Baseline Quality-of-Life of Caregivers of Patients With Heart Failure Prior to Advanced Therapies: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT) Study.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ2 tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R2 = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

Depression and religiosity in older age.

We investigated the hypothesis that religious commitment could help counter general affective distress, accompanying depressive symptoms, in older age. A total of 34 older adults, all catholic believers, completed self-reported questionnaires on the presence of depressive symptoms, religiosity, health, worry, and the style of coping with stress. The depressive and non-depressive subgroups were then created. The prevalence of depressive symptoms was 50%, with the substantial predominance of females. Regression analyses indicate that health expectations and worry significantly worsen with increasing intensity of depressive symptoms. The results further show that religious engagement was not different between the depressive and non-depressive subgroups. Religiosity failed to influence the intensity of depressive symptoms or the strategy of coping with stress in either subgroup, although a trend was noted for better health expectations with increasing religious engagement in depressive subjects. We conclude that religiosity is unlikely to significantly ameliorate dysphoric distress accompanying older age.

Behavioural state affects motion-sensitive neurones in the fly visual system.

The strength of stimulus-induced responses at the neuronal and the behavioural level often depends on the internal state of an animal. Within pathways processing sensory information and eventually controlling behavioural responses, such gain changes can originate at several sites. Using motion-sensitive lobula plate tangential cells (LPTCs) of blowflies, we address whether and in which way information processing changes for two different states of motor activity. We distinguish between the two states on the basis of haltere movements. Halteres are the evolutionarily transformed hindwings of flies. They oscillate when the animals walk or fly. LPTCs mediate, amongst other behaviours, head optomotor responses. These are either of large or small amplitude depending on the state of motor activity. Here we find that LPTC responses also depend on the motor activity of flies. In particular, LPTC responses are enhanced when halteres oscillate. Nevertheless, the response changes of LPTCs do not account for the corresponding large gain changes of head movements. Moreover, haltere activity itself does not change the activity of LPTCs. Instead, we propose that a central signal associated with motor activity changes the gain of head optomotor responses and the response properties of LPTCs.

Variability in spike trains during constant and dynamic stimulation.

In a recent study, it was concluded that natural time-varying stimuli are represented more reliably in the brain than constant stimuli are. The results presented here disagree with this conclusion, although they were obtained from the same identified neuron (H1) in the fly's visual system. For large parts of the neuron's activity range, the variability of the responses was very similar for constant and time-varying stimuli and was considerably smaller than that in many visual interneurons of vertebrates.

Temporal precision of the encoding of motion information by visual interneurons.

BACKGROUND: There is much controversy about the timescale on which neurons process and transmit information. On the one hand, a vast amount of information can be processed by the nervous system if the precise timing of individual spikes on a millisecond timescale is important. On the other hand, neuronal responses to identical stimuli often vary considerably and stochastic response fluctuations can exceed the mean response amplitude. Here, we examined the timescale on which neural responses could be locked to visual motion stimuli. RESULTS: Spikes of motion-sensitive neurons in the visual system of the blowfly are time-locked to visual motion with a precision in the range of several tens of milliseconds. Nevertheless, different motion-sensitive neurons with largely overlapping receptive fields generate a large proportion of spikes almost synchronously. This precision is brought about by stochastic rather than by motion-induced membrane-potential fluctuations elicited by the common peripheral input. The stochastic membrane-potential fluctuations contain more power at frequencies above 30-40 Hz than the motion-induced potential changes. A model of spike generation indicates that such fast membrane-potential changes are a major determinant of the precise timing of spikes. CONCLUSIONS: The timing of spikes in neurons of the motion pathway of the blowfly is controlled on a millisecond timescale by fast membrane-potential fluctuations. Despite this precision, spikes do not lock to motion stimuli on this timescale because visual motion does not induce sufficiently rapid changes in the membrane potential.

Encoding of motion in real time by the fly visual system.

