Paraneoplastic hypoglycaemia secondary to IGF-2 secretion from a metastatic gastrointestinal stromal tumour

We report the case of a 79-year-old male with previous history of non-Hodgkin's lymphoma in remission, who presented acutely to the Accident and Emergency department with recurrent episodes of hypoglycaemia. At the time of presentation, a random glucose was low at 1.4 mmol/l, which upon correction resolved his symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 2 months to which he did not give much notice. While hospitalized, he continued having episodes of symptomatic hypoglycaemia, requiring treatment with intravenous dextrose and per os steroids. Once stable, he was discharged on oral prednisolone and dietary advice. A computed tomography scan performed during inpatient stay showed multiple deposits in the abdomen. An ultrasound guided biopsy of one of the liver deposits was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. The diagnosis of non-islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=105.9 nmol/l; IGF2:IGF1 ratio 23, Upper Level of Normal (ULN) <10). Targeted cytoreductive treatment with Imatinib mesylate following assessment of the tumour's mutational status was successful in preventing hypoglycaemia over a 21-month follow-up observation period

Brane Cosmology with a Non-Minimally Coupled Bulk-Scalar Field

We consider the cosmological evolution of a brane in the presence of a bulk scalar field coupled to the Ricci scalar through a term f(\phi)R. We derive the generalized Friedmann equation on the brane in the presence of arbitrary brane and bulk-matter, as well as the scalar field equation, allowing for a general scalar potential V(phi). We focus on a quadratic form of the above non-minimal coupling and obtain a class of late-time solutions for the scale factor and the scalar field on the brane that exhibit accelerated expansion for a range of the non-minimal coupling parameter.Comment: 15 page

Brown fat depots in adult humans remain static in their locations on PET/CT despite changes in seasonality

Active brown adipose tissue (BAT) in humans has been demonstrated through use of positron emission tomography with 2-deoxy-2-(fluorine-18) fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) scans. The aim of our study was to determine whether active human BAT depots shown on 18F-FDG PET/CT scans remain static in their location over time. This was a retrospective study. Adult human subjects (n = 15) who had had 18F-FDG PET/CT imaging (n = 38 scans in total) for clinical reasons were included on the basis of 18F-FDG uptake patterns consistent with BAT activity. For each subject, 18F-FDG BAT uptake pattern on serial 18F-FDG PET/CT images was compared to an index 18F-FDG PET/CT image with the largest demonstrable BAT volume. Object-based colocalization was expressed as Mander's correlation coefficient (where 1 = 100% overlap, 0 = no overlap). Distribution of 18F-FDG BAT activity over time and across multiple 18F-FDG BAT scans was equivalent in 60% (n = 9) of the subjects. The degree of consistency in the pattern of 18F-FDG BAT uptake in each subject over time was greater than expected by chance in 87% (n = 13) of the subjects (pair-wise agreement 75–100%, Fleiss’ κ 0.4–1). The degree of BAT colocalization on serial scans was greater than that expected by chance in 93% (n = 14) of the subjects (mean Mander's coefficient 0.81 ± 0.21 [95% CI]). To our knowledge, our study provides the most conclusive evidence to date to support the notion that active BAT depots in humans (volumes and activities of which were measured through use of 18F-FDG PET/CT scans) remain static in location over sustained periods

Multiplexity of human brain oscillations as a personal brain signature

Human individuality is likely underpinned by the constitution of functional brain networks that ensure consistency of each person's cognitive and behavioral profile. These functional networks should, in principle, be detectable by noninvasive neurophysiology. We use a method that enables the detection of dominant frequencies of the interaction between every pair of brain areas at every temporal segment of the recording period, the dominant coupling modes (DoCM). We apply this method to brain oscillations, measured with magnetoencephalography (MEG) at rest in two independent datasets, and show that the spatiotemporal evolution of DoCMs constitutes an individualized brain fingerprint. Based on this successful fingerprinting we suggest that DoCMs are important targets for the investigation of neural correlates of individual psychological parameters and can provide mechanistic insight into the underlying neurophysiological processes, as well as their disturbance in brain diseases

DGP Cosmology with a Non-Minimally Coupled Scalar Field on the Brane

We construct a DGP inspired braneworld scenario where a scalar field non-minimally coupled to the induced Ricci curvature is present on the brane. First we investigate the status of gravitational potential with non-minimal coupling and observational constraints on this non-minimal model. Then we further deepen the idea of embedding of FRW cosmology in this non-minimal setup. Cosmological implications of this scenario are examined with details and the quintessence and late-time expansion of the universe within this framework are examined. Some observational constraints imposed on this non-minimal scenario are studied and relation of this model with dark radiation formalism is determined with details.Comment: 26 pages, 3 eps figure

Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump

The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least ≈2 x 10(6) s(-1)

Male obesity associated gonadal dysfunction and the role of bariatric surgery

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction