Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

A comparison of static and dynamic characteristics between rectus eye muscle and linear muscle model predictions.

The characteristics of a muscle model are analyzed using rectus eye muscle parameter values and compared to rectus eye muscle data. The muscle is modeled as a viscoelastic parallel combination connected to a parallel combination of active state tension generator, viscosity element, and length tension elastic element. Each of the elements is linear and their existence is supported with physiological evidence. The static and dynamic properties of the muscle model are compared to rectus eye muscle data. The length-tension characteristics of the model are in good agreement with the data within the operating region of the muscle. With the muscle model incorporated into a lever system to match the isotonic experiment paradigm, simulation results for this linear system yield a nonlinear force-velocity curve. Moreover, the family of force-velocity curves generated with different stimulus rates reported in the literature match the predictions of the model without parametric changes. The results of this paper are important in studies involving the oculomotor plant and oculomotor neural networks. Additionally, these results may be applicable to other muscles.

The electroencephalographic pattern during electroconvulsive therapy: V. Observations on the origins of phase III delta energy and the mechanism of action of ECT.

The generation of the spike-wave activity of Phase III of ECT seizures is attributed to the recurrence of synchronized, prolonged periods of intense inhibitory current flow (hyperpolarization), and associated rebound spike bursts, produced by the inhibitory circuit relationships and intrinsic electrophysiological properties of thalamic neurons. An anatomical and neurophysiological model of the development of generalized, synchronous 3-Hz spike-wave seizure activity is proposed which outlines the origin, maintenance, slowing, and termination of this fundamental seizure rhythm. Phase III inhibitory current flow (delta energy) and/or spike bursts may bring about therapeutic benefit by initiating a chain of agonist-independent and agonist-dependent events which results in long-term augmentation of serotonergic and noradrenergic neurotransmission and diminution of cholinergic neurotransmission in the forebrain. A specific anatomical and functional model of the mechanism of action of ECT is proposed, in which: (1) adrenergic and cholinergic pathways in the forebrain are assumed to be massively stimulated during ECT seizures, whereas serotonergic pathways are assumed to be inhibited during these seizures; (2) the beneficial effects of ECT are considered to be more dependent upon ECT-induced changes in 5-HT neurotransmission than upon alteration of noradrenergic function; (3) these beneficial effects involve up-regulation of 5-HT2 and down-regulation of M1- and M2-muscarinic receptor densities by both agonist-independent and agonist-dependent mechanisms, coupled with functional augmentation of noradrenergic neurotransmission; and (4) these effects may be brought about by Phase III inhibitory current flow- and/or spike burst-induced alteration of the function of second-messenger generator systems.

The electroencephalographic pattern during electroconvulsive therapy. IV. Spectral energy distributions with methohexital, innovar and ketamine anesthesias.

During Phase III of nondominant unilateral ECT seizures, total energy, total peak energy, total delta energy, and 1/2-power duration of total delta energy are all less (shorter) in the unstimulated, dominant hemisphere than they are in the stimulated hemisphere. Interhemispheric differences in total energy are greatest in the lateral frontotemporal cortex, where they average 40 percent with both methohexital and ketamine anesthesias in F8 greater than F7 and T4 greater than T3. This circumstance probably explains the characteristic memory sparing associated with nondominant unilateral ECT. The magnitudes of total and peak energies in each frequency band decrease in the order: delta greater than theta greater than alpha greater than beta. Delta energy constitutes approximately three-fourths of the unilateral ECT seizure's total energy, and Phase III delta energy may be the therapeutically effective agent in this treatment. Seizures induced during ketamine anesthesia are associated with a higher percentage of delta energy, with higher magnitudes of total energy and of total and peak delta energy, and with longer 1/2-power durations of delta energy. Nondominant unilateral ECT with ketamine anesthesia offers promise as the treatment of choice for patients resistant to ECT administered with methohexital anesthesia.

The electroencephalographic pattern during electroconvulsive therapy. III. Analysis of frontotemporal and nasopharyngeal spectral energy.

This study analyzes the frontotemporal and nasopharyngeal spectral energy of an ECT-induced seizure, in order to investigate the origin of the final Phase III activity, which contains most of the seizure's energy. Data supports these findings: energy in the delta frequency band is responsible for the generation, propagation, and maintenance of Phase III of the ECT-induced seizure; the synchronous "delta-firing" depolarizations of Phase III are recurrently initiated by an ECT-induced "generator" process; higher magnitudes of energy are generated centrally than are generated laterally during Phase III; and the lessened memory impairment associated with nondominant unilateral ECT is attributable to the markedly lower peak and total energies observed in the unstimulated temporal lobe.

[Activity of artificial pacemaker surveillance units at the Hôpital Brugmann]. / Activite de l'unité de surveillance des stimulateurs artificiels à l'Hôpital Brugmann

1. The pacemaker clinic is of invaluable help in the follow-up of patients with implanted cardiac pacemakers. 2. Photoanalysis provides important information in the study of functionating pacemakers and electrodes.

Frequency response analysis of human saccadic eye movements: estimation of stochastic muscle forces.

A frequency response method is used to estimate parameters of a fourth-order model of the oculomotor system and the active state tensions during a saccadic eye movement. The lateral and medial rectus muscle of each eye is modeled as a parallel combination of an active state tension generator with a viscosity and elastic element, connected to a series elastic element. The eyeball is modeled as a sphere connected to a viscosity and elastic element. Each of these elements is assumed to be ideal and linear. The active state tension for each muscle is modeled by a low-pass filtered pulse-step waveform. Initial estimates of the oculomotor mechanical components are based on physiological evidence. Initial estimates of the active state tension are based on an extrapolation of the eye movement trajectory. Horizontal saccadic eye movements were recorded from infrared signals reflected from the anterior surface of the cornea and then digitized. Parameter estimates were calculated for the model by using a conjugate gradient search program which minimizes the integral of the absolute value of the squared error between the model and the data. The predictions of the model are shown to be in good agreement with the data. Final estimates of motoneuronal activity demonstrate that the agonist muscle is maximally stimulated during the early portion of a saccadic eye movement regardless of the amplitude of the saccade; only the duration of the maximal stimulation affects the size of the saccade. The antagonist muscle is completely inhibited during the period of maximum agonist muscle stimulation. Furthermore, it is demonstrated that saccade motoneuronal activity is a stochastic phenomenon.

Observations on pilot neurosensory control performance during saccadic eye movements.

Saccadic eye movement system performance was investigated to determine whether neurosensory and motor system function is improved by training. There were 2 populations studied--12 Air National Guard pilots, individuals with extensive visual training, and 12 nonpilots. Each subject executed 54 saccadic eye movements while tracking an LED target which moved at random from one location to another. The target display consisted of nine small LED's, each separated by 5 degrees. The ordering of the target movements, as well as the time interval between target movements, were randomized. Horizontal saccadic eye movements were recorded from infrared signals reflected from the anterior surface of the cornea. Signals for bilateral tracking were digitized using an analog-to-digital converter and stored in the hard disk of an IBM/XT. Results using advanced digital processing techniques indicate no significant differences in neurosensory and motor system function during saccadic eye movements between the two populations. A time-optimal central nervous system control mechanism is described which cannot be improved upon by training or exercise.

Relationships between manual reaction time and saccade latency in response to visual and auditory stimuli.

Manual reaction time (RT) responses were analyzed from seven human subjects. Responses were recorded using four kinds of target presentations: fixed visual target, moving visual target, fixed auditory target, and moving auditory target. Moving targets (moving in the horizontal plane) were presented at constant intensity and provided only a motion cue. Fixed targets "popped on" at the primary position and provided only an onset cue. RTs for the fixed and moving visual targets were 241.5 ms and 233.1 ms, respectively. The 8.4 ms (3.5%) advantage for the moving visual target over the fixed visual target was statistically significant, p less than 0.05. RT for the moving auditory target varied with target movement amplitude and ranged from 219 ms for 40 degree movements to 268 ms for 5 degree movements. For the fixed auditory target in the sagittal plane, average RT was 182.9 ms. Thus, sound-source motion detection was from 36 to 85 ms slower than sound onset detection, p less than 0.001. The RT results were compared to saccade latency measurements from an earlier study. Both RT and saccade latency showed the same dependency upon target movement amplitude. For small target displacements, saccade latencies for the moving auditory target were longer than for the moving visual target. The longer latencies for the moving auditory target are attributed to the increased processing time required to detect the sound-source motion.

