Chromatic pupil responses: preferential activation of the melanopsin-mediated versus outer photoreceptor-mediated pupil light reflex.

OBJECTIVE: To weight the rod-, cone-, and melanopsin-mediated activation of the retinal ganglion cells, which drive the pupil light reflex by varying the light stimulus wavelength, intensity, and duration. DESIGN: Experimental study. PARTICIPANTS: Forty-three subjects with normal eyes and 3 patients with neuroretinal visual loss. METHODS: A novel stimulus paradigm was developed using either a long wavelength (red) or short wavelength (blue) light given as a continuous Ganzfeld stimulus with stepwise increases over a 2 log-unit range. The pupillary movement before, during, and after the light stimulus was recorded in real time with an infrared illuminated video camera. MAIN OUTCOME MEASURES: The percent pupil contraction of the transient and sustained pupil response to a low- (1 cd/m(2)), medium- (10 cd/m(2)), and high-intensity (100 cd/m(2)) red- and blue-light stimulus was calculated for 1 eye of each subject. From the 43 normal eyes, median and 25th, 75th, 5th, and 95th percentile values were obtained for each stimulus condition. RESULTS: In normal eyes at lower intensities, blue light evoked much greater pupil responses compared with red light when matched for photopic luminance. The transient pupil contraction was generally greater than the sustained contraction, and this disparity was greatest at the lowest light intensity and least apparent with bright (100 cd/m(2)) blue light. A patient with primarily rod dysfunction (nonrecordable scotopic electroretinogram) showed significantly reduced pupil responses to blue light at lower intensities. A patient with achromatopsia and an almost normal visual field showed selective reduction of the pupil response to red-light stimulation. A patient with ganglion cell dysfunction owing to anterior ischemic optic neuropathy demonstrated global loss of pupil responses to red and blue light in the affected eye. CONCLUSIONS: Pupil responses that differ as a function of light intensity and wavelength support the hypothesis that selected stimulus conditions can produce pupil responses that reflect phototransduction primarily mediated by rods, cones, or melanopsin. Use of chromatic pupil responses may be a novel way to diagnose and monitor diseases affecting either the outer or inner retina.

Are oxygen uptake kinetics modified when using a respiratory snorkel?

PURPOSE: The aim of this study was to compare VO2 kinetics during constant power cycle exercise measured using a conventional facemask (CM) or a respiratory snorkel (RS) designed for breath-by-breath analysis in swimming. METHODS: VO2 kinetics parameters-obtained using CM or RS, in randomized counterbalanced order-were compared in 10 trained triathletes performing two submaximal heavy-intensity cycling square-wave transitions. These VO2 kinetics parameters (ie, time delay: td1, td2; time constant: τ1, τ2; amplitude: A1, A2, for the primary phase and slow component, respectively) were modeled using a double exponential function. In the case of the RS data, this model incorporated an individually determined snorkel delay (ISD). RESULTS: Only td1 (8.9 ± 3.0 vs 13.8 ± 1.8 s, P < .01) differed between CM and RS, whereas all other parameters were not different (τ1 = 24.7 ± 7.6 vs 21.1 ± 6.3 s; A1 = 39.4 ± 5.3 vs 36.8 ± 5.1 mL x min(-1) x kg(-1); td2 = 107.5 ± 87.4 vs 183.5 ± 75.9 s; A2' (relevant slow component amplitude) = 2.6 ± 2.4 vs 3.1 ± 2.6 mL x min(-1) x kg(-1) for CM and RS, respectively). CONCLUSIONS: Although there can be a small mixture of breaths allowed by the volume of the snorkel in the transition to exercise, this does not appear to significantly influence the results. Therefore, given the use of an ISD, the RS is a valid instrument for the determination of VO2 kinetics within submaximal exercise.

Individual monitoring of medical staff working in interventional radiology in Switzerland using double dosimetry

Physicians who frequently perform fluoroscopic examinations are exposed to high intensity radiation fields. The exposure monitoring is performed with a regular personal dosimeter under the apron in order to estimate the effective dose. However, large parts of the body are not protected by the apron (e.g. arms, head). Therefore, it is recommended to wear a supplemental dosimeter over the apron to obtain a better representative estimate of the effective dose. The over-apron dosimeter can also be used to estimate the eye lens dose. The goal of this study was to investigate the relevance of double dosimetry in interventional radiology. First the calibration procedure of the dosimeters placed over the apron was tested. Then, results of double dosimetry during the last five years were analyzed. We found that the personal dose equivalent measured over a lead apron was underestimated by ∼20% to ∼40% for X-ray beam qualities used in radiology. Measurements made over five-year period confirm that the use of a single under-apron dosimeter is inadequate for personnel monitoring. Relatively high skin dose (>10 mSv/month) would have remained undetected without a second dosimeter placed on the apron.

Effect of acute and chronic exercise on fat oxidation and hormonal and plasma metabolite kinetics in obese and severely obese men

Acute exercise increases energy expenditure (EE) during exercise and post-exercise recovery [excess post-exercise oxygen consumption (EPOC)] and therefore may be recommended as part of the multidisciplinary management of obesity. Moreover, chronic exercise (training) effectively promotes an increase in insulin sensitivity, which seems to be associated with increased fat oxidation rates (FORs). The main purpose of this thesis is to investigate 1) FORs and extra-muscular factors (hormones and plasma metabolites) that regulate fat metabolism during acute and chronic exercise; and 2) EPOC during acute post-exercise recovery in obese and severely obese men (class II and III). In the first study, we showed that obese and severely obese men present a lower exercise intensity (Fatmax) eliciting maximal fat oxidation and a lower reliance on fat oxidation at high, but not at low and moderate, exercise intensities compared to lean men. This was most likely related to an impaired muscular capacity to oxidize non-esterified fatty acids (NEFA) rather than decreased plasma NEFA availability or a change in the hormonal milieu during exercise. In the second study, we developed an accurate maximal incremental test to correctly and simultaneously evaluate aerobic fitness and fat oxidation kinetics during exercise in this population. This test may be used for the prescription of an appropriate exercise training intensity. In the third study, we demonstrated that only 2 wk of exercise training [continuous training at Fatmax and adapted high-intensity interval training (HIIT)], matched with respect to mechanical work, may be effective to improve aerobic fitness, FORs during exercise and insulin sensitivity, which suggest that FORs might be rapidly improved and that adapted HIIT is feasible in this population. The increased FORs concomitant with the lack of changes in lipolysis during exercise suggest an improvement in the mismatching between NEFA availability and oxidation, highlighting the importance of muscular (oxidative capacity) rather than extra-muscular (hormones and plasma metabolites) factors in the regulation of fat metabolism after a training program. In the fourth study, we observed a positive correlation between EE during exercise and EPOC, suggesting that a chronic increase in the volume or intensity of exercise may increase EE during exercise and during recovery. This may have an impact in weight management in obesity. In conclusion, these findings might have practical implications for exercise training prescriptions in order to improve the therapeutic approaches in obesity and severe obesity. -- L'exercice aigu augmente la dépense énergétique (DE) pendant l'exercice et la récupération post-exercice [excès de consommation d'oxygène post-exercise (EPOC)] et peut être utilisé dans la gestion multidisciplinaire de l'obésité. Quant à l'exercice chronique (entraînement), il est efficace pour augmenter la sensibilité à l'insuline, ce qui semble être associé à une amélioration du débit d'oxydation lipidique (DOL). Le but de cette thèse est d'étudier 1) le DOL et les facteurs extra-musculaires (hormones et métabolites plasmatiques) qui régulent le métabolisme lipidique pendant l'exercice aigu et chronique et 2) l'EPOC lors de la récupération aiguë post-exercice chez des hommes obèses et sévèrement obèses (classe II et III). Dans la première étude nous avons montré que les hommes obèses et sévèrement obèses présentent une plus basse intensité d'exercice (Fatmax) correspondant au débit d'oxydation lipidique maximale et un plus bas DOL à hautes, mais pas à faibles et modérées, intensités d'exercice comparé aux sujets normo-poids, ce qui est probablement lié à une incapacité musculaire à oxyder les acides gras non-estérifiés (AGNE) plutôt qu'à une diminution de leur disponibilité ou à un changement du milieu hormonal pendant l'exercice. Dans la deuxième étude nous avons développé un test maximal incrémental pour évaluer simultanément l'aptitude physique aérobie et la cinétique d'oxydation des lipides pendant l'exercice chez cette population. Dans la troisième étude nous avons montré que seulement deux semaines d'entraînement (continu à Fatmax et intermittent à haute intensité), appariés par la charge de travail, sont efficaces pour améliorer l'aptitude physique aérobie, le DOL pendant l'exercice et la sensibilité à l'insuline, ce qui suggère que le DOL peut être rapidement amélioré chez cette population. Ceci, en absence de changements de la lipolyse pendant l'exercice, suggère une amélioration de la balance entre la disponibilité et l'oxydation des AGNE, ce qui souligne l'importance des facteurs musculaires (capacité oxydative) plutôt que extra-musculaires (hormones et métabolites plasmatiques) dans la régulation du métabolisme lipidique après un entraînement. Dans la quatrième étude nous avons observé une corrélation positive entre la DE pendant l'exercice et l'EPOC, ce qui suggère qu'une augmentation chronique du volume ou de l'intensité de l'exercice pourrait augmenter la DE lors de l'exercice et lors de la récupération post-exercice. Ceci pourrait avoir un impact sur la gestion du poids chez cette population. En conclusion, ces résultats pourraient avoir des implications pratiques lors de la prescription des entraînements dans le but d'améliorer les approches thérapeutiques de l'obésité et de l'obésité sévère.

