Correction: Martinez-Gonzalez et al. Adaptation and Validation of the Diabetic Foot Ulcer Scale-Short Form in Spanish Subjects. J. Clin. Med. 2020, 9, 2497.

In the original publication [...].

Pupillary behavior during wakefulness, non-REM sleep, and REM sleep in birds is opposite that of mammals.

Mammalian pupils respond to light1,2 and dilate with arousal, attention, cognitive workload, and emotions,3 thus reflecting the state of the brain. Pupil size also varies during sleep, constricting during deep non-REM sleep4-7 and dilating slightly during REM sleep.4-6 Anecdotal reports suggest that, unlike mammals, birds constrict their pupils during aroused states, such as courtship and aggression,8-10 raising the possibility that pupillary behavior also differs between mammals and birds during sleep. Here, we measured pupil size in awake pigeons and used their translucent eyelid to investigate sleep-state-dependent changes in pupil size. Male pigeons constricted their pupils during courtship and other male-female interactions but not while engaging in other waking behaviors. Unlike mouse pupils, the pigeons' pupils were dilated during non-REM sleep, while over 1,000 bursts of constriction and relaxation, which we call rapid iris movements (RIMs), occurred primarily during REM sleep. Consistent with the avian iris being composed largely of striated muscles,11-15 rather than smooth muscles, as in mammals, pharmacological experiments revealed that RIMs are mediated by nicotinic cholinergic receptors in the iris muscles. Despite receiving input from a parasympathetic nucleus, but consistent with its striated nature, the avian iris sphincter muscle behaves like skeletal muscles controlled by the somatic nervous system, constricting during courtship displays, relaxing during non-REM sleep, and twitching during REM sleep. We speculate that during wakefulness, pupillary constrictions are involved in social communication, whereas RIMs occurring during REM sleep might maintain the efficacy of this motor system and/or reflect the processing of associated memories.

Psychometric Validation of the Cardiff Wound Impact Schedule Questionnaire in a Spanish Population with Diabetic Foot Ulcer.

Diabetic foot ulcers (DFU) negatively affect the quality of life (QoL) of people with diabetes. The Cardiff Wound Impact Schedule (CWIS) questionnaire has been designed to measure the QoL of people with chronic foot wounds. However, no studies have been specifically designed to validate this instrument in a Spanish population. In this prospective study, a total of 141 subjects with DFU were recruited. DFU was determined by performing physical examinations. Medical records were exhaustively reviewed to collect clinical variables. The CWIS was transculturally adapted by a group of experts and a group of patients with DFU. The SF-36 and EQ-5D generic instruments were used as reference tools. The questionnaires were administered at 7 days and 4, 12, and 26 weeks after the baseline assessment by personal interview with each of the study subjects. The psychometric properties of the instrument were assessed using statistical methods. The content validity had an average of 3.63 (90.7% of the maximum score of 4). The internal consistency of the CWIS subscales had a standardized Cronbach's alpha range from 0.715 to 0.797. The reproducibility was moderate with an intraclass correlation coefficient (ICC) range from 0.606 to 0.868. Significant correlations between CWIS domains and SF-36 and EQ-5D subscales were observed, demonstrating a good criterion validity of the CWIS questionnaire (p < 0.001). However, the construct validity of the CWIS was not validated with a comparative fit index (CFI) of 0.69, a root mean square error of approximation (RMSEA) of 0.09, and a standardized root mean square residual (SRMR) of 0.10. The sensitivity to changes over time was optimal in the three domains (i.e., social life, well-being, and physical symptoms) (p < 0.001). In conclusion, the Spanish version of the CWIS shows acceptable psychometric properties to assess the QoL of subjects with DFU, except for its construct validity.

Comparative Perspectives that Challenge Brain Warming as the Primary Function of REM Sleep.

Rapid eye movement (REM) sleep is a paradoxical state of wake-like brain activity occurring after non-REM (NREM) sleep in mammals and birds. In mammals, brain cooling during NREM sleep is followed by warming during REM sleep, potentially preparing the brain to perform adaptively upon awakening. If brain warming is the primary function of REM sleep, then it should occur in other animals with similar states. We measured cortical temperature in pigeons and bearded dragons, lizards that exhibit NREM-like sleep and REM-like sleep with brain activity resembling wakefulness. In pigeons, cortical temperature decreased during NREM sleep and increased during REM sleep. However, brain temperature did not increase when dragons switched from NREM-like to REM-like sleep. Our findings indicate that brain warming is not a universal outcome of sleep states characterized by wake-like activity, challenging the hypothesis that their primary function is to warm the brain in preparation for wakefulness.

Adaptation and Validation of the Diabetic Foot Ulcer Scale-Short Form in Spanish Subjects.

Diabetic foot ulcer (DFU) is a chronic complication that negatively affects the quality of life (QoL) of diabetic patients. In Spain, there is no specifically designed and validated instrument to assess the QoL of patients with DFU. Our aim was to adapt the Diabetic Foot Ulcer Scale-Short Form (DFS-SF) questionnaire to a Spanish population and validate it. A prospective, observational design was used. The DFS-SF was administered by personal interview. The validated SF-36 and EQ-5D generic instruments were used as reference tools. The reliability, validity, and sensitivity to changes were assessed using standard statistical methods. A sample of 141 patients with DFU was recruited. The content validity was 3.46 on average (maximum score of 4). The internal consistency of the DFS-SF subscales showed a standardized Cronbach's α range between 0.720 and 0.948. The DFS-SF domains showed excellent reproducibility measures (intraclass correlation coefficient from 0.77-0.92). The criterion validity was good with significant correlations between each DFS-SF subscale and its corresponding SF-36 and EQ-5D subscales (p < 0.001). However, the questionnaire structure was not validated (comparative fit index = 0.844, root mean square error of approximation = 0.095, and standardized root mean square residual = 0.093). The instrument showed high sensitivity to ulcer changes over time (p < 0.001). The adapted and validated Spanish version of the DFS-SF questionnaire has good psychometric properties and shows good sensitivity to ulcer changes, although the construct validity was not optimal. The adapted questionnaire will be a useful tool specifically to assess the QoL in subjects with diabetic foot ulcers in the clinical and research settings in Spain.

Neurophysiology of Avian Sleep: Comparing Natural Sleep and Isoflurane Anesthesia.

Propagating slow-waves in electroencephalogram (EEG) or local field potential (LFP) recordings occur during non-rapid eye-movement (NREM) sleep in both mammals and birds. Moreover, in both, input from the thalamus is thought to contribute to the genesis of NREM sleep slow-waves. Interestingly, the general features of slow-waves are also found under isoflurane anesthesia. However, it is unclear to what extent these slow-waves reflect the same processes as those giving rise to NREM sleep slow-waves. Similar slow-wave spatio-temporal properties during NREM sleep and isoflurane anesthesia would suggest that both types of slow-waves are based on related processes. We used a 32-channel silicon probe connected to a transmitter to make intra-cortical recordings of the visual hyperpallium in naturally sleeping and isoflurane anesthetized pigeons (Columba livia) using a within-bird design. Under anesthesia, the amplitude of LFP slow-waves was higher when compared to NREM sleep. Spectral power density across all frequencies (1.5-100 Hz) was also elevated. In addition, slow-wave coherence between electrode sites was higher under anesthesia, indicating higher synchrony when compared to NREM sleep. Nonetheless, the spatial distribution of slow-waves under anesthesia was more comparable to NREM sleep than to wake or REM sleep. Similar to NREM sleep, slow-wave propagation under anesthesia mainly occurred in the thalamic input layers of the hyperpallium, regions which also showed the greatest slow-wave power during both recording conditions. This suggests that the thalamus could be involved in the genesis of slow-waves under both conditions. Taken together, although slow-waves under isoflurane anesthesia are stronger, they share spatio-temporal activity characteristics with slow-waves during NREM sleep.

Intra-"cortical" activity during avian non-REM and REM sleep: variant and invariant traits between birds and mammals.

Several mammalian-based theories propose that the varying patterns of neuronal activity occurring in wakefulness and sleep reflect different modes of information processing. Neocortical slow-waves, hippocampal sharp-wave ripples, and thalamocortical spindles occurring during mammalian non-rapid eye-movement (NREM) sleep are proposed to play a role in systems-level memory consolidation. Birds show similar NREM and REM (rapid eye-movement) sleep stages to mammals; however, it is unclear whether all neurophysiological rhythms implicated in mammalian memory consolidation are also present. Moreover, it is unknown whether the propagation of slow-waves described in the mammalian neocortex occurs in the avian "cortex" during natural NREM sleep. We used a 32-channel silicon probe connected to a transmitter to make intracerebral recordings of the visual hyperpallium and thalamus in naturally sleeping pigeons (Columba livia). As in the mammalian neocortex, slow-waves during NREM sleep propagated through the hyperpallium. Propagation primarily occurred in the thalamic input layers of the hyperpallium, regions that also showed the greatest slow-wave activity (SWA). Spindles were not detected in both the visual hyperpallium, including regions receiving thalamic input, and thalamus, using a recording method that readily detects spindles in mammals. Interestingly, during REM sleep fast gamma bursts in the hyperpallium (when present) were restricted to the thalamic input layers. In addition, unlike mice, the decrease in SWA from NREM to REM sleep was the greatest in these layers. Taken together, these variant and invariant neurophysiological aspects of avian and mammalian sleep suggest that there may be associated mechanistic and functional similarities and differences between avian and mammalian sleep.

Melanin-concentrating hormone (MCH) neurons in the developing chick brain.

The present study was undertaken because no previous developmental studies exist on MCH neurons in any avian species. After validating a commercially-available antibody for use in chickens, immunohistochemical examinations first detected MCH neurons around embryonic day (E) 8 in the posterior hypothalamus. This population increased thereafter, reaching a numerical maximum by E20. MCH-positive cell bodies were found only in the posterior hypothalamus at all ages examined, restricted to a region showing very little overlap with the locations of hypocretin/orexin (H/O) neurons. Chickens had fewer MCH than H/O neurons, and MCH neurons also first appeared later in development than H/O neurons (the opposite of what has been found in rodents). MCH neurons appeared to originate from territories within the hypothalamic periventricular organ that partially overlap with the source of diencephalic serotonergic neurons. Chicken MCH fibers developed exuberantly during the second half of embryonic development, and they became abundant in the same brain areas as in rodents, including the hypothalamus (by E12), locus coeruleus (by E12), dorsal raphe nucleus (by E20) and septum (by E20). These observations suggest that MCH cells may play different roles during development in chickens and rodents; but once they have developed, MCH neurons exhibit similar phenotypes in birds and rodents.

Vitamin D deficiency is associated with poorer satisfaction with diabetes-related treatment and quality of life in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: In this cross-sectional study, we assessed the possible association of vitamin D deficiency with self-reported treatment satisfaction and health-related quality of life in patients with type 2 diabetes. METHODS: We performed a sub-analysis of a previous study and included a total of 292 type 2 diabetic patients. We evaluated treatment satisfaction and health-related quality of life through specific tools: the Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life. Vitamin D deficiency was defined as 25 (OH) D serum levels < 15 ng/mL. RESULTS: Multivariable linear regression models were used to estimate the relationship of vitamin D deficiency with both outcomes once adjusted for self-reported patient characteristics. Vitamin D deficiency was significantly associated with the final score of the Diabetes Treatment Satisfaction Questionnaire and the single "diabetes-specific quality of life" dimension of the Audit of Diabetes-Dependent Quality of Life (p = 0.0198 and p = 0.0070, respectively). However, lower concentrations of 25-OH vitamin D were not associated with the overall quality of life score or the perceived frequency of hyperglycaemia and hypoglycaemia. CONCLUSIONS: Our study shows the association between vitamin D deficiency and both the self-reported diabetes treatment satisfaction and the diabetes-specific quality of life in patients with type 2 diabetes.

Activation of state-regulating neurochemical systems in newborn and embryonic chicks.

Coordinated activity in different sets of widely-projecting neurochemical systems characterize waking (W) and sleep (S). How and when this coordination is achieved during development is not known. We used embryos and newborns of a precocial bird species (chickens) to assess developmental activation in different neurochemical systems using cFos expression, which has been extensively employed to examine cellular activation during S and W in adult mammals. Similarly to adult mammals, newborn awake chicks showed significantly higher cFos expression in W-active hypocretin/orexin (H/O), serotonergic Dorsal Raphe, noradrenergic Locus Coeruleus and cholinergic Laterodorsal and Pedunculopontine Tegmental (Ch-LDT/PT) neurons when compared to sleeping chicks. cFos expression was significantly correlated both between these systems, and with the amount of W. S-active melanin-concentrating hormone (MCH) neurons showed very low cFos expression with no difference between sleeping and awake chicks, possibly due to the very short duration of S episodes. In embryonic chicks, cFos expression was low or absent across all five systems at embryonic day (E) 12. Unexpectedly, a strong activation was seen at E16 in H/O neurons. The highest activation of Ch-LDT/PT (also S-active) and MCH neurons was seen at E20. These data suggest that maturation of arousal systems is achieved soon after hatching, while S-control networks are active in late chick embryos.

Association of low oleic acid intake with diabetic retinopathy in type 2 diabetic patients: a case-control study.

BACKGROUND: The objective of this study was to describe the intake of macronutrient, especially fatty acids, and explore their possible effect on diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. METHODS: In this case-control study, we included a total of 146 patients with DR and 148 without DR. The intake of macronutrient was evaluated using a validated food frequency questionnaire. We used logistic regression adjusted for sex, age, diabetes duration, energy intake, educational level, physical activity, waist circumference, systolic blood pressure, high-density lipoprotein cholesterol and diabetes treatment, to estimate odds ratio (ORs) of DR. RESULTS: Patients with DR had significantly lower intake of fibre, monounsaturated fatty acids (MUFA), and palmitic and oleic acid. Inverse associations were observed between MUFA and oleic acid intake in DR. Subjects with intermediate and high MUFA intake were less likely to have DR than those with lower MUFA intake, with ORs of 0.46 (95 % CI: 0.22-0.93) and 0.42 (95 % CI: 0.18-0.97), respectively. Similarly, intermediate and high oleic acid intake were associated with reduced DR frequency compared with low oleic acid intake, with OR values of 0.48 (95 % CI: 0.23-0.97) and 0.37 (95 % CI: 0.16-0.85), respectively. These associations were stronger in patients with a longer diabetes duration. CONCLUSION: In type 2 diabetes mellitus, MUFA and oleic acid intake were inversely associated with DR.

Ecology and neurophysiology of sleep in two wild sloth species.

STUDY OBJECTIVES: Interspecific variation in sleep measured in captivity correlates with various physiological and environmental factors, including estimates of predation risk in the wild. However, it remains unclear whether prior comparative studies have been confounded by the captive recording environment. Herein we examine the effect of predation pressure on sleep in sloths living in the wild. DESIGN: Comparison of two closely related sloth species, one exposed to predation and one free from predation. SETTING: Panamanian mainland rainforest (predators present) and island mangrove (predators absent). PARTICIPANTS: Mainland (Bradypus variegatus, five males and four females) and island (Bradypus pygmaeus, six males) sloths. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Electroencephalographic (EEG) and electromyographic (EMG) activity was recorded using a miniature data logger. Although both species spent between 9 and 10 h per day sleeping, the mainland sloths showed a preference for sleeping at night, whereas island sloths showed no preference for sleeping during the day or night. Standardized EEG activity during nonrapid eye movement (NREM) sleep showed lower low-frequency power, and increased spindle and higher frequency power in island sloths when compared to mainland sloths. CONCLUSIONS: In sloths sleeping in the wild, predation pressure influenced the timing of sleep, but not the amount of time spent asleep. The preference for sleeping at night in mainland sloths may be a strategy to avoid detection by nocturnal cats. The pronounced differences in the NREM sleep EEG spectrum remain unexplained, but might be related to genetic or environmental factors.

Developmental neurobiology: awakening the brain for the first time.

Imaging of the chicken embryo in the egg has revealed that the entire brain can be switched on for the first time earlier than expected by exposure to maternal vocalizations.

Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

Hippocampal memory consolidation during sleep: a comparison of mammals and birds.

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region--the caudolateral nidopallium (NCL)--involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups.

Avian sleep homeostasis: convergent evolution of complex brains, cognition and sleep functions in mammals and birds.

