Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression

Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT1A) receptors, both in receptor binding and in mRNA levels, in the aggressive line. The aim of this experiment was to study whether similar differences in 5-HT1A receptors exist in individuals from a random-bred rat strain, varying in aggressiveness. In addition, because little is known about the functional consequences of these receptor differences, a response mediated via postsynaptic 5-HT1A receptors (i.e., hypothermia) was studied both in the selection lines of mice and in the randomly bred rats. The difference in receptor binding, as demonstrated in mice previously, could not be shown in rats. However, both in rats and mice, the hypothermic response to the 5-HT1A agonist alnespirone was larger in aggressive individuals. So, in the rat strain as well as in the mouse lines, there is, to a greater or lesser extent, an enhanced sensitivity of postsynaptic 5-HT1A receptors in aggressive individuals. This could be a compensatory up-regulation induced by a lower basal 5-HT neurotransmission, which is in agreement with the serotonin deficiency hypothesis of aggression.

Stability and Asymmetry of Tide-Influenced River Bifurcations

Bifurcations are important geomorphological features in tide-influenced deltas. At bifurcations, river flow and tides distribute sediment over the channel network and determine the morphodynamic evolution of the entire delta. Using a one-dimensional numerical model, we study the effects of tides on the morphological evolution of bifurcations from river-dominated to tide-dominated systems. In accordance with previous studies, bifurcations with small tidal influence, in which the flood flow hardly drives morphological change, have a larger range of Shields stress and width-to-depth ratio conditions for which symmetric bifurcations are stable to depth perturbations, compared to their river-dominated counterparts. We extended the existing studies to tide-dominated conditions. When bifurcations become increasingly tide-dominated, the range of conditions under which balance discharge partition (symmetric morphology) can exist, shrinks. Under these conditions, the bed can also change during the flood phase and growth of the bed asymmetry is larger than the decay during ebb. However, the bed asymmetry in equilibrium becomes less pronounced with increasing tidal dominance. We conclude that tides reduce the tendency of closure and abandonment of one of the downstream channels compared to river-dominated bifurcations, either by inhibiting the instability or by reducing asymmetry

Dissociative recombination and electron-impact de-excitation in CH photon emission under ITER divertor-relevant plasma conditions

For understanding carbon erosion and redeposition in nuclear fusion devices, it is important to understand the transport and chemical break-up of hydrocarbon molecules in edge plasmas, often diagnosed by emission of the CH A^2\Delta - X^2\Pi Ger\"o band around 430 nm. The CH A-level can be excited either by electron-impact or by dissociative recombination (D.R.) of hydrocarbon ions. These processes were included in the 3D Monte Carlo impurity transport code ERO. A series of methane injection experiments was performed in the high-density, low-temperature linear plasma generator Pilot-PSI, and simulated emission intensity profiles were benchmarked against these experiments. It was confirmed that excitation by D.R. dominates at T_e < 1.5 eV. The results indicate that the fraction of D.R. events that lead to a CH radical in the A-level and consequent photon emission is at least 10%. Additionally, quenching of the excited CH radicals by electron impact de-excitation was included in the modeling. This quenching is shown to be significant: depending on the electron density, it reduces the effective CH emission by a factor of 1.4 at n_e=1.3*10^20 m^-3, to 2.8 at n_e=9.3*10^20 m^-3. Its inclusion significantly improved agreement between experiment and modeling

Germinal centres in diagnostic labial gland biopsies of patients with primary Sjogren's syndrome are not predictive for parotid MALT lymphoma development

Objective Patients with primary Sjogren's syndrome (pSS) have an increased risk of developing non-Hodgkin's lymphoma (NHL), particularly parotid gland mucosaassociated lymphoid tissue (MALT) lymphomas. Presence of germinal centres (GCs) in labial gland biopsies has been suggested as predictive factor for NHL. We assessed whether presence of GCs is increased in labial gland biopsies from patients with pSS who developed parotid MALT lymphoma, the dominant NHL-subtype in pSS, compared with patients with pSS who did not develop lymphoma. Methods Eleven labial gland biopsies from patients with pSS that were taken prior to parotid MALT lymphoma development were compared with biopsies of 22 matched pSS controls (1: 2) who did not develop lymphoma. Biopsies were evaluated for GCs (H&E and Bcl6). Results Labial gland biopsies of pSS MALT lymphoma patients, revealed GCs in 2/11 (18%) H&E sections and 3/11 (27%) Bcl6 stained sections. In controls, GCs were present in 4/22 (18%) of H&E sections and 5/22 (23%) of Bcl6 stained sections. Conclusion P resence of GCs in labial gland biopsies does not differ between patients with pSS that develop parotid MALT lymphoma and patients with pSS who do not develop lymphoma. The presence of GCs in labial gland biopsies is therefore not a predictive factor for pSS-associated parotid MALT lymphomas

Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy

ObjectivesAmbiguous results have been reported on the predictive value of the Ki-67 proliferation index (Ki-67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early-stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut-off values are attributing factors. Our aim was to elucidate the predictive value of the Ki-67 PI for LC and disease-specific survival (DSS) using a well-defined series of T1-T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA). MethodsA consecutive and well-defined cohort of 208 patients with T1-T2 LSCC treated with primary RT was selected. The Ki-67 PI was determined using DIA. Mann-Whitney U-tests, logistic and Cox regression analyses were performed to assess associations between Ki-67 PI, clinicopathological variables, LC and DSS. ResultsIn multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06-4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20-6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16-8.64; P = .03). Ki-67 PI was not associated with LC (HR 1.59; 95% CI 0.89-2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57-1.66; P = .97). In addition, continuous Ki-67 PI was not associated with LC (HR 2.03; 95% CI 0.37-11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05-8.28; P = .72). ConclusionThe Ki-67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment-related decision-making for LSCC

Imaging in Primary Sjogren's Syndrome

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction and lymphocytic infiltration of the salivary and lacrimal glands. Besides the characteristic sicca complaints, pSS patients can present a spectrum of signs and symptoms, which challenges the diagnostic process. Various imaging techniques can be used to assist in the diagnostic work-up and follow-up of pSS patients. Developments in imaging techniques provide new opportunities and perspectives. In this descriptive review, we discuss imaging techniques that are used in pSS with a focus on the salivary glands. The emphasis is on the contribution of these techniques to the diagnosis of pSS, their potential in assessing disease activity and disease progression in pSS, and their contribution to diagnosing and staging of pSS-associated lymphomas. Imaging findings of the salivary glands will be linked to histopathological changes in the salivary glands of pSS patients

Biological tumor markers associated with local control after primary radiotherapy in laryngeal cancer:A systematic review

Background The choice of treatment in laryngeal cancer is mainly based on tumor stage, post-treatment morbidity and quality of life. Biological tumor markers might also be of potential clinical relevance. Objective of the review The aim was to systematically review the value of published biological tumor markers to predict local control in laryngeal cancer patients treated with definitive radiotherapy. Type of Review Systematic review. Search strategy PubMed, Embase, Cochrane Library. Evaluation Method A literature search was performed using multiple terms for laryngeal cancer, radiotherapy, biological markers, detection methods and local control or survival. Studies regarding the relation between biological tumor markers and local control or survival in laryngeal cancer patients primarily treated with radiotherapy were included. Markers were clustered on biological function. Quality of all studies was assessed. Study selection, data extraction and quality assessment was performed by two independent reviewers. Results A total of 52 studies out of 618 manuscripts, concerning 118 markers, were included. EGFR and P53 showed consistent evidence for not being predictive of local control after primary radiotherapy, whereas proliferation markers (ie high Ki-67 expression) showed some, but no consistent, evidence for being predictive of better local control. Other clusters of markers (markers involved in angiogenesis and hypoxia, apoptosis markers, cell cycle, COX-2 and DNA characteristics) showed no consistent evidence towards being predictors of local control after primary radiotherapy. Conclusions Cell proliferation could be of potential interest for predicting local control after primary radiotherapy in laryngeal cancer patients, whereas EGFR and p53 are not predictive in contrast to some previous analyses. Large diversity in research methods is found between studies, which results in contradictory outcomes. Future studies need to be more standardised and well described according to the REMARK criteria in order to have better insight into which biomarkers can be used as predictors of local control after primary radiotherapy

Bcl6 for identification of germinal centres in salivary gland biopsies in primary Sjogren's syndrome

Histopathological assessment of salivary gland biopsies is an important element of the diagnostic work-up of Sjögren's syndrome (SS) (Fox, 2017; Kroese et al., 2018). Microscopic evaluation of salivary glands of primary SS (pSS) patients reveals characteristic periductal lymphocytic infiltrates (foci), which mainly consist of T- and B-lymphocytes, as well as a variety of non-lymphoid cells, including dendritic cells and macrophages. Over time, these infiltrates may become organised to ectopic lymphoid tissue with T/B cell compartmentalisation, presence of CD21+ follicular dendritic cell (FDC) networks and high endothelial venules (Fisher et al., 2017; Kroese et al., 2014; Kroese et al., 2018; Salomonsson et al., 2003)

Progenitor cell niche senescence reflects pathology of the parotid salivary gland in primary Sjogren's syndrome

Objective. Salivary gland (SG) progenitor cells (SGPCs) maintain SG homeostasis. We have previously shown that in primary Sjogren's syndrome (pSS), SGPCs are likely to be senescent, and may underpin SG dysfunction. This study assessed the extent of senescence of cells in a SGPC niche in pSS patients' SGs, and its correlation with functional and clinical parameters. Methods. The expression of p16 and p21 as markers of senescence in both total SG epithelium and a SGPC niche (basal striated duct cells, BSD) was examined in SGs of pSS (n = 35) , incomplete pSS (n = 1 3) (patients with some signs of pSS, but not fulfilling all classification criteria) and non-SS sicca control (n = 21) patients. This was correlated with functional and clinical parameters. Results. pSS patient SGs contained significantly more p16(+) cells both in the epithelium in general (P Conclusion. These findings suggest SGPC senescence may be an early feature of primary Sjogren's syndrome and may contribute to defective SG function in pSS but not to systemic disease activity