Aerobic and functional capacities in a selected active population of European octogenarians

Master athletes are often considered to represent the ideal rate of decline of aerobic function; however, most of the studies interested in active elderly people are often limited to people younger than 75. We aimed to determine the physiological adaptations and aerobic fitness in a selected European population of active octogenarians during maximal and submaximal exercise tests. Aerobic capacity was measured during maximal incremental tests on treadmill (TR) and cycle-ergometer (CE) and functional capacity during a 6-minute walk test (6-MWT) in 17 subjects aged 81.2 +/- 0.8 years. Pulmonary gas exchange and heart rate (HR) were continuously measured during the different exercise tests. Maximal oxygen consumption (V.O (2max)) on TR and CE was significantly higher than predicted values (TR: 28.7 +/- 1.2 vs. 17 +/- 0.5 ml . kg (-1) . min (-1); CE: 23 +/- 1.2 vs. 16 +/- 0.6 ml . kg (-1) . min (-1) for measured and predicted values respectively). V.O (2max) and HR (max), as well as V.O (2) and HR at the ventilatory threshold (V.O (2)T (V.E) and HR T (V.E)) were significantly higher on TR than on CE (HR (max): 144 +/- 4 vs. 138 +/- 4 bpm; V.O (2)T (V.E): 22.5 +/- 0.8 vs. 17.7 +/- 0.9 ml . kg (-1) . min (-1) for TR and CE respectively). V.O (2)T (V.E) and HR T (V.E) on TR were equivalent to V.O (2) and HR measured during the 6-MWT. HR T (V.E) on TR and mean HR during the 6-MWT were strongly correlated (R = 0.82, p < 0.01). Maintenance of regular physical activity provides high aerobic fitness, in octogenarians, as was shown by the higher values of our subjects in comparison to predicted values. Moreover, the close relation between the intensity developed at T (V.E) on TR and 6-MWT could support the idea that a walk test is a submaximal test performed at high intensity that could provide a basis for exercise prescription in an individualized manner in active elderly people.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT), or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

Dynamic responses of O2 uptake at the onset and end of exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in .VO2 are found in the literature. Therefore the purpose of this study was to examine .VO2on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. .VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT) or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of .VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of .VO2 during cycling exercise in the heavy-intensity domain.