The design and development of a biosensor to measure the concentration of meconium in amniotic fluid.

Meconium aspiration syndrome occurs in 0.2% to 1% of all deliveries and has a mortality rate as high as 18%. The disease is responsible for 2% of all perinatal deaths. Meconium may be classified as being thick or thin, but this assessment is normally performed visually by clinicians. A "meconiumcrit" analysis has been developed to objectively define the concentration of meconium. However, this analysis does not provide real-time continuous readings. This study focused on the design and development of a sensor to provide an objective, continuous, real-time assessment of meconium thickness. Meconium has an absorption spectrum centered at 410 nm and observes Beer's law. Blue light centered at 430 nm was delivered through meconium solutions, and a photodiode translated the strength of the incoming light into a voltage. This voltage was analyzed by a microcontroller to determine the concentration of meconium.

Carbohydrate intake and glycemic index affect substrate oxidation during a controlled weight cycle in healthy men.

BACKGROUND/OBJECTIVES: Because both, glycemic index (GI) and carbohydrate content of the diet increase insulin levels and could thus impair fat oxidation, we hypothesized that refeeding a low GI, moderate-carbohydrate diet facilitates weight maintenance. SUBJECTS/METHODS: Healthy men (n=32, age 26.0±3.9 years; BMI 23.4±2.0 kg/m(2)) followed 1 week of controlled overfeeding, 3 weeks of caloric restriction and 2 weeks of hypercaloric refeeding (+50, -50 and +50% energy requirement) with low vs high GI (41 vs 74) and moderate vs high CHO intake (50% vs 65% energy). We measured adaptation of fasting macronutrient oxidation and the capacity to supress fat oxidation during an oral glucose tolerance test. Changes in fat mass were measured by quantitative magnetic resonance. RESULTS: During overfeeding, participants gained 1.9±1.2 kg body weight, followed by a weight loss of -6.3±0.6 kg and weight regain of 2.8±1.0 kg. Subjects with 65% CHO gained more body weight compared with 50% CHO diet (P<0.05) particularly with HGI meals (P<0.01). Refeeding a high-GI diet led to an impaired basal fat oxidation when compared with a low-GI diet (P<0.02), especially at 65% CHO intake. Postprandial metabolic flexibility was unaffected by refeeding at 50% CHO but clearly impaired by 65% CHO diet (P<0.05). Impairment in fasting fat oxidation was associated with regain in fat mass (r=0.43, P<0.05) and body weight (r=0.35; P=0.051). CONCLUSIONS: Both higher GI and higher carbohydrate content affect substrate oxidation and thus the regain in body weight in healthy men. These results argue in favor of a lower glycemic load diet for weight maintenance after weight loss.

Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome.

Body composition is related to various physiological and pathological states. Characterization of individual body components adds to understand metabolic, endocrine and genetic data on obesity and obesity-related metabolic risks, e.g. insulin resistance. The obese phenotype is multifaceted and can be characterized by measures of body fat, leg fat, liver fat and skeletal muscle mass rather than by body mass index. The contribution of either whole body fat or fat distribution or individual fat depots to insulin resistance is moderate, but liver fat has a closer association with (hepatic) insulin resistance. Although liver fat is associated with visceral fat, its effect on insulin resistance is independent of visceral adipose tissue. In contrast to abdominal fat, appendicular or leg fat is inversely related to insulin resistance. The association between 'high fat mass + low muscle mass' (i.e. 'sarcopenic adiposity') and insulin resistance deserves further investigation and also attention in daily clinical practice. In addition to cross-sectional data, longitudinal assessment of body composition during controlled under- and overfeeding of normal-weight healthy young men shows that small decreases and increases in fat mass are associated with corresponding decreases and increases in insulin secretion as well as increases and decreases in insulin sensitivity. However, even under controlled conditions, there is a high intra- and inter-individual variance in the changes of (i) body composition; (ii) the 'body composition-glucose metabolism relationship' and (iii) glucose metabolism itself. Combining individual body components with their related functional aspects (e.g. the endocrine, metabolic and inflammatory profiles) will provide a suitable basis for future definitions of a 'metabolically healthy body composition'.