A simple deep breathing test reveals altered cerebral autoregulation in type 2 diabetic patients

Aims/hypothesis: Patients with diabetes mellitus have an increased risk of stroke and other cerebrovascular complications. The purpose of this study was to evaluate the autoregulation of cerebral blood flow in diabetic patients using a simple method that could easily be applied to the clinical routine screening of diabetic patients. Methods: We studied ten patients with type 2 diabetes mellitus and 11 healthy volunteer control participants. Continuous and non-invasive measurements of blood pressure and cerebral blood flow velocity were performed during deep breathing at 0.1 Hz (six breaths per minute). Cerebral autoregulation was assessed from the phase shift angle between breathing-induced 0.1 Hz oscillations in mean blood pressure and cerebral blood flow velocity. Results: The controls and patients all showed positive phase shift angles between breathing-induced 0.1 Hz blood pressure and cerebral blood flow velocity oscillations. However, the phase shift angle was significantly reduced (p < 0.05) in the patients (48 ± 9°) compared with the controls (80 ± 12°). The gain between 0.1 Hz oscillations in blood pressure and cerebral blood flow velocity did not differ significantly between the patients and controls. Conclusions/interpretation: The reduced phase shift angle between oscillations in mean blood pressure and cerebral blood flow velocity during deep breathing suggests altered cerebral autoregulation in patients with diabetes and might contribute to an increased risk of cerebrovascular disorder

Experimental estimates of the photon background in a potential light-by-light scattering study

High power short pulse lasers provide a promising route to study the strong field effects of the quantum vacuum, for example by direct photon–photon scattering in the all-optical regime. Theoretical predictions based on realistic laser parameters achievable today or in the near future predict scattering of a few photons with colliding Petawatt laser pulses, requiring single photon sensitive detection schemes and very good spatio-temporal filtering and background suppression. In this article, we present experimental investigations of this photon background by employing only a single high power laser pulse tightly focused in residual gas of a vacuum chamber. The focal region was imaged onto a single-photon sensitive, time gated camera. As no detectable quantum vacuum signature was expected in our case, the setup allowed for characterization and first mitigation of background contributions. For the setup employed, scattering off surfaces of imperfect optics dominated below residual gas pressures of 1 × 10−4 mbar. Extrapolation of the findings to intensities relevant for photon–photon scattering studies is discussed

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15 Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0 °C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25 mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p < 0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation

Neuroanatomic Correlates of Female Sexual Dysfunction in Multiple Sclerosis

OBJECTIVE: This study intended to determine associations between alterations of female sexual arousal as well as vaginal lubrication and the site of cerebral multiple sclerosis (MS) lesions. METHODS: In 44 women with MS (mean age: 36.5 ± 9.9 years), we assessed their medical history and evaluated sexual function using the Female Sexual Function Index scores for arousal and vaginal lubrication. We determined potential confounding factors of sexual dysfunction: age; disease duration; physical disability; depression; bladder or urinary dysfunction; and total volume of cerebral lesions. Arousal and lubrication scores were correlated with one another and with potential confounding factors. Cerebral MS lesions were recorded on imaging scans. A voxel-based lesion symptom mapping (VLSM) analysis adjusted for confounding variables was performed correlating cerebral sites of MS lesions with arousal and lubrication scores. RESULTS: Decreased arousal scores correlated with decreased lubrication scores; decreased lubrication scores were associated with bladder or urinary symptoms. Arousal and lubrication scores were not associated with any other variables. Multivariate VLSM analysis, including arousal and lubrication scores as covariables of interest, showed right occipital lesions associated with impaired arousal and left insular lesions associated with decreased lubrication. Impaired lubrication remained associated with left insular lesions after adjustment for bladder or urinary dysfunction. INTERPRETATION: Our data indicate that impaired female sexual arousal is associated with MS lesions in the occipital region, integrating visual information and modulating attention toward visual input. Impaired lubrication correlated with lesions in the left insular region, contributing to mapping and generating visceral arousal states

Proton acceleration by irradiation of isolated spheres with an intense laser pulse

We report on experiments irradiating isolated plastic spheres with a peak laser intensity of 2-3 x 10(20) W cm(-2). With a laser focal spot size of 10 mu m full width half maximum (FWHM) the sphere diameter was varied between 520 nm and 19.3 mu m. Maximum proton energies of similar to 25 MeV are achieved for targets matching the focal spot size of 10 mu m in diameter or being slightly smaller. For smaller spheres the kinetic energy distributions of protons become nonmonotonic, indicating a change in the accelerating mechanism from ambipolar expansion towards a regime dominated by effects caused by Coulomb repulsion of ions. The energy conversion efficiency from laser energy to proton kinetic energy is optimized when the target diameter matches the laser focal spot size with efficiencies reaching the percent level. The change of proton acceleration efficiency with target size can be attributed to the reduced cross-sectional overlap of subfocus targets with the laser. Reported experimental observations are in line with 3D3V particle in cell simulations. They make use of well-defined targets and point out pathways for future applications and experiments.DFG via the Cluster of Excellence Munich-Centre for Advanced Photonics (MAP) Transregio SFB TR18NNSA DE-NA0002008Super-MUC pr48meIvo CermakCGC Instruments in design and realization of the Paul trap systemIMPRS-APSLMUexcellent Junior Research FundDAAD|ToIFEEuropean Union's Horizon research and innovation programme 633053Physic

The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease – A systematic literature review by a European panel of experts

BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage