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Because the United States often seems (and seems eager to present itself as) the home of the technological imperative and of determination to brand all challenges to it in end-of-life care as a descent into death panels, the prospects look unpromising for progress in US public policies that would expand the range of choices of medical treatments available to individuals preparing for death. Beneath this obdurate and intermittently hysterical surface, however, the diffusion across US states and communities of living wills, advanced directives, palliative care, hospice services and debates about assisted suicide is gradually strengthening not so much 'personal autonomy' as the authority, cultural and formal, of individuals and their loved ones not merely to shape but to lead the inevitably 'social' conversations on which decisions about care at the end of life depend. In short, the nation appears to be (in terms taken from John Donne's mediations on death) 'stealing on insensibly'--making incremental progress toward the replacement of clinical and other types of dogma with end-of-life options that honor the preferences of the dying. [ABSTRACT FROM AUTHOR]

Native American youth suffer disproportionately from a range of adverse health conditions. Empowering youth leaders to work on community-based solutions has proved effective in reducing tobacco use and gun violence and is now emerging as a promising approach to improving fitness and health. This article, based on direct observation and interviews with key informants, examines the implementation of a Robert Wood Johnson Foundation-funded project that gave tribal youth councils minigrants to design and run diverse projects that encourage physical activity in their communities. The article highlights the institutional challenges that confront health-promotion strategies for disadvantaged populations. Unless they take proper account of organizational, political, environmental, and cultural forces, funders' interventions have limited chances for success and sustainability. [ABSTRACT FROM AUTHOR]

In few fields of public policy are the use and cost of services so powerfully driven by technological change as they are in medicine. To manage technology, policy-makers have expanded their investment in evaluative research. This paper addresses three underexamined challenges in using evidence: those inherent in the dynamics of technological change itself; those inherent in the analytical enterprise; and the ways in which political factors shape the translation of evidence into policy decisions. The design of institutional arrangements and processes that seek to blend evidence with politics merit closer attention, and existing cross-national arrangements deserve careful study. [ABSTRACT FROM AUTHOR]

In 1993 Germany joined the small but swelling ranks of societies determined to explore managed competition as a means of slowing the growth of health spending by giving stakeholders new incentives for efficiency. Realizing the benefits of competition, however, demands changes in institutional norms and regulatory practices that now largely handcuff those who would follow competitive logic into 'managed care.' In time Germany's system of 'manacled competition' may evolve into a happy higher synthesis of managed care and managed competition. Or policymakers may conclude that the political price of installing workable market forces in health care is too high and reconcile themselves to more traditional applications of political pressure. [ABSTRACT FROM AUTHOR]

Most communities support their safety-net facilities, but few supply health coverage for uninsured residents. In 1991 Hillsborough County, Florida, created a health care plan that raised the sales tax by a half-cent, used the proceeds to cover about 30,000 uninsured county residents, and assured the public that this would save money. In time, however, various conflicts combined to call into question the plan's ends and means. These challenges reinvigorated advocacy by the plan's supporters, who steered the adoption of changes that seemed to have 'institutionalized' it. Community-based reformers might find this local innovation instructive as they ponder how to build enduring programs. [ABSTRACT FROM AUTHOR]

The Robert Wood Johnson Foundation's Communities in Charge (CIC) program funded projects in fourteen communities that aimed to expand health insurance coverage and improve care for their uninsured residents. Our examination of seven program sites suggests that despite solid community leadership and carefully crafted plans, political, economic, and organizational obstacles precluded much expansion of coverage and constrained reforms. Redistribution of financial and organizational resources among both mainstream and safety-net institutions in these communities was hard to achieve. CIC's record offers little evidence that communities are better equipped than are other sectors of U.S. society to solve the problem of uninsurance. [ABSTRACT FROM AUTHOR]

Fetal glucagon concentrations are elevated in the presence of a compromised intrauterine environment, as in cases of placental insufficiency and perinatal acidaemia. Our objective was to investigate the impact of late gestation fetal hyperglucagonaemia on in vivo insulin secretion and pancreatic islet structure. Chronically catheterized late gestation fetal sheep received an intravenous infusion of glucagon at low (5 ng/kg/min; GCG-5) or high (50 ng/kg/min; GCG-50) concentrations or a vehicle control (CON) for 8-10 days. Glucose-stimulated fetal insulin secretion (GSIS) was measured following 3 h (acute response) and 8-10 days (chronic response) of experimental infusions. Insulin, glucose and amino acid concentrations were measured longitudinally. The pancreas was collected at the study end for histology and gene expression analysis. Acute exposure (3 h) to GCG-50 induced a 3-fold increase in basal insulin concentrations with greater GSIS. Meanwhile, chronic exposure to both GCG-5 and GCG-50 decreased basal insulin concentrations 2-fold by day 8-10. Chronic GCG-50 also blunted GSIS at the study end. Fetal amino acid concentrations were decreased within 24 h of GCG-5 and GCG-50, while there were no differences in fetal glucose. Histologically, GCG-5 and GCG-50 had lower β- and α-cell proliferation, as well as lower α-cell mass and pancreas weight, while GCG-50 had lower islet area. This study demonstrates that chronic glucagon elevation in late gestation fetuses impairs β-cell proliferation and insulin secretion, which has the potential to contribute to later-life diabetes risk. We speculate that the action of glucagon in lower circulating fetal amino acid concentrations may have a suppressive effect on insulin secretion. KEY POINTS: We have previously demonstrated in a chronically catheterized fetal sheep model that experimentally elevated glucagon in the fetus impairs placental function, reduces fetal protein accretion and lowers fetal weight. In the present study, we further characterized the effects of elevated fetal glucagon on fetal physiology with a focus on pancreatic development and β-cell function. We show that experimentally elevated fetal glucagon results in lower β- and α-cell proliferation, as well as decreased insulin secretion after 8-10 days of glucagon infusion. These results have important implications for β-cell reserve and later-life predisposition to diabetes., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Substance use-related problems continue to be a national public health crisis despite years of prevention efforts. Community anti-drug coalitions are well positioned to address substance use at local levels. Coalitions often rely on their members to connect to resources they need to address community issues and plan for sustainability over time. Such capacity building occurs through voluntary cooperation among members, making it essential to understand the role network connections play. This study sought to determine whether structural characteristics of coalitions' resource sharing networks impact members' perceptions of community improvement and coalition sustainability. Surveys at two timepoints collected data from 68 coalitions in Pennsylvania and Missouri on members' connections or ties to share information, personnel, money, or other types of collaboration. Analyses examined how coalition-level measurements of sectoral diversity, density, and resource sharing centralization, respectively, were associated with members' perceptions of community improvement, sustainability planning, and coalition sustainability. Sectoral diversity and centralization were unrelated to study outcomes. Density was also unrelated with perceived community improvement and sustainability planning. However, two facets of cooperative density were positively associated with perceived coalition sustainability: the density of ties to share information and the density of multiple types of collaborative ties. This study suggests that both information and other collaborative ties foster perceived coalition sustainability, although not community improvement., (© 2024. The Author(s).)

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US., Methods: Four trained, bilingual (English/Spanish) Community Health Workers (CHWs) recruited small businesses (i.e., ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee., Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked at least 13 of the 17 controls identified to mitigate risk., Conclusions: Tailored, culturally sensitive outreach led by CHWs identified and educated businesses on critical hazards, and these methods may be transferable to similar communities., Competing Interests: Disclosures of Conflicts of Interest: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Fleas (Siphonaptera) are holometabolous insects with larval and adult stages that exhibit vastly different ecologies from each other. Adult fleas are parasitic and feed exclusively on the blood of a vertebrate host, whereas flea larvae do not live on hosts and consume dried faecal blood from adult fleas. Because flea larvae rely on adult flea faeces for food, excrement and eggs must fall in the same location; thus, larval density is likely high in these restricted habitats. However, the influence of larval density on the subsequent adult stage has not been examined. In the present study, we utilized egg density to investigate density-dependent effects on larval development and adult body size in the cat flea (Ctenocephalides felis Bouché) (Siphonaptera: Pulicidae). Specifically, eggs were collected to create three different larval densities (n = 50, 100 and 150 per 56.7 cm 2 ), and hatched larvae from all groups were fed an excess amount of adult faecal pellets. Larval development was measured by recording the proportion of eggs that developed to the pupal stage and the proportion of eggs that reached adulthood (eclosion). The body size of eclosed adults was quantified for both sexes using head length and length of the total body. We found that the number of eggs had no effect on the proportion of larvae that pupated or the proportion of larvae that eclosed; however, higher egg densities resulted in larger body sizes for both sexes. Overall, these data yield significant insight into how the ecology of larval fleas impacts the biology of the resultant adults., (© 2024 Royal Entomological Society.)

Insulin-like growth factor 1 (IGF-1) is a critical fetal anabolic hormone. IGF-1 infusion to the normally growing sheep fetus increases the weight of some organs but does not consistently increase body weight. However, IGF-1 infusion profoundly decreases fetal plasma insulin concentrations, which may limit fetal growth potential. In this study, normally growing late-gestation fetal sheep received an intravenous infusion of either: IGF-1 (IGF), IGF-1 with insulin and dextrose to maintain fetal euinsulinemia and euglycemia (IGF+INS), or vehicle control (CON) for 1 week. The fetus underwent a metabolic study immediately prior to infusion start and after 1 week of the infusion to measure uterine and umbilical uptake rates of nutrients and oxygen. IGF+INS fetuses were 23% heavier than CON (P = 0.0081) and had heavier heart, liver, and adrenal glands than IGF and CON (P < 0.01). By design, final fetal insulin concentrations in IGF were 62% and 65% lower than IGF+INS and CON, respectively. Final glucose concentrations were similar in all groups. IGF+INS had lower final oxygen content than IGF and CON (P < 0.0001) and lower final amino acid concentrations than CON (P = 0.0002). Final umbilical oxygen uptake was higher in IGF+INS compared to IGF and CON (P < 0.05). Final umbilical uptake of several essential amino acids was higher in IGF+INS compared to CON (P < 0.05). In summary, maintaining euinsulinemia and euglycemia during fetal IGF-1 infusion is necessary to maximally support body growth. We speculate that IGF-1 and insulin stimulate placental nutrient transport to support fetal growth.

Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth-restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1-3, Leak Omy , and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI-CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment. KEY POINTS: Growth-restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood. Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids. We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed. Our data show that the mitochondria respiration levels in the growth-restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified. These results indicate an impaired metabolic maturation of the growth-restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Objective: Peer support workers are a substantial and growing part of the mental health workforce. Because little research has investigated how to effectively support and supervise peer support workers, the authors evaluated the efficacy of a training program to strengthen the peer support workforce and the supervision of its workers., Methods: Mental health services sites with peer support workers and supervisors in Los Angeles County were recruited for this cluster-randomized trial and 10-month follow-up. Of 348 peer support workers and 143 supervisors at 85 sites, 251 (72%) peer support workers and 115 (80%) supervisors completed baseline surveys. SHARE! the Self-Help And Recovery Exchange, a peer-run organization, delivered four training sessions on strategies to reduce stigma and to build an effective peer workforce, cultural competence, and a trauma-informed developmental model of supervision. Primary outcomes were peer-supportive organizational climate, mental health stigma, and peer support worker recovery., Results: Intention-to-treat analyses indicated that sites receiving the training had significantly higher scores on peer-supportive organizational climate (Cohen's d=0.35, 95% CI=0.02-0.68, p=0.04) relative to sites not receiving the training. No significant differences were found between the two conditions for mental health stigma (Cohen's d=0.04) or peer support worker recovery (Cohen's d=0.14)., Conclusions: The training had no impact on mental health stigma or peer support worker recovery. However, the findings suggest that the training increased the value organizations gave to peer support work, which may help improve peer support worker retention and outcomes among those served. Efforts to incorporate principles of the training into practice may strengthen outcomes., Competing Interests: The authors report no financial relationships with commercial interests.

In human pregnancy, metformin administered to the mother crosses the placenta resulting in metformin exposure to the fetus. However, the effects of metformin exposure on the fetus are poorly understood and difficult to study in humans. Pregnant sheep are a powerful large animal model for studying fetal physiology. The objective of this study was to determine if maternally administered metformin at human dose-equivalent concentrations crosses the ovine placenta and equilibrates in the fetal circulation. To test this, metformin was administered to the pregnant ewe via continuous intravenous infusion or supplementation in the drinking water. Both administration routes increased maternal metformin concentrations to human dose-equivalent concentrations of ~ 10 µM, yet metformin was negligible in the fetus even after 3-4 days of maternal administration. In cotyledon and caruncle tissue, expression levels of the major metformin uptake transporter organic cation transporter 1 (OCT1) were < 1% of expression levels in the fetal liver, a tissue with abundant expression. Expression of other putative uptake transporters OCT2 and OCT3, and efflux transporters multidrug and toxin extrusion (MATE)1 and MATE2were more abundant. These results demonstrate that the ovine placenta is impermeable to maternal metformin administration. This is likely due to anatomical differences and increased interhaemal distance between the maternal and umbilical circulations in the ovine versus human placenta limiting placental metformin transport., (© 2024. The Author(s).)