Understanding the supports needed for policy implementation: a comparative analysis of the placement of intermediaries across three mental health systems.

BACKGROUND: Intermediaries are organisations or programmes that work between policy-makers and service providers to facilitate effective implementation of evidence-informed policies, programmes and practices. A number of intermediaries now exist in well-established mental health systems; however, research on them, and how they may be optimised to support implementation is lacking. This research seeks to understand the puzzling variation in the system placement of intermediaries supporting policy implementation in the mental health systems of Canada (Ontario), New Zealand and Scotland. METHODS: Using a comparative case study approach, the analytic goal was to compare intermediaries across jurisdictions and explain differences in their placement using explanatory frameworks from political science. Data for this analysis were derived from several sources, including key informant interviews, a literature search of published and grey literature on intermediaries and on policy implementation in mental health systems, a review of relevant policy documents and websites, as well as documents and websites relating to the various intermediaries and other interest groups within each system. RESULTS: Through the analysis, we argue that the placement of intermediaries supporting policy implementation can be explained through an understanding of the political structures, the policy legacies leading to the current public/private mix of mental health service delivery, and the differing administrative capacities of mental health systems. CONCLUSIONS: This research contributes to our growing understanding of policy-related intermediaries supporting implementation at scale and how we might build appropriate infrastructure in systems to support the implementation of policy and achieve better outcomes for citizens.

Elevated levels of Interleukin (IL)-33 induce bone pathology but absence of IL-33 does not negatively impact normal bone homeostasis.

Interleukin (IL)-33 is a member of the IL-1 family. IL-33 effects are mediated through its receptor, ST2 and IL-1RAcP, and its signaling induces the production of a number of pro-inflammatory mediators, including TNFα, IL-1ß, IL-6, and IFN-γ. There are conflicting reports on the role of IL-33 in bone homeostasis, with some demonstrating a bone protective role for IL-33 whilst others show that IL-33 induces inflammatory arthritis with concurrent bone destruction. To better clarify the role IL-33 plays in bone biology in vivo, we studied IL-33 KO mice as well as mice in which the cytokine form of IL-33 was overexpressed. Mid-femur cortical bone mineral density (BMD) and bone strength were similar in the IL-33 KO mice compared to WT animals during the first 8months of life. However, in the absence of IL-33, we observed higher BMD in lumbar vertebrae and distal femur in female mice. In contrast, overexpression of IL-33 resulted in a marked and rapid reduction of bone volume, mineral density and strength. Moreover, this was associated with a robust increase in inflammatory cytokines (including IL-6 and IFN-γ), suggesting the bone pathology could be a direct effect of IL-33 or an indirect effect due to the induction of other mediators. Furthermore, the detrimental bone effects were accompanied by increases in osteoclast number and the bone resorption marker of C-terminal telopeptide collagen-I (CTX-I). Together, these results demonstrate that absence of IL-33 has no negative consequences in normal bone homeostasis while high levels of circulating IL-33 contributes to pathological bone loss.

Bernice Lott (1930-2022).

This article memorializes Bernice Lott (1930-2022), professor emerita of psychology and women's studies at the University of Rhode Island and the first dean of the school's University College, a trailblazing social psychologist who redefined how we understand gender, ethnicity, and social class; a fierce feminist social justice pioneer and activist; and an extraordinary mentor and colleague. Highlights of Lott's career and professional contributions are noted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

COVID-19-related stressors exacerbate food insecurity and depressive symptoms among graduate students receiving campus basic needs services: Cross-sectional findings from seven California public universities.

Prior to the COVID-19 pandemic, food insecurity and depression were growing public health concerns among graduate students. Yet, little is known about how COVID-19-related stressors exacerbated these health outcomes among graduate students. To address this research gap, this study examined two types of COVID-19-related stressors, anticipated concerns about remote learning and challenges interfering with academic and research responsibilities, in relation to food insecurity and depressive symptoms among public university graduate students. Between August and October 2020, 631 graduate students who utilised basic needs services from seven University of California campuses completed an online survey assessing the effects of COVID-19 on their academic experiences, mental health, and basic needs security. Regression analyses examined associations of COVID-19-related concerns and COVID-19-related challenges with food insecurity as well as COVID-19-related concerns and COVID-19-related challenges in relation to depressive symptoms. All four models were adjusted for age, sex, race and ethnicity, campus affiliation, and living with a partner. Models examining food security status as the dependent variable were adjusted for depressive symptoms and vice versa. Graduate students concerned about delayed graduation, post-graduate employment, isolation from faculty and not having access to healthcare reported higher counts of depressive symptoms. Challenges associated with higher counts of depressive symptoms included caring for family more than usual, spending more time on errands and not paying for utilities in full. Students concerned about accessing healthcare had higher odds of experiencing food insecurity. Challenges associated with food insecurity included spending more time on errands, being unable to afford housing and sending money to family members during the pandemic. Our findings illuminate the pandemic's deleterious consequences on graduate students' mental health and food security, underscoring the need for strong academic and basic needs programs and policies.

