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Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury.

The long history of studying the propagation of an action potential has revealed that an electrical signal is accompanied by mechanical and thermal effects. All these effects together generate an ensemble of waves. The consistent models of such a complex phenomenon can be derived by using properly the fundamental physical principles. In this paper, attention is paid to the analysis of concepts of continuum physics that constitute a basis for deriving the mathematical models which describe the emergence and propagation of a wave ensemble in an axon. Such studies are interdisciplinary and based on biology, physics, mathematics, and chemistry. The governing equations for the action potential together with mechanical and thermal effects are derived starting from basics: Maxwell equations, conservation of momentum, Fourier's law, etc., but modified following experimental studies in electrophysiology. Several ideas from continuum physics like external forces and internal variables can also be used in deriving the corresponding models. Some mathematical concepts used in modeling are also briefly described. A brief overview of several mathematical models is presented that allows us to analyze the present ideas of modeling. Most mathematical models deal with the propagation of signals in a healthy axon. Further analysis is needed for better modeling the pathological situations and the explanation of the influence of the structural details like the myelin sheath or the cytoskeleton in the axoplasm. The future possible trends in improving the models are envisaged., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peets, Tamm and Engelbrecht.)

The propagation of an action potential in nerves is accompanied by mechanical and thermal effects. Several mathematical models explain the deformation of the unmyelinated axon wall (a mechanical wave). In this paper, the deformation of the myelinated axon wall is studied. The mathematical model is inspired by the mechanics of microstructured materials with multiple scales. The model involves a Boussinesq-type equation together with a modification that describes the process in the myelin sheath. The dispersion analysis of such a model explains the behaviour of group and phase velocities. In addition, it is shown how dissipative effects may influence the process. Numerical calculations demonstrate the changes in velocities and wave profiles in the myelinated axon wall., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The in silico simulations are widely used in contemporary systems biology including the analysis of nerve pulse propagation. As known from numerous experiments, the propagation of an action potential is accompanied by mechanical and thermal effects. This calls for an analysis at the interface of physics, physiology and mathematics. In this paper, the background of the model equations governing the effects in nerve fibres is analysed from a physical viewpoint and then discussed how to unite them into a system by using the coupling forces. The leading hypothesis associates the coupling to the changes of variables, not to their values or amplitudes. This hypothesis models actually the physiological mechanisms of energy transductions in a fibre. The general assumptions in modelling the processes and the properties of the coupled system of equations are described. The dimensionless mathematical model which couples the action potential with mechanical waves together with temperature effects is presented in "Appendix". This model generates an ensemble of waves including the electrical signal and mechanical and thermal effects.

The propagation of an action potential (AP) in a nerve fibre is accompanied by mechanical and thermal effects. In this paper, an attempt is made to build up a mathematical model which couples the AP with a possible pressure wave (PW) in the axoplasm and waves in the nerve fibre wall (longitudinal-LW and transverse-TW) made of a lipid bilayer (biomembrane). A system of differential equations includes the governing equations of single waves with coupling forces between them. The single equations are kept as simple as possible in order to carry out the proof of concept. An assumption based on earlier studies is made that the coupling forces depend on changes (the gradient, time derivative) of the voltage. In addition, it is assumed that the transverse displacement of the biomembrane can be calculated from the gradient of the LW in the biomembrane. The computational simulation is focused to determining the influence of possible coupling forces on the emergence of mechanical waves from the AP. As a result, an ensemble of waves (AP, PW, LW, TW) emerges. The further experiments should verify assumptions about coupling forces.

Experiments have demonstrated that signals in nerve fibers are composed by electrical and mechanical components. In this paper a coupled mathematical model is described which unites the governing equations for the action potential, the pressure wave in the axoplasm and the longitudinal and the transverse waves in the surrounding biomembrane into one system of equations. As a solution of this system, an ensemble of waves is generated. The main hypotheses of such a model are related to the nature of coupling forces between the single waves in the ensemble. These coupling forces are assumed to have bi-polar shapes leading to energetically stable solutions. The in silico modeling demonstrates the qualitative resemblance of computed wave profiles to experimental ones. The ideas of possible experimental validation of the model are briefly described., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The propagation of action potentials in nerve fibres is usually described by models based on the ionic hypotheses. However, this hypothesis does not provide explanation of other experimentally verified phenomena like the swelling of fibres and heat production during the nerve pulse propagation. Heimburg and Jackson (Proc Natl Acad Sci USA 102(28):9790-9795, 2005, Biophys Rev Lett 2:57-78, 2007) have proposed a model describing the swelling of fibres like a mechanical wave related to changes of longitudinal compressibility of the cylindrical membrane. In this paper, the possible dispersive effects in such microstructured cylinders are analysed from the viewpoint of solid mechanics, particularly using the information from the analysis of the well-known rod models. A more general governing equation is proposed which satisfies the conditions imposed by the physics of wave processes. The numerical simulations demonstrate the influence of nonlinearities, the role of various dispersion terms and the formation and propagation of solitary waves along the wall together with the corresponding transverse displacement. It is conjectured that due to the coupling effects between longitudinal and transverse displacements of a cylinder, the transverse displacement (i.e. swelling) is related to the derivative of the longitudinal displacement. In this way, the correspondence between theoretical and experimental (Tasaki in Physiol Chem Phys Med NMR 20:251-268, 1988) results can be described.

Background: The aim of this study was to assess and compare patients' access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differences between countries., Material/methods: This is a multi-country survey study, based on a combination of desk research and direct contact with national RA stakeholders. Data was collected using a pre-defined questionnaire. Affordability was measured using an affordability index, calculated comparing the index of health care expenditures to the price index, using Poland as an index of 1., Results: The percentage of patients on biologic treatment in 2009 was highest in Hungary (5% RA patients on biologic treatment), followed by Slovenia (4.5%), Slovakia (3.5%), Czech Republic (2.92%), Romania (2.2%), Estonia (1.8%), and Croatia, Serbia, Poland (below 1.5%). Infliximab, etanercept, adalimumab and rituximab were included in the reimbursement system in all countries, but abatacept and tocilizumab were included only in Slovakia. In Slovenia, public payer covered 75% of the price, and 25% is covered by supplementary health insurance; in Bulgaria public payer covered 50% of etanercept and adalimumab costs, and 75% of rituximab cost. In other countries, biologic drugs are reimbursed at 100%. Affordability index for biologic drugs was the lowest in Slovenia (0.4). In each country national guidelines define which patients are eligible for biologic treatment. Disease Activity Score (DAS28) of over 5.1 and failure of 2 or more disease-modifying anti-RA drugs, including methotrexate, are commonly used criteria., Conclusions: The most important factors limiting access to biologic anti-RA treatment in the CEE region are macroeconomic conditions and restrictive treatment guidelines.

Objectives: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status., Methods: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures., Results: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category)., Conclusions: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Introduction: Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA)., Methods: The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents., Results: Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies., Conclusions: In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.