Liraglutide restores impaired associative learning in individuals with obesity

Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. To that end, neural circuits receive and integrate external environmental cues and internal metabolic signals to form learned sensory associations, consequently motivating and adapting our behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic signals, including intestinal peptides, such as glucagon-like peptide 1 (GLP-1). In a single-blinded, randomized, controlled, crossover basic human functional magnetic resonance imaging study relying on a computational model of the adaptive learning process underlying behavioural responses, we show that adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity (participants: N = 30 with normal insulin sensitivity; N = 24 with impaired insulin sensitivity). Treatment with the GLP-1 receptor agonist liraglutide normalizes impaired learning of sensory associations in men and women with obesity. Collectively, our findings reveal that GLP-1 receptor activation modulates associative learning in people with obesity via its central effects within the mesoaccumbens pathway. These findings provide evidence for how metabolic signals can act as neuromodulators to adapt our behaviour to our body’s internal state and how GLP-1 receptor agonists work in clinics

An agenda for future Social Sciences and Humanities research on energy efficiency : 100 priority research questions

Decades of techno-economic energy policymaking and research have meant evidence from the Social Sciences and Humanities (SSH)-including critical reflections on what changing a society's relation to energy (efficiency) even means-have been underutilised. In particular, (i) the SSH have too often been sidelined and/or narrowly pigeonholed by policymakers, funders, and other decision-makers when driving research agendas, and (ii) the setting of SSH-focused research agendas has not historically embedded inclusive and deliberative processes. The aim of this paper is to address these gaps through the production of a research agenda outlining future SSH research priorities for energy efficiency. A Horizon Scanning exercise was run, which sought to identify 100 priority SSH questions for energy efficiency research. This exercise included 152 researchers with prior SSH expertise on energy efficiency, who together spanned 62 (sub-)disciplines of SSH, 23 countries, and a full range of career stages. The resultant questions were inductively clustered into seven themes as follows: (1) Citizenship, engagement and knowledge exchange in relation to energy efficiency; (2) Energy efficiency in relation to equity, justice, poverty and vulnerability; (3) Energy efficiency in relation to everyday life and practices of energy consumption and production; (4) Framing, defining and measuring energy efficiency; (5) Governance, policy and political issues around energy efficiency; (6) Roles of economic systems, supply chains and financial mechanisms in improving energy efficiency; and (7) The interactions, unintended consequences and rebound effects of energy efficiency interventions. Given the consistent centrality of energy efficiency in policy programmes, this paper highlights that well-developed SSH approaches are ready to be mobilised to contribute to the development, and/or to understand the implications, of energy efficiency measures and governance solutions. Implicitly, it also emphasises the heterogeneity of SSH policy evidence that can be produced. The agenda will be of use for both (1) those new to the energy-SSH field (including policyworkers), for learnings on the capabilities and capacities of energy-SSH, and (2) established energy-SSH researchers, for insights on the collectively held futures of energy-SSH research.Peer reviewe

The unprecedented 2017-2018 stratospheric smoke event : Decay phase and aerosol properties observed with the EARLINET

© Author(s) 2019. This open access work is distributed under the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm-pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22-23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21-23 August 2017 to 0.005-0.03 until 5-10 September and was mainly 0.003-0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001-0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50-200 Mm-1 until the beginning of September and on the order of 1 Mm-1 (0.5- 5 Mm-1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05-0.5 μg m-3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50-500 L-1 until the first days in September and afterwards 5-50 L-1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of -55 ?C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15-0.25 (August-September) to values of 0.05-0.10 (October-November) and < 0.05 (December-January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32-35? N, that ascended from heights of about 18-19 to 22-23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures.Peer reviewe

The unprecedented 2017–2018 stratospheric smoke event: decay phase and aerosol properties observed with the EARLINET

Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm–pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22–23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21–23 August 2017 to 0.005–0.03 until 5–10 September and was mainly 0.003–0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001–0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50–200 Mm−1 until the beginning of September and on the order of 1 Mm−1 (0.5–5 Mm−1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05–0.5 µg m−3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50–500 L−1 until the first days in September and afterwards 5–50 L−1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of −55 ∘C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15–0.25 (August–September) to values of 0.05–0.10 (October–November) and < 0.05 (December–January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32–35∘ N, that ascended from heights of about 18–19 to 22–23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures

Lipoprotein(a) Management: Pharmacological and Apheretic Treatment

Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are < 50 mg/dl. A plasma concentration of 60 mg/dl is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment for other cardiovascular risk factors. Extended-release niacin is an option for decreasing elevated Lp(a) levels (by similar to 20-30%) but it is often poorly tolerated. Dietary measures, exercise and lipid-lowering drugs such as statins and ezetimibe are without significant effect. In patients with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis can decrease Lp(a) concentrations. The method is expensive and impractical for most patients and its feasibility depends mainly on the healthcare reimbursement system. Since no established treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial that evaluated whether decreasing Lp(a) concentrations translates to clinical benefits. Recently, an antisense oligonucleotide against apo(a), IONIS-APO(a) Rx, has been shown to selectively decrease Lp(a) by almost 80%. A phase 2 study with this drug has been completed in late 2015 and results are expected to be published soon

Increased meso-striatal connectivity mediates trait impulsivity in FTO variant carriers

ObjectiveWhile variations in the first intron of the fat mass and obesity-associated gene (FTO, rs9939609 T/A variant) have long been identified as a major contributor to polygenic obesity, the mechanisms underlying weight gain in risk allele carriers still remain elusive. On a behavioral level, FTO variants have been robustly linked to trait impulsivity. The regulation of dopaminergic signaling in the meso-striatal neurocircuitry by these FTO variants might represent one mechanism for this behavioral alteration. Notably, recent evidence indicates that variants of FTO also modulate several genes involved in cell proliferation and neuronal development. Hence, FTO polymorphisms might establish a predisposition to heightened trait impulsivity during neurodevelopment by altering structural meso-striatal connectivity. We here explored whether the greater impulsivity of FTO variant carriers was mediated by structural differences in the connectivity between the dopaminergic midbrain and the ventral striatum.MethodsEighty-seven healthy normal-weight volunteers participated in the study; 42 FTO risk allele carriers (rs9939609 T/A variant, FTO+ group: AT, AA) and 39 non-carriers (FTO− group: TT) were matched for age, sex and body mass index (BMI). Trait impulsivity was assessed via the Barratt Impulsiveness Scale (BIS-11) and structural connectivity between the ventral tegmental area/substantia nigra (VTA/SN) and the nucleus accumbens (NAc) was measured via diffusion weighted MRI and probabilistic tractography.ResultsWe found that FTO risk allele carriers compared to non-carriers, demonstrated greater motor impulsivity (p = 0.04) and increased structural connectivity between VTA/SN and the NAc (p&lt; 0.05). Increased connectivity partially mediated the effect of FTO genetic status on motor impulsivity.ConclusionWe report altered structural connectivity as one mechanism by which FTO variants contribute to increased impulsivity, indicating that FTO variants may exert their effect on obesity-promoting behavioral traits at least partially through neuroplastic alterations in humans

Management of Blood Pressure and Heart Rate in Patients with Diabetes Mellitus

Background: In patients with diabetes mellitus (DM) there is a clear association between blood pressure (BP) levels and macrovascular and microvascular complications. However, the BP targets that need to be achieved for optimal outcomes remain controversial. Methods: The purpose of this narrative review is to discuss BP targets and management in patients with DM. The subject of elevated heart rate, which has been associated with mortality in many populations, and which is observed in some patients with DM will also be addressed. Results: Most guidelines recommend a target BP in patients with DM of <140/90 mmHg. Most consistently recommended first-line pharmacotherapy for the treatment of hypertension in non-black patients with DM is an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) while for black patients a calcium channel blocker or a thiazide diuretic. Newer antidiabetic drugs, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and the sodium glucose co-transporter-2 (SGLT2) inhibitors lower not only blood glucose but also BP levels. The SGLT2 inhibitor-associated decrease in BP is not accompanied by an increase in heart rate, which is observed however with GLP-1 receptor agonists. Conclusion: The most widely accepted BP target for patients with DM among guidelines is <140/90 mmHg and the most widely accepted pharmacotherapy to achieve these goals are ACE inhibitors and ARBs. Newer antidiabetic medications have been shown to also lower BP and decrease cardiovascular events, thus representing a promising new therapeutic option for patients with DM and hypertension

The relationship between religiosity/spirituality and well-being among Eritrean female refugees living in Norwegian asylum centres.

Abstract Background: Women are more vulnerable to mental health problems than men after migration, but little is known about the influence of religiosity/spirituality on their quality of life. The purpose of this study was to explore religiosity/spirituality, in relationships with various domains of quality of life, among female Eritrean refugees staying in Norwegian asylum centres. Method: A questionnaire assessing sociodemographic characteristics was used together with the World Health OrganizationQuality of Life – Spirituality, Religiosity and Personal Beliefs (WHOQOL-SRPB) questionnaire, which assesses religiosity/spirituality and domains of quality of life. A total of 63 adult female Eritrean refugees who had been granted asylum but were still living in asylum reception centres located in southern and central Norway participated. Results: Religiosity/spirituality was independently associated with psychological quality of life (B = 0.367, p < .001), level of independence (B = 0.184, p = .028), social quality of life (B = 0.500, p = .003), environmental quality of life (B = 0.323,p < .001) and overall quality of life (B = 0.213, p < .001), but not with physical quality of life (B = 0.056, p = .679). There were no significant differences between religious affiliations on religiosity/spirituality or quality of life measures. Conclusion: Consistent with previous research, this study highlights the correlation between religiosity/spirituality and overall quality of life. We recommend a longitudinal follow-up study of similar populations, after they are resettled and integrated into their host countries, to understand the associations between quality of life and religiosity/spirituality over time