Neurogenesis from Sox2 expressing cells in the adult cerebellar cortex

We identified a rare undifferentiated cell population that is intermingled with the Bergmann glia of the adult murine cerebellar cortex, expresses the stem cell markers Sox2 and Nestin, and lacks markers of glial or neuronal differentiation. Interestingly, such Sox2(+) S100(-) cells of the adult cerebellum expanded after adequate physiological stimuli in mice (exercise), and Sox2(+) precursors acquired positivity for the neuronal marker NeuN over time and integrated into cellular networks. In human patients, SOX2(+) S100(-) cells similarly increased in number after relevant pathological insults (infarcts), suggesting a similar expansion of cells that lack terminal glial differentiation

Increased incidence of syphilis in men who have sex with men and risk management strategies, Germany, 2015.

In Germany, the number of reported syphilis cases increased between 11% and 22% per year between 2010 and 2014. We analysed syphilis surveillance data and data of four behavioural surveys on men who have sex with men (MSM) in Germany (2003, 2007, 2010, 2013) to assess if this rise is ongoing and to find possible explanations for it. Syphilis notifications increased in 2015 by 19% to a total of 6,834. This was mainly due to increasing notifications in MSM of all age groups in larger German cities. Data from the behavioural surveys on MSM in Germany showed a simultaneous increase of selective condom use as HIV-status-bases risk management strategy and the number of syphilis cases. MSM diagnosed with HIV reported condomless anal intercourse with non-steady partners more frequent than MSM not diagnosed with HIV or untested for HIV, but the latter also reported higher frequencies of this behaviour in the more recent surveys. Transmission in HIV-positive MSM probably plays an important, but not exclusive role, for the syphilis dynamics in Germany. A risk adapted routine screening for sexually active MSM and potentially innovative approaches to increase early screening and treatment of syphilis such as internet counselling, home sampling, home testing and broadening venue-based (rapid) testing, should be critically evaluated to effectively reduce syphilis infections

Trajectories of depression in sepsis survivors: an observational cohort study

Background: Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU. Methods: Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling. Results: A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p = 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within 1 month after ICU discharge (p < 0.035). Conclusions: In the first year after discharge from ICU, sepsis survivors showed three different trajectories of depressive symptoms. Course and severity of depressive symptoms were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain and posttraumatic stress within 1 year after ICU may be considered

Sphaleron Effects Near the Critical Temperature

We discuss one-loop radiative corrections to the sphaleron-induced baryon number-violating transition rate near the electroweak phase transition in the standard model. We emphasize that in the case of a first-order transition a rearrangement of the loop expansion is required close to the transition temperature. The corresponding expansion parameter, the effective 3-dimensional gauge coupling approaches a finite $\lambda$ dependent value at the critical temperature. The $\lambda$ (Higgs mass) dependence of the 1-loop radiative corrections is discussed in the framework of the heat kernel method. Radiative corrections are small compared to the leading sphaleron contribution as long as the Higgs mass is small compared to the W mass. To 1-loop accuracy, there is no Higgs mass range compatible with experimental limits where washing-out of a B+L asymmetry could be avoided for the minimal standard model with one Higgs doublet.Comment: 17 pages, RevTeX, (4 figures in a separate uuencoded file), HD-THEP-93-23re

SBMLsqueezer: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks

<p>Abstract</p> <p>Background</p> <p>The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language). This effort is accompanied by the ongoing development of the human-readable diagrammatic representation SBGN (Systems Biology Graphical Notation). The graphical SBML editor CellDesigner allows direct translation of SBGN into SBML, and vice versa. For the assignment of kinetic rate laws, however, this process is not straightforward, as it often requires manual assembly and specific knowledge of kinetic equations.</p> <p>Results</p> <p>SBMLsqueezer facilitates exactly this modeling step via automated equation generation, overcoming the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or simple molecules) as well as the regulatory relations (activation, inhibition or other modulations) of the SBGN diagram. Such information allows distinctions between, for example, translation, phosphorylation or state transitions. The types of kinetics considered are numerous, for instance generalized mass-action, Hill, convenience and several Michaelis-Menten-based kinetics, each including activation and inhibition. These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory, signal transduction and mixed networks. Whenever multiple kinetics are applicable to one reaction, parameter settings allow for user-defined specifications. After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which can then be simulated in CellDesigner or with external ODE solvers. Furthermore, the equations can be exported to SBML, LaTeX or plain text format.</p> <p>Conclusion</p> <p>SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for each reaction, only applicable kinetic formulas are considered. This modeling scheme creates kinetics in accordance with the diagrammatic representation. In contrast most previously published tools have relied on the stoichiometry and generic modulators of a reaction, thus ignoring and potentially conflicting with the information expressed through the process diagram. Additional material and the source code can be found at the project homepage (URL found in the Availability and requirements section).</p

Healthcare Utilization and Costs in Sepsis Survivors in Germany-Secondary Analysis of a Prospective Cohort Study

Background: Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization. Methods: Secondary analysis was performed on data in 210 sepsis patients prospectively enrolled from nine intensive care study centers across Germany. Data was collected via structured surveys among their Primary care (Family-) physicians (PCPs) within the first month after discharge from ICU (baseline) and again at 6, 12 and 24 months after discharge, each relating to the period following the last survey. Costs were assessed by standardized cost unit rates from a health care system’s perspective. Changes in healthcare utilization and costs over time were calculated using the Wilcoxon rank-sum test. Results: Of the 210 patients enrolled, 146 (69.5%) patients completed the 24 months follow-up. In total, 109 patients were hospitalized within the first 6 months post-intensive care. Mean total direct costs per patient at 0–6 months were €17,531 (median: €6047), at 7–12 months €9029 (median: €3312), and at 13–24 months €18,703 (median: €12,828). The largest contributor to the total direct costs within the first 6 months was re-hospitalizations (€13,787 (median: €2965). After this first half year, we observed a significant decline in inpatient care costs for re-hospitalizations (p ≤ 0.001). PCPs were visited by more than 95% of patients over 24 months. Conclusions: Sepsis survivors have high health care utilization. Hospital readmissions are frequent and costly. Highest costs and hospitalizations were observed in more than half of patients within the first six months post-intensive care. Among all outpatient care providers, PCPs were consulted most frequently. Clinical impact: Sepsis survivors have a high healthcare utilization and related costs which persist after discharge from hospital. Within outpatient care, possible needs of sepsis survivors as physiotherapy or psychotherapy seem not to be met appropriately. Development of sepsis aftercare programs for early detection and treatment of complications should be prioritized

Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 µg/l, total prostate-specific antigen (PSA) 0.03 µg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys® 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel ‘hands-on-time' could be reduce