Bariatric surgery and brain health: A longitudinal observational study investigating the effect of surgery on cognitive function and gray matter volume

Dietary modifications leading to weight loss have been suggested as a means to improve brain health. In morbid obesity, bariatric surgery (BARS)—including different procedures, such as vertical sleeve gastrectomy (VSG), gastric banding (GB), or Roux-en-Y gastric bypass (RYGB) surgery—is performed to induce rapid weight loss. Combining reduced food intake and malabsorption of nutrients, RYGB might be most effective, but requires life-long follow-up treatment. Here, we tested 40 patients before and six months after surgery (BARS group) using a neuropsychological test battery and compared them with a waiting list control group. Subsamples of both groups underwent structural MRI and were examined for differences between surgical procedures. No substantial differences between BARS and control group emerged with regard to cognition. However, larger gray matter volume in fronto-temporal brain areas accompanied by smaller volume in the ventral striatum was seen in the BARS group compared to controls. RYGB patients compared to patients with restrictive treatment alone (VSG/GB) had higher weight loss, but did not benefit more in cognitive outcomes. In sum, the data of our study suggest that BARS might lead to brain structure reorganization at long-term follow-up, while the type of surgical procedure does not differentially modulate cognitive performance

Weight loss reduces head motion: Re-visiting a major confound in neuroimaging

Head motion during magnetic resonance imaging (MRI) induces image artifacts that affect virtually every brain measure. In parallel, cross‐sectional observations indicate a correlation of head motion with age, psychiatric disease status and obesity, raising the possibility of a systematic artifact‐induced bias in neuroimaging outcomes in these conditions, due to the differences in head motion. Yet, a causal link between obesity and head motion has not been tested in an experimental design. Here, we show that a change in body mass index (BMI) (i.e., weight loss after bariatric surgery) systematically decreases head motion during MRI. In this setting, reduced imaging artifacts due to lower head motion might result in biased estimates of neural differences induced by changes in BMI. Overall, our finding urges the need to rigorously control for head motion during MRI to enable valid results of neuroimaging outcomes in populations that differ in head motion due to obesity or other conditions

Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection

Objective Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. Design Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air–liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. Results The resulting ‘mucosoid cultures’, so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness—reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome. Conclusion Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.</p

Structural Properties of Self-Attracting Walks

Self-attracting walks (SATW) with attractive interaction u > 0 display a swelling-collapse transition at a critical u_{\mathrm{c}} for dimensions d >= 2, analogous to the \Theta transition of polymers. We are interested in the structure of the clusters generated by SATW below u_{\mathrm{c}} (swollen walk), above u_{\mathrm{c}} (collapsed walk), and at u_{\mathrm{c}}, which can be characterized by the fractal dimensions of the clusters d_{\mathrm{f}} and their interface d_{\mathrm{I}}. Using scaling arguments and Monte Carlo simulations, we find that for u<u_{\mathrm{c}}, the structures are in the universality class of clusters generated by simple random walks. For u>u_{\mathrm{c}}, the clusters are compact, i.e. d_{\mathrm{f}}=d and d_{\mathrm{I}}=d-1. At u_{\mathrm{c}}, the SATW is in a new universality class. The clusters are compact in both d=2 and d=3, but their interface is fractal: d_{\mathrm{I}}=1.50\pm0.01 and 2.73\pm0.03 in d=2 and d=3, respectively. In d=1, where the walk is collapsed for all u and no swelling-collapse transition exists, we derive analytical expressions for the average number of visited sites and the mean time to visit S sites.Comment: 15 pages, 8 postscript figures, submitted to Phys. Rev.

Quenched Averages for self-avoiding walks and polygons on deterministic fractals

We study rooted self avoiding polygons and self avoiding walks on deterministic fractal lattices of finite ramification index. Different sites on such lattices are not equivalent, and the number of rooted open walks W_n(S), and rooted self-avoiding polygons P_n(S) of n steps depend on the root S. We use exact recursion equations on the fractal to determine the generating functions for P_n(S), and W_n(S) for an arbitrary point S on the lattice. These are used to compute the averages $, ,$ and $<log W_n(S)>$ over different positions of S. We find that the connectivity constant $\mu$, and the radius of gyration exponent $\nu$ are the same for the annealed and quenched averages. However, $~ n log \mu + (\alpha_q -2) log n$, and $~ n log \mu + (\gamma_q -1)log n$, where the exponents $\alpha_q$ and $\gamma_q$ take values different from the annealed case. These are expressed as the Lyapunov exponents of random product of finite-dimensional matrices. For the 3-simplex lattice, our numerical estimation gives $\alpha_q \simeq 0.72837 \pm 0.00001$; and $\gamma_q \simeq 1.37501 \pm 0.00003$, to be compared with the annealed values $\alpha_a = 0.73421$ and $\gamma_a = 1.37522$.Comment: 17 pages, 10 figures, submitted to Journal of Statistical Physic

Swelling-collapse transition of self-attracting walks

We study the structural properties of self-attracting walks in d dimensions using scaling arguments and Monte Carlo simulations. We find evidence for a transition analogous to the \Theta transition of polymers. Above a critical attractive interaction u_c, the walk collapses and the exponents \nu and k, characterising the scaling with time t of the mean square end-to-end distance ~ t^{2 \nu} and the average number of visited sites ~ t^k, are universal and given by \nu=1/(d+1) and k=d/(d+1). Below u_c, the walk swells and the exponents are as with no interaction, i.e. \nu=1/2 for all d, k=1/2 for d=1 and k=1 for d >= 2. At u_c, the exponents are found to be in a different universality class.Comment: 6 pages, 5 postscript figure

Modeling Vortex Swarming In Daphnia

Based on experimental observations in \textit{Daphnia}, we introduce an agent-based model for the motion of single and swarms of animals. Each agent is described by a stochastic equation that also considers the conditions for active biological motion. An environmental potential further reflects local conditions for \textit{Daphnia}, such as attraction to light sources. This model is sufficient to describe the observed cycling behavior of single \textit{Daphnia}. To simulate vortex swarming of many \textit{Daphnia}, i.e. the collective rotation of the swarm in one direction, we extend the model by considering avoidance of collisions. Two different ansatzes to model such a behavior are developed and compared. By means of computer simulations of a multi-agent system we show that local avoidance - as a special form of asymmetric repulsion between animals - leads to the emergence of a vortex swarm. The transition from uncorrelated rotation of single agents to the vortex swarming as a function of the swarm size is investigated. Eventually, some evidence of avoidance behavior in \textit{Daphnia} is provided by comparing experimental and simulation results for two animals.Comment: 24 pages including 11 multi-part figs. Major revisions compared to version 1, new results on transition from uncorrelated rotation to vortex swarming. Extended discussion. For related publications see http://www.sg.ethz.ch/people/scfrank/Publication

Polymers in long-range-correlated disorder

We study the scaling properties of polymers in a d-dimensional medium with quenched defects that have power law correlations ~r^{-a} for large separations r. This type of disorder is known to be relevant for magnetic phase transitions. We find strong evidence that this is true also for the polymer case. Applying the field-theoretical renormalization group approach we perform calculations both in a double expansion in epsilon=4-d and delta=4-a up to the 1-loop order and secondly in a fixed dimension (d=3) approach up to the 2-loop approximation for different fixed values of the correlation parameter, 2=<a=<3. In the latter case the numerical results need appropriate resummation. We find that the asymptotic behavior of self-avoiding walks in three dimensions and long-range-correlated disorder is governed by a set of separate exponents. In particular, we give estimates for the 'nu' and 'gamma' exponents as well as for the correction-to-scaling exponent 'omega'. The latter exponent is also calculated for the general m-vector model with m=1,2,3.Comment: 13 pages, 5 figure

Targeting lyn kinase in chorea-acanthocytosis: A translational treatment approach in a rare disease

Background: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChA

Weak quenched disorder and criticality: resummation of asymptotic(?) series

In these lectures, we discuss the influence of weak quenched disorder on the critical behavior in condensed matter and give a brief review of available experimental and theoretical results as well as results of MC simulations of these phenomena. We concentrate on three cases: (i) uncorrelated random-site disorder, (ii) long-range-correlated random-site disorder, and (iii) random anisotropy. Today, the standard analytical description of critical behavior is given by renormalization group results refined by resummation of the perturbation theory series. The convergence properties of the series are unknown for most disordered models. The main object of these lectures is to discuss the peculiarities of the application of resummation techniques to perturbation theory series of disordered models.Comment: Lectures given at the Second International Pamporovo Workshop on Cooperative Phenomena in Condensed Matter (28th July - 7th August 2001, Pamporovo, Bulgaria). 51 pages, 12 figures, 1 style files include