Innervation of Entorhinal Principal Cells by Neurons of the Nucleus Reuniens Thalami. Anterograde PHA-L Tracing Combined with Retrograde Fluorescent Tracing and Intracellular Injection with Lucifer Yellow in the Rat

The innervation of dendrites of identified entorhinal principal cells by fibres originating in the nucleus reuniens thalami was studied in the rat. The lectin Phaseolus vulgaris-leucoagglutinin (PHA-L, anterograde tracer) was injected into the nucleus reuniens and the fluorescent dye Fast Blue (retrograde tracer) into the hippocampus. After survival, perfusion-fixation and the preparation of brain slices, entorhinal neurons retrogradely labelled with Fast Blue were intracellularly injected with the dye Lucifer yellow to introduce a specific marker into their dendrites. The transported PHA-L and the injected Lucifer yellow were visualized through dual peroxidase immunohistochemistry. Varicosities on PHA-L labelled reuniens fibres abut ascending and descending Lucifer yellow-filled secondary dendrites of multipolar and pyramidal principal entorhinal neurons that possess either spiny or sparsely spiny dendrites, but they do not appose the perikarya of these cells. In the electron microscope, PHA-L labelled boutons in the entorhinal cortex were observed forming asymmetrical synaptic contacts with dendritic spines (50%) or shafts (50%). The results indicate that direct thalamic input occurs on dendrites of neurons in the entorhinal cortex which project to the hippocampus.     

Anti‐erosive effects of fluoride and phytosphingosine: an in vitro study

A selection of commercially available products containing stannous fluoride (SnF₂)/sodium fluoride (NaF), SnF₂/amorphous calcium phosphate (ACP), SnF₂/NaF/ACP, tin (Sn)/fluorine (F)/chitosan were compared with phytosphingosine (PHS) with respect to their anti‐erosive properties in vitro. One‐hundred and twenty bovine enamel specimens were immersed in the respective product slurries for 2 min, twice daily. The formulations were diluted with either remineralization solution or artificial saliva. After each treatment, an erosive challenge was performed for 10 min, twice daily, using citric acid, pH 3.4. The specimens were stored in remineralization solution or artificial saliva until the next treatment‐erosion challenge. After 10 d, tissue loss was determined using profilometry. Enamel softening was determined through surface microhardness measurements. Tissue‐loss values (measured in μm and expressed as mean ± SD) for PHS, SnF₂/NaF, SnF₂/ACP, SnF₂/ACP/NaF, and Sn/F/chitosan treatment groups and for the negative‐control group, were, respectively, 35.6 ± 2.8, 15.8 ± 1.8, 22.1 ± 2.0, 22.9 ± 1.8, 16.2 ± 1.2, and 51.2 ± 4.4 in the presence of remineralization solution and 31.7 ± 3.3, 15.6 ± 2.9, 16.5 ± 2.7, 16.8 ± 2.1, 13.1 ± 3.0, and 50.7 ± 2.8 in the presence of artificial saliva. There were no significant differences in surface microhardness measurements between the treatment groups. In conclusion, PHS resulted in a significant reduction of tissue loss compared with the negative control, but in comparison, the toothpastes containing Sn²⁺ and F^? ions were significantly more effective compared with PHS.     

von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII

It has been proposed that von Willebrand factor might affect factor VIII immunogenicity by reducing factor VIII uptake by antigen presenting cells. Here we investigate the interaction of recombinant von Willebrand factor with immature monocyte-derived dendritic cells using flow cytometry and confocal microscopy. Surprisingly, von Willebrand factor was not internalized by immature dendritic cells, but remained bound to the cell surface. As von Willebrand factor reduces the uptake of factor VIII, we investigated the repertoire of factor VIII presented peptides when in complex with von Willebrand factor. Interestingly, factor VIII-derived peptides were still abundantly presented on major histocompatibility complex class II molecules, even though a reduction of factor VIII uptake by immature dendritic cells was observed. Inspection of peptide profiles from 5 different donors showed that different core factor VIII peptide sequences were presented upon incubation with factor VIII/von Willebrand factor complex when compared to factor VIII alone. No von Willebrand factor peptides were detected when immature dendritic cells were pulsed with different concentrations of von Willebrand factor, confirming lack of von Willebrand factor endocytosis. Several von Willebrand factor derived peptides were recovered when cells were pulsed with von Willebrand factor/factor VIII complex, suggesting that factor VIII promotes endocytosis of small amounts of von Willebrand factor by immature dendritic cells. Taken together, our results establish that von Willebrand factor is poorly internalized by immature dendritic cells. We also show that von Willebrand factor modulates the internalization and presentation of factor VIII-derived peptides on major histocompatibility complex class II.     

Social Role Participation and Satisfaction With Life: A Study Among Patients With Ankylosing Spondylitis and Population Controls

Objective

Participation in society of persons with chronic diseases receives increasing attention. However, little is known about which components of participation are most relevant to life satisfaction. This study examines the association between several aspects of social role participation and satisfaction with life (SWL) in patients with ankylosing spondylitis (AS) compared to population controls.

Methods

In a cross‐sectional study, participants completed the Social Role Participation Questionnaire (SRPQ) and SWL scale. The SRPQ assesses several dimensions of participation (importance, satisfaction with performance, and satisfaction with time and physical difficulty) in 11 roles representing 3 domains (interpersonal relations, leisure, and work). For individuals with AS and controls, the association between role domains and SWL was examined using linear regression for each participation dimension separately, in the total and the employed population, adjusting for age, sex, education, and income.

Results

A total of 246 AS patients (mean ± SD age 51 ± 12 years, 62% males, mean ± SD disease duration 17 ± 12 years) and 510 controls (mean ± SD age 42 ± 15 years, 70% males) were included. AS patients were more frequently (extremely) dissatisfied with life (17.9% versus 8.6%; P < 0.05). In the total and the employed population, less physical difficulty and higher satisfaction with interpersonal relations and leisure were associated with higher SWL, and this was somewhat stronger in patients than in controls (P < 0.1). In employed controls, but not in employed patients, satisfaction with work was independently associated with SWL.

Conclusion

These findings highlight the importance of supporting persons with AS in ameliorating social role participation, particularly in areas like close relationships and leisure activities, which are typically ignored when treating AS.

     

Constrained spherical deconvolution of nonspherically sampled diffusion MRI data

Constrained spherical deconvolution (CSD) of diffusion‐weighted MRI (DW‐MRI) is a popular analysis method that extracts the full white matter (WM) fiber orientation density function (fODF) in the living human brain, noninvasively. It assumes that the DW‐MRI signal on the sphere can be represented as the spherical convolution of a single‐fiber response function (RF) and the fODF, and recovers the fODF through the inverse operation. CSD approaches typically require that the DW‐MRI data is sampled shell‐wise, and estimate the RF in a purely spherical manner using spherical basis functions, such as spherical harmonics (SH), disregarding any radial dependencies. This precludes analysis of data acquired with nonspherical sampling schemes, for example, Cartesian sampling. Additionally, nonspherical sampling can also arise due to technical issues, for example, gradient nonlinearities, resulting in a spatially dependent bias of the apparent tissue densities and connectivity information. Here, we adopt a compact model for the RFs that also describes their radial dependency. We demonstrate that the proposed model can accurately predict the tissue response for a wide range of b‐values. On shell‐wise data, our approach provides fODFs and tissue densities indistinguishable from those estimated using SH. On Cartesian data, fODF estimates and apparent tissue densities are on par with those obtained from shell‐wise data, significantly broadening the range of data sets that can be analyzed using CSD. In addition, gradient nonlinearities can be accounted for using the proposed model, resulting in much more accurate apparent tissue densities and connectivity metrics.     

Improving oral cavity cancer diagnosis and treatment with fluorescence molecular imaging

Early diagnosis and radical surgical excision of oral squamous cell carcinomas are essential for achieving optimal treatment outcomes. To date, diagnostic tools that rely on anatomical anomalies provide limited information and resolution in clinical practice. As a result, oral cancer is often detected in an advanced stage. Also, no reliable real‐time intraoperative tools are readily available for the evaluation of surgical resection margins. Fluorescence imaging visualises biological processes that occur in early carcinogenesis and could, therefore, enable detection of small tumours in early stages. Furthermore, due to the high sensitivity and spatial resolution, fluorescence imaging could assist in resection margin assessment during surgery. In this review, we discuss several techniques that employ fluorescence for early diagnosis and surgical guidance in oral squamous cell carcinoma and present future perspectives on the potential of fluorescence imaging in oral cancer in the near future.