Understanding the implementation of evidence-informed policies and practices from a policy perspective: a critical interpretive synthesis.

BACKGROUND: The fields of implementation science and knowledge translation have evolved somewhat independently from the field of policy implementation research, despite calls for better integration. As a result, implementation theory and empirical work do not often reflect the implementation experience from a policy lens nor benefit from the scholarship in all three fields. This means policymakers, researchers, and practitioners may find it challenging to draw from theory that adequately reflects their implementation efforts. METHODS: We developed an integrated theoretical framework of the implementation process from a policy perspective by combining findings from these fields using the critical interpretive synthesis method. We began with the compass question: How is policy currently described in implementation theory and processes and what aspects of policy are important for implementation success? We then searched 12 databases as well as gray literature and supplemented these documents with other sources to fill conceptual gaps. Using a grounded and interpretive approach to analysis, we built the framework constructs, drawing largely from the theoretical literature and then tested and refined the framework using empirical literature. RESULTS: A total of 11,434 documents were retrieved and assessed for eligibility and 35 additional documents were identified through other sources. Eighty-six unique documents were ultimately included in the analysis. Our findings indicate that policy is described as (1) the context, (2) a focusing lens, (3) the innovation itself, (4) a lever of influence, (5) an enabler/facilitator or barrier, or (6) an outcome. Policy actors were also identified as important participants or leaders of implementation. Our analysis led to the development of a two-part conceptual framework, including process and determinant components. CONCLUSIONS: This framework begins to bridge the divide between disciplines and provides a new perspective about implementation processes at the systems level. It offers researchers, policymakers, and implementers a new way of thinking about implementation that better integrates policy considerations and can be used for planning or evaluating implementation efforts.

Psychology's contributions to understanding and alleviating poverty and economic inequality: Introduction to the special section.

In the United States and around the world, economic inequality is one of the greatest challenges of our time. Psychological research is crucial to illuminating and interrupting the damaging consequences of economic hardship and disparities, understanding interpersonal and institutional responses to poverty and economic inequality, and developing effective poverty alleviation programs and policies. The articles in this special section explore psychology's contributions to understanding and alleviating poverty and economic inequality, focusing on mitigating the effects of economic hardship on children and youth, how employment and work-related dynamics contribute to economic inequality, and psychology's presence in federal policymaking. Collectively, this body of work highlights the need for psychologists' engagement in a full spectrum of antipoverty and economic justice initiatives. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A Fresh Approach to Reform? A Policy Analysis of the Development and Implementation of Ontario's Mental Health and Addictions Strategy.

Background: Open Minds, Healthy Minds, Ontario's Comprehensive Mental Health and Addictions Strategy commits to the transformation of mental health and addictions services for all Ontarians. Objective: We analyzed the formulation and implementation of this Strategy to address the question: What are the prospects for transformative change in Ontario's current approach to mental health and addictions? Methods: Qualitative policy analysis using interpretive description of key documents of the policy process, drawing on policy network and horizontal governance theory. Results: Three features set this policy process apart from previous reform efforts: (1) expansion of the state pluralist network to those outside of health, (2) extension of the policy network approach into the Strategy's implementation stage and (3) the combined presence of political and policy leadership. Conclusions: There is reason for optimism that the approach of the Strategy has increased the prospects for the transformation of Ontario's mental health and addictions system.

Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism.

