Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFÉ£ on human gingival mesenchymal stem cells properties.

AIMS: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes. METHODS: Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1ß[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 µg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR. RESULTS: G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p > .05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10-5 (Q25/Q75)] were utmost in control - [2.6607 (2.0804/4.5357)], followed by cytokine - [0.0433 (0.0026/1.4215)] and significantly lowered in the oxLDL group [0.0274 (0.0023/0.7290); p = .0047]. Osteogenic differentiation [median relative Ca2+ content(Q25/Q75)] was significantly lower in cytokine - [0.0066 (0.0052/0.0105)] compared to oxLDL - [0.0144 (0.0108/0.0216)] (p = .0133), with no differences notable for chondrogenic and adipogenic differentiation (p > .05). CONCLUSIONS: Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.

Training in the use of the water jet and cold atmospheric plasma jet for the decontamination of dental implants.

OBJECTIVES: Clinical trials testing new devices require prior training on dummies to minimize the "learning curve" for patients. Dentists were trained using a novel water jet device for mechanical cleaning of dental implants and with a novel cold plasma device for surface functionalisation during a simulated open flap peri-implantitis therapy. The hypothesis was that there would be a learning curve for both devices. MATERIALS AND METHODS: 11 dentists instrumented 44 implants in a dummy-fixed jaw model. The effect of the water jet treatment was assessed as stain removal and the effect of cold plasma treatment as surface wettability. Both results were analysed using photographs. To improve treatment skills, each dentist treated four implants and checked the results immediately after the treatment as feedback. RESULTS: Water jet treatment significantly improved from the first to the second implant from 62.7% to 75.3% stain removal, with no further improvement up to the fourth implant. The wettability with cold plasma application reached immediately a high level at the first implant and was unchanged to the 4th implant (mean scores 2.7 out of 3). CONCLUSION: A moderate learning curve was found for handling of the water jet but none for handling of the cold plasma. CLINICAL RELEVANCE: Scientific rational for study: Two new devices were developed for peri-implantitis treatment (Dental water jet, cold plasma). Dentists were trained in the use of these devices prior to the trial to minimize learning effects. PRINCIPAL FINDINGS: Experienced dentists learn the handling of the water jet very rapidly and for cold plasma they do not need much training. PRACTICAL IMPLICATIONS: A clinical study is in process. When the planned clinical study will be finished, we will find out, if this dummy head exercise really minimised the learning curve for these devices.

Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis.

Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.

Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.

BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. METHODS: To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63.z), composite CD28-CD3ζ or CD137-CD3ζ signaling domains (CARs 63.28.z and 63.137.z). RESULTS: Exposure of CD19-positive targets to CAR NK-92 cells resulted in formation of conjugates between NK and cancer cells, NK-cell degranulation and selective cytotoxicity toward established B-cell leukemia and lymphoma cells. Likewise, the CAR NK cells displayed targeted cell killing of primary pre-B-ALL blasts that were resistant to parental NK-92. Although all three CAR NK-92 cell variants were functionally active, NK-92/63.137.z cells were less effective than NK-92/63.z and NK-92/63.28.z in cell killing and cytokine production, pointing to differential effects of the costimulatory CD28 and CD137 domains. In a Raji B-cell lymphoma model in NOD-SCID IL2R γnull mice, treatment with NK-92/63.z cells, but not parental NK-92 cells, inhibited disease progression, indicating that selective cytotoxicity was retained in vivo. CONCLUSIONS: Our data demonstrate that it is feasible to generate CAR-engineered NK-92 cells with potent and selective antitumor activity. These cells may become clinically useful as a continuously expandable off-the-shelf cell therapeutic agent.

Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival.

Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease. CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-major histocompatibility complex (MHC)-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B-ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3ζ domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B-ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent antileukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL.

Integration of conventional quantitative and phospho-proteomics reveals new elements in activated Jurkat T-cell receptor pathway maintenance.

