The Swedish supreme courts as part of the public administration, rather than as independent actors - Political, legal, and administrative reasons behind this positioning - A recent trend shifts the ...position of the supreme courts - Endogenous forces (e.g. a more 'conflictual' political climate) and exogenous reasons (e.g. the increasing importance of the judicial-made EU law) - Swedish supreme courts nearer to being a body with the primary duty of safeguarding the law against the executive and legislative powers - 'Full' positioning of supreme courts within the judicial core not an essential institutional requirement for a democracy - Important role of the public administration's degree of dependence on the legislative power.
This article explores and discusses the model of legislative policy adopted by Sweden in the wake of the 2015 migration crisis. In particular, it discusses the best legislative channel (or ...legislative policy model) to deal with the crisis. Using Sweden as an example, the article suggests that the model of legislative policy to be preferred is one which moves legislative law-making processes closer to the judicial system. Shifting law-making away from public agencies allows judicial bodies to develop a regulatory regime more protective of the fundamental rights of persons, in line with international and EU law. Section one presents an ideal-typology of three possible models of legislative policy, namely the administrative, the judicial, and the statutory legislative policy models. Section two outlines the administrative model chosen by Swedish law-makers, in building the legal regime of migration (also during the crisis). Finally, section three points out how, regardless of content, the modality chosen in the Swedish regulation suffers from serious drawback and how, instead, opting for a judicial legislative policy would have been a better solution.
Brown and Beige Adipose Tissue and Aging Zoico, Elena; Rubele, Sofia; De Caro, Annamaria ...
Frontiers in endocrinology (Lausanne),
06/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
Across aging, adipose tissue (AT) changes its quantity and distribution: AT becomes dysfunctional with an increase in production of inflammatory peptides, a decline of those with anti-inflammatory ...activity and infiltration of macrophages. Adipose organ dysfunction may lead to age-related metabolic alterations. Aging is characterized by an increase in adiposity and a decline in brown adipose tissue (BAT) depots and activity, and UCP1 expression. There are many possible links to age-associated involution of BAT, including the loss of mitochondrial function, impairment of the sympathetic nervous system, age-induced alteration of brown adipogenic stem/progenitor cell function and changes in endocrine signals. Aging is also associated with a reduction in beige adipocyte formation. Beige adipocytes are known to differentiate from a sub-population of progenitors resident in white adipose tissue (WAT); a defective ability of progenitor cells to proliferate and differentiate has been hypothesized with aging. The loss of beige adipocytes with age may be caused by changes in trophic factors in the adipose tissue microenvironment, which regulate progenitor cell proliferation and differentiation. This review focuses on possible mechanisms involved in the reduction of BAT and beige activity with aging, along with possible targets for age-related metabolic disease therapy.
Sarcopenic obesity is a clinical and functional condition characterized by the coexistence of excess fat mass and sarcopenia. Currently, different definitions of sarcopenic obesity exist and its ...diagnostic criteria and cut-offs are not universally established. Therefore, the prevalence and sensitivity of this condition for any disease risk prediction is affected significantly.
This work was conducted under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). An international expert panel performed a systematic review as an initial step to analyze and summarize the available scientific literature on the definitions and the diagnostic criteria for sarcopenic obesity proposed and/or applied in human studies to date.
The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in April 2018 in three databases (PubMed, Scopus, Web of Science). Human studies conducted in both sexes, irrespective of ethnicity, and published from 2007 to 2018 were included; cohorts of individuals with obesity and acute or chronic conditions and treatments reported to negatively influence skeletal muscle mass and function independently of obesity were excluded from final analyses. The quality of the studies was evaluated using the Newcastle–Ottawa Scale (NOS) adapted for cross sectional studies.
The electronic search retrieved 2335 papers of which 75 met the eligibility criteria. A marked heterogeneity in definitions and approaches to diagnose sarcopenic obesity was observed. This was mainly due to differences in the definitions of obesity and sarcopenia, in the methodologies used to assess body composition and physical function, and in the reference values for the variables that have been used (different cut-offs, interquartile analysis, diverse statistical stratification methods). This variability may be attributable, at least in part, to the availability of the methodologies in the different settings, to the variability in specialties and backgrounds of the researcher, and to the different settings (general population, clinical settings, etc.) where studies were performed.
The results of the current work support the need for consensus proposals on: 1) definition of sarcopenic obesity; 2) diagnostic criteria both at the level of potential gold-standards and acceptable surrogates with wide clinical applicability, and with related cut-off values; 3) methodologies to be used in actions 1 and 2. First steps should be aimed at reaching consensus on plausible proposals that would need subsequent validation based on homogeneous studies and databases, possibly based on analyses of existing cohorts, to help define the prevalence of the condition, its clinical and functional relevance as well as most effective prevention and treatment strategies.
Abstract Background and aim In elderly patients, age-related changes in body composition, as well as the increased prevalence of obesity, determine a combination of excess weight and reduced muscle ...mass or strength, recently defined as sarcopenic obesity (SO). This review examines the main studies regarding sarcopenic obesity in the elderly. Data synthesis Definition of SO necessarily combines those of sarcopenia and obesity. The prevalence of sarcopenia and SO increases with age. Muscle and fat mass are strongly interconnected from a pathogenetic point of view. A better understanding of the mechanisms which lead from loss of muscle mass to fat gain or vice versa from fat gain to muscle loss seems to be crucial. Recent data suggest that peptides produced by adipose tissue may play an important role in the pathophysiology of SO, thus more research is needed to better characterize this new area. Obesity and Sarcopenia in the elderly may potentiate each other maximizing their effects on disability, morbidity and mortality. Identifying elderly subjects with SO should be mandatory; effective treatment of sarcopenia and SO may attenuate its clinical impact. Conclusion The concept of SO may help to clarify the relationship between obesity, morbidity and mortality in the elderly.
