Pseudoangiomatous Stromal Hyperplasia: A Case Report

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferating breast condition. It was first reported in 1986 when Vuitch, Rosen, and Erlandson described nine cases of benign well-circumscribed, breast masses that simulated vascular lesions consisting of mammary stromal proliferations (Vuitch et al. (1986)). Since then there have been few reported cases of PASH in the literature (Taira et al. (2005)). We describe a large PASH, mimicking inflammatory carcinoma in a young lady that was excised with excellent cosmetic results

Nonlinear Evolution of the Magnetothermal Instability in Two Dimensions

In weakly magnetized, dilute plasmas in which thermal conduction along magnetic field lines is important, the usual convective stability criterion is modified. Instead of depending on entropy gradients, instability occurs for small wavenumbers when (dP/dz)(dln T/dz) > 0, which we refer to as the Balbus criterion. We refer to the convective instability that results in this regime as the magnetothermal instability (MTI). We use numerical MHD simulations which include anisotropic electron heat conduction to follow the growth and saturation of the MTI in two-dimensional, plane parallel atmospheres that are unstable according to the Balbus criterion. The linear growth rates measured in the simulations agree with the weak field dispersion relation. We investigate the effect of strong fields and isotropic conduction on the linear properties and nonlinear regime of the MTI. In the nonlinear regime, the instability saturates and convection decays away, when the atmosphere becomes isothermal. Sustained convective turbulence can be driven if there is a fixed temperature difference between the top and bottom edges of the simulation domain, and if isotropic conduction is used to create convectively stable layers that prevent the formation of unresolved, thermal boundary layers. The largest component of the time-averaged heat flux is due to advective motions. These results have implications for a variety of astrophysical systems, such as the temperature profile of hot gas in galaxy clusters, and the structure of radiatively inefficient accretion flows.Comment: 37 pages, 17 figures, accepted for publication in ApJ Corrected sign typo in instability criterio

Free-sugar, total-sugar, fibre and micronutrient intake within elite youth British soccer players: a nutritional transition from schoolboy to fulltime soccer player.

It is recommended that soccer players consume a high carbohydrate (CHO) diet to augment performance. However, growing evidence suggests that there is a link between high free-sugar (FS) intake (>5% total energy intake; TEI) and metabolic diseases. Furthermore, foods that are often high in sugar, such as processed foods, are typically lacking in nutrient quality. We therefore analysed total- and FS, dietary fibre and micronutrient intake of players from an English Premier League academy under(U) 18 (n=13); U15/16 (n=25); U13/14 (n=21) using a 7-day food diary. Data was compared to current UK dietary reference value (DRV) for free-sugar via a t-test. The U13/14s (1018 %) and U15/16s (1130 %) both consumed higher amounts of free-sugar in comparison to the UK DRV of 5% TEI 5% (P<0.01), conversely, the U18s did not exceed the DRV (513 %). Furthermore, FS intake of the U18s was significantly lower than the U13/14s and U15/16s (P<0.01). Dietary fibre was below the DRV (25g/d for U13/14 & U15/16s; 30g/d for U18s) for all squads (19.04.7; 19.68.3; 17.14.2 g/d, respectively), but not different between squads. Additionally, micronutrient reference intakes were generally met. In conclusion, we provide novel data on dietary sugar, fibre and micronutrient intake within elite youth soccer players. We report an apparent 'nutritional transition' from schoolboy to fulltime soccer player, with U18s showing a significantly lower intake of sugar in comparison to younger squads, and a similar intake of FS to the UK DRVs. Practitioners should target improving player education around sugar and fibre consumption

My School? Critiquing the abstraction and quantification of education

This paper draws upon and critiques the Australian federal government's website My School as an archetypal example of the current tendency to abstract and quantify educational practice. Arguing in favour of a moral philosophical account of educational practice, the paper reveals how the My School website reduces complex educational practices to simple, supposedly objective, measures of student attainment, reflecting the broader 'audit' society/culture within which it is located. By revealing just how extensively the My School website reduces educational practices to numbers, the paper argues that we are in danger of losing sight of the 'internal' goods of Education which cannot be readily and simply codified, and that the teacher learning encouraged by the site marginalises more active and collective approaches. While having the potential to serve some beneficial diagnostic purposes, the My School website reinforces a view of teachers as passive consumers of information generated beyond their everyday practice

Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling

Adenosine 5′-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Ra/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore, our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway. 2016</p

The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels

Canagliflozin, dapagliflozin and empagliflozin, all recently approved for treatment of Type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose re-uptake by SGLT2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMP-activated protein kinase (AMPK), an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials, and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of ACC1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue or spleen. As phosphorylation of acetyl-CoA carboxylase by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared to other SGLT2 inhibitors

Protein kinase C phosphorylates AMP-activated protein kinase α1 Ser487

The key metabolic regulator, AMP-activated protein kinase (AMPK) is reported to be downregulated in metabolic disorders, but the mechanisms are poorly characterised. Recent studies have identified phosphorylation of the AMPKα1/α2 catalytic subunit isoforms at Ser487/491 respectively as an inhibitory regulation mechanism. Vascular endothelial growth factor (VEGF) stimulates AMPK and protein kinase B (Akt) in cultured human endothelial cells. As Akt has been demonstrated to be an AMPKα1 Ser487 kinase, the effect of VEGF on inhibitory AMPK phosphorylation in cultured primary human endothelial cells was examined. Stimulation of endothelial cells with VEGF rapidly increased AMPKα1 Ser487 phosphorylation in an Akt-independent manner, without altering AMPKα2 Ser491 phosphorylation. In contrast, VEGF-stimulated AMPKα1 Ser487 phosphorylation was sensitive to inhibitors of protein kinase C (PKC) and PKC activation using phorbol esters or overexpression of PKC stimulated AMPKα1 Ser487 phosphorylation. Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle. These data indicate a novel regulatory role of PKC to inhibit AMPKα1 in human cells. As PKC activation is associated with insulin resistance and obesity, PKC may underlie the reduced AMPK activity reported in response to overnutrition in insulin-resistant metabolic and vascular tissues

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation

AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. This has led to considerable interest in AMPK as a therapeutic target for the metabolic dysfunction observed in obesity and insulin resistance. The role of AMPK in skeletal muscle and the liver has been extensively studied, such that AMPK has been demonstrated to inhibit synthesis of fatty acids, cholesterol and isoprenoids, hepatic gluconeogenesis and translation while increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake. The role of AMPK in the other principal metabolic and insulin-sensitive tissue, adipose, remains poorly characterized in comparison, yet increasing evidence supports an important role for AMPK in adipose tissue function. Obesity is characterized by hypertrophy of adipocytes and the development of a chronic sub-clinical pro-inflammatory environment in adipose tissue, leading to increased infiltration of immune cells. This combination of dysfunctional hypertrophic adipocytes and a pro-inflammatory environment contributes to insulin resistance and the development of Type 2 diabetes. Exciting recent studies indicate that AMPK may not only influence metabolism in adipocytes, but also act to suppress this pro-inflammatory environment, such that targeting AMPK in adipose tissue may be desirable to normalize adipose dysfunction and inflammation. In the present review, we discuss the role of AMPK in adipose tissue, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions