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The ERG-determined spectral sensitivity of dark-adapted individuals of all strains peaks around 520 nm. When light-adapted, the spectral sensitivity of the Nagano strain narrows and its peak shifts to 580 nm, while that in other strains remains unchanged. All tested strains appear to be identical in terms of the basic structure of the eye, the pigment migration in response to light- and dark-adaptation, and the molecular structure of long-wavelength absorbing visual pigments. However, the color of the perirhabdomal pigment clearly differs; it is orange in the Nagano strain and purple in the others. The action spectrum of phototaxis appears to be shifted towards longer wavelengths in the Nagano individuals.
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where R n(λ) are the templates defined by their peak parameters λ max,n [19] and f n are their relative contributions. This model assumes a single intensity-response function, ignoring metarhodopsin absorption and waveguide effects [20]. Screening pigments function as simple optical filters absorbing some light before it reaches the visual pigment, especially in the light-adapted state. We estimated the transmittance of the pigments T i as:
The eye sensitivity changes upon dark- and light-adaptations. Figure 4b and c each shows a set of spectra based on the spectral sweeps before (supposedly dark-adapted) and after (supposedly light-adapted) intense white illumination lasting 5 min. In both Niigata (Fig. 4b) and Nagano (Fig. 4c) strains, light-adaptation lowers the overall sensitivity about one log unit. (Dotted lines are replots of the light-adapted spectra on the expanded axis on the right). Light-adaptation narrows the spectral sensitivity and shifts its peak in the Nagano individual (Fig. 4c).
Modelled spectra of dark- (blue line) and light- (red line) adapted eyes with the recorded spectral sensitivities shown in Fig. 4 b and c (circles). Model fits were performed over the wavelength range for which pigment spectra were available. For coefficients, see Table 1. a Niigata strain. Dotted spectra show visual pigment templates (grey, S; blue, M; green, L) with their relative peak values according to f i. The solid black line denotes the sum of these three spectra, i.e. the sensitivity in the absence of screening pigment. b Nagano strain. For illustration (because the light-adapted spectrum is based on a single individual and may therefore be noisy), half-filled squares show the averaged spectral sensitivity shown in Fig. 4 a with open triangles, scaled to the appropriate amplitude
Type 2 diabetes mellitus (T2D) increases the risk of incident heart failure (HF), whose earliest fingerprint is effort intolerance (i.e. impaired peak oxygen consumption, or VO2peak). In the uncomplicated T2D population, however, the prevalence of effort intolerance and the underpinning mechanistic bases are uncertain. Leveraging the multiparametric characterization allowed by imaging-cardiopulmonary exercise testing (iCPET), the aim of this study is to quantify effort intolerance in T2D and to dissect the associated cardiopulmonary alterations.
Eighty-eight adults with well-controlled and uncomplicated T2D and no criteria for HF underwent a maximal iCPET with speckle tracking echocardiography, vascular and endothelial function assessment, as well as a comprehensive biohumoral characterization. Effort intolerance was defined by a VO2peak below 80% of maximal predicted oxygen uptake.
Effort intolerance and reduced VO2peak is a severe and highly prevalent condition in uncomplicated, otherwise asymptomatic T2D. It results from a major defect in skeletal muscle oxygen extraction coupled with a subtle myocardial systolic dysfunction.
With the present study, we aim at quantifying the prevalence of effort intolerance in an outpatient, uncomplicated, and otherwise asymptomatic T2D population. Participants underwent exercise echocardiography during a maximal imaging-CPET (iCPET), which allows the dissection of the pathophysiological mechanisms underlying a reduced VO2peak by simultaneous measurement of the major determinants of exercise physiology.
All patients performed a maximal exercise test, as defined by the maximal respiratory exchange ratio steadily greater than 1.05 at peak exercise according to guidelines [1]. The group with reduced exercise capacity achieved a 24% lower VO2peak and a 10% lower peak workload and peak heart rate, while the mean systolic and diastolic blood pressure values were comparable throughout the test. We observed similar results at the sensitivity analysis to exclude drug-related chronotropic insufficiency, observing similar results (see Additional file 1: Table S4); however, these data should be interpreted considering the decrease in sample size. No difference was identified in ventilatory or gas exchange parameters, while the anaerobic threshold (AT) was reached earlier in the subjects with effort intolerance both in absolute terms, as well as when expressed as % of VO2peak. The group with reduced exercise capacity showed a higher prevalence of chronotropic incompetence, a lower VO2/workload slope, a reduced oxygen pulse at peak, as well as an impaired peripheral oxygen extraction [(a-v)ΔO2] at peak. These results are reported in Table 2 and in Fig. 1.
The study population was homogeneous in demographic parameters, glycemic control, duration of diabetes, cardio-active and glucose-lowering therapy, vascular and endothelial function parameters, as well as the prevalence of comorbidities (Table 1). It is thus very difficult to predict effort intolerance based on the resting clinical phenotype alone. The difference in HDL cholesterol was small and seemingly driven by the slightly higher prevalence of male and overweight subjects in the group with low VO2peak. This, together with the presence of a small difference in age, prompted the decision to verify the differences in iCPET data after adjusting for age, sex and BMI (Table 2). Since effort intolerance is the hallmark of HF irrespective of LVEF [2], and that cardiorespiratory fitness is known to be a strong predictor of incident HFpEF in the T2D population [6], we sought to determine the associated alterations and mechanisms underpinning the reduced VO2peak in T2D patients to gain insight on the earliest defects at the bases of the their higher HF vulnerability. Previous findings reported early development of fatigue in T2D as a perceived limitation of force-generating capacity that requires higher intensity of effort that might eventually reduce the exercise duration, and that can be highlighted by an early appearance of exhaustion during exercise and in higher fatigue with respect to controls at any given workload, even when adjusted for the reduced VO2peak [29, 30]. Still, the reasons for the decreased exercise tolerance are far from being clear, possibly encompassing any combination of myocardiogenic, skeletal myogenic, vasculogenic, or neurogenic determinants [4]; we sought to determining the associated alterations in the different organs and systems.
The two groups of our study did not differ in biohumoral values, endothelial function, indices of pulmonary function, diastolic function indices, right heart indices, mean arterial pressure, and systemic vascular resistances throughout the entire iCPET. The subjects with effort intolerance showed higher prevalence of chronotropic incompetence. The large difference, however, is driven by the fact the patients of our study group fall close to the 80% threshold (mean HR peak%: 86.1%) thus a small difference in peak HR generates a major recruitment of subject with a diagnosis of chronotropic incompetence. In quantitative terms, the difference between the groups was small; subjects with effort intolerance exploited their HR reserve only 8% less than the others (82.6 vs 90.2%) with a difference in peak HR of just 8 beats/minute (129 vs 137 bpm). If we also consider that no subject had evidence of CAN at conventional tests and, more importantly, that HR kinetics and peak CO were superimposable in the two groups throughout the whole iCPET, it is unlikely that chronotropic incompetence is the cause of effort intolerance in our patient; it might rather be the consequence of their lower fitness.
Taken together, the results of the present study suggest a myogenic limitation of whole-body oxygen uptake in T2D limiting exercise tolerance, with a tight interplay between myocardial and skeletal muscles. Whether this is secondary to a reduced number of mitochondria, a mitochondrial functional impairment, altered myofibrillar structure and/or composition, muscle microvasculature, or to systemic regulators of muscle perfusion [4] goes beyond the purpose of this study. However, the lack of relationships with total peripheral resistances and endothelial function supports a primitive muscle cell impairment involving both skeletal and myocardial muscle. The lower anaerobic threshold, also when expressed in terms of % VO2peak, indicates a reduced aerobic capacity and strongly supports the hypothesis of a mitochondrial defect either in number or in function, as previously observed in this population [52, 53]. The observation that exercise training can increase whole-body oxygen consumption through an amelioration of skeletal muscle energetics further sustains this point [54, 55].
Hello Danny. Thank you for the comment. Weatherwise August - September is a very good time for walking the Camino del Norte. You won't get a lot of rain it will be mostly summy and warm. August is the peak holiday season you can expect higher prices. Some places during the peak season don't rent rooms only for one night it might be the reason why you see a limited supply for your dates. I'm busy updating the PDFs with places to stay I'm adding more options. The later you start the walk the easier it'll be to find accommodation. Some places don't accept bookings that far ahead. If a place is not available for booking I doubt a company will be able to book it for you. As I said for August - September I would definitely recommend booking places in advance especially if you want to stay in private rooms as in smaller places there is a limited supply.As for luggage transfer, it's not difficult to arrange by yourself. Overall the Camino del Norte especially the first half of it works out more expensive than any other Camino route because of accommodation prices. Finding reasonably-prices private rooms on the Camino Portuguese for example is a lot easier.Buen Camino 041b061a72