Orexin A in cortical cultures: expression and effect on synaptogenesis during development

Orexin-A (OXA) is an excitatory hypothalamic neurotransmitter and ligand for Orexin Receptor-1 (OR1), isolated from a small group of hypothalamic neurons. OXA orchestrates different brain functions, and at the cognitive level some of the effects of insufficiency of OXA are well-known, for example in Parkinson’s disease. It is widely assumed that deteriorated cognitive processes are related to impaired network connectivity. However, little is known about the effects of OXA in network connectivity and synaptogenesis. Therefore, to obtain insight into this problem we designed experiments with two groups of networks of dissociated cortical neurons: one group incubated in a plain medium and another chronically treated with OXA. After one, two, three or four weeks in vitro we applied immunocytochemistry for detection of OXA, OR1 and synaptic marker synaptophysin. Shortly after plating, 91±8% of the neurons cultivated in a plain medium expressed OXA-immunoreactivity, which does normally not occur in vivo indicating that neurons may change their phenotype under non-natural culture conditions to develop synaptically coupled networks. The fraction of orexinergic neurons decreased to 33±21% after 4 weeks in vitro. OXA expression was highest in the first week of network formation, the period of maximum synaptogenesis, and then decreased and stabilized in the weeks thereafter. Our hypothesis that OXA plays a role in the network development as a synaptogenic factor was supported by higher levels, earlier onset, and sustained increase of synaptophysin-expression in experiments with chronic OXA application to the culture medium

Influence of the sample geometry on the vortex matter in superconducting microstructures

The dependence of the vortex penetration and expulsion on the geometry of mesoscopic superconductors is reported. Hall magnetometry measurements were performed on a superconducting Al square and triangle. The stability of the vortex patterns imposed by the sample geometry is discussed. The field-temperature $H-T$ diagram has been reconstructed showing the transitions between states with different vorticity. We have found that the vortex penetration is only weakly affected by the vortex configuration inside the sample while the expulsion is strongly controlled by the stability of the vortex patterns. A qualitative explanation for this observation is given.Comment: 6 pages, 4 figures, accepted for publication in Phys. Rev.

Critical Kauffman networks under deterministic asynchronous update

We investigate the influence of a deterministic but non-synchronous update on Random Boolean Networks, with a focus on critical networks. Knowing that ``relevant components'' determine the number and length of attractors, we focus on such relevant components and calculate how the length and number of attractors on these components are modified by delays at one or more nodes. The main findings are that attractors decrease in number when there are more delays, and that periods may become very long when delays are not integer multiples of the basic update step.Comment: 8 pages, 3 figures, submitted to a journa

Intrinsic optical bistability of thin films of linear molecular aggregates: The one-exciton approximation

We perform a theoretical study of the nonlinear optical response of an ultrathin film consisting of oriented linear aggregates. A single aggregate is described by a Frenkel exciton Hamiltonian with uncorrelated on-site disorder. The exciton wave functions and energies are found exactly by numerically diagonalizing the Hamiltonian. The principal restriction we impose is that only the optical transitions between the ground state and optically dominant states of the one-exciton manifold are considered, whereas transitions to other states, including those of higher exciton manifolds, are neglected. The optical dynamics of the system is treated within the framework of truncated optical Maxwell-Bloch equations in which the electric polarization is calculated by using a joint distribution of the transition frequency and the transition dipole moment of the optically dominant states. This function contains all the statistical information about these two quantities that govern the optical response, and is obtained numerically by sampling many disorder realizations. We derive a steady-state equation that establishes a relationship between the output and input intensities of the electric field and show that within a certain range of the parameter space this equation exhibits a three-valued solution for the output field. A time-domain analysis is employed to investigate the stability of different branches of the three-valued solutions and to get insight into switching times. We discuss the possibility to experimentally verify the bistable behavior.Comment: 13 two-column pages, 8 figures, accepted to the Journal of Chemical Physic

Differential effect sizes of growth hormone replacement on quality of life, well-being and health status in growth hormone deficient patients: a meta-analysis

BACKGROUND: Patients with growth hormone deficiency (GHD) frequently report to suffer from an impaired Quality of Life (QoL) and growth hormone (GH) substitution is found to improve this. However, the same test may be used for measuring QoL, well-being or health status in different studies. QoL has been defined as the subjective appraisal of one's current life based primarily on psychological function. The most important in the appraisal of well-being is mental function and concerning health status patients evaluate physical function as most important. To differentiate the effects of GH replacement on psychological variables in patients with GHD we carried out a number of meta-analyses, classifying questionnaires into instruments measuring QoL, psychological well-being and health status. METHODS: We searched the electronic databases PUBMED and PiCarta from 1985 to 2004. Studies were included that evaluated the effect of GH on patient-reported outcomes in adults with GHD (aged 18 years and above). According to generally accepted definitions we classified the questionnaires as instruments measuring QoL, well-being and health status. By means of meta-analyses the average effect size (d) for QoL, well-being and health status was calculated. RESULTS AND DISCUSSION: Based on open studies GH replacement is found to improve QoL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47) and health status with a small effect size (d = 0.26). As the effect size of well-being is most pronounced the generally reported effects of GH replacement on QoL may be overestimated and actually reflect the effect on well-being. CONCLUSION: To get more insight in the specific psychological effects of GH treatment it is recommended that instruments selected for these studies should be more consistently classified as instruments measuring QoL, well-being or health status

A comparison of the spatial dependence of body mass index among adults and children in a Swiss general population.

