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1.
Immunity ; 47(5): 928-942.e7, 2017 11 21.
Article in English | MEDLINE | ID: mdl-29166590

ABSTRACT

Pancreatic-islet inflammation contributes to the failure of ß cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1ß, and palmitate). IL-33 promoted ß cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In turn, local RA signaled to the ß cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute ß cell stress but was defective during chronic obesity. Accordingly, IL-33 injections rescued islet function in obese mice. Our findings provide evidence that an immunometabolic crosstalk between islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion.


Subject(s)
Insulin/metabolism , Interleukin-33/pharmacology , Islets of Langerhans/drug effects , Lymphocytes/drug effects , Myeloid Cells/metabolism , Tretinoin/metabolism , Animals , Humans , Inflammation/immunology , Insulin Secretion , Interleukin-33/biosynthesis , Islets of Langerhans/immunology , Islets of Langerhans/pathology , Lymphocytes/physiology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Vitamin A/physiology
2.
Sensors (Basel) ; 21(8)2021 Apr 19.
Article in English | MEDLINE | ID: mdl-33921865

ABSTRACT

The ability to track the structural condition of existing structures is one of the main concerns of bridge owners and operators. In the context of bridge maintenance programs, visual inspection predominates nowadays as the primary source of information. Yet, visual inspections alone are insufficient to satisfy the current needs for safety assessment. From this perspective, extensive research on structural health monitoring has been developed in recent decades. However, the transfer rate from laboratory experiments to real-case applications is still unsatisfactory. This paper addresses the main limitations that slow the deployment and the acceptance of real-size structural health monitoring systems (SHM) and presents a novel real-time analysis algorithm based on random variable correlation for condition monitoring. The proposed algorithm was designed to respond automatically to detect unexpected events, such as local structural failure, within a multitude of random dynamic loads. The results are part of a project on SHM, where a high sensor-count monitoring system based on long-gauge fiber Bragg grating sensors (LGFBG) was installed on a prestressed concrete bridge in Neckarsulm, Germany. The authors also present the data management system developed to handle a large amount of data, and demonstrate the results from one of the implemented post-processing methods, the principal component analysis (PCA). The results showed that the deployed SHM system successfully translates the massive raw data into meaningful information. The proposed real-time analysis algorithm delivers a reliable notification system that allows bridge managers to track unexpected events as a basis for decision-making.

3.
Surg Endosc ; 33(10): 3291-3299, 2019 10.
Article in English | MEDLINE | ID: mdl-30535542

ABSTRACT

BACKGROUND: Paraesophageal hernias (PEH) tend to occur in elderly patients and the assumed higher morbidity of PEH repair may dissuade clinicians from seeking a surgical solution. On the other hand, the mortality rate for emergency repairs shows a sevenfold increase compared to elective repairs. This analysis evaluates the complication rates after elective PEH repair in patients 80 years and older in comparison with younger patients. METHODS: In total, 3209 patients with PEH were recorded in the Herniamed Registry between September 1, 2009 and January 5, 2018. Using propensity score matching, 360 matched pairs were formed for comparative analysis of general, intraoperative, and postoperative complication rates in both groups. RESULTS: Our analysis revealed a disadvantage in general complications (6.7% vs. 14.2%; p = 0.002) for patients ≥ 80 years old. No significant differences were found between the two groups for intraoperative (4.7% vs. 5.8%, p = 0.627) and postoperative complications (2.2% vs. 2.8%, p = 0.815) or for complication-related reoperations (1.7% vs. 2.2%, p = 0.791). CONCLUSIONS: Despite a higher risk of general complications, PEH repair in octogenarians is not in itself associated with increased rates of intraoperative and postoperative complications or associated reoperations. Therefore, PEH repair can be safely offered to elderly patients with symptomatic PEH, if general medical risk factors are controlled.


Subject(s)
Hernia, Hiatal/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Postoperative Complications/epidemiology , Propensity Score , Registries , Aged, 80 and over , Elective Surgical Procedures/methods , Female , Humans , Male , Morbidity/trends , Risk Factors , Switzerland/epidemiology
4.
Health Promot Int ; 33(2): 318-324, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-27594140

ABSTRACT

In 2003, the German Federal Centre for Health Education (BZgA) initiated the national Cooperation-Network (CN) 'Equity in Health'. The CN is constantly increasing in size and scope, supporting setting approaches aimed at reducing health inequalities. A detailed description of the CN has not yet been available in English. The CN comprises a total of 66 institutional cooperation partners. Information concerning the structure and activities can be found on a special website. Coordination Centres (CC) have been established in the 16 federal states, for the coordination of all state-specific activities. Funding for the CN and CC is provided by the BZgA, the German statutory sickness funds and by the state-specific ministries of health. These partners also support the continuous quality improvement, which is based on the good-practice criteria developed by the Advisory Committee of the CN. In 2011, the 'Municipal Partner Process (MPP)' has been launched, specifically supporting local partners and integrated life-course approaches focussing on children. In 2015, the focus has been widened to include all age-groups. In July 2015, a new national health law concerning health promotion and prevention has been ratified by the federal Parliament, with a focus on reducing health inequalities. Currently, the details of its implementation are discussed on a nationwide basis. The CN has long advocated for such a law, and today the CN is a well-accepted partner providing concepts, methods and a strong and long-standing network. The article closes with future challenges faced by the CN.


Subject(s)
Cooperative Behavior , Health Education , Health Promotion/standards , Healthcare Disparities/organization & administration , Adolescent , Adult , Child , Germany , Humans , Organizational Objectives , Quality Improvement
5.
J Prosthet Dent ; 120(2): 214-219, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29627210

ABSTRACT

STATEMENT OF PROBLEM: Two-piece abutments consisting of a prefabricated titanium luting base and a zirconia abutment are used widely in implant restorations. Straightforward and reliable procedures for bonding titanium and zirconia are necessary for ensuring low failure rates in such restorations. PURPOSE: The purpose of this in vitro study was to evaluate the tensile load of zirconia copings on prefabricated titanium abutments using 4 different self-adhesive resin cements. MATERIAL AND METHODS: A total of 128 industrially manufactured partially yttria-stabilized zirconia ceramic copings were bonded to titanium abutments with a luting space of about 60 µm or 100 µm. The bonding surfaces were airborne-particle abraded with 50 µm alumina and cleaned ultrasonically. The zirconia copings were bonded with Panavia SA Cement Automix (SA), RelyX Unicem 2 Automix (RU), MaxCem Elite (ME), or SmartCem 2 (SC). Specimens from each cement group were randomly assigned to be stored either in distilled water (37°C) for 3 days or subjected to 37 500 thermocycles over 150 days. After debonding in tension, failure modes (adhesive or cohesive) were analyzed, and basic fuchsin dye penetration tests were performed using optical microscopy and scanning electron microscopy. Three-way ANOVA and Tukey HSD tests were used for statistical analysis (α=.05). RESULTS: Three-way ANOVA results determined that the luting resin used and the luting space had a significant effect (P≤.002), while the storage time did not have an overall effect (P>.05). The interaction between the luting resin used and storage time was significant (P<.001). After storage for 3 days, the retentive force of SA (1002 N) was highest, followed by that for RU (614 N), ME (550 N), and SC (346 N) (P≤.05); the forces for RU and ME were not significantly different (P>.05). However, after thermocycling, RU had the highest retentive force (848 N), followed by SA (646 N), ME (475 N), and SC (364 N) (P≤.05). Retentive forces for ME and SC were not significantly different (P>.05). The failure modes of the zirconia abutment surfaces were predominantly adhesive, while those of the titanium surfaces were mainly cohesive. The SA specimens showed the lowest dye penetration, followed by the RU, ME, and SC specimens. CONCLUSIONS: The greatest mean retention was found with Panavia SA Cement Automix and RelyX Unicem 2 Automix with a luting space of 60 µm when bonding zirconia copings to titanium.


Subject(s)
Dental Abutments , Dental Implants , Dental Prosthesis Retention , Materials Testing , Resin Cements/chemistry , Titanium/chemistry , Zirconium/chemistry , Analysis of Variance , Dental Bonding/methods , Dental Etching/methods , Dental Materials , Dental Stress Analysis , Glass Ionomer Cements , Humans , Stress, Mechanical , Surface Properties , Temperature , Time Factors
6.
Mol Pharm ; 14(6): 2070-2078, 2017 06 05.
Article in English | MEDLINE | ID: mdl-28485970

ABSTRACT

A general, easy-to-implement strategy for mapping the structure of organic phases integrated in mesoporous silica drug delivery devices is presented. The approach based on a few straightforward solid-state NMR techniques has no limitations regarding concentrations of the active compounds and enables straightforward discrimination of various organic phases. This way, among a range of typical arrangements of the active compounds and solvent molecules, a unique, previously unknown organogel phase of the self-assembled tapentadol in glucofurol as a solvent was unveiled and clearly identified. Subsequently, with an aid of 2D 1H-1H MAS NMR and high-level quantum-chemical calculations this uncommon low-molecular-weight organogel phase, existing exclusively in the porous system of the silica carrier, was described in detail. The optimized model revealed the tendency of tapentadol molecules to form hydrophobic arrangements through -OH···π interactions combined with π-π stacking occurring in the core of API aggregates, thus precluding the formation of hydrogen bonds with the solvent. Overall, the proposed experimental approach allows for clear discrimination of a variety of local structures of active compounds loaded in mesoporous silica drug delivery devices in reasonably short time being applicable for advancement of novel drug delivery systems in pharmaceutical industry.


Subject(s)
Drug Delivery Systems/methods , Silicon Dioxide/chemistry , Solvents/chemistry , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Surface Properties
7.
J Adhes Dent ; 19(6): 491-496, 2017.
Article in English | MEDLINE | ID: mdl-29234754

ABSTRACT

PURPOSE: The purpose of this in vitro study was twofold: 1. To evaluate the surface conditioning effect of a self-etching ceramic primer on lithium disilicate and zirconia ceramics; (2) to study the bond durability provided by the self-etching ceramic primer after artificial aging compared with conventional ceramic conditioning methods. MATERIALS AND METHODS: Lithium disilicate blocks (10 × 10 mm, 3.4 mm thick) and zirconia disks (8 mm diameter, 3.4 mm thick) were each divided into two groups. In group 1, the lithium disilicate disks (Li) were etched with hydrofluoric acid (HF), while zirconia (Zr) disks were treated with airborne-particle abrasion, both followed by application of a universal primer for restorative materials (MP; Monobond Plus, Ivoclar Vivadent). In group 2, Li disks were not etched with HF, while Zr disks were treated with airborne-particle abrasion, both followed by a self-etching primer (ME; Monobond Etch & Prime, Ivoclar Vivadent). Surface conditioning effects were evaluated using SEM. The specimens in both groups were bonded to a composite with a luting resin and divided into two subgroups. Subgroup 1 was stored in water (37°C) for 3 days, and subgroup 2 was stored in water for 30 days before undergoing 7500 thermal cycles (5°C to 55°C). RESULTS: The self-etching ceramic primer had a significant effect only on the lithium disilicate surface topography. The mean initial bond strength of ME-Zr was relatively low (24.4 MPa) in comparison with all other material combinations (MP-Li: 34.3 MPa; ME-Li: 33.5 MPa; MP-Zr: 31.1 MPa). After 30 days of water storage and thermocycling, the bond strength decreased significantly in all groups. CONCLUSION: The self-etching primer provided bond strengths to lithium disilicate ceramic comparable with those of the well-established bonding method using hydrofluoric acid etching and a primer containing silane. To zirconia ceramic, however, it provided statistically significantly lower bond strength than did the established bonding method.


Subject(s)
Dental Bonding , Resin Cements , Ceramics , Dental Etching , Dental Porcelain , Materials Testing , Silanes , Surface Properties , Zirconium
8.
J Adhes Dent ; 19(4): 323-329, 2017.
Article in English | MEDLINE | ID: mdl-28849798

ABSTRACT

PURPOSE: To evaluate the efficacy of different surface treatments on the repair of veneered zirconia ceramics. MATERIALS AND METHODS: Forty-eight zirconia disks were divided into three groups according to the method of surface treatment: polished surface, air abraded, or ground using a special silicon carbide bur (SiC Grinding Bur). All specimens were primed using a primer containing MDP (Cimara Zircon, Voco) and then bonded to composite in Plexiglas tubes using dual-curing adhesive resin (Bifix QM, Voco). Each of the three groups was further divided into two subgroups (n = 8) stored either in water at 37°C for 3 days without thermocycling or stored in water at 37°C for 150 days with an additional 37,500 thermocycles between 5°C and 55°C. After storage, tensile bond strength (TBS) was measured in a universal testing machine. RESULTS: After 3 days of storage, silicon carbide bur and air-abraded groups showed high TBS that ranged from 32.7 to