Activity and Profile of the Users of a Novel Mobile Application Supporting Proper Diet Among Maintenance Hemodialysis Patients.

OBJECTIVE: Diet plays a key role in the management of chronic kidney disease. The aim of our study was to evaluate the usage of a self-developed mobile application supporting proper dietary choices among maintenance hemodialysis (HD) patients. METHODS: The primary functions of the application are to provide databases of products and recipes. Data on user activity recorded using Internet solutions were collected for 12 months from April 2021. The application was promoted both via the Internet and directly to patients. Additionally, a questionnaire was employed to evaluate the usage of the software. RESULTS: The application was downloaded by 841 smartphone users, 44.4% of whom were from 2 regions of Poland with the largest populations of HD patients. Residents of cities with a population above 250,000 accounted for 86.0% of users. Sixty HD patients (32 males, 28 females; age 56.2 ± 14.8 years) filled the questionnaire. All features of the application scored a median of 4.0 points or higher on a 5-point Likert scale; however, 63.3% of respondents indicated the need to improve particular functions of the application. There was a significant difference in dialysis vintage between respondents who used the application for less than 1 month and others (1.0 vs. 3.3 years; P = .02). The positive perception of its influence on diet adherence was significantly higher among younger (<50 years) compared to older users (5.0 vs. 4.0; P = .03) and among women compared to men (5.0 vs. 4.0; P = .01). CONCLUSION: HD patients showed interest in dietary mobile applications, and Internet channels were effective in promoting the software. Place of residency, age, gender, and dialysis vintage are factors that influence patient satisfaction with and the time of using the mobile application.

Existence of a Long-Range Caudo-Rostral Sensory Influence in Terrestrial Locomotion.

In multisegmented locomotion, coordination of all appendages is crucial for the generation of a proper motor output. In running for example, leg coordination is mainly based on the central interaction of rhythm generating networks, called central pattern generators (CPGs). In slower forms of locomotion, however, sensory feedback, which originates from sensory organs that detect changes in position, velocity and load of the legs' segments, has been shown to play a more crucial role. How exactly sensory feedback influences the activity of the CPGs to establish functional neuronal connectivity is not yet fully understood. Using the female stick insect Carausius morosus, we show for the first time that a long-range caudo-rostral sensory connection exists and highlight that load as sensory signal is sufficient to entrain rhythmic motoneuron (MN) activity in the most rostral segment. So far, mainly rostro-caudal influencing pathways have been investigated where the strength of activation, expressed by the MN activity in the thoracic ganglia, decreases with the distance from the stepping leg to these ganglia. Here, we activated CPGs, producing rhythmic neuronal activity in the thoracic ganglia by using the muscarinic agonist pilocarpine and enforced the stepping of a single, remaining leg. This enabled us to study sensory influences on the CPGs' oscillatory activity. Using this approach, we show that, in contrast to the distance-dependent activation of the protractor-retractor CPGs in different thoracic ganglia, there is no such dependence for the entrainment of the rhythmic activity of active protractor-retractor CPG networks by individual stepping legs.SIGNIFICANCE STATEMENT We show for the first time that sensory information is transferred not only to the immediate adjacent segmental ganglia but also to those farther away, indicating the existence of a long-range caudo-rostral sensory influence. This influence is dependent on stepping direction but independent of whether the leg is actively or passively moved. We suggest that the sensory information comes from unspecific load signals sensed by cuticle mechanoreceptors (campaniform sensilla) of a leg. Our results provide a neuronal basis for the long-established behavioral rules of insect leg coordination. We thus provide a breakthrough in understanding the neuronal networks underlying multilegged locomotion and open new vistas into the neuronal functional connectivity of multisegmented locomotion systems across the animal kingdom.

A Paradoxical Kind of Sleep in Drosophila melanogaster.

