Resistenzen gegenüber medikamentöser Tumortherapie

In the past multiple mechanisms could be identified that are involved in anticancer drug resistance; however, diagnostic assays for prediction of therapy response to classical cytostatic drugs did not enter routine clinical diagnostics. Only when new targeted drugs, e.g. tyrosine kinase inhibitors or therapeutic antibodies, were introduced in oncology were diagnostics for prediction of therapy response routinely preformed. First and foremost this was the result of the development of highly standardized techniques, i.e. exact mutation analysis in functional relevant codons of genes encoding signal proteins of cancer-related signal transduction pathways targeted by the new drugs. Due to increasing costs of health systems, in the future predictive diagnostics will probably become more and more important. Therefore, it will be necessary to develop improved diagnostic assays for prediction of individual therapy response.     

Novel Rhizobium lineages isolated from root nodules of the common bean (Phaseolus vulgaris L.) in Andean and Mesoamerican areas

The taxonomic affiliations of nineteen root-nodule bacteria isolated from the common bean (Phaseolus vulgaris L.) in Mexico, Ecuador and Brazil were investigated by analyses of 16S rRNA and of four protein-coding housekeeping genes. One strain from Mexico could be assigned to Rhizobium etli and two from Brazil to Rhizobium leucaenae, whereas another from Mexico corresponded to a recently described bean-nodulating species-level lineage related to R. etli and Rhizobium phaseoli. Ten strains isolated in Ecuador and Mexico corresponded to three novel Rhizobium lineages that fall into the R. phaseoli/R. etli/Rhizobium leguminosarum clade. One of those lineages, with representatives isolated mostly from Ecuador, seems to be dominant in beans from that Andean region. Only one of the Mexican strains clustered within the Rhizobium tropici clade, but as an independent lineage. Interestingly, four strains were affiliated with species within the Rhizobium radiobacter clade. The existence of yet non-described native Rhizobium lineages in both the Andean and Mesoamerican areas is discussed in relation to common-bean diversity and environmental conditions.     

Creating a Network of High‐Quality Skilled Nursing Facilities: Preliminary Data on the Postacute Care Quality Improvement Experiences of an Accountable Care Organization

Postacute care (PAC) is an important source of cost growth and variation in the Medicare program and is critical to accountable care organization (ACO) and bundled payment efforts to improve quality and value in the Medicare program, but ACOs must often look outside their walls to identify high‐value external PAC partners, including skilled nursing facilities (SNFs). As a solution to this problem, the integrated health system, Partners HealthCare System (PHS) and its Pioneer ACO launched the PHS SNF Collaborative Network in October 2013 to identify and partner with high‐quality SNFs. This study details the method by which PHS selected SNFs using minimum criteria based on public scores and secondary criteria based on self‐reported measures, describes the characteristics of selected and nonselected SNFs, and reports SNF satisfaction with the collaborative. The selected SNFs (n = 47) had significantly higher CMS Five‐Star scores than the nonselected SNFs (n = 93) (4.6 vs 3.2, P < .001) and were more likely than nonselected SNFs that met the minimum criteria (n = 35) to have more than 5 days of clinical coverage (17.0% vs 2.9%, P = .02) and to have a physician see admitted individuals within 24 (38.3% vs 17.1%, P = .02) and 48 hours (93.6% vs 80.0%, P = .03). A survey sent to collaborative SNFs found high satisfaction with the process (average satisfaction, 4.6/5, with 1 = very dissatisfied and 5 = very satisfied, n = 19). Although the challenges of improving care in SNFs remain daunting, this approach can serve as a first step toward greater clinical collaboration between acute and postacute settings that will lead to better outcomes for frail older adults.     

Infrared LED light therapy influences the expression of fibronectin and tenascin in skin wounds of malnourished rats—A preliminary study

The aim of this investigation was to evaluate the effect of infrared (λ 846 ± 20 nm) LED irradiation on the expression profile of the extracellular matrix protein components, tenascin and fibronectin on skin wounds induced in well nourished and malnourished rats. Eighteen albino rats (21 days old) were randomly divided into a well-nourished group (standard diet) and a malnourished group (regional basic diet). After receiving the diet for 70 days, skin wounds were created and the animals were subdivided into three groups: well-nourished control (n = 6), malnourished control (n = 6), and malnourished + LED irradiated (λ 846 ± 20 nm, 100 mW, 4 J/cm²) (n = 6). The animals were sacrificed 3 and 7 days after injury and histological sections were immunostained for both proteins. They were examined for the presence, intensity, distribution and pattern of immunolabeling. At 3 days, the distribution of tenascin was shown to be greater in the wound bed of malnourished animals compared to the well-nourished group. The intensity and distribution of tenascin was shown to be lower in the malnourished LED irradiated group compared to the malnourished control. There was a significant difference regarding the presence of fibronectin in the malnourished and well-nourished groups after 7 days (p = 0.03). The intensity of fibronectin was slight (100%) in the irradiated group and moderate to intense in the malnourished control group. The results of the present study indicate that infrared LED irradiation modulates positively the expression of tenascin and particularly fibronectin.     

