Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 +/- 3.2, 56.0 +/- 6.1, and 75.9 +/- 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 +/- 0.6, 14.8 +/- 2.7, 29.9 +/- 5.8, and 50.1 +/- 12.5 ml 100 ml(-1) min(-1), respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 +/- 1.4, 8.7 +/- 0.7, 12.9 +/- 1.7, and 12.2 +/- 1.8 ml 100 ml(-1) min(-1), respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output (r = 0.994, P = 0.006), 2) the work of breathing (r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure (r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.

Alzheimer disease (AD) is a chronic neurodegenerative disease with no effective cure so far. The current review focuses on the epigenetic mechanisms of AD and how nutrition can influence the course of this disease through regulation of gene expression, according to the latest scientific findings. The search strategy was the use of scientific databases such as PubMed and Scopus in order to find relative research or review articles published in the years 2012-2015. By showing the latest data of various nutritional compounds, this study aims to stimulate the scientific community to recognize the value of nutrition in this subject. Epigenetics is becoming a very attractive subject for researchers because it can shed light on unknown aspects of complex diseases like AD. DNA methylation, histone modifications, and microRNAs are the principal epigenetic mechanisms involved in AD pathophysiology. Nutrition is an environmental factor that is related to AD through epigenetic pathways. Vitamin B-12, for instance, can alter the one-carbon metabolism and thus interfere in the DNA methylation process. The research results might seem ambiguous about the clinical role of nutrition, but there is strengthening evidence that proper nutrition can not only change epigenetic biomarker levels but also prevent the development of late-onset AD and attenuate cognition deficit. Nutrition might grow to become a preventive and even therapeutic alternative against AD, especially if combined with other antidementia interventions, brain exercise, physical training, etc. Epigenetic biomarkers can be a very helpful tool to help researchers find the exact nutrients needed to create specific remedies, and perhaps the same biomarkers can be used even in patient screening in the future.

Previous work suggests that exercise-induced arterial hypoxaemia (EIAH), causing only moderate arterial oxygen desaturation (S aO 2 : 92 ± 1%), does not exaggerate diaphragmatic fatigue exhibited by highly trained endurance athletes. Since changes in arterial O 2 tension have a significant effect on the rate of development of locomotor muscle fatigue during strenuous exercise, the present study investigated whether hypoxia superimposed on EIAH exacerbates the exercise-induced diaphragmatic fatigue in these athletes. Eight trained cyclists (V O 2 max : 67.0 ± 2.6 ml kg −1 min −1 ; mean ± S.E.M.) completed in balanced order four 5 min exercise tests leading to different levels of end-exercise S aO 2 (64 ± 2, 83 ± 1, 91 ± 1 and 96 ± 1%) via variations in inspired O 2 fraction (F IO 2 : 0.13, 0.17, 0.21 and 0.26, respectively). Measurements were made at corresponding intensities (65 ± 3, 80 ± 3, 85 ± 3 and 90 ± 3% of normoxic maximal work rate, respectively) in order to produce the same tidal volume, breathing frequency and respiratory muscle load at each F IO 2 . The mean pressure time product of the diaphragm did not differ across the four exercise tests and ranged between 312 ± 28 and 382 ± 22 cmH 2 O s min −1 . Ten minutes into recovery, twitch transdiaphragmatic pressure (P di,tw ) determined by bilateral phrenic nerve stimulation, was significantly (P = 0.0001) reduced after all tests. After both hypoxic tests (F IO 2 : 0.13, 0.17) the degree of fall in P di,tw (by 26.9 ± 2.7 and 27.4 ± 2.6%, respectively) was significantly greater (P < 0.05) than after the normoxic test (by 20.1 ± 3.4%). The greater amount of diaphragmatic fatigue in hypoxia at lower leg work rates (presumably requiring smaller leg blood flow compared with normoxia at higher leg work rates), suggests that when ventilatory muscle load is similar between normoxia and hypoxia, hypoxia exaggerates diaphragmatic fatigue in spite of potentially greater respiratory muscle blood flow availability.

Optimal surgical therapy for brain tumors is the combination of complete resection with minimal invasion and damage to the adjacent normal tissue. To achieve this goal, we need advanced imaging techniques on a scale from macro- to microscopic resolution. In the last decade, the development of fluorescence-guided surgery has been the most influential breakthrough, marginally improving outcomes in brain tumor surgery. Multispectral fluorescence microscopy (MFL) is a novel imaging technique that allows the overlapping of a fluorescent image and a white light image in real-time, with delivery of the merged image to the surgeon through the eyepieces of a surgical microscope. MFL permits the detection and characterization of brain tumors using fluorescent molecular markers such as 5-aminolevulinic acid (5-ALA) or indocyanine green (ICG), while simultaneously obtaining high definition white light images to create a pseudo-colored composite image in real-time. Limitations associated with the use of MFL include decreased light imaging intensity and decreased levels of magnification that may compromise maximal tumor resection on a cellular scale. Confocal laser endomicroscopy (CLE) is another novel advanced imaging technique that is based on miniaturization of the microscope imaging head in order to provide the possibility of in vivo microscopy at the cellular level. Clear visualization of the cellular cytoarchitecture can be achieved with 400-fold−1,000-fold magnification. CLE allows on the one hand the intra-operative detection and differentiation of single tumor cells (without the need for intra-operative histologic analysis of biopsy specimens) as well as the definition of borders between tumor and normal tissue at a cellular level, dramatically improving the accuracy of surgical resection. The application and implementation of CLE-assisted surgery in surgical oncology increases not only the number of options for real-time diagnostic imaging, but also the therapeutic options by extending the resection borders of cancer at a cellular level and, more importantly, by protecting the functionality of normal tissue in the adjacent areas of the human brain. In this article, we describe our experience using these new techniques of confocal-assisted fluorescent surgery including analysis on the technology, usability, indications, limitations, and further developments.

Asynchronous breathing movements may be observed in the presence of pulmonary disease, such as chronic obstructive pulmonary disease (COPD). This study was undertaken in an attempt to propose a reliable methodology to quantify this asynchrony. Five methods for estimating phase differences between two signals, based on the phase angle of the Fourier Transform (PhD(FT)), paradoxical motion (PhD(PM)), the Lissajous figure (PhD(LF)), maximal linear correlation (PhD(P)) and least-squares filtering (PhD(LS)), were compared. Frequency-modulated signals, simulating compartmental chest wall volumes, were used to evaluate the methods. Breathing asynchrony was quantified in two ways; by estimating (a) a single PhD value for the entire recording and (b) time-varying PhDs, representing non-stationarities of human breathing. PhD(PM) and PhD(LF) had the lowest average errors (4%), and PhD(LS) had a slightly higher error. PhD(FT) had zero error when estimating a single PhD value but a considerable error when estimating time-varying PhDs. PhD(P) presented the highest errors in all cases. An application of this methodology is proposed in real compartmental chest wall volume signals of normal and COPD subjects. Preliminary results indicate that the methodology is promising in quantifying differences in asynchronous breathing between thoracic volumes of COPD patients and healthy controls.