Four temporal and four spectral parameters of heart rate variability were compared after they were computed with two different time series generation methods: the RR intervals and the numerical values of heart rate provided by the Finapres. Recordings were obtained from 10 healthy subjects throughout five experimental conditions: supine, standing, controlled breathing, exercise and recovery. The mean and the RMS value of successive differences showed significant differences between the two methods. The spectral parameters were statistically different only during standing and exercise. The larger high frequency component and the lower HF/LF ratio by the Finapres method, observed during exercise, can be explained by the higher breathing influence on the peak-to-peak pressure intervals, in relation to RR intervals. Therefore, the high frequency component within mechanic intervals could possibly reflect the non-neural respiratory influence. In conclusion, values of heart rate provided by the Finapres are not completely interchangeable with those obtained from the ECG during the studied conditions.

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Background and Purpose-Facial nerve stimulation has been proposed as a new treatment of ischemic stroke because autonomic components of the nerve dilate cerebral arteries and increase cerebral blood flow when activated. A noninvasive facial nerve stimulator device based on pulsed magnetic stimulation was tested in a dog middle cerebral artery occlusion model. Methods-We used an ischemic stroke dog model involving injection of autologous blood clot into the internal carotid artery that reliably embolizes to the middle cerebral artery. Thirty minutes after middle cerebral artery occlusion, the geniculate ganglion region of the facial nerve was stimulated for 5 minutes. Brain perfusion was measured using gadoliniumenhanced contrast MRI, and ATP and total phosphate levels were measured using 31 P spectroscopy. Separately, a dog model of brain hemorrhage involving puncture of the intracranial internal carotid artery served as an initial examination of facial nerve stimulation safety. Results-Facial nerve stimulation caused a significant improvement in perfusion in the hemisphere affected by ischemic stroke and a reduction in ischemic core volume in comparison to sham stimulation control. The ATP/total phosphate ratio showed a large decrease poststroke in the control group versus a normal level in the stimulation group. The same stimulation administered to dogs with brain hemorrhage did not cause hematoma enlargement. Conclusions-These

20 patients with stroke more than one year earlier were evaluated, admitted to a novel therapy including constraint-induced and computer game-motivated therapy. Statistically significant improvements after 4 weeks of late therapy were seen in all 20 patients on nine out of eleven quantified clinical evaluation scales. The patients looked forward to and enjoyed the therapy. These same late stroke patients were studied via fMRI BOLD immediately before therapy and post therapy. fMRI BOLD studies confirm brain functional reorganization; 3 of the 20 fMRI cases are presented here. We propose that fMRI can help in the process of designing effective stroke therapy programs based on biological principles of brain plasticity.

BackgroundMagnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients.MethodsInitial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer’s ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period.ResultsIn pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3–1.9 Tesla power and for 2- to 5-min duration. No clear dose–response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non-serious adverse events that were limited to the 2-min stimulation period. Tolerability was greatly improved by gentle encouragement from the study staff, which enabled most volunteers to tolerate 1.6–1.8 Tesla of stimulation power. CBF measures taken approximately 10 min after stimulation demonstrated on average a 32 ± 6% increase in CBF, with ≥ 25% increases in CBF occurring in 10 of the 31 volunteers who had adequate CBF measurements.ConclusionsThe minimal effective stimulation parameters defined by increased CBF, as identified in the pig study, translated into safe, tolerable, and effective stimulation of healthy volunteers. These results support the future development and evaluation of non-invasive facial nerve stimulation for the emergency treatment of ischemic stroke.Trial Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on June 6, 2017

Objective: A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design: Cross-sectional study. Methods: We evaluated carriers (n = 72) and non-carriers (n = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic-hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results: Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (β = −0.164, P = 0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) (P = 0.02) and of 7.34 U/L in gammaglutamyltransferase (GGT) (P = 0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher (P < 0.001). European Journal of Endocrinology180:2 100 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com Conclusions: Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight. European Journal of Endocrinology 180:2 101 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 102 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 103 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 104 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 105 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 106 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity https://eje.bioscientifica.com European Journal of Endocrinology 180:2 107 Clinical Study P Almeda-Valdes and others SLC16A11 and insulin sensitivity

This paper proposes a discrete random time series modeling for the VO2 and VCO2 measurement in the indirect calorimetry technique (ICT). Mathematical equations are developed in order to establish clear differences between the breath-by-breath and mixing chamber measurement based calorimeters. This simple model offers not only a physiological ICT definition approach but also defines the idea of VO2 and VCO2 short-term variability information for research. The preliminary results show a new physiological information when a computer oriented algorithm model implementation was applied to a data acquisition system in order to obtain the power spectrum analysis from a typical observation subject submitted to the clino-ortho maneuver.

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