Osteogenic potential of mesenchymal cells embedded in the provisional matrix after a 6-week healing period in augmented and non-augmented extraction sockets: an immunohistochemical prospective pilot study in humans

Purpose: The aim of the present clinical study was the evaluation of the osteogenic potential of mesenchymal cells embedded in the provisional matrix of non‐augmented and with Bio‐Oss collagen‐augmented human extraction sockets after 6 weeks of healing time. Methods: Twenty‐five patients with 47 extraction sites participated in the present study. After tooth removal, the extraction sockets were augmented with Bio‐Oss collagen or not augmented. At implant placement, bone biopsies of the extraction sockets were obtained. The immunohistochemical analysis of the osteogenic potential of the mesenchymal cells in the provisional matrix was performed using three monoclonal antibodies: core‐binding factor α1 (Cbfa1)/runt‐related protein (Runx)2, osteonectin (OSN/secreted protein acidic and rich in cyst [SPARC]) and osteocalcin (OC). The statistical analysis was performed using two‐factorial analysis for repeated measures, Mann–Whitney U‐test and Spearman's rank‐order correlation coefficient. Results: Of 47 extraction sockets examined, 17 sockets demonstrated an almost complete ossification. Hence, the provisional matrix of the 30 remaining extraction sockets (21 non‐augmented, 9 augmented) was immunohistochemically investigated. No evidence of acute or chronic inflammation was noted in any of the specimens. In the provisional matrix of the non‐grafted socket, the median amount of Cbfa1/Runx2‐positive cells was 72.3%, of OSN (SPARC) 66.9% and of OC 23.4%, whereas in the grafted sockets the median rate of immunopositive cells staining with Cbfa1/Runx2 was 73.3%, of OSN (SPARC) 61.4% and of OC 20.1%. There was no significant difference in the proportion of positive cells expressed by Cbfa1/Runx2, OSN/SPARC and OC between the grafted and non‐grafted socket. Furthermore, the cell density did not correlate to the quantity of stained cells independent of the used proteins. Discussion: After a 6‐week healing period, the provisional matrix was demonstrated to have a high proportion of cells displaying a maturation of mature osteoprogenitor cells to osteoblasts. The grafting procedure did not influence the quantity of osteogenic cells in the extraction socket. To cite this article:
Heberer S, Wustlich A, Lage H, Nelson JJ, Nelson K. Osteogenic potential of mesenchymal cells embedded in the provisional matrix after a 6‐week healing period in augmented and non‐augmented extraction sockets: an immunohistochemical prospective pilot study in humans.
Clin. Oral Impl. Res. 23 , 2012; 19–27.
doi: 10.1111/j.1600‐0501.2010.02148.x     

Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi

Protozoan parasites of the genus Trypanosoma can infect virtually all mammalian species. Within this genus, Trypanosoma dionisii from bats and Trypanosoma cruzi that causes Chagas' disease, belonging to the subgenus Schizotrypanum, can invade mammalian cells. The mechanisms of cell invasion by T. dionisii are poorly understood. To address that question, metacyclic trypomastigotes (MT) and human epithelial HeLa cells were used. Similarly to genetically divergent T. cruzi strains G (TcI) and CL (TcVI), associated, respectively with marsupial and human infections, T. dionisii infectivity increased under nutritional stress, a condition that induces host cell lysosome exocytosis required for parasite internalization. For efficient internalization, T. dionisii depended on MT protein tyrosine kinase (PTK) and Ca(2+) mobilization from acidocalcisomes, whereas T. cruzi strains also relied on phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC) and Ca(2+) released from thapsigargin-sensitive compartments. T. dionisii-induced signaling in host cells implicated PKC and Ca(2+) mobilized from thapsigargin-sensitive stores, like T. cruzi, but without PI3K involvement. Unlike T. cruzi, T. dionisii metacyclic forms did not use l-proline as source of energy required for internalization. Molecules related to T. cruzi surface glycoproteins involved in MT-host cell interaction were undetectable in T. dionisii. The difference in the surface profile of the two species was also inferred from the susceptibility of T. dionisii metacyclic forms to complement-mediated lysis, as opposed to complete resistance of T. cruzi. In summary, the two Trypanosoma species display distinct surface profiles but invade host cells through a common mechanism involving lysosome mobilization to the site of parasite entry.