The dynamic nature of sleep in many animals suggests distinct stages that serve different functions. Genetic sleep induction methods in animal models provide a powerful way to disambiguate these stages and functions, although behavioral methods alone are insufficient to accurately identify what kind of sleep is being engaged. In Drosophila, activation of the dorsal fan-shaped body (dFB) promotes sleep, but it remains unclear what kind of sleep this is, how the rest of the fly brain is behaving, or if any specific sleep functions are being achieved. Here, we developed a method to record calcium activity from thousands of neurons across a volume of the fly brain during spontaneous sleep and compared this to dFB-induced sleep. We found that spontaneous sleep typically transitions from an active "wake-like" stage to a less active stage. In contrast, optogenetic activation of the dFB promotes sustained wake-like levels of neural activity even though flies become unresponsive to mechanical stimuli. When we probed flies with salient visual stimuli, we found that the activity of visually responsive neurons in the central brain was blocked by transient dFB activation, confirming an acute disconnect from the external environment. Prolonged optogenetic dFB activation nevertheless achieved a key sleep function by correcting visual attention defects brought on by sleep deprivation. These results suggest that dFB activation promotes a distinct form of sleep in Drosophila, where brain activity appears similar to wakefulness, but responsiveness to external sensory stimuli is profoundly suppressed.

Oscillations in the central brain of Drosophila are phase locked to attended visual features.

Object-based attention describes the brain's capacity to prioritize one set of stimuli while ignoring others. Human research suggests that the binding of diverse stimuli into one attended percept requires phase-locked oscillatory activity in the brain. Even insects display oscillatory brain activity during visual attention tasks, but it is unclear if neural oscillations in insects are selectively correlated to different features of attended objects. We addressed this question by recording local field potentials in the Drosophila central complex, a brain structure involved in visual navigation and decision making. We found that attention selectively increased the neural gain of visual features associated with attended objects and that attention could be redirected to unattended objects by activation of a reward circuit. Attention was associated with increased beta (20- to 30-Hz) oscillations that selectively locked onto temporal features of the attended visual objects. Our results suggest a conserved function for the beta frequency range in regulating selective attention to salient visual features.

Innate visual preferences and behavioral flexibility in Drosophila.

Visual decision making in animals is influenced by innate preferences as well as experience. Interaction between hard-wired responses and changing motivational states determines whether a visual stimulus is attractive, aversive or neutral. It is, however, difficult to separate the relative contribution of nature versus nurture in experimental paradigms, especially for more complex visual parameters such as the shape of objects. We used a closed-loop virtual reality paradigm for walking Drosophila to uncover innate visual preferences for the shape and size of objects, in a recursive choice scenario allowing the flies to reveal their visual preferences over time. We found that Drosophila melanogaster display a robust attraction/repulsion profile for a range of object sizes in this paradigm, and that this visual preference profile remains evident under a variety of conditions and persists into old age. We also demonstrate a level of flexibility in this behavior: innate repulsion to certain objects could be transiently overridden if these were novel, although this effect was only evident in younger flies. Finally, we show that a neuromodulatory circuit in the fly brain, Drosophila neuropeptide F (dNPF), can be recruited to guide visual decision making. Optogenetic activation of dNPF-expressing neurons converted a visually repulsive object into a more attractive object. This suggests that dNPF activity in the Drosophila brain guides ongoing visual choices, to override innate preferences and thereby provide a necessary level of behavioral flexibility in visual decision making.

Acute control of the sleep switch in Drosophila reveals a role for gap junctions in regulating behavioral responsiveness.

Sleep is a dynamic process in most animals, involving distinct stages that probably perform multiple functions for the brain. Before sleep functions can be initiated, it is likely that behavioral responsiveness to the outside world needs to be reduced, even while the animal is still awake. Recent work in Drosophila has uncovered a sleep switch in the dorsal fan-shaped body (dFB) of the fly's central brain, but it is not known whether these sleep-promoting neurons also govern the acute need to ignore salient stimuli in the environment during sleep transitions. We found that optogenetic activation of the sleep switch suppressed behavioral responsiveness to mechanical stimuli, even in awake flies, indicating a broader role for these neurons in regulating arousal. The dFB-mediated suppression mechanism and its associated neural correlates requires innexin6 expression, suggesting that the acute need to reduce sensory perception when flies fall asleep is mediated in part by electrical synapses.

Oscillatory brain activity in spontaneous and induced sleep stages in flies.

Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABAA agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.

Investigating inter-segmental connections between thoracic ganglia in the stick insect by means of experimental and simulated phase response curves.

The neuronal networks that control the motion of the individual legs in insects, in particular in the stick insect, are located in the pro-, meso- and meta-thoracic ganglia. They ensure high flexibility of movement control. Thus, the legs can move in an apparently independent way, e.g., during search movements, but also in tight coordination during locomotion. The latter is evidently a very important behavioural mode. It has, therefore, inspired a large number of studies, all aiming at uncovering the nature of the inter-leg coordination. One of the basic questions has been as to how the individual control networks in the three thoracic ganglia are connected to each other. One way to study this problem is to use phase response curves. They can reveal properties of the coupling between oscillatory systems, such as the central pattern generators in the control networks in the thoracic ganglia. In this paper, we report results that we have achieved by means of a combined experimental and modelling approach. We have calculated phase response curves from data obtained in as yet unpublished experiments as well as from those in previously published ones. By using models of the connected pro- and meso-thoracic control networks of the protractor and retractor neuromuscular systems, we have also produced simulated phase response curves and compared them with the experimental ones. In this way, we could gain important information of the nature of the connections between the aforementioned control networks. Specifically, we have found that connections from both the protractor and the retractor "sides" of the pro-thoracic network to the meso-thoracic one are necessary for producing phase response curves that show close similarity to the experimental ones. Furthermore, the strength of the excitatory connections has been proven to be crucial, while the inhibitory connections have essentially been irrelevant. We, thus, suggest that this type of connection might also be present in the stick insect, and possibly in other insect species.

A neuro-mechanical model explaining the physiological role of fast and slow muscle fibres at stop and start of stepping of an insect leg.

Stop and start of stepping are two basic actions of the musculo-skeletal system of a leg. Although they are basic phenomena, they require the coordinated activities of the leg muscles. However, little is known of the details of how these activities are generated by the interactions between the local neuronal networks controlling the fast and slow muscle fibres at the individual leg joints. In the present work, we aim at uncovering some of those details using a suitable neuro-mechanical model. It is an extension of the model in the accompanying paper and now includes all three antagonistic muscle pairs of the main joints of an insect leg, together with their dedicated neuronal control, as well as common inhibitory motoneurons and the residual stiffness of the slow muscles. This model enabled us to study putative processes of intra-leg coordination during stop and start of stepping. We also made use of the effects of sensory signals encoding the position and velocity of the leg joints. Where experimental observations are available, the corresponding simulation results are in good agreement with them. Our model makes detailed predictions as to the coordination processes of the individual muscle systems both at stop and start of stepping. In particular, it reveals a possible role of the slow muscle fibres at stop in accelerating the convergence of the leg to its steady-state position. These findings lend our model physiological relevance and can therefore be used to elucidate details of the stop and start of stepping in insects, and perhaps in other animals, too.

Quadrupedal gaits in hexapod animals - inter-leg coordination in free-walking adult stick insects.

The analysis of inter-leg coordination in insect walking is generally a study of six-legged locomotion. For decades, the stick insect Carausius morosus has been instrumental for unravelling the rules and mechanisms that control leg coordination in hexapeds. We analysed inter-leg coordination in C. morosus that freely walked on straight paths on plane surfaces with different slopes. Consecutive 1.7 s sections were assigned inter-leg coordination patterns (which we call gaits) based on footfall patterns. Regular gaits, i.e. wave, tetrapod or tripod gaits, occurred in different proportions depending on surface slopes. Tetrapod gaits were observed most frequently, wave gaits only occurred on 90 deg inclining slopes and tripod gaits occurred most often on 15 deg declining slopes, i.e. in 40% of the sections. Depending on the slope, 36-66% of the sections were assigned irregular gaits. Irregular gaits were mostly due to multiple stepping by the front legs, which is perhaps probing behaviour, not phase coupled to the middle legs' cycles. In irregular gaits, middle leg and hindleg coordination was regular, related to quadrupedal walk and wave gaits. Apparently, front legs uncouple from and couple to the walking system without compromising middle leg and hindleg coordination. In front leg amputees, the remaining legs were strictly coordinated. In hindleg and middle leg amputees, the front legs continued multiple stepping. The coordination of middle leg amputees was maladapted, with front legs and hindlegs performing multiple steps or ipsilateral legs being in simultaneous swing. Thus, afferent information from middle legs might be necessary for a regular hindleg stepping pattern.