Intrinsically photosensitive retinal ganglion cells.

The recent discovery of melanopsin-expressing retinal ganglion cells that mediate the pupil light reflex has provided new insights into how the pupil responds to different properties of light. These ganglion cells are unique in their ability to transduce light into electrical energy. There are parallels between the electrophysiologic behavior of these cells in primates and the clinical pupil response to chromatic stimuli. Under photopic conditions, a red light stimulus produces a pupil constriction mediated predominantly by cone input via trans-synaptic activation of melanopsin-expressing retinal ganglion cells, whereas a blue light stimulus at high intensity produces a steady-state pupil constriction mediated primarily by direct intrinsic photoactivation of the melanopsin-expressing ganglion cells. Preliminary data in humans suggest that under photopic conditions, cones primarily drive the transient phase of the pupil light reflex, whereas intrinsic activation of the melanopsin-expressing ganglion cells contributes heavily to sustained pupil constriction. The use of chromatic light stimuli to elicit transient and sustained pupil light reflexes may become a clinical pupil test that allows differentiation between disorders affecting photoreceptors and those affecting retinal ganglion cells.

Affymetrix Whole-Transcript Human Gene 1.0 ST array is highly concordant with standard 3' expression arrays.

The recently released Affymetrix Human Gene 1.0 ST array has two major differences compared with standard 3' based arrays: (i) it interrogates the entire mRNA transcript, and (ii) it uses DNA targets. To assess the impact of these differences on array performance, we performed a series of comparative hybridizations between the Human Gene 1.0 ST and the Affymetrix HG-U133 Plus 2.0 and the Illumina HumanRef-8 BeadChip arrays. Additionally, both RNA and DNA targets were hybridized on HG-U133 Plus 2.0 arrays. The results show that the overall reproducibility of the Gene 1.0 ST array is best. When looking only at the high intensity probes, the reproducibility of the Gene 1.0 ST array and the Illumina BeadChip array is equally good. Concordance of array results was assessed using different inter-platform mappings. Agreements are best between the two labeling protocols using HG-U133 Plus 2.0 array. The Gene 1.0 ST array is most concordant with the HG-U133 array hybridized with cDNA targets. This may reflect the impact of the target type. Overall, the high degree of correspondence provides strong evidence for the reliability of the Gene 1.0 ST array.

The evolution of information suppression in communicating robots with conflicting interests.

Reliable information is a crucial factor influencing decision-making and, thus, fitness in all animals. A common source of information comes from inadvertent cues produced by the behavior of conspecifics. Here we use a system of experimental evolution with robots foraging in an arena containing a food source to study how communication strategies can evolve to regulate information provided by such cues. The robots could produce information by emitting blue light, which the other robots could perceive with their cameras. Over the first few generations, the robots quickly evolved to successfully locate the food, while emitting light randomly. This behavior resulted in a high intensity of light near food, which provided social information allowing other robots to more rapidly find the food. Because robots were competing for food, they were quickly selected to conceal this information. However, they never completely ceased to produce information. Detailed analyses revealed that this somewhat surprising result was due to the strength of selection on suppressing information declining concomitantly with the reduction in information content. Accordingly, a stable equilibrium with low information and considerable variation in communicative behaviors was attained by mutation selection. Because a similar coevolutionary process should be common in natural systems, this may explain why communicative strategies are so variable in many animal species.

Massive nest-box supplementation boosts fecundity, survival and even immigration without altering mating and reproductive behaviour in a rapidly recovered bird population.

