Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.

Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis

Validation of Annual Growth-Zone Formation in Gray Triggerfish Balistes capriscus Dorsal Spines, Fin Rays, and Vertebrae

The goal of this study was to validate annual growth-zone formation in the gray triggerfish Balistes capriscus dorsal spines, fin rays, and vertebrae. Adult gray triggerfish (n = 4) were chemically marked by injecting with 50 mg of oxytetracycline (OTC) per kilogram body mass and reared in a 2,300-liter aquaculture tank. Fish were exposed to ambient light and water temperature mimicked bottom temperatures observed at an approximately 30-m depth in the northern Gulf of Mexico. Fish died after 262 d and their first dorsal spines, pectoral fin rays, and vertebrae were extracted and sectioned. One translucent zone formed distal to the OTC mark in all hardpart types during the study period. Additional fin rays and vertebrae with corresponding dorsal spines were sampled from fish (n = 27 and 59, respectively) during fishery-independent surveys to compare translucent zone counts between hardparts. There was a significant difference between translucent zone counts between fin ray and dorsal spine sections (tdf = 1,25 = 23.15, P = 0.004). Fin ray counts on average were one zone greater than dorsal spine counts. Translucent zone counts in vertebrae were similar to those counted in dorsal spines with no significant difference between structures (tdf = 1,57 = 1.90, P = 0.062). The percentage of dorsal spines with translucent margins increased in winter months, peaking in February, and dropped to the lowest values in summer. The combined results of this study validate annual translucent zone formation in gray triggerfish hardparts, with dorsal spines being the preferred ageing structure for production ageing

A multistage combined approach to promote diabetic wound healing in COVID-19 era

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), and other advanced moist wound dress- ing have been proposed. During Coronavirus disease 2019 (COVID-19) pan- demic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non-healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the post- operative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti-inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis

Overcoming the myths of mainstream economics to enable a newwellbeing economy

Increasingly, empirical evidence refutes many of the theoretical pillars of mainstream economics. These theories have persisted despite the fact that they support unsustainable and undesirable environmental, social, and economic outcomes. Continuing to embrace them puts at risk the possibility of achieving the Sustainable Development Goals and overcoming other global challenges. We discuss a selection of paradoxes and delusions surrounding mainstream economic theories related to: (1) efficiency and resource use, (2) wealth and wellbeing, (3) economic growth, and (4) the distribution of wealth within and between rich and poor nations. We describe a wellbeing economy as an alternative for guiding policy development. In 2018, a network of Wellbeing Economy Governments (WEGo), (supported by, but distinct from, the larger Wellbeing Economy Alliance-WEAll) promoting new forms of governance that diverge from the ones on which the G7 and G20 are based, has been launched and is now a living project. Members of WEGo aim at advancing the three key principles of a wellbeing economy: Live within planetary ecological boundaries, ensure equitable distribution of wealth and opportunity, and efficiently allocate resources (including environmental and social public goods), bringing wellbeing to the heart of policymaking, and in particular economic policymaking. This network has potential to fundamentally re-shape current global leadership still anchored to old economic paradigms that give primacy to economic growth over environmental and social wealth and wellbeing

Surgical Treatment with Locoregional Flap for the Nose

Nonmelanotic skin cancers (NMSCs) are the most frequent of all neoplasms and nasal pyramid represents the most common site for the presentation of such cutaneous malignancies, particularly in sun-exposed areas: ala, dorsum, and tip. Multiple options exist to restore functional and aesthetic integrity after skin loss for oncological reasons; nevertheless, the management of nasal defects can be often challenging and the best "reconstruction" is still to be found. In this study, we retrospectively reviewed a total of 310 patients who presented to our Department of Plastic and Reconstructive Surgery for postoncological nasal reconstruction between January 2011 and January 2016. Nasal region was classified into 3 groups according to the anatomical zones affected by the lesion: proximal, middle, and distal third. We included an additional fourth group for complex defects involving more than one subunit. Reconstruction with loco regional flaps was performed in all cases. Radical tumor control and a satisfactory aesthetic and functional result are the primary goals for the reconstructive surgeon. Despite tremendous technical enhancements in nasal reconstruction techniques, optimal results are usually obtained when "like is used to repair like." Accurate evaluation of the patients clinical condition and local defect should be always considered in order to select the best surgical option

