Subdiffusion and lateral diffusion coefficient of lipid atoms and molecules in phospholipid bilayers

We use a long, all-atom molecular dynamics (MD) simulation combined with theoretical modeling to investigate the dynamics of selected lipid atoms and lipid molecules in a hydrated diyristoyl-phosphatidylcholine (DMPC) lipid bilayer. From the analysis of a 0.1 $\mu$s MD trajectory we find that the time evolution of the mean square displacement, [\delta{r}(t)]^2, of lipid atoms and molecules exhibits three well separated dynamical regions: (i) ballistic, with [\delta{r}(t)]^2 ~ t^2 for t < 10 fs; (ii) subdiffusive, with [\delta{r}(t)]^2 ~ t^{\beta} with \beta<1, for 10 ps < t < 10 ns; and (iii) Fickian diffusion, with [\delta{r}(t)]^2 ~ t for t > 30 ns. We propose a memory function approach for calculating [\delta{r}(t)]^2 over the entire time range extending from the ballistic to the Fickian diffusion regimes. The results are in very good agreement with the ones from the MD simulations. We also examine the implications of the presence of the subdiffusive dynamics of lipids on the self-intermediate scattering function and the incoherent dynamics structure factor measured in neutron scattering experiments.Comment: Submitted to Phys. Rev.

Universal reduction of pressure between charged surfaces by long-wavelength surface charge modulation

We predict theoretically that long-wavelength surface charge modulations universally reduce the pressure between the charged surfaces with counterions compared with the case of uniformly charged surfaces with the same average surface charge density. The physical origin of this effect is the fact that surface charge modulations always lead to enhanced counterion localization near the surfaces, and hence, fewer charges at the midplane. We confirm the last prediction with Monte Carlo simulations.Comment: 8 pages 1 figure, Europhys. Lett., in pres

Counterion Condensation and Fluctuation-Induced Attraction

We consider an overall neutral system consisting of two similarly charged plates and their oppositely charged counterions and analyze the electrostatic interaction between the two surfaces beyond the mean-field Poisson-Boltzmann approximation. Our physical picture is based on the fluctuation-driven counterion condensation model, in which a fraction of the counterions is allowed to ``condense'' onto the charged plates. In addition, an expression for the pressure is derived, which includes fluctuation contributions of the whole system. We find that for sufficiently high surface charges, the distance at which the attraction, arising from charge fluctuations, starts to dominate can be large compared to the Gouy-Chapmann length. We also demonstrate that depending on the valency, the system may exhibit a novel first-order binding transition at short distances.Comment: 15 pages, 8 figures, to appear in PR

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort

ObjectiveLong-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab.MethodsThe study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records.ResultsThe study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with >= 1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P ConclusionsUstekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.</div

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations