Validation of diffuse correlation spectroscopy against 15O-water PET for regional cerebral blood flow measurement in neonatal piglets

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm²/s. We have validated DCS against positron emission tomography using ¹⁵O-labeled water (¹⁵O-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring ¹⁵O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94, p < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)×10⁹× (ml/100g/min)/(cm²/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.     

Nano-topography: Quicksand for cell cycle progression?

The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells.     

Poly(4‐vinyl imidazole): A pH‐Responsive Trigger for Hierarchical Self‐Assembly of Multicompartment Micelles Based upon Triblock Terpolymers

Poly(vinyl pyridine) has widely been used as a pH‐responsive polymer to trigger changes in self‐assembly of block copolymer micelles. However, the polymer is known to display toxic features, which limits its ultimate applicability for biological applications. Here, poly(4‐vinyl imidazole) (P4VIm), a much more biocompatible polymer, is used as a pH‐responsive block to modulate the self‐assembly of ABC triblock terpolymers. In this article, the synthesis of the poly(1‐acryloyl fructopyranose)‐block‐ poly(n‐butyl acrylate)‐block‐ poly(4‐vinyl imidazole) (PFruA₅₂‐b‐PBuA₃₀₀‐b‐P4VIm₂₅₀) triblock terpolymers is first discussed by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Subsequently, the structure formation of the triblock terpolymer is elucidated by step‐wise solvent exchange. The polymer readily dissolves in methanol, but self‐assembles into micelles with PBuA cores and mixed shell in methanol–water mixtures. Solvent exchange against buffer solutions of pH 6–6.5 leads to collapse of P4VIm due to deprotonation and induces self‐assembly into caterpillar‐like non‐spherical nanoparticles, most likely via the formation of intermediate Janus particles. The rearrangement into larger hierarchical structure, as seen by small angle X‐ray scattering (SAXS), is found to process within several hours. The article is concluded by demonstrating lower cytotoxicity values for the present polymer in comparison to a structurally analogous triblock terpolymer based on poly(vinyl pyridine).     

Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.     

Medizinstudierendenauswahl in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Das Bundesverfassungsgericht überprüft aktuell, ob das Vergabeverfahren der Medizinstudienplätze mit dem...     

Longitudinal dental arch changes in the mixed dentition

The purpose of this study was to investigate dental arch changes that occurred during the mixed dentition in 30 normal occlusion children. Two analyses were done. The first one was at the age of early mixed dentition and the second at the age of late mixed dentition. Most width variables were greater in the males, and depth variables greater in the female subjects. A directionally larger left side of the maxilla and right side of the mandible were observed. Our findings indicate that most arch width dimensions are established in the early mixed dentition. We conclude that the period between the early and late mixed dentition is suitable for environmental factors to disrupt the ideal symmetrical developmental pattern because more growth and developmental changes occur after a relatively stabile period of deciduous dentition.     

Evaluation of the debonding strength of orthodontic brackets using three different bonding systems

The aim of this work was to investigate the stability of the bracket-adhesive-enamel interface, as a function of adhesive material and of debonding procedure, in order to assess which debonding technique is the least detrimental to the enamel. Ninety lower adult bovine incisors were selected and metallic orthodontic brackets were bonded using three adhesive systems: Concise, Transbond, and Fuji Ortho. Three different debonding procedures were used based on tensile, shear, and torsional stresses. One-way analysis of variance statistical analysis was employed to compare mechanical properties, while the adhesive remnant index was used to evaluate fracture properties. Each adhesive material used showed a statistical difference in tensile failure. The difference between shear and torsion failure loads was statistically significant only for the Fuji GC sample (P < 0.01). The shear test was the most damaging to the enamel surface. Transbond luting resulted in greater adhesion than the Concise or Fuji Ortho systems. Fuji Ortho was more prone to accidental debonding, while Transbond tended to cause enamel lesions, since high loads were required to debond the bracket. Of the three modes examined, torsional debonding stress resulted in the least enamel damage.     

Cognitive correlates of under-ambiguity and under-risk decision making in high-functioning patients with relapsing remitting multiple sclerosis

Introduction: Impairment of decision making in relapsing remitting multiple sclerosis is still controversial, and its neuropsychological correlates have never been explored thoroughly, especially in patients with minimal physical and cognitive deficits. In the present study we investigated the cognitive underpinnings of decision making under ambiguous and explicit conditions in patients with very mild relapsing remitting multiple sclerosis, using a dice and a card gambling game. Method: The study sample included 60 patients and 35 healthy subjects. In the Game of Dice Task, winning and losing probabilities are obvious to the subject, while in the Iowa Gambling Task they are initially ambiguous and have to be gradually identified. Performance at the two tasks was correlated with scores obtained at tests investigating cognitive processing speed, memory, language and executive functions. Results: Patients’ performance did not differ from that of controls at either gambling task. There was only a trend for them to be significantly slower than healthy subjects in progressively recognizing advantageous decks in the Iowa Gambling Task. While the Game of Dice was unrelated to neuropsychological tests, predictors of performance at the Iowa task were Letter Fluency and the Symbol Digit Modalities Test for the initial, under-ambiguity, trials and the Wisconsin Card Sorting Test for the last, purely under-risk, trials. Conclusions: Our results suggest that high-functioning patients with relapsing remitting multiple sclerosis are substantially capable of making advantageous decisions, even if they may be slower in processing options and shifting strategy when selection criteria are not explicit.