Search for Cosmic-Ray Electron and Positron Anisotropies with Seven Years of Fermi Large Area Telescope Data.

The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.

Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope.

We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12} GeV^{-1} for ALP masses 0.5≲m_{a}≲5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the γ-ray opacity of the Universe.

Resolving the Extragalactic γ-Ray Background above 50 GeV with the Fermi Large Area Telescope.

The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN/dS, of extragalactic γ-ray sources at E>50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (∼8×10^{-12} ph cm^{-2} s^{-1}). We employ a one-point photon fluctuation analysis to constrain the behavior of dN/dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, S_{b}, in the range [8×10^{-12},1.5×10^{-11}] ph cm^{-2} s^{-1} and power-law indices below and above the break of α_{2}∈[1.60,1.75] and α_{1}=2.49±0.12, respectively. Integration of dN/dS shows that point sources account for at least 86_{-14}^{+16}% of the total extragalactic γ-ray background. The simple form of the derived source count distribution is consistent with a single population (i.e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism.

Melanomas are characterised by accelerated cell proliferation and metabolic reprogramming resulting from the contemporary dysregulation of the MAPK pathway, glycolysis and the tricarboxylic acid (TCA) cycle. Here, we suggest that the oncogenic transcription factor EB (TFEB), a key regulator of lysosomal biogenesis and function, controls melanoma tumour growth through a transcriptional programme targeting ERK1/2 activity and glucose, glutamine and cholesterol metabolism. Mechanistically, TFEB binds and negatively regulates the promoter of DUSP-1, which dephosphorylates ERK1/2. In melanoma cells, TFEB silencing correlates with ERK1/2 dephosphorylation at the activation-related p-Thr185 and p-Tyr187 residues. The decreased ERK1/2 activity synergises with TFEB control of CDK4 expression, resulting in cell proliferation blockade. Simultaneously, TFEB rewires metabolism, influencing glycolysis, glucose and glutamine uptake, and cholesterol synthesis. In TFEB-silenced melanoma cells, cholesterol synthesis is impaired, and the uptake of glucose and glutamine is inhibited, leading to a reduction in glycolysis, glutaminolysis and oxidative phosphorylation. Moreover, the reduction in TFEB level induces reverses TCA cycle, leading to fatty acid production. A syngeneic BRAFV600E melanoma model recapitulated the in vitro study results, showing that TFEB silencing sustains the reduction in tumour growth, increase in DUSP-1 level and inhibition of ERK1/2 action, suggesting a pivotal role for TFEB in maintaining proliferative melanoma cell behaviour and the operational metabolic pathways necessary for meeting the high energy demands of melanoma cells.

[A rare cause of dyspnea on exertion]. / Una rara causa di dispnea da sforzo.

Vascular rings are rare anomalies accounting for 1% to 3% of all congenital heart diseases with a similar frequency in both sexes, which can result in a variable degree of extrinsic compression of the trachea and esophagus. We report the case of a 46-year-old woman with symptomatic dyspnea and double aortic arch that caused esophageal tracheal compression. Considering the little impact of the functional vascular anomaly in our case, a conservative approach was adopted with clinical and functional annual follow-up.

Measurement of the high-energy gamma-ray emission from the Moon with the Fermi Large Area Telescope.

We have measured the gamma-ray emission spectrum of the Moon using the data collected by the Large Area Telescope onboard the Fermi satellite during its first seven years of operation, in the energy range from 30 MeV up to a few GeV. We have also studied the time evolution of the flux, finding a correlation with the solar activity. We have developed a full Monte Carlo simulation describing the interactions of cosmic rays with the lunar surface. The results of the present analysis can be explained in the framework of this model, where the production of gamma rays is due to the interactions of cosmic-ray proton and helium nuclei with the surface of the Moon. Finally, we have used our simulation to derive the cosmic-ray proton and helium spectra near Earth from the Moon gamma-ray data.

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

BACKGROUND AND AIMS: A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. PATIENTS AND METHODS: We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. RESULTS: In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. CONCLUSION: Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

Blood glucose monitoring in the normal population: the PREDICA study.

In the PREdiction of DIabetes from CApillary blood glucose (PREDICA) study, we propose a novel approach based on multiple capillary blood glucose (CBG) measurements, assuming that weekly measurements performed for 2 months may be an efficient strategy to screen for diabetes. We studied 538 Caucasian subjects (247 men and 291 women) without a history of diabetes, consecutively recruited by 50 GPs from the Italian provinces of Rome and Frosinone. Subjects were asked to perform 8 fasting glucose and 8 post-prandial glucose measurements during a frame time of 2 months (Glucometer Accu-chek AVIVA Roche Diagnostics). Study subjects were 55 ± 9 years old (range 22-77 years of age), 50% were overweight and 16% obese. Fifty-eight percent of subjects have performed 13 to 16 CBG measurements during the study, 68% of subjects have performed at least 5 out of 8, both fasting and post-prandial measurements. Among 492 subjects who had at least two fasting measurements, 63.6% had normal glucose levels, 25.4% showed IFG, and 11.0% were diabetic. Considering post-prandial measurements, 74.2% had normal glucose levels, 23.0% had IGT, and 2.8% were diabetic. Combined IFG + IGT was detected in 7% of study subjects, while in 0.8% diagnosis of diabetes was confirmed with both fasting and post-prandial measurements. In this study, we found a high adherence to a novel screening strategy based on self-glucose monitoring in the general population. Our results show that multiple CBG measurements may represent a simple and efficient method for diabetes screening.

Computer use, free time activities and metabolic control in patients with type 1 diabetes.

We investigated the influence of computer's use on metabolic control in 115 patients with type 1 diabetes (DM1). Multiple linear regression showed that HbA1c% was not related to age, DM1 duration, TV watching or computer use but was independently and negatively related to the weekly hours spent on physical exercise.

Frequency of diabetes and thyroid autoantibodies in patients with autoimmune endocrine disease from Cameroon.

BACKGROUND: Diabetes is a major cause of morbidity and mortality in both industrialized and developing countries. In Africa, there are little data on the prevalence and immunological features of patients with autoimmune endocrine diseases. AIM OF THE STUDY: The present hospital-based study was carried out to evaluate disease-associated autoantibodies in both type 1 diabetes and thyrotoxicosis attending the Central Hospital of Yaoundee in Cameroon. PATIENTS AND METHODS: Samples were collected from a total of 101 subjects, 47 of whom clinically had established type 1 diabetes (mean age 30.1 years +/- 7.6, mean disease duration 3.3 years), 18 had thyrotoxicosis (mean age 32.7 years +/- 7.6, mean disease duration 6.3 years +/- 2.8) and 36 normal subjects (mean age 26 years +/- 4.5). All subjects were tested for diabetes-associated glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA2) autoantibodies using antigen-specific radioimmunoassay as well as thyroiditis-associated thyroglobulin (Tg) and thyroid peroxidase (TPO) autoantibodies using commercially available kits. RESULTS: Of 47 patients with type 1 diabetes, 16 (34%) had GAD autoantibodies (Abs), 3 (6.4%) had IA2 Abs, and 2 (4.3%) had TPO Abs. Of 18 patients with thyrotoxicosis 4 (22.2%) had GAD Abs, 5 (27.8%) showed IA2 Abs, while 8 patients (44.4%) were TPO Abs positive. No patients in either group had Tg Abs. Among normal subjects, 2 (5.6%) showed GAD Abs, and one of these was also IA2 Abs positive, but none had thyroid autoantibodies. CONCLUSION: Adult-onset type 1 diabetic patients some years post-diagnosis from central Africa show GAD, IA2 or TPO Abs; and surprisingly, patients with thyrotoxicosis had a similar frequency of diabetes-associated autoantibodies. We conclude that, despite a different genetic and environmental background to European populations, islet cell autoimmunity is common in autoimmune endocrine patients in central Africa.

Porphyria cutanea tarda in a haemodialysed patient.

A bullous dermatosis, that arose about 2 years after the beginning of haemodialysis treatment, was due to a geniune hereditary porphyria cutanea tarda (PCT). The plasma porphyrins were extraordinarily high. Neither the residual renal function nor the haemodialysis--using different techniques and different materials--succeeded in reducing the plasma porphyrin levels to that usually found in PCT. The serious and rapid evolution of the cutaneous lesions towards a scleroderma-like state might have been due to this level of plasma porphyrins and to their passage into the tissues. The clearance of porphyrins is compared with that of 162 subjects affected by PCT. The porphyrin content in the plasma of seventy-five non-porphyric subjects undergoing maintenance dialysis was also studied.