Birds are the only taxonomic group other than mammals that exhibit high-amplitude slow-waves in the electroencephalogram (EEG) during sleep. This defining feature of slow-wave sleep (SWS) apparently evolved independently in mammals and birds, as reptiles do not exhibit similar EEG activity during sleep. In mammals, the level of slow-wave activity (SWA) (low-frequency spectral power density) during SWS increases and decreases as a function of prior time spent awake and asleep, respectively, and therefore reflects homeostatically regulated sleep processes potentially tied to the function of SWS. Although birds also exhibit SWS, previous sleep deprivation studies in birds did not detect a compensatory increase in SWS-related SWA during recovery, as observed in similarly sleep-deprived mammals. This suggested that, unlike mammalian SWS, avian SWS is not homeostatically regulated, and therefore might serve a different function. However, we recently demonstrated that SWA during SWS increases in pigeons following short-term sleep deprivation. Herein we summarize research on avian sleep homeostasis, and cast our evidence for this phenomenon within the context of theories for the function of SWS in mammals. We propose that the convergent evolution of homeostatically regulated SWS in mammals and birds was directly linked to the convergent evolution of large, heavily interconnected brains capable of performing complex cognitive processes in each group. Specifically, as has been proposed for mammals, the interconnectivity that forms the basis of complex cognition in birds may also instantiate slow, synchronous network oscillations during SWS that in turn maintain interconnectivity and cognition at an optimal level.

Increased EEG spectral power density during sleep following short-term sleep deprivation in pigeons (Columba livia): evidence for avian sleep homeostasis.

Birds provide a unique opportunity to evaluate current theories for the function of sleep. Like mammalian sleep, avian sleep is composed of two states, slow-wave sleep (SWS) and rapid eye-movement (REM) sleep that apparently evolved independently in mammals and birds. Despite this resemblance, however, it has been unclear whether avian SWS shows a compensatory response to sleep loss (i.e., homeostatic regulation), a fundamental aspect of mammalian sleep potentially linked to the function of SWS. Here, we prevented pigeons (Columba livia) from taking their normal naps during the last 8 h of the day. Although time spent in SWS did not change significantly following short-term sleep deprivation, electroencephalogram (EEG) slow-wave activity (SWA; i.e., 0.78-2.34 Hz power density) during SWS increased significantly during the first 3 h of the recovery night when compared with the undisturbed night, and progressively declined thereafter in a manner comparable to that observed in similarly sleep-deprived mammals. SWA was also elevated during REM sleep on the recovery night, a response that might reflect increased SWS pressure and the concomitant 'spill-over' of SWS-related EEG activity into short episodes of REM sleep. As in rodents, power density during SWS also increased in higher frequencies (9-25 Hz) in response to short-term sleep deprivation. Finally, time spent in REM sleep increased following sleep deprivation. The mammalian-like increase in EEG spectral power density across both low and high frequencies, and the increase in time spent in REM sleep following sleep deprivation suggest that some aspects of avian and mammalian sleep are regulated in a similar manner.

Predator-induced plasticity in sleep architecture in wild-caught Norway rats (Rattus norvegicus).

Sleep is a prominent behaviour in the lives of animals, but the unresponsiveness that characterizes sleep makes it dangerous. Mammalian sleep is composed of two neurophysiological states: slow wave sleep (SWS) and rapid-eye-movement (REM) sleep. Given that the intensity of stimuli required to induce an arousal to wakefulness is highest during deep SWS or REM sleep, mammals may be most vulnerable during these states. If true, then animals should selectively reduce deep SWS and REM sleep following an increase in the risk of predation. To test this prediction, we simulated a predatory encounter with 10 wild-caught Norway rats (Rattus norvegicus), which are perhaps more likely to exhibit natural anti-predator responses than laboratory strains. Immediately following the encounter, rats spent more time awake and less time in SWS and REM sleep. The reduction of SWS was due to the shorter duration of SWS episodes, whereas the reduction of REM sleep was due to a lower number of REM sleep episodes. The onset of SWS and REM sleep was delayed post-encounter by about 20 and 100 min, respectively. The reduction of REM sleep was disproportionately large during the first quarter of the sleep phase, and slow wave activity (SWA) (0.5-4.5 Hz power density) was lower during the first 10 min of SWS post-encounter. An increase in SWA and REM sleep was observed later in the sleep phase, which may reflect sleep homeostasis. These results suggest that aspects of sleep architecture can be adjusted to the prevailing risk of predation.