Direction-selective cells in the fly visual system that have large receptive fields play a decisive role in encoding the time-dependent optic flow the animal encounters during locomotion. Recent experiments on the computations performed by these cells have highlighted the significance of dendritic integration and have addressed the role of spikes versus graded membrane potential changes in encoding optic flow information. It is becoming increasingly clear that the way optic flow is encoded in real time is constrained both by the computational needs of the animal in visually guided behaviour as well as by the specific properties of the underlying neuronal hardware.

Reliability of a fly motion-sensitive neuron depends on stimulus parameters.

The variability of responses of sensory neurons constrains how reliably animals can respond to stimuli in the outside world. We show for a motion-sensitive visual interneuron of the fly that the variability of spike trains depends on the properties of the motion stimulus, although differently for different stimulus parameters. (1) The spike count variances of responses to constant and to dynamic stimuli lie in the same range. (2) With increasing stimulus size, the variance may slightly decrease. (3) Increasing pattern contrast reduces the variance considerably. For all stimulus conditions, the spike count variance is much smaller than the mean spike count and does not depend much on the mean activity apart from very low activities. Using a model of spike generation, we analyzed how the spike count variance depends on the membrane potential noise and the deterministic membrane potential fluctuations at the spike initiation zone of the neuron. In a physiologically plausible range, the variance is affected only weakly by changes in the dynamics or the amplitude of the deterministic membrane potential fluctuations. In contrast, the amplitude and dynamics of the membrane potential noise strongly influence the spike count variance. The membrane potential noise underlying the variability of the spike responses in the motion-sensitive neuron is concluded to be affected considerably by the contrast of the stimulus but by neither its dynamics nor its size.

Transfer of visual motion information via graded synapses operates linearly in the natural activity range.

Synaptic transmission between a graded potential neuron and a spiking neuron was investigated in vivo using sensory stimulation instead of artificial excitation of the presynaptic neuron. During visual motion stimulation, individual presynaptic and postsynaptic neurons in the brain of the fly were electrophysiologically recorded together with concentration changes of presynaptic calcium (Delta[Ca(2+)](pre)). Preferred-direction motion leads to depolarization of the presynaptic neuron. It also produces pronounced increases in [Ca(2+)](pre) and the postsynaptic spike rate. Motion in the opposite direction was associated with hyperpolarization of the presynaptic cell but only a weak reduction in [Ca(2+)](pre) and the postsynaptic spike rate. Apart from this rectification, the relationships between presynaptic depolarizations, Delta[Ca(2+)](pre), and postsynaptic spike rates are, on average, linear over the entire range of activity levels that can be elicited by sensory stimulation. Thus, the inevitably limited range in which the gain of overall synaptic signal transfer is constant appears to be adjusted to sensory input strengths.

Synaptic transfer of dynamic motion information between identified neurons in the visual system of the blowfly.

Synaptic transmission is usually studied in vitro with electrical stimulation replacing the natural input of the system. In contrast, we analyzed in vivo transfer of visual motion information from graded-potential presynaptic to spiking postsynaptic neurons in the fly. Motion in the null direction leads to hyperpolarization of the presynaptic neuron but does not much influence the postsynaptic cell, because its firing rate is already low during rest, giving only little scope for further reductions. In contrast, preferred-direction motion leads to presynaptic depolarizations and increases the postsynaptic spike rate. Signal transfer to the postsynaptic cell is linear and reliable for presynaptic graded membrane potential fluctuations of up to approximately 10 Hz. This frequency range covers the dynamic range of velocities that is encoded with a high gain by visual motion-sensitive neurons. Hence, information about preferred-direction motion is transmitted largely undistorted ensuring a consistent dependency of neuronal signals on stimulus parameters, such as motion velocity. Postsynaptic spikes are often elicited by rapid presynaptic spike-like depolarizations which superimpose the graded membrane potential. Although the timing of most of these spike-like depolarizations is set by noise and not by the motion stimulus, it is preserved at the synapse with millisecond precision.

Temperature-dependence of neuronal performance in the motion pathway of the blowfly calliphora erythrocephala

Raising the head temperature within a behaviourally relevant range has strong effects on the performance of an identified neuron, the H1 neuron, in the visual motion pathway of blowflies. The effect is seen as an increase in the mean amplitude of the responses to motion under both transient and steady-state conditions, a considerable decrease in the response latency and an improvement in the reliability of the responses to motion. These temperature-dependent effects are independent of whether the animal is exposed to transient temperature changes or is maintained continuously at the same temperature for its entire life. The changes in the neuronal response properties with temperature may be of immediate functional significance for the animal under its normal operating conditions. In particular, the decrease in latency and the improvement in the reliability with increasing temperature may be relevant for the fly when executing its extremely virtuosic flight manoeuvres.

Photo-ablation of single neurons in the fly visual system reveals neural circuit for the detection of small moving objects.

Many animals use relative motion to segregate objects from their background. Nerve cells tuned to this visual cue have been found in various animal groups, such as insects, amphibians, birds and mammals. Well examined examples are the figure detection (FD) cells in the visual system of the blowfly. The mechanism that tunes a particular FD-cell, the FD1-cell, to small-field motion is analyzed by injecting individual visual interneurons with a fluorescent dye and ablating them by illumination with a laser beam. In this way, it is shown that the FD1-cell acquires its specific spatial tuning by inhibitory input from an identified GABAergic cell, the ventral centrifugal horizontal (VCH)-cell which is most sensitive to coherent large-field motion in front of both eyes. For the first time, the detection of small objects by evaluation of their motion parallax, thus, can be attributed to synaptic interactions between identified neurons.

Response latency of a motion-sensitive neuron in the fly visual system: dependence on stimulus parameters and physiological conditions.

The response latency of an identified motion-sensitive neuron in the blowfly visual system strongly depends on stimulus parameters. The latency decreases with increasing contrast and temporal frequency of a moving pattern, but changes only little when the pattern size and thus the number of activated inputs is increased. The latency does not only depend on visual stimuli, but is also affected by temperature changes and the age of the fly. Since response latencies cover a range of one order of magnitude, the latency changes are expected to be of relevance in visually guided orientation behaviour.

Outdoor performance of a motion-sensitive neuron in the blowfly.

We studied an identified motion-sensitive neuron of the blowfly under outdoor conditions. The neuron was stimulated by oscillating the fly in a rural environment. We analysed whether the motion-induced neuronal activity is affected by brightness changes ranging between bright sunlight and dusk. In addition, the relationship between spike rate and ambient temperature was determined. The main results are: (1) The mean spike rate elicited by visual motion is largely independent of brightness changes over several orders of magnitude as they occur as a consequence of positional changes of the sun. Even during dusk the neuron responds strongly and directionally selective to motion. (2) The neuronal spike rate is not significantly affected by short-term brightness changes caused by clouds temporarily occluding the sun. (3) In contrast, the neuronal activity is much affected by changes in ambient temperature.

Comparison of solcoseryl and epidermal growth factors (EGF) in healing of chronic gastroduodenal ulcerations and mucosal growth in rats.

Solcoseryl, a deproteinized extract of calf blood, and EGF, produced by salivary glands, have been shown to enhance the healing of peptic ulcerations, but the mechanism of this effect is unknown. Since both solcoseryl and EGF have been reported to stimulate cell proliferation, we designed the study to compare the ulcer healing and growth promoting actions of these two agents in the same animals. Gastric and duodenal ulcerations were produced by serosal application of 100% acetic acid on an area of 13.8 mm2 of gastric and duodenal wall, respectively. In the control animals, 7 days after ulcer induction, the mean ulcer area was reduced to 7.1 +/- 1.2 mm2 in the stomach, and to 6.1 +/- 0.8 mm2 in the duodenum. After 14 days all ulcers were healed, both in the stomach and duodenum. Oral administration of solcoseryl (10 ml/kg-day) or EGF (30 micrograms/kg-day) for 7 days after ulcer induction resulted in a significant reduction in the ulcer area in the stomach, and to a greater extent in the duodenum. This enhancement of ulcer healing by solcoseryl was accompanied by a significant increase in the weight of the duodenal mucosa and the total contents of DNA and RNA after 7 days of treatment, and in the weight and nucleic acid contents in both the gastric and duodenal mucosa after 14 days of treatment. EGF also increased the weights and the nucleic acid contents in gastric and duodenal mucosa, but this was significant only after 14 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of blowfly head optomotor responses.

Behavioural responses of an animal are variable even when the animal experiences the same sensory input several times. This variability can arise from stochastic processes inherent to the nervous system. Also, the internal state of an animal may influence a particular behavioural response. In the present study, we analyse the variability of visually induced head pitch responses of tethered blowflies by high-speed cinematography. We found these optomotor responses to be highly variable in amplitude. Most of the variability can be attributed to two different internal states of the flies with high and low optomotor gain, respectively. Even within a given activity state, there is some variability of head optomotor responses. The amount of this variability differs for the two optomotor gain states. Moreover, these two activity states can be distinguished on a fine timescale and without visual stimulation, on the basis of the occurrence of peculiar head jitter movements. Head jitter goes along with high gain optomotor responses and haltere oscillations. Halteres are evolutionary transformed hindwings that oscillate when blowflies walk or fly. Their main function is to serve as equilibrium organs by detecting Coriolis forces and to mediate gaze stabilisation. However, their basic oscillating activity was also suggested to provide a gain-modulating signal. Our experiments demonstrate that halteres are not necessary for high gain head pitch to occur. Nevertheless, we find the halteres to be responsible for one component of head jitter movements. This component may be the inevitable consequence of their function as equilibrium and gaze-stabilising organs.

How reliably does a neuron in the visual motion pathway of the fly encode behaviourally relevant information?

How reliably neurons convey information depends on the extent to which their activity is affected by stochastic processes which are omnipresent in the nervous system. The functional consequences of neuronal noise can only be assessed if the latter is related to the response components that are induced in a normal behavioural situation. In the present study the reliability of neural coding was investigated for an identified neuron in the pathway processing visual motion information of the fly (Lucilia cuprina). The stimuli used to investigate the neuronal performance were not exclusively defined by the experimenter. Instead, they were generated by the fly itself, i.e. by its own actions and reactions in a behavioural closed-loop experiment, and subsequently replayed to the animal while the activity of an identified motion-sensitive neuron was recorded. Although the time course of the neuronal responses is time-locked to the stimulus, individual response traces differ slightly from each other due to stochastic fluctuations in the timing and number of action potentials. Individual responses thus consist of a stimulus-induced and a stochastic response component. The stimulus-induced response component can be recovered most reliably from noisy neuronal signals if these are smoothed by intermediate-sized time windows (40-100 ms). At this time scale the best compromise is achieved between smoothing out the noise and maintaining the temporal resolution of the stimulus-induced response component. Consequently, in the visual motion pathway of the fly, behaviourally relevant motion stimuli can be resolved best at a time scale where the timing of individual spikes does not matter.

On the performance of biological movement detectors and ideal velocity sensors in the context of optomotor course stabilization.

It is often assumed that the ultimate goal of a motion-detection system is to faithfully represent the time-dependent velocity of a moving stimulus. This assumption, however, may be an arbitrary standard since the requirements for a motion-detection system depend on the task that is to be solved. In the context of optomotor course stabilization, the performance of a motion-sensitive neuron in the fly's optomotor pathway and of a hypothetical velocity sensor are compared for stimuli as are characteristic of a normal behavioral situation in which the actions and reactions of the animal directly affect its visual input. On average, tethered flies flying in a flight simulator are able to compensate to a large extent the retinal image displacements as are induced by an external disturbance of their flight course. The retinal image motion experienced by the fly under these behavioral closed-loop conditions was replayed in subsequent electrophysiological experiments to the animal while the activity of an identified neuron in the motion pathway was recorded. The velocity fluctuations as well as the corresponding neuronal signals were analyzed with a statistical approach taken from signal-detection theory. An observer scrutinizing either signal performs almost equally well in detecting the external disturbance.