Recently, there has been a growing body of evidence showing a negative effect of the white adipose tissue (WAT) dysfunction on the skeletal muscle function and quality. However, little is known about ...the effects of senescent adipocytes on muscle cells.
Therefore, to explore potential mechanisms involved in age-related loss of muscle mass and function, we performed an in vitro experiment using conditioned medium obtained from cultures of mature and aged 3 T3-L1 adipocytes, as well as from cultures of dysfunctional adipocytes exposed to oxidative stress or high insulin doses, to treat C2C12 myocytes.
The results from morphological measures indicated a significant decrease in diameter and fusion index of myotubes after treatment with medium of aged or stressed adipocytes. Aged and stressed adipocytes presented different morphological characteristics as well as a different gene expression profile of proinflammatory cytokines and ROS production. In myocytes treated with different adipocytes' conditioned media, we demonstrated a significant reduction of gene expression of myogenic differentiation markers as well as a significant increase of genes involved in atrophy. Finally, a significant reduction in protein synthesis as well as a significant increase of myostatin was found in muscle cells treated with medium of aged or stressed adipocytes compared to controls.
In conclusion, these preliminary results suggest that aged adipocytes could influence negatively trophism, function and regenerative capacity of myocytes by a paracrine network of signaling.
•Senescent adipocytes negatively influence myocytes trophism.•Senescent adipocytes alter expression of genes involved in muscle atrophy.•Senescent and stressed adipocytes tendentially reduce protein synthesis in myocytes.•Myocytes exposition to aged adipocytes medium activates myostatin pathway.
The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included ...representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as ‘presarcopenia’, ‘sarcopenia’ and ‘severe sarcopenia’. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
The dysfunction of adipose tissue with aging and the accumulation of senescent cells has been implicated in the pathophysiology of chronic diseases. Recently interventions capable of reducing the ...burden of senescent cells and in particular the identification of a new class of drugs termed senolytics have been object of extensive investigation. We used an in vitro model of induced senescence by treating both pre-adipocytes as well as mature adipocytes with hydrogen peroxide (H
O
) at a sub-lethal concentration for 3 h for three consecutive days, and hereafter with 20 uM quercetin at a dose that in preliminary experiments resulted to be senolytic without cytotoxicity. H
O
treated pre-adipocytes and adipocytes showed typical senescence-associated features including increased beta-galactosidase activity (SA-ß-gal) and p21, activation of ROS and increased expression of pro-inflammatory cytokines. The treatment with quercetin in senescent pre-adipocytes and adipocytes was associated to a significant decrease in the number of the SA-β-gal positive cells along with the suppression of ROS and of inflammatory cytokines. Besides, quercetin treatment decreased miR-155-5p expression in both models, with down-regulation of p65 and a trend toward an up-regulation of SIRT-1 in complete cell extracts. The senolytic compound quercetin could affect AT ageing by reducing senescence, induced in our in vitro model by oxidative stress. The downregulation of miRNA-155-5p, possibly through the modulation of NF-κB and SIRT-1, could have a key role in the effects of quercetin on both pre-adipocytes and adipocytes.
Arterial hypertension is strongly related to overweight and obesity. In obese subjects, several mechanisms may lead to hypertension such as insulin and leptin resistance, perivascular adipose tissue ...dysfunction, renal impairment, renin-angiotensin-aldosterone-system activation and sympathetic nervous system activity. Weight loss (WL) seems to have positive effects on blood pressure (BP). The aim of this review was to explain the mechanisms linking obesity and hypertension and to evaluate the main studies assessing the effect of WL on BP. We analysed studies published in the last 10 years (13 studies either interventional or observational) showing the effect of WL on BP. Different WL strategies were taken into account-diet and lifestyle modification, pharmacological intervention and bariatric surgery. Although a positive effect of WL could be identified in each study, the main difference seems to be the magnitude and the durability of BP reduction over time. Nevertheless, further follow-up data are needed: there is still a lack of evidence about long term effects of WL on hypertension. Hence, given the significant results obtained in several recent studies, weight management should always be pursued in obese patients with hypertension.
Fat mass and fat tissue distribution change dramatically throughout life. In old age, fat becomes dysfunctional and is redistributed from subcutaneous to intra-abdominal visceral depots as well as ...other ectopic sites, including bone marrow, muscle and the liver. These changes are associated with increased risk of metabolic syndrome. Fat tissue is a nutrient storage, endocrine and immune organ that undergoes renewal throughout the lifespan. Preadipocytes, which account for 15–50% of cells in fat tissue, give rise to new fat cells. With aging, declines in preadipocyte proliferation and differentiation likely contribute to increased systemic exposure to lipotoxic free fatty acids. Age-related fat tissue inflammation is related to changes that occur in preadipocytes and macrophages in a fat depot-dependent manner. Fat tissue inflammation frequently leads to further reduction in adipogenesis with aging, more lipotoxicity and activation of cellular stress pathways that, in turn, exacerbate inflammatory responses of preadipocytes and immune cells, establishing self-perpetuating cycles that lead to systemic dysfunction. In this review, we will consider how inherent, age-related, depot-dependent alterations in preadipocyte function contribute to age-related fat tissue redistribution and metabolic dysfunction.
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