BACKGROUND: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether BMI clusters among children and how age-specific BMI clusters are related remains unknown. We aimed to identify and compare the spatial dependence of BMI in adults and children in a Swiss general population, taking into account the area's income level. METHODS: Geo-referenced data from the Bus Santé study (adults, n=6663) and Geneva School Health Service (children, n=3601) were used. We implemented global (Moran's I) and local (local indicators of spatial association (LISA)) indices of spatial autocorrelation to investigate the spatial dependence of BMI in adults (35-74 years) and children (6-7 years). Weight and height were measured using standardized procedures. Five spatial autocorrelation classes (LISA clusters) were defined including the high-high BMI class (high BMI participant's BMI value correlated with high BMI-neighbors' mean BMI values). The spatial distributions of clusters were compared between adults and children with and without adjustment for area's income level. RESULTS: In both adults and children, BMI was clearly not distributed at random across the State of Geneva. Both adults' and children's BMIs were associated with the mean BMI of their neighborhood. We found that the clusters of higher BMI in adults and children are located in close, yet different, areas of the state. Significant clusters of high versus low BMIs were clearly identified in both adults and children. Area's income level was associated with children's BMI clusters. CONCLUSIONS: BMI clusters show a specific spatial dependence in adults and children from the general population. Using a fine-scale spatial analytic approach, we identified life course-specific clusters that could guide tailored interventions

Low health literacy is associated with worse postoperative outcomes following hepato-pancreato-biliary cancer surgery

Background: Low health literacy (HL) can lead to worse health outcomes for patients with chronic diseases and could also lead to worse postoperative outcomes. This retrospective cohort study investigates the association between HL and postoperative textbook outcome (TO) after hepato-pancreato-biliary (HPB) cancer surgery. Methods: Patients that consented and underwent surgery for a premalignant andmalignant HPB tumor were included. Preoperatively, HL was measured by the brief health literacy screen (BHLS). Patients were categorized as having low or adequate HL. Primary outcome was TO (length of hospital stay (LOS) ≤ 75th percentile; and no severe complication; and no readmission and mortality within 30 days after discharge). Secondary outcomes were LOS and emergency department (ED) visits within 30 days after discharge. Results: In total, 137 patients were included, of whom thirty-six patients had low HL. In patients with low HL (vs. adequate HL), rate of TO was lower (55.6% vs. 72.3%; p = 0.095), LOS was significantly longer (13.5 vs. 9 days; p = 0.007) and there was only a slight difference in ED visits (14.3% vs. 11.0%; p = 0.560). Patients with low HL had a significant lower chance of achieving TO (OR 0.400, 95%-CI 0.169–0.948; p = 0.037). Conclusion: Low HL leads to worse postoperative outcome after HPB cancer surgery. Better preoperative education and guidance of patients with low HL could lead to better postoperative outcomes. Therefore, HL could be the next modifiable risk factor before major surgery

A Lattice Boltzmann Model for Squirmers

The squirmer is a simple yet instructive model for microswimmers, which employs an effective slip velocity on the surface of a spherical swimmer to describe its self-propulsion. We solve the hydrodynamic flow problem with the lattice Boltzmann (LB) method, which is well-suited for time-dependent problems involving complex boundary conditions. Incorporating the squirmer into LB is relatively straight-forward, but requires an unexpectedly fine grid resolution to capture the physical flow fields and behaviors accurately. We demonstrate this using four basic hydrodynamic tests: Two for the far-field flow---accuracy of the hydrodynamic moments and squirmer-squirmer interactions---and two that require the near field to be accurately resolved---a squirmer confined to a tube and one scattering off a spherical obstacle---which LB is capable of doing down to the grid resolution. We find good agreement with (numerical) results obtained using other hydrodynamic solvers in the same geometries and identify a minimum required resolution to achieve this reproduction. We discuss our algorithm in the context of other hydrodynamic solvers and present an outlook on its application to multi-squirmer problems.Comment: 9 pages, 7 figure

The costs of complications and unplanned readmissions after pancreatoduodenectomy for pancreatic and periampullary tumors:Results from a single academic center

SIMPLE SUMMARY: Complications lead to unplanned readmissions (UR) and are reported to be associated with a two- to threefold increase in hospital admission costs. Since healthcare costs are increasing worldwide, cost containment is the major challenge for future healthcare. In the literature, there are only a few studies that analysed hospital costs after pancreatoduodenectomy (PD). In this study, we aimed to create an understanding of the costs of complications and UR in patients who underwent a PD. ABSTRACT: Background/Objectives: Complications after pancreatoduodenectomy (PD) lead to unplanned readmissions (UR), with a two- to threefold increase in admission costs. In this study, we aimed to create an understanding of the costs of complications and UR in this patient group. Furthermore, we aimed to generate a detailed cost overview that can be used to build a theoretical model to calculate the cost efficacy for prehabilitation. Methods: A retrospective cohort analysis was performed using the Dutch Pancreatic Cancer Audit (DPCA) database of patients who underwent a PD at our institute between 2013 and 2017. The total costs of the index hospital admission and UR related to the PD were collected. Results: Of the 160 patients; 35 patients (22%) had an uncomplicated course; 87 patients (54%) had minor complications, and 38 patients (24%) had severe complications. Median costs for an uncomplicated course were EUR 25.682, and for a complicated course, EUR 32.958 (p = 0.001). The median costs for minor complications were EUR 30.316, and for major complications, EUR 42.664 (p = 0.001). Costs were related to the Comprehensive Complication Index (CCI). The median costs of patients with one or more UR were EUR 41.199. Conclusions: Complications after PD led to a EUR 4.634–EUR 16.982 (18–66%) increase in hospital costs. A UR led to a cost increase of EUR 12.567 (44%). Since hospital costs are directly related to the CCI, reduction in complications will lead to cost-effectiveness

Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study Transcription Factor AP-2B associated with obesity

This is a post-peer-review, pre-copyedit version of an article published in International Journal of Obesity.The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age