Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer’s disease

BackgroundThe prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer’s disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer’s disease animal models have been developed. The Tg2576 model of Alzheimer’s disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer’s disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice.MethodsAfter governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models.ResultsDuring general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits.ConclusionIsoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare

Assessment of mobilization capacity in 10 different ICU scenarios by different professions

Background: Mobilization of intensive care patients is a multi-professional task. Aim of this study was to explore how different professions working at Intensive Care Units (ICU) estimate the mobility capacity using the ICU Mobility Score in 10 different scenarios. Methods: Ten fictitious patient-scenarios and guideline-related knowledge were assessed using an online survey. Critical care team members in German-speaking countries were invited to participate. All datasets including professional data and at least one scenario were analyzed. Kruskal Wallis test was used for the individual scenarios, while a linear mixed-model was used over all responses. Results: In total, 515 of 788 (65%) participants could be evaluated. Physicians (p = 0.001) and nurses (p = 0.002) selected a lower ICU Mobility Score (-0.7 95% CI -1.1 to -0.3 and -0.4 95% CI -0.7 to -0.2, respectively) than physical therapists, while other specialists did not (p = 0.81). Participants who classified themselves as experts or could define early mobilization in accordance to the "S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders" correctly selected higher mobilization levels (0.2 95% CI 0.0 to 0.4, p = 0.049 and 0.3 95% CI 0.1 to 0.5, p = 0.002, respectively). Conclusion: Different professions scored the mobilization capacity of patients differently, with nurses and physicians estimating significantly lower capacity than physical therapists. The exact knowledge of guidelines and recommendations, such as the definition of early mobilization, independently lead to a higher score. Interprofessional education, interprofessional rounds and mobilization activities could further enhance knowledge and practice of mobilization in the critical care team

Implementing Systematically Collected User Feedback to Increase User Retention in a Mobile App for Self-Management of Low Back Pain: Retrospective Cohort Study

Background: Promising first results for Kaia, a mobile app digitalizing multidisciplinary rehabilitation for low back pain, were recently published. It remains unclear whether the implementation of user feedback in an updated version of this app leads to desired effects in terms of increased app usage and clinical outcomes. Objective: The aim is to elucidate the effect on user retention and clinical outcomes of an updated version of the Kaia app where user feedback was included during development. Methods: User feedback of the initial app versions (0.x) was collected in a quality management system and systematically analyzed to define requirements of a new version. For this study, the anonymized data of Kaia users was analyzed retrospectively and users were grouped depending on the available version at the time of the sign-up (0.x vs 1.x). The effect on the duration of activity of users in the app, the number of completed exercises of each type, and user-reported pain levels were compared. Results: Overall, data of 1251 users fulfilled the inclusion criteria, of which 196 users signed up using version 0.x and 1055 users signed up with version 1.x. There were significant differences in the demographic parameters for both groups. A log-rank test showed no significant differences for the duration of activity in the app between groups (P=.31). Users signing up during availability of the 1.x version completed significantly more exercises of each type in the app (physical exercises: 0.x mean 1.99, SD 1.61 units/week vs 1.x mean 3.15, SD 1.72 units/week;P<.001;mindfulness exercises: 0.x mean 1.36, SD 1.43 units/week vs 1.x mean 2.42, SD 1.82 units/week;P<.001;educational content: 0.x mean 1.51, SD 1.42 units/week vs 1.x mean 2.71, SD 1.89 units/week;P<.001). This translated into a stronger decrease in user-reported pain levels in versions 1.x (F1,1233=7.084, P=.008). Conclusions: Despite the limitations of retrospective cohort studies, this study indicates that the implementation of systematically collected user feedback during development of updated versions can contribute to improvements in terms of frequency of use and potentially even clinical endpoints such as pain level. The clinical efficiency of the Kaia app needs to be validated in prospective controlled trials to exclude bias

Simple Model for the Variation of Superfluid Density with Zn Concentration in YBCO

We describe a simple model for calculating the zero-temperature superfluid density of Zn-doped YBa_2Cu_3O_{7-\delta} as a function of the fraction x of in-plane Cu atoms which are replaced by Zn. The basis of the calculation is a ``Swiss cheese'' picture of a single CuO_2 layer, in which a substitutional Zn impurity creates a normal region of area $\pi\xi_{ab}^2$ around it as originally suggested by Nachumi et al. Here $\xi_{ab}$ is the zero-temperature in-plane coherence length at x = 0. We use this picture to calculate the variation of the in-plane superfluid density with x at temperature T = 0, using both a numerical approach and an analytical approximation. For $\delta = 0.37$, if we use the value $\xi_{ab}$ = 18.3 angstrom, we find that the in-plane superfluid decreases with increasing x and vanishes near $x_c = 0.01$ in the analytical approximation, and near $x_c = 0.014$ in the numerical approach. $x_c$ is quite sensitive to $\xi_{ab}$, whose value is not widely agreed upon. The model also predicts a peak in the real part of the conductivity, Re$\sigma_e(\omega, x)$, at concentrations $x \sim x_c$, and low frequencies, and a variation of critical current density with x of the form $J_c(x) \propto n_{S,e}(x)^{7/4}$ near percolation, where $n_{S,e}(x)$ is the in-plane superfluid density.Comment: 19 pages including 6 figures, submitted to Physica

Interplay of disorder and magnetic field in the superconducting vortex state

We calculate the density of states of an inhomogeneous superconductor in a magnetic field where the positions of vortices are distributed completely at random. We consider both the cases of s-wave and d-wave pairing. For both pairing symmetries either the presence of disorder or increasing the density of vortices enhances the low energy density of states. In the s-wave case the gap is filled and the density of states is a power law at low energies. In the d-wave case the density of states is finite at zero energy and it rises linearly at very low energies in the Dirac isotropic case (\alpha_D=t/\Delta_0=1, where t is the hopping integral and \Delta_0 is the amplitude of the order parameter). For slightly higher energies the density of states crosses over to a quadratic behavior. As the Dirac anisotropy increases (as \Delta_0 decreases with respect to the hopping term) the linear region decreases in width. Neglecting this small region the density of states interpolates between quadratic and back to linear as \alpha_D increases. The low energy states are strongly peaked near the vortex cores.Comment: 12 REVTeX pages, 15 figure

Critical temperature and superfluid density suppression in disordered high-TcT_c cuprate superconductors

We argue that the standard Abrikosov-Gorkov (AG) type theory of $T_c$ in disordered $d$-wave superconductors breaks down in short coherence length high-$T_c$ cuprates. Numerical calculations within the Bogoliubov-de Gennes formalism demonstrate that the correct description of such systems must allow for the spatial variation of the order parameter, which is strongly suppressed in the vicinity of impurities but mostly unaffected elsewhere. Suppression of $T_c$ as measured with respect to the attendant decrease in the superfluid density is found to be significantly weaker than that predicted by the AG theory, in good agreement with experiment.Comment: REVTeX, 4 pages, 3 ps figures included [The version to appear in PRB Sept. 1. Conclusions of the paper unchanged; several changes in text and figures for added clarity, discussion of phase fluctuations added.

The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty