Essential role of CCL2 in clustering of splenic ERTR-9+ macrophages during infection of BALB/c mice by Listeria monocytogenes

Early interactions between pathogens and host cells are often decisive for the subsequent course of infection. Here we investigated early events during infection by Listeria monocytogenes, a ubiquitously occurring facultative intracellular microorganism that exhibits severe pathogenicity, mainly in immunocompromised individuals. We show that the inflammatory chemokine CCL2 is highly up-regulated early after Listeria infection in spleens of BALB/c mice. ERTR-9+ macrophages of the marginal zone were identified as the only infected cells and exclusive producers of CCL2 at the early time point. Consequently, clusters of different cell types were formed around infected ERTR-9+ cells. Metallophilic MOMA-1+ marginal zone macrophages were, however, excluded from the clusters and migrated into the B-cell follicles. Depletion of CCL2 during infection resulted in a different composition of cell clusters in the spleen and increased the mortality rate of treated mice. Interestingly, ERTR-9+ macrophages no longer were part of clusters in such mice but remained at their original location in the marginal zone.     

Endothelial cells of human colorectal cancer and healthy colon reveal phenotypic differences in culture

Antiangiogenic drugs have been used successfully for the treatment of colorectal cancer (CRC). Viable tumor endothelial cells (TEC) and normal endothelial cells (NEC) of uninvolved colon tissue of the same patient have not been available to optimize treatment strategies in vitro. Therefore, our target was to establish a protocol for the isolation of TEC and NEC. These cells were isolated with very high purity via magnetic cell sorting of tissue samples obtained from CRC and healthy colon of eight patients. TEC and NEC expressed CD31, CD105, VE-cadherin, VCAM-1, ICAM-1 and E-selectin, formed capillaries in basal membrane extract and were able to take up acetylated low-density lipoprotein. They were negative for podoplanin, CD45, CD68 and cytokeratin-20 indicating blood vessel endothelial lineage. Intense staining of von Willebrand factor (vWF) was observed in five of eight NEC cultures, whereas vWF was absent or only slightly expressed in all TEC cultures in vitro. Low intracellular concentration of vWF was also detected in TEC and NEC at the tissue level. This demonstrated that differences exhibited by TEC and NEC in vivo are stably perpetuated in culture. The isolated cultures may provide a useful in vitro model to elucidate epigenetic effects on angiogenesis in cancer and to optimize antiangiogenic therapy.     

Rapid antidepressant effect of S-ketamine in schizophrenia

Rapid anti-suicidal and antidepressant effects of ketamine have repeatedly been confirmed in unipolar and bipolar depression. Although meaningful antidepressant efficacy of ketamine has also been shown in depressed patients with a history of psychotic symptoms, its administration in psychotic disorders has largely been neglected due to its potential to exacerbate dissociative or psychotic symptoms. Presenting a case of a young female inpatient suffering from schizophrenia with a severe post-psychotic depression, we demonstrate a robust anti-suicidal and antidepressant effect of S-ketamine infusions administered thrice weekly for 3 weeks in total. Importantly, no relevant psychotic or dissociative symptoms occurred during the whole augmentation treatment period leading to a sustained remission of depressive symptoms and suicidality. Our safe and effective experience with intravenous S-ketamine might encourage researchers and clinicians to widen its administration range beyond the diagnosis of depression to enrich the current knowledge of ketamine effects in psychotic disorders.     

Cross-cultural validation of the German version of the Four-Dimensional Symptom Questionnaire (4DSQ) in multimorbid elderly people

Purpose

Psychosomatic symptoms and mental health problems are highly prevalent in multimorbid elderly people challenging general practitioners to differentiate between normal stress and psychopathological conditions. The 4DSQ is a Dutch questionnaire developed to detect anxiety, depression, somatization, and distress in primary care. This study aims to analyze measurement equivalence between a German version and the original Dutch instrument.

Methods

A Dutch and a German sample of multimorbid elderly people, matched by gender and age, were analyzed. Equivalence of scale structures was assessed by confirmatory factor analysis (CFA). To evaluate measurement equivalence across languages, differential item functioning (DIF) was analyzed using Mantel–Haenszel method and hybrid ordinal logistic regression analysis. Differential test functioning (DTF) was assessed using Rasch analysis.

Results

A total of 185 German and 185 Dutch participants completed the questionnaire. The CFA confirmed one-factor models for all scales of both 4DSQ versions. Nine items in three scales were flagged with DIF. The anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale impact of DIF.

Conclusions

The German 4DSQ demonstrated measurement equivalence to the original Dutch instrument. Hence, it can be considered a valid questionnaire for the screening for mental health problems in primary care.

     

Immediate functional loading of single-tooth TiO2 grit-blasted implant restoration. A controlled prospective study in a porcine model. Part II: Histology and histomorphometry

Background: Evidently, there is a fast‐moving shift from delayed to immediate implant loading. The hypothesis to be tested was that bone reactions adjacent to single TiO₂‐microthreaded implants exposed to immediate masticatory loading for 10 weeks after placement would modulate osseointegration. Materials and Methods: Cylindrical‐ and tapered‐designed implants (Astra Tech AB, Mölndal, Sweden) replaced first and third mandibular premolars respectively in 12 pigs. The animals were allocated into two groups based on soft and hard diet feeding. Each animal received, at random positions, four different masticatory loading conditions: implant with either (1) a cover screw only, (2) a healing abutment, (3) an implant with a crown without occlusal contact, or (4) an implant with a crown in contact with the antagonistic teeth. Results: Histomorphometry showed that there were no statistically significant differences in bone‐implant contact (BIC), bone mass inside/outside of the threads and soft tissue ingrowth ratio for all the implants at 10 weeks after placement irrespective of masticatory loading condition. Bone loss showed a trend of progressive increase for implants with a healing abutment toward implants with occlusal contact. Conclusions: The results of this study rejected the hypothesis and could be explained by the fact that grit‐blasted acid‐etched implants were already placed in dense bone.     

Quality of impressions using hydrophilic polyvinyl siloxane in a clinical study of 249 patients

PURPOSE: This study aimed to evaluate the clinical success of a hydrophilic polyvinyl siloxane impression material for fixed dental restorations under various clinical conditions. MATERIALS AND METHODS: A total of 1,466 preparations for fixed restorations in maxillary and mandibular anterior and posterior teeth were evaluated. The study contained inlay, onlay, crown, veneer, post, and adhesive-wing preparations and implants for gold, porcelain-fused-to-metal, and ceramic restorations. The preparation finish line relative to the crest of the marginal gingiva, type of restoration, and position of the teeth were recorded. Three categories were established to rate impression quality: perfect impressions, with an absence of any voids or bubbles and perfect reproduction of the preparation finish line, were rated Criteria I; acceptable impressions, with minimal defects (< or = 2 mm) not involving the preparation finish line, were rated Criteria II; and unacceptable impressions, with larger voids or bubbles (> 2 mm) or defects involving the preparation finish line, were rated Criteria III. RESULTS: Overall, 96.86% of the final impressions were clinically acceptable, 89.43% of which were rated Criteria I and 7.43% of which were rated Criteria II. Only 3.14% of the impressions were unacceptable and rated Criteria III. A significant influence on impression quality was found when the preparation finish line was more than 2 mm subgingival (P < .004), as well as when a beveled preparation was used (P < .004). The position of the teeth (P > .404) had no significant effect. CONCLUSION: Surface-activated polyvinyl siloxane impression material offers high predictability to avoid bubbles and voids in the final impression.     

A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study

Etomoxir is an inhibitor of mitochondrial CPT1 (carnitine palmitoyltransferase 1) and thereby switches energy metabolism from fatty acids to glucose oxidation. Such a metabolic change may be beneficial in CHF (congestive heart failure). The ERGO (etomoxir for the recovery of glucose oxidation) study was designed in which etomoxir was tested at a dose of 80 and 40 mg compared with placebo for a period of 6 months in patients with CHF. As the principle measure of efficacy, a maximal exercise tolerance test and a submaximal 6-min corridor walk test were used. Secondary end points were echocardiographical dimensions and quality-of-life assessment scores. A total of 350 patients were planned to be screened, with the expectation that end point data would be available from approx. 260 patients. However, the study had to be stopped prematurely, because unacceptably high liver transaminase levels were detected in four patients taking etomoxir. At the termination of the study, 121 patients were randomized to placebo, 118 to 40 mg of etomoxir and 108 to 80 mg of etomoxir. At that time, 21 patients in the placebo group, 16 in the 40 mg of etomoxir group and 14 patients in the 80 mg of etomoxir group had completed the study. The mean increases in exercise time were 3.3, 10.2 and 19.4 s for the placebo, 40 mg of etomoxir and 80 mg of etomoxir groups respectively (P value was not significant). No changes were obvious in the 6-min corridor walk test or in echocardiographical parameters from baseline. The number of patients that completed the study was too small to demonstrate significant effects on exercise time, although there was a tendency towards an increase in exercise time. Therefore, before rejecting the hypothesis that inhibition of fatty acid oxidation might be beneficial in CHF, similar studies have to be performed using different inhibitors of fatty acid oxidation targeting CPT1 and other enzymes in this metabolic pathway.