Habitat restoration measures may result in artificially high breeding density, for instance when nest-boxes saturate the environment, which can negatively impact species' demography. Potential risks include changes in mating and reproductive behaviour such as increased extra-pair paternity, conspecific brood parasitism, and polygyny. Under particular cicumstances, these mechanisms may disrupt reproduction, with populations dragged into an extinction vortex. With the use of nuclear microsatellite markers, we investigated the occurrence of these potentially negative effects in a recovered population of a rare secondary cavity-nesting farmland bird of Central Europe, the hoopoe (Upupa epops). High intensity farming in the study area has resulted in a total eradication of cavity trees, depriving hoopoes from breeding sites. An intensive nest-box campaign rectified this problem, resulting in a spectacular population recovery within a few years only. There was some concern, however, that the new, high artificially-induced breeding density might alter hoopoe mating and reproductive behaviour. As the species underwent a serious demographic bottleneck in the 1970-1990s, we also used the microsatellite markers to reconstitute the demo-genetic history of the population, looking in particular for signs of genetic erosion. We found i) a low occurrence of extra-pair paternity, polygyny and conspecific brood parasitism, ii) a high level of neutral genetic diversity (mean number of alleles and expected heterozygosity per locus: 13.8 and 83%, respectively) and, iii) evidence for genetic connectivity through recent immigration of individuals from well differentiated populations. The recent increase in breeding density did thus not induce so far any noticeable detrimental changes in mating and reproductive behaviour. The demographic bottleneck undergone by the population in the 1970s-1990s was furthermore not accompanied by any significant drop in neutral genetic diversity. Finally, genetic data converged with a concomitant demographic study to evidence that immigration strongly contributed to local population recovery.

Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia.

Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea level but train under hypoxic conditions, has gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic' or 'anaerobic' interval training, it is believed that IHT would potentiate greater performance improvements compared to similar training at sea level. A thorough analysis of studies including IHT, however, leads to strikingly poor benefits for sea-level performance improvement, compared to the same training method performed in normoxia. Despite the positive molecular adaptations observed after various IHT modalities, the characteristics of optimal training stimulus in hypoxia are still unclear and their functional translation in terms of whole-body performance enhancement is minimal. To overcome some of the inherent limitations of IHT (lower training stimulus due to hypoxia), recent studies have successfully investigated a new training method based on the repetition of short (<30 s) 'all-out' sprints with incomplete recoveries in hypoxia, the so-called repeated sprint training in hypoxia (RSH). The aims of the present review are therefore threefold: first, to summarise the main mechanisms for interval training and repeated sprint training in normoxia. Second, to critically analyse the results of the studies involving high-intensity exercises performed in hypoxia for sea-level performance enhancement by differentiating IHT and RSH. Third, to discuss the potential mechanisms underpinning the effectiveness of those methods, and their inherent limitations, along with the new research avenues surrounding this topic.

Chromatic pupillometry in patients with retinitis pigmentosa.

OBJECTIVE:: To evaluate the chromatic pupillary response as a means of assessing outer and inner retinal function in patients with retinitis pigmentosa (RP). DESIGN:: Evaluation of diagnostic technology. PARTICIPANTS:: Thirty-two patients with RP and visual loss and 43 normal subjects. METHODS:: Patients were tested with a chromatic pupillometer using red and blue lights (1, 10, and 100 cd/m(2)), and their pupil responses were compared with those from 43 normal subjects (reported previously). Visual field and electroretinography (ERG) results were examined and compared with the pupil responses. MAIN OUTCOME MEASURES:: The percent pupil contraction of the transient response to a low-intensity (1 cd/m(2)) blue light and high-intensity (100 cd/m(2)) red light and the sustained response to a high-intensity blue light was calculated for 1 eye of each subject. RESULTS:: The pupil responses to red and blue light at all intensities were recordable in all patients except 1, whose pupil responded only to bright blue light. There was a significant difference of the pupil response between patients with RP and normal subjects in testing conditions that emphasized rod (1 cd/m(2) blue light) or cone (100 cd/m(2) red light) contribution (P<0.001). Patients with a non-recordable scotopic ERG showed significantly reduced pupil responses (P<0.001) to low-intensity blue light (1 cd/m(2)). Patients with a non-recordable or abnormal photopic ERG showed significantly reduced pupil responses (P<0.05) to high-intensity red light (100 cd/m(2)). Patients with a nonrecordable ERG had the most visual field loss and reduced pupil responses. Unexpectedly, patients with RP showed a slower re-dilation of the pupil after termination of bright blue light compared with red light, a pattern not observed in normal subjects. CONCLUSIONS:: Pupil responses to red and blue light stimuli weighted to favor cone or rod input are significantly reduced in patients with RP but are still recordable in patients having a non-recordable ERG. In addition, outer photoreceptor disease appears to unmask a post-illumination pupillary constriction to bright blue light, most likely mediated by intrinsic activation of melanopsin ganglion cells. Chromatic pupillometry provides a novel, noninvasive method for following retinal functional status, particularly in patients with severe RP and non-recordable ERG. FINANCIAL DISCLOSURE(S):: Proprietary or commercial disclosure may be found after the references.

Electrically assisted ocular gene therapy.

Electrotransfer and iontophoresis are being developed as innovative non-viral gene delivery systems for the treatment of eye diseases. These two techniques rely on the use of electric current to allow for higher transfection yield of various ocular cell types in vivo. Short pulses of relatively high-intensity electric fields are used for electrotransfer delivery, whereas the iontophoresis technique is based on the application of low voltage electric current. The basic principles of these techniques and their potential therapeutic application for diseases of the anterior and posterior segments of the eye are reviewed. Iontophoresis has been found most efficient for the delivery of small nucleic acid fragments such as antisense oligonucleotides, siRNA, or ribozymes. Electrotransfer, on the other hand, is being developed for the delivery of oligonucleotides or custom designed plasmids. The wide range of strategies already validated and the potential for targeting specific types of cells confirm the promising early observations made using electrotransfer and iontophoresis. These two nonviral delivery systems are safe and can be used efficiently for targeted gene delivery to ocular tissues in vivo. At the present, their application for the treatment of ocular human diseases is nearing its final stages of adaptation and practical implementation at the bedside.

Cardiovascular and metabolic responses during isokinetic shoulder rotators strength testing in healthy subjects

Background: Although there have been many studies on isokinetic shoulder exercises in evaluation and rehabilitation programs, the cardiovascular and metabolic responses of those modes of muscle strength exercises have been poorly investigated. Objective: To analyze cardiovascular and metabolic responses during a standardized test used to study the internal (IR) and external (ER) rotators maximal isokinetic strength. Methods: Four days after an incremental exercise test on cycle ergometer, ten healthy subjects performed an isokinetic shoulder strength evaluation with cardiovascular (Heart rate, HR) and metabolic gas exchange (&Vdot;O_{2}) analysis. The IR and ER isokinetic strength, measured in seated position with 45° of shoulder abduction in scapular plane, was evaluated concentrically at 60, 120 and 240°/s and eccentrically at 60°/s, for both shoulder sides. An endurance test with 30 repetitions at 240°/s was performed at the end of each shoulder side testing. Results: There was a significant increase of mean HR with isokinetic exercise (P< 0.05). Increases of HR was 42-71% over the resting values. During endurance testing, increases of HR was 77-105% over the resting values, and corresponded to 85-86% of the maximal HR during incremental test. Increase of &Vdot;O_{2} during isokinetic exercises was from 6-11 ml/min/kg to 20-43 ml/min/kg. Conclusion: This study performed significant cardiovascular and metabolic responses to isokinetic exercise of rotators shoulder muscles. A warm-up should be performed before maximal high-intensity isokinetic shoulder testing. Our results indicated that observation and supervision are important during testing and/or training sessions, especially in subjects with risk for cardiovascular disorders.