BACKGROUND AND PURPOSE: Human parathyroid hormone (PTH) is critical for maintaining physiological calcium homeostasis and plays an important role in the formation and maintenance of the bone. Full-length PTH and a truncated peptide form are approved for treatment of hypoparathyroidism and osteoporosis respectively. Our initial goal was to develop an improved PTH therapy for osteoporosis, but clinical development was halted. The novel compound was then repurposed as an improved therapy for hypoparathyroidism. EXPERIMENTAL APPROACH: A longer-acting form of PTH was synthesised by altering the peptide to increase cell surface residence time of the bound ligand to its receptor. In vitro screening identified a compound, which was tested in an animal model of osteoporosis before entering human trials. This compound was subsequently tested in two independent animal models of hypoparathyroidism. KEY RESULTS: The peptide identified, LY627-2K, exhibited delayed internalization kinetics. In an ovariectomy-induced bone loss rat model, LY627-2K demonstrated improved vertebral bone mineral density and biomechanical properties at skeletal sites and a modest increase in serum calcium. In a Phase I clinical study, dose-dependent increases in serum calcium were reproduced. These observations prompted us to explore a second indication, hypoparathyroidism. In animal models of this disease, LY627-2K restored serum calcium, comparing favourably to treatment with wild-type PTH. CONCLUSIONS AND IMPLICATIONS: We summarize the repositioning of a therapeutic candidate with substantial preclinical and clinical data. Our results support its repurposing and continued development, from a common indication (osteoporosis) to a rare disease (hypoparathyroidism) by exploiting a shared molecular target. LINKED ARTICLES: This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Intersections of ethnicity and social class in provider advice regarding reproductive health.

OBJECTIVES: We examined how ethnicity and social class influence women's perceptions of reproductive health care. Of primary interest was assessing whether health care providers are perceived as advising low-income women, particularly women of color, to limit their childbearing and to what extent they feel they are discouraged by providers from having future children. METHODS: Ethnically diverse, low-income (n=193) and middle-class women (n=146) completed a questionnaire about their pregnancy-related health care experiences. RESULTS: Logistic regression analyses revealed that low-income women of color experienced greater odds of being advised to limit their childbearing than did middle-class White women. A separate model demonstrated that low-income Latinas reported greater odds of being discouraged from having children than did middle-class White women. CONCLUSIONS: Low-income women of color were more likely to report being advised to limit their childbearing and were more likely to describe being discouraged from having children than were middle-class White women. More research is needed regarding how ethnicity and social class impact women's experiences with reproductive health care.

Social class and policy preferences: implications for economic inequality and interclass relations.

Record-setting levels of income and wealth inequality are deepening social class divisions. The adoption of strong progressive redistributive policies is crucial to reducing class inequities, yet many barriers to doing so exist. This review examines class-based policy preferences, focusing on the effects of economic self-interest, system justification, and classist, racist, and sexist stereotypes on policy support. The impact of broader economic conditions is also considered. Collectively, this body of research makes clear that building stronger cross-class support for redistributive policies and programs will prove difficult without addressing both class-based power differences and beliefs that justify inequality. Reducing stereotypes and developing a shared sense of societal responsibility that cuts across class lines can help advance these goals. Social psychological research is vital to informing these efforts.

2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy.

A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.

Molecular targets of androgen signaling that characterize skeletal muscle recovery and regeneration.

The high regenerative capacity of adult skeletal muscle relies on a self-renewing depot of adult stem cells, termed muscle satellite cells (MSCs). Androgens, known mediators of overall body composition and specifically skeletal muscle mass, have been shown to regulate MSCs. The possible overlapping function of androgen regulation of muscle growth and MSC activation has not been carefully investigated with regards to muscle regeneration.Therefore, the aim of this study was to examine coinciding androgen-mediated genetic changes in an in vitro MSC model and clinically relevant in vivo models. A gene signature was established via microarray analysis for androgen-mediated MSC engagement and highlighted several markers including follistatin (FST), IGF-1, C-X-C chemokine receptor 4 (CXCR4), hepatocyte growth factor (HGF) and glucocorticoid receptor (GR). In an in vivo muscle atrophy model, androgen re-supplementation significantly increased muscle size and expression of IGF-1, FST, and HGF, while significantly decreasing expression of GR. Biphasic gene expression profiles over the 7-day re-supplementation period identified temporal androgen regulation of molecular targets involved in satellite cell engagement into myogenesis. In a muscle injury model, removal of androgens resulted in delayed muscle recovery and regeneration. Modifications in the androgen signaling gene signature, along with reduced Pax7 and MyoD expression, suggested that limited MSC activation and increased inflammation contributed to the delayed regeneration. However, enhanced MSC activation in the androgen-deplete mouse injury model was driven by an androgen receptor (AR) agonist. These results provide novel in vitro and in vivo evidence describing molecular targets of androgen signaling, while also increasing support for translational use of AR agonists in skeletal muscle recovery and regeneration.

From the front lines of welfare reform: an analysis of social worker and welfare recipient attitudes.

Social workers and welfare recipients operate within the same institutional framework and share a working and/or lived knowledge of poverty, but they occupy different social and economic positions. To gain a better understanding of intergroup attitudes, the author compared how social workers and welfare recipients explain poverty and perceive the welfare system. The results highlight important similarities and differences between the two groups. Although the author did not find differences for individualistic attributions, welfare recipients regarded prejudice as playing a greater role in causing poverty than did social workers. Welfare recipients also expressed stronger support for increased welfare funding and progressive welfare policies than did social workers. The author discussed implications for strengthening interclass alliances, particularly the relationship between social service providers and welfare recipients.

Factors influencing service use among homeless youths with co-occurring disorders.

OBJECTIVE: Given high rates of co-occurring mental and substance use disorders among homeless youths and poorly understood facilitators of and barriers to service use, this study explored factors influencing service use among homeless youths with co-occurring disorders. METHODS: Focus groups were conducted with 23 youths age 18 to 26 with co-occurring disorders. Group discussion was audio-recorded and transcribed verbatim, and transcripts were examined with thematic content analysis. RESULTS: The factors identified as influencing service use were grouped into three broad categories: individual (motivation, support, and therapeutic relationship), program (flexibility and comprehensiveness of services and availability of harm reduction services), and systemic (stigma and accessibility). CONCLUSIONS: Multilevel factors appear to influence service use among homeless youths with co-occurring disorders. Given the lack of evidence to support specific treatments in this population, these findings may be used to guide the development of thoughtfully designed interventions to engage homeless youths with co-occurring disorders.

Prevention of substance use in children/adolescents with mental disorders: a systematic review.

OBJECTIVE: WE CONDUCTED A SYSTEMATIC REVIEW TO ANSWER THE QUESTION: Among youth ≤18 years of age with a mental disorder, does substance use prevention compared to no prevention result in reduced rates of substance use/abuse/disorder (SUD)? The review was requested by the Ontario Ministry of Health and Long-term Care through the Canadian Institutes for Health Research Evidence on Tap program. METHODS: A four-step search process was used: Search 1 and 2: Randomized controlled trials (RCTs) that evaluated a SUD prevention intervention in individuals with a mental disorder who were: 1) ≤18 years; or, 2) any age. Search 3: Observational studies of an intervention to prevent SUD in those with mental disorder. Search 4: RCTs that evaluated a SUD primary prevention skills-based intervention in high-risk youth ≤18 years. RESULTS: Searches 1 and 2: one RCT conducted in youth was found; Search 3: two observational studies were found. All three studies reported statistically significant reductions in substance use. Search 4: five RCTs were found with mixed results. Methodological weaknesses including inadequate study power may explain the results. CONCLUSIONS: Little is known about effective interventions to prevent SUD in youth with a mental disorder. Effective SUD primary prevention programs exist and should be evaluated in this high-risk group.

The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand.

Guggulsterone (GS) is the active substance in guggulipid, an extract of the guggul tree, Commiphora mukul, used to treat a variety of disorders in humans, including dyslipidemia, obesity, and inflammation. The activity of GS has been suggested to be mediated by antagonism of the receptor for bile acids, the farnesoid X receptor (FXR). Here, we demonstrate that both stereoisomers of the plant sterol, (E)- and (Z)-GS, bind to the steroid receptors at a much higher affinity than to FXR. Both stereoisomers bind to the mineralocorticoid receptor (MR) with a Ki value of approximately 35 nM, which is greater than 100 times more potent than their affinity for FXR. Both (E)- and (Z)-GS also displayed high affinity for other steroid receptors, including the androgen (AR), glucocorticoid (GR), and progesterone receptors (PR) with Ki values ranging from 224 to 315 nM. In cell-based functional cotransfection assays, GSs behaved as antagonists of AR, GR, and MR, but as agonists of PR. Agonist activity was also demonstrated with estrogen receptor (ER) alpha; however, the potency was very low (EC50 > 5000 nM). In addition, GS displayed activity in functional assays in cell lines expressing endogenous AR, GR, ER, and PR. These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors.