Accommodating conscientious objection in the midwifery workforce: a ratio-data analysis of midwives, birth and late abortions in 18 European countries in 2016.

BACKGROUND: In recent years, the role of a midwife has expanded to include the provision of abortion-related care. The laws on abortion in many European countries allow for those who hold a conscientious objection to participating to refrain from such participation. However, some writers have expressed concerns that this may have a detrimental effect on the workforce and limit women's access to the service. METHOD: The aim of this study was to provide a picture of the potential exposure midwives in Europe have to late abortions, an important factor in the integration of accommodation of conscientious objection to abortion by midwives into workload planning. We collected data from Ministries of Health or government statistical departments in 32 European countries on numbers of births, abortions, late abortions and midwives in 2016. We conducted a ratio-data analysis in those countries that met the inclusion criteria. RESULTS: Eighteen of the 32 countries provided full data; thus, our calculations are based on a total of 4 036 633 live births, 49 834 late abortions and a total of 132 071 midwives. The calculated ratios of live births to midwife, abortions to midwife and late abortions to midwife illustrate the wide variations between countries in relation to ratios of midwives to live births (15.22-53.99) and late abortions (0.17-1.47) CONCLUSIONS: This study provides the first comprehensive insight to ratios relating to birth and abortion, especially late abortion services, with regard to the midwifery workforce. It is essential to improve the reporting of abortion data and access to it within Europe to support evidence-informed decisions on optimising the contribution of the midwifery workforce especially within highly contentious fields such as abortion services. The study's findings suggest that there should be neither be any difficulty for those who are responsible for workload allocation nor compromises to a women's right to abortion services

Pre- and Posttranslational Regulation of Β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment

There appear to be two anatomically distinct Β-endorphin (ΒE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on ΒE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different ΒE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total ΒE-ir, different molecular weight immunoreactive Β-endorphin (ΒE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total ΒE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on ΒE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ∼ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length ΒE 1–31 to more processed ΒE-ir peptides (i.e., ΒE 1–27 and ΒE 1–26 ) tended to increase in a dose-dependent manner in diencephalic areas. Because ΒE 1–31 is the only POMC product that possesses opioid agonist properties, and ΒE 1–27 has been posited to function as an endogenous anatgonist of ΒE 1–31 , the NTX-induced changes in the relative concentrations of ΒE 1–31 and ΒE 1–27 /ΒE 1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65603/1/j.1471-4159.1993.tb05820.x.pd

J Neurosci

The endogenous dynorphin-kappa opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38alpha MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38alpha MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(-/-) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38alpha MAPK activation did not. Surprisingly, while p38alpha MAPK inactivation blocked U50,488-CPA, p38alpha MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38alpha MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that kappa opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38alpha MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT: Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of kappa receptor activation required arrestin-dependent p38alpha MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective kappa opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

Stressors motivate an array of adaptive responses ranging from \u27fight or flight\u27 to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF\u27s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders

Disequilibrium in development finance: the contested politics of institutional accountability and transparency at the World Bank inspection panel

This article examines the dynamic nature with which independent accountability mechanisms operate. Focusing on the World Bank, the authors argue that its Inspection Panel evolves according to internal and external pressures. In seeking to achieve equilibrium, and protect its authority and independence, the Panel has gone through several distinct phases: negotiation, emergence, protracted resistance, assertion of independence and authority, renewed tension, and contestation. The core novelty of the article is its application of concepts from outside the field of development studies — notably institutional accountability from the governance literature, and judicialization from the legal studies literature — to the topic of the Inspection Panel. Examining the Panel in this way demonstrates that accountability mechanisms represent a hybrid of transnational governance influenced by a range of actors including project-affected peoples, national governments, managers and development donors. Accountability in development finance is about competing interests as well as competing conceptions and expectations of accountability. In such a complex and multi-scalar system, the Panel is not only concerned with delivering well-researched investigation reports; it is also an entity seeking to ensure its own survival, as well as an arbiter of its own brand of legitimacy and accountability. © 2018 The Authors. Development and Change published by John Wiley & Sons Ltd on behalf of Institute of Social Studie

The evolution of fetal protection policies

This article examines the evolution of fetal protection policies (FPPs) by detailing their historical legacy and a range of contemporary social forces that have contributed to their maintenance. It is based on a case study of the 1977 U.S. Department of Labor, Occupational Safety and Health Administration (OSHA) hearings to revise the industrial lead standard, the 1991 U.S. Supreme Court decision that such policies are unconstitutional ( United Auto Workers v. Johnson Controls , 1991), and the case law preceding that decision. A primary issue is the notion that women and fetuses are disproportionately susceptible to lead. This study reveals the ways in which this belief is framed, disputed, and appropriated by various parties to the fetal protection policy debate. Implications of this case study for family health policy are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44656/1/10834_2006_Article_BF02353687.pd

Structure of the human κ-opioid receptor in complex with JDTic

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and—in the case of κ-opioid receptor (κ-OR)—dysphoria and psychotomimesis. Here we report the crystal structure of the human κ-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 Å resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human κ-OR. Modelling of other important κ-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5′-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure–activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for κ-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human κ-OR