Recent years have seen a constant development of tools for the global assessment of phosphoproteins. Here, we outline a concept for integrating approaches for quantitative proteomics and phosphoproteomics. The strategy was applied to the analysis of changes in signalling and protein synthesis occurring after activation of the T-cell receptor (TCR) pathway in a T-cell line (Jurkat cells). For this purpose, peptides were obtained from four biological replicates of activated and control Jurkat T-cells and phosphopeptides enriched via a TiO2-based chromatographic step. Both phosphopeptide-enriched and flow-through fractions were analyzed by LC-MS. We observed 1314 phosphopeptides in the enriched fraction whereas 19 were detected in the flow-through, enabling the quantification of 414 and eight phosphoproteins in the respective fractions. Pathway analysis revealed the differential regulation of many metabolic pathways. Among the quantified proteins, 11 kinases with known TCR-related function were detected. A kinase-substrate database search for the phosphosites identified also confirmed the activity of a further ten kinases. In total, these two approaches provided evidence of 19 unique TCR-related kinases. The combination of phosphoproteomics and conventional quantitative shotgun analysis leads to a more comprehensive assessment of the signalling networks needed for the maintenance of the activated status of Jurkat T-cells.

A proteomics workflow for quantitative and time-resolved analysis of adaptation reactions of internalized bacteria.

The development of a mass spectrometric workflow for the sensitive identification and quantitation of the kinetics of changes in metaproteomes, or in particular bacterial pathogens after internalization by host cells, is described. This procedure employs three essential stages: (i) SILAC pulse-chase labeling and infection assay; (ii) isolation of bacteria by GFP-assisted cell sorting; (iii) mass spectrometry-based proteome analysis. This approach displays greater sensitivity than techniques relying on conventional cell sorting and protein separation, due to an efficient combination of a filtration-based purification and an on-membrane digestion. We exemplary describe the use of the workflow for the identification and quantitation of the proteome of 106 cells of Staphylococcus aureus after internalization by S9 human bronchial epithelial cells. With minor modifications, the workflow described can be applied for the characterization of other host-pathogen pairs, permitting identification and quantitation of hundreds of bacterial proteins over a time range of several hours post infection.

Navigational exploration of bony defect mimicking a solid lesion of the mandible compared to conventional surgery by young professionals.

INTRODUCTION: The aim of the current study was to evaluate the accuracy of resection a solid lesion in an acrylic lower jaw by young professionals using a dynamic computer-assisted surgical system comparted to conventional surgery technique. MATERIAL AND METHODS: Twenty students performed the removal of the lesion conventionally and twenty students did the operation with a dynamic computer-assisted surgical system. Both groups were compared regarding the defect size, operation time, and surgical complications. RESULTS: The defect size in the jaw was significant smaller with the navigated surgery (p < 0.001). Operation time was shorter without navigation system, but no significance was found (p = 0.137). Without navigation system three young professionals perforated the lingual cortex. DISCUSSION: Navigated surgery can immediately be used by young professionals and support young surgeons in everyday clinical practice, especially in operations with difficult anatomic situations.

Bone regeneration in critical-size defects of the mandible using biomechanically adapted CAD/CAM hybrid scaffolds: An in vivo study in miniature pigs.

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2. For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO2-TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 µg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue. Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2. Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region.

Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism.

There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50nM and 5µM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5µM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P.

Pronounced mediastinal emphysema after restorative treatment of the lower left molar-a case report and a systematic review of the literature.

This case report presents an iatrogenic induced mediastinal emphysema after restorative treatment of the lower left second molar, aimed to highlight the potential life-threatening consequences, and providing diagnostics and treatment concepts of complicated dental induced emphysema based on literature review. A 74-year-old female patient was admitted to the emergency department due to a fall on her shoulder. Additional finding was a significant swelling of the face and neck. In the computer tomography of the head, neck, and thorax, a humerus fracture and pronounced soft tissue emphysema from the infraorbital region to the mediastinum was detected. The patient reported that she had been treated by her dentist 4 days earlier. The treatment had to be discontinued after beginning of a pronounced swelling. Other reasons for the emphysema could be excluded out on an interdisciplinary teamwork. The patient was monitored as an inpatient for 5 days and received intravenous antibiotic therapy. This case report shows the rare complication of pronounced mediastinal emphysema after root canal treatment. Emphysema should always be a differential diagnosis of soft tissue swelling and, in case of doubt, a general medical presentation should be made.

Fracture strength test of digitally produced ceramic-filled and unfilled dental resin restorations via 3d printing: An in vitro study.

Background: Purpose of this study was to investigate the mechanical efficiency of 3D-printed permanent and provisional implant cemented fixed bridges produced via CAD/CAM technology using an interim and a permanent ceramic filled hybrid material. Material and Methods: Two groups with twenty specimens each were designed and 3D-printed via digital light processing technology (DLP). A fracture strength test was performed. Statistical analysis was performed (p>0.05) for impression distance and force. Results: For the fracture resistance and impression distance no significant difference (p = 0.643) were detected. The specimens of interim resin showed a mean value of 365.90 ± 86.67 N. Whereas specimens of permanent ceramic filled hybrid material showed a mean value of 363.45 ± 87.57 N. Conclusions: In this in vitro study 3D-printed ceramic filled hybrid material and interim resin based on methacrylic acid esters showed an acceptable resistance to bite forces with no differences in fracture mechanism. Key words:CAD-CAM, dental resin, 3D printing.

Decontaminative Properties of Cold Atmospheric Plasma Treatment on Collagen Membranes Used for Guided Bone Regeneration.

Background cold atmospheric plasma (CAP) is known to be a surface-friendly yet antimicrobial and activating process for surfaces such as titanium. The aim of the present study was to describe the decontaminating effects of CAP on contaminated collagen membranes and their influence on the properties of this biomaterial in vitro. Material and Methods: A total of n = 18 Bio-Gide® (Geistlich Biomaterials, Baden-Baden, Germany) membranes were examined. The intervention group was divided as follows: n = 6 membranes were treated for one minute, and n = 6 membranes were treated for five minutes with CAP using kINPen® MED (neoplas tools GmbH, Greifswald, Germany) with an output of 5 W, respectively. A non-CAP-treated group (n = 6) served as the control. The topographic alterations were evaluated via X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Afterward, the samples were contaminated with E. faecalis for 6 days, and colony-forming unit (CFU) counts and additional SEM analyses were performed. The CFUs increased with CAP treatment time in our analyses, but SEM showed that the surface of the membranes was essentially free from bacteria. However, the deeper layers showed remaining microbial conglomerates. Furthermore, we showed, via XPS analysis, that increasing the CAP time significantly enhances the carbon (carbonyl group) concentration, which also correlates negatively with the decontaminating effects of CAP. Conclusions: Reactive carbonyl groups offer a potential mechanism for inhibiting the growth of E. faecalis on collagen membranes after cold atmospheric plasma treatment.

Systematic review on diabetes mellitus and dental implants: an update.

PURPOSE: Dental implant surgery was developed to be the most suitable and comfortable instrument for dental and oral rehabilitation in the past decades, but with increasing numbers of inserted implants, complications are becoming more common. Diabetes mellitus as well as prediabetic conditions represent a common and increasing health problem (International Diabetes Federation in IDF Diabetes Atlas, International Diabetes Federation, Brussels, 2019) with extensive harmful effects on the entire organism [(Abiko and Selimovic in Bosnian J Basic Med Sci 10:186-191, 2010), (Khader et al., in J Diabetes Complicat 20:59-68, 2006, https://doi.org/10.1016/j.jdiacomp.2005.05.006 )]. Hence, this study aimed to give an update on current literature on effects of prediabetes and diabetes mellitus on dental implant success. METHODS: A systematic literature research based on the PRISMA statement was conducted to answer the PICO question "Do diabetic patients with dental implants have a higher complication rate in comparison to healthy controls?". We included 40 clinical studies and 16 publications of aggregated literature in this systematic review. RESULTS: We conclude that patients with poorly controlled diabetes mellitus suffer more often from peri-implantitis, especially in the post-implantation time. Moreover, these patients show higher implant loss rates than healthy individuals in long term. Whereas, under controlled conditions success rates are similar. Perioperative anti-infective therapy, such as the supportive administration of antibiotics and chlorhexidine, is the standard nowadays as it seems to improve implant success. Only few studies regarding dental implants in patients with prediabetic conditions are available, indicating a possible negative effect on developing peri-implant diseases but no influence on implant survival. CONCLUSION: Dental implant procedures represent a safe way of oral rehabilitation in patients with prediabetes or diabetes mellitus, as long as appropriate precautions can be adhered to. Accordingly, under controlled conditions there is still no contraindication for dental implant surgery in patients with diabetes mellitus or prediabetic conditions.

Changes in hormones of the thyroid axis after tracheostomy and their influence on regeneration in patients with head and neck cancer: A prospective study.

This prospective study aimed to compare and evaluate changes in hormones of the thyroid axis affected by tracheostomy due to surgical treatment in patients with oral cancer. The patients were evaluated with regard to serum levels of the thyroid axis - free T3/triiodothyronine (fT3) and free T4/thyroxine (fT4), as well as thyroid-stimulating hormone (TSH) - at fixed perioperative time points: during the tumor staging about 1 week before operation, immediately before and within 6 h after operation, 2 days after operation, and about 10 days after operation. Additionally, data on the patients' characteristics (age, gender), relevant secondary diagnoses, duration of ventilation in the intensive care unit, and perioperative complications were obtained and analyzed. In total, 51 patients with an average age of 68.29 years (±11.82) were included. Analyses of thyroid hormones directly before and after tracheostomy showed a significant postoperative decrease in circulating TSH (p = 0.005) and fT3 (p < 0.001), whilst a significant increase in fT4 values (p < 0.001) was found. Nine patients showed perioperative complications, such as infection, emphysema, or requiring a revision operation. Eleven patients were diagnosed with a cardiac problem or suffered from agitation after operation. Within the limitations of the study it seems that hormonal changes following tracheostomy in critically ill patients should be monitored and thyroid hormone adjustment should be taken into account because the latter might lead to lower mortality and morbidity during hospitalization in these patients. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00023942.

Learning Curve and Comparison of Dynamic Implant Placement Accuracy Using a Navigation System in Young Professionals.

The aim of the current study was to evaluate the learning curve and accuracy of implant placement by young professionals using a dynamic computer-assisted surgical system for dental implant placement. Ten students tried to place eight implants with a dynamic surgical system in predefined positions on two consecutive weekends, resulting in 160 implant placements in total. Postoperatively, the positions of the implants were scanned with an intraoral scanner and compared for deviations at the entry point, the apex, as well as angular deviations to the master model. The mean values of all measurements improved; statistical significance was found for the changes in the angle as well as for the position of the implants to the apex (p < 0.001). Furthermore, the young professionals indicated subjective improvement in handling the dynamic surgery system. Navigated surgical dental implant placement can be learned quickly and can support young professionals in everyday clinical practice, especially in difficult anatomic situations.

Vitamin C and Omega-3 Fatty Acid Intake Is Associated with Human Periodontitis-A Nested Case-Control Study.

Vitamins and omega-3 fatty acids (Ω3FA) modulate periodontitis-associated inflammatory processes. The aim of the current investigation was to evaluate associations of oral nutrient intake and corresponding serum metabolites with clinical severity of human periodontitis. Within the Food Chain Plus cohort, 373 periodontitis patients­245 without (POL) and 128 with tooth loss (PWL)­were matched to 373 controls based on sex, smoking habit, age and body mass index in a nested case-control design. The amount of oral intake of vitamins and Ω3FAs was assessed from nutritional data using a Food Frequency Questionnaire. Oral intake and circulatory bioavailability of vitamins and Ω3FA serum metabolomics were compared, using ultra-high-resolution mass spectrometry. Periodontitis patients exhibited a significantly higher oral intake of vitamin C and Ω3FA Docosapentaenoic acid (p < 0.05) compared to controls. Nutritional intake of vitamin C was higher in PWL, while the intake of Docosapentaenoic acid was increased in POL (p < 0.05) compared to controls. In accordance, serum levels of Docosapentaenoic acid were also increased in POL (p < 0.01) compared to controls. Vitamin C and the Ω3FA Docosapentaenoic acid might play a role in the pathophysiology of human periodontitis. Further studies on individualized nutritional intake and periodontitis progression and therapy are necessary.

ERBB2-CAR-Engineered Cytokine-Induced Killer Cells Exhibit Both CAR-Mediated and Innate Immunity Against High-Risk Rhabdomyosarcoma.

High-risk rhabdomyosarcoma (RMS) occurring in childhood to young adulthood is associated with a poor prognosis; especially children above the age of 10 with advanced stage alveolar RMS still succumb to the disease within a median of 2 years. The advent of chimeric antigen receptor (CAR)-engineered T cells marked significant progress in the treatment of refractory B cell malignancies, but experience for solid tumors has proven challenging. We speculate that this is at least in part due to the poor quality of the patient's own T cells and therefore propose using CAR-modified cytokine-induced killer (CIK) cells as effector cells. CIK cells are a heterogeneous population of polyclonal T cells that acquire phenotypic and cytotoxic properties of natural killer (NK) cells through the cultivation process, becoming so-called T-NK cells. CIK cells can be genetically modified to express CARs. They are minimally alloreactive and can therefore be acquired from haploidentical first-degree relatives. Here, we explored the potential of ERBB2-CAR-modified random-donor CIK cells as a treatment for RMS in xenotolerant mice bearing disseminated high-risk RMS tumors. In otherwise untreated mice, RMS tumors engrafted 13-35 days after intravenous tumor cell injection, as shown by in vivo bioluminescence imaging, immunohistochemistry, and polymerase chain reaction for human gDNA, and mice died shortly thereafter (median/range: 62/56-66 days, n = 5). Wild-type (WT) CIK cells given at an early stage delayed and eliminated RMS engraftment in 4 of 6 (67%) mice, while ERBB2-CAR CIK cells inhibited initial tumor load in 8 of 8 (100%) mice. WT CIK cells were detectable but not as active as CAR CIK cells at distant tumor sites. CIK cell therapies during advanced RMS delayed but did not inhibit tumor progression compared to untreated controls. ERBB2-CAR CIK cell therapy also supported innate immunity as evidenced by selective accumulation of NK and T-NK cell subpopulations in disseminated RMS tumors, which was not observed for WT CIK cells. Our data underscore the power of heterogenous immune cell populations (T, NK, and T-NK cells) to control solid tumors, which can be further enhanced with CARs, suggesting ERBB2-CAR CIK cells as a potential treatment for high-risk RMS.

Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis.

AIM: To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. METHODS: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31st, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1). RESULTS: All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes. CONCLUSION: Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Characterization of the Key Aroma Compounds in Heat-Processed Licorice (Succus Liquiritiae) by Means of Molecular Sensory Science.

Application of the sensomics concept elucidated the key odorants of heat-processed licorice (Succus Liquiritiae). Forty-nine aroma-active compounds with flavor dilution (FD) factors between 16 and 2048 were detected; 47 thereof were identified, 23 for the first time in heated licorice. 4-Hydroxy-2,5-dimethylfuran-3(2H)-one revealed the highest FD factor of 2048, followed by 3-hydroxy-4,5-dimethylfuran-2(5H)-one, 4-hydroxy-3-methoxybenzaldehyde, 3-hydroxy-2-methyl-4H-pyran-4-one, and 2-methoxyphenol (all 1024). Forty-two substances were quantitated by stable isotope dilution assays (SIDAs), and odor activity values (OAVs; ratio of concentration to the respective odor threshold) were calculated revealing OAVs ≥ 1 for 29 compounds. Thereby, 3-hydroxy-4,5-dimethylfuran-2(5H)-one, 2,3-butanedione, 2-methoxyphenol, and 1,8-cineole showed the highest OAVs in Succus Liquiritiae. To validate the obtained data, a reconstitution model based on an aqueous sucrose solution (50%) was prepared, containing all 29 odorants with an OAV ≥ 1 in their naturally occurring concentrations. The recombinate elicited an aroma profile matching very well with the profile of the original heat-processed licorice, proving the correct identification and quantitation of all key aroma compounds of Succus Liquiritiae.