to interact with the mu, delta, and kappa-opioid receptors based upon studies involving both binding and functional assays. 4-hydroxyatomoxetine was determined to be a partial agonist of the kappa-opioid receptor.