Civil society and financial markets : what is not happening and why

Why have commercial financial flows – as a major force in contemporary society with a number of significant problematic consequences – attracted relatively little effective public-interest response from civil society? Change-oriented NGOs, labour unions, faith-based organisations and other social movements have mostly remained in the shadows vis-à-vis private financial markets. Impacts from these citizen associations have not gone beyond promoting modest rises in public awareness, certain limited policy shifts, and minor institutional reforms of a few public governance agencies. The reasons for these scant achievements are partly related to capacities and practices in civil society groups, relevant governance agencies, and financial firms. Also important in constraining civil society impacts to reform and transform contemporary financial markets are deeper structural circumstances such as embedded social hierarchies (among countries, classes, etc.), the pivotal role of finance capital in accumulation processes today, and the entrenchment of prevailing neoliberal policy discourses

Doing Biopolitics Differently? Radical Potential in the Post-2015 MDG and SDG Debates

Post print On institutional repository or subject-based repository after a 18 months embargo, withdraw

World scientists’ warnings into action, local to global

‘We have kicked the can down the road once again – but we are running out of road.’ – Rachel Kyte, Dean of Fletcher School at Tufts University. We, in our capacities as scientists, economists, governance and policy specialists, are shifting from warnings to guidance for action before there is no more ‘road.’ The science is clear and irrefutable; humanity is in advanced ecological overshoot. Our overexploitation of resources exceeds ecosystems’ capacity to provide them or to absorb our waste. Society has failed to meet clearly stated goals of the UN Framework Convention on Climate Change. Civilization faces an epochal crossroads, but with potentially much better, wiser outcomes if we act now. What are the concrete and transformative actions by which we can turn away from the abyss? In this paper we forcefully recommend priority actions and resource allocation to avert the worst of the climate and nature emergencies, two of the most pressing symptoms of overshoot, and lead society into a future of greater wellbeing and wisdom. Humanity has begun the social, economic, political and technological initiatives needed for this transformation. Now, massive upscaling and acceleration of these actions and collaborations are essential before irreversible tipping points are crossed in the coming decade. We still can overcome significant societal, political and economic barriers of our own making. Previously, we identified six core areas for urgent global action – energy, pollutants, nature, food systems, population stabilization and economic goals. Here we identify an indicative, systemic and time-limited framework for priority actions for policy, planning and management at multiple scales from household to global. We broadly follow the ‘Reduce-Remove-Repair’ approach to rapid action. To guide decision makers, planners, managers, and budgeters, we cite some of the many experiments, mechanisms and resources in order to facilitate rapid global adoption of effective solutions. Our biggest challenges are not technical, but social, economic, political and behavioral. To have hope of success, we must accelerate collaborative actions across scales, in different cultures and governance systems, while maintaining adequate social, economic and political stability. Effective and timely actions are still achievable on many, though not all fronts. Such change will mean the difference for billions of children and adults, hundreds of thousands of species, health of many ecosystems, and will determine our common future

Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling

1939-327X (Electronic) Journal articleObjective : Recent data demonstrate that glucose sensing in different tissues is initiated by an intracellular redox-signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain-glucose hypersensitivity present in obese Zucker rat is related to an alteration in redox signaling. Research design and Methods: Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in ROS levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications of redox state and mitochondrial function were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide dismutase, aconitase activities and mitochondrial respiration. Results : Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated with 1) increased ROS levels in response to this low glucose load, 2) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial level, and 3) over-expression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced-glutathione infusion in the third ventricle fully reversed the cerebral hypersensitivity to glucose. Conclusions : Altogether, these data demonstrate that obese Zucker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an abnormal redox signaling, which originates from mitochondria dysfunction

Functional heterogeneity of POMC neurons relies on mTORC1 signaling.

Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior