Dynamic Production of Soluble Extracellular Polysaccharides by Streptococcus mutans

Caries development in the presence of Streptococcus mutans is associated not only with the production of extracellular water-insoluble polymers but also is based on water-soluble polysaccharides. The aim of this study was the evaluation of a novel glucan-specific Lectin assay for monitoring water-soluble EPS produced by S. mutans during several growth periods in different media. S. mutans cultures were grown for 24 h, 48 h, and 144 h in medium deficient of sucrose (A) and medium supplemented with 5% sucrose (B). Microtiter well plates were coated with cell-free supernatants followed by the addition of labeled Concanavalin-A and enzyme substrate. The substrate reactions were kinetically detected at 405 nm. The validation of the assay was performed using carbohydrates dextran, xanthan, and sucrose as reference. This new Concanavalin-A-based assay showed the highest sensitivity for dextran and revealed that the glucan production of S. mutans reached its maximum at 144 h in medium B according to bacterial maturation

Odontogenic Fibromyxoma of the Maxilla: A Case Report and Review of the Literature

Fibromyxoma represents a rare benign neoplasm that mostly affects the posterior region of the mandible. Here, we report the case of a 46-year-old male with a swelling of the right maxilla. After proper diagnosis, he was treated with enucleation and curettage of the tumor. The defect was filled with a pedicled buccal fat pad flap. The mesenchymal origin from the dental follicle of the fibromyxoma is the most plausible explanation. Radiological examination with MRI, CT, and conventional radiography contributes to the differential diagnosis from other benign tumors, such as the ameloblastoma. Its management is surgical and comprises enucleation and curettage or en bloc resection. Patients must be monitored for at least two years postoperatively in order to diagnose possible recurrence. According to the literature, the maxilla is a rare location of a fibromyxoma and, to our knowledge, our case is the 30th presented case of a fibromyxoma of the maxilla

Bisphosphonate’s effect in hepatic rat cells: An electron microscopy study

Σκοπός: Τα διφωσφονικά αποτελούν εκλεκτικούς αναστολείς της οστικής απορρόφησης και η μακροχρόνια χρήση τους έχει συσχετισθεί με ανεπιθύμητες επιδράσεις στο γαστρεντερικό σύστημα. Σκοπός της εργασίας είναι η διερεύνηση των πιθανών επιδράσεων των διφωσφονικών στη δομή των ηπατικών κυττάρων. Υλικά και μέθοδος: Ελήφθησαν δείγματα ηπατικού ιστού από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που έλαβαν Αλενδρονάτη από του στόματος για 13 εβδομάδες και από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που δεν έλαβαν το φάρμακο και χρησιμοποιήθηκαν ως μάρτυρες. Τα δείγματα μελετήθηκαν με το ηλεκτρονικό μικροσκόπιο. Αποτελέσματα: Στα ηπατικά κύτταρα των ποντικιών που έλαβαν Αλενδρονάτη βρέθηκαν εκτεταμένη απώλεια γλυκογόνου, διαφόρου μεγέθους κενοτόπια, διευρυμένα κολπώδη τριχοειδή, καθώς και απουσία των μικρολαχνών σε πολλά σημεία του χώρου του Disse. Συμπέρασμα: Πρόκειται για την πρώτη μελέτη με ηλεκτρονικό μικροσκόπιο ηπατικών δειγμάτων μετά τη χορήγηση διφωσφονικών, η οποία υποδεικνύει ήπια ηπατική βλάβη. Μια πιθανή συσχέτιση μεταξύ της χρήσης της Αλενδρονάτης και της ηπατικής λειτουργίας καθίσταται εμφανής. Ωστόσο, εξαιτίας του μικρού αριθμού δειγμάτων περισσότερες μελέτες είναι απαραίτητες ώστε να διαλευκανθεί αυτή η συσχέτιση.Purpose: Bisphosphonates (BPs) are selective inhibitors of osteoclast mediated bone resorption, used for the treatment of bone disorders as well as for tumors, whereas long-term bisphosphonate use is associated with adverse gastrointestinal effects. The objective of the study is to investigate the possible effects of BPs in hepatic structure. Materials and methods: Specimens from the liver of ten female 12-month old Wistar rats were used as control group and of ten female 12-month old Wistar rats to which Alendronate (Fosamax, Merck) was administered per os for 13 weeks, were used as experimental group. Samples were observed under a Transmission Electron Microscope. Results: In the experimental group, extensive depletion of the glycogen, different sized vacuoles and enlarged sinusoids were found in hepatic cells. Furthermore, there was lack of microvilli of hepatocytes in the Disse’s space. The same findings were reported in all sections of the experimental group. Conclusion: This is the first study of liver structure after the administration of bisphosphonates, with electron microscopy. This report, indicate the presence of mild hepatic damage in liver tissues studied. Our study demonstrates a possible correlation between alendronate administration and hepatic cell function, nevertheless due to the small specimen further research is needed

A presynaptic phosphosignaling hub for lasting homeostatic plasticity

Stable function of networks requires that synapses adapt their strength to levels of neuronal activity, and failure to do so results in cognitive disorders. How such homeostatic regulation may be implemented in mammalian synapses remains poorly understood. Here we show that the phosphorylation status of several positions of the active-zone (AZ) protein RIM1 are relevant for synaptic glutamate release. Position RIMS1045 is necessary and sufficient for expression of silencing-induced homeostatic plasticity and is kept phosphorylated by serine arginine protein kinase 2 (SRPK2). SRPK2-induced upscaling of synaptic release leads to additional RIM1 nanoclusters and docked vesicles at the AZ and is not observed in the absence of RIM1 and occluded by RIMS1045E. Our data suggest that SRPK2 and RIM1 represent a presynaptic phosphosignaling hub that is involved in the homeostatic balance of synaptic coupling of neuronal networks

Author Correction: Traps and transport resistance are the next frontiers for stable non-fullerene acceptor solar cells.

Stability is one of the most important challenges facing material research for organic solar cells (OSC) on their path to further commercialization. In the high-performance material system PM6:Y6 studied here, we investigate degradation mechanisms of inverted photovoltaic devices. We have identified two distinct degradation pathways: one requires the presence of both illumination and oxygen and features a short-circuit current reduction, the other one is induced thermally and marked by severe losses of open-circuit voltage and fill factor. We focus our investigation on the thermally accelerated degradation. Our findings show that bulk material properties and interfaces remain remarkably stable, however, aging-induced defect state formation in the active layer remains the primary cause of thermal degradation. The increased trap density leads to higher non-radiative recombination, which limits the open-circuit voltage and lowers the charge carrier mobility in the photoactive layer. Furthermore, we find the trap-induced transport resistance to be the major reason for the drop in fill factor. Our results suggest that device lifetimes could be significantly increased by marginally suppressing trap formation, leading to a bright future for OSC

Final Evaluation of a Clinical Phase III Trial Comparing Treosulfan to Busulfan-Based Conditioning Therapy Prior to Allogeneic Hematopoietic Stem Cell Transplantation of Adult Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients Ineligible to Standard Myeloablative Regimens

Background Allogeneic hematopoietic stem cell transplantation (HCT) remains a challenge in elderly and comorbid AML and MDS patients. This patient population is at increased risk for non-relapse mortality (NRM) when treated with standard myeloablative conditioning and was selected to compare a newly developed treosulfan-based with a well-established reduced intensity busulfan-based preparative regimen in a prospective randomized clinical phase III trial. Methods Adult patients with AML in remission or MDS scheduled for HCT from matched related or unrelated donors, aged ≥50 years or with a comorbidity index (HCT-CI) of >2 were enrolled by a central stratified randomization procedure. Treatment arms consisted of intravenous (IV) treosulfan (10 g/m²/day [d-4 to d-2]) or IV busulfan (3.2 mg/kg/day [d-4 to d-3]), both combined with IV fludarabine (30 mg/m²/day [d-6 to d-2]). The primary objective was to compare event-free survival (EFS) at two years with relapse/progression of disease, graft failure, or death reported as events. Secondary endpoints were safety evaluation (according to CTCAE v4.03), engraftment, chimerism, overall survival (OS), relapse/progression incidence (RI), NRM and acute or chronic GvHD. After a previously conducted confirmatory interim analysis (based on 476 patients), which resulted in early termination of patient accrual due to significant non-inferiority of treosulfan treatment with improved EFS, NRM and OS (Beelen et al., ASH 2017), results of the final analysis of all 570 randomized patients including post surveillance data are provided here. Results Median age of the 551 patients (352 AML; 199 MDS) included in the full analysis set (268 treosulfan; 283 busulfan) was 60 years (range: 31, 70). Frequencies of early adverse events (d-6 to d+28) and incidences of acute and chronic GvHD were largely comparable between the two regimens, while extensive chronic GvHD was numerically in favor of treosulfan (19.7% vs. 26.7%; p=0.0750). Primary neutrophil recovery at day +28 was comparable, while the rate of complete donor-type chimerism (day +28) was higher after treosulfan (93.2% vs. 83.3%; p Conclusions Final evaluation of this phase III trial substantiates the previous confirmatory analysis resulting in significantly improved survival after treosulfan-based conditioning. Due to the reduction of NRM a major clinical benefit of the new treosulfan conditioning regimen was demonstrated in the selected AML/MDS patient population

Development of the VEGANScreener, : a Tool for a Quick Diet Quality Assessment among Vegans in Europe

Peer reviewe

A genome-wide association study of the longitudinal course of executive functions

Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest P value = 7.2 × 10(−10) with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 (P value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics

Association of early life stress and cognitive performance in patients with schizophrenia and healthy controls

As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance. The sample comprised 215 patients with schizophrenia (age, 42.9 ± 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 ± 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance. ELS was reported by 52.1 % of patients and 24.9 % of controls. Independent of ELS, cognitive performance on neuropsychological tests was lower in patients than controls (p < 0.001). ELS load was more closely associated with neurocognitive deficits (cognitive composite score) in controls (r = −0.305, p < 0.001) than in patients (r = −0.163, p = 0.033). Moreover, the higher the ELS load, the more cognitive deficits were found in controls (r = −0.200, p = 0.006), while in patients, this correlation was not significant after adjusting for PANSS. ELS load was more strongly associated with cognitive deficits in healthy controls than in patients. In patients, disease-related positive and negative symptoms may mask the effects of ELS-related cognitive deficits. ELS subtypes were associated with impairments in various cognitive domains. Cognitive deficits appear to be mediated through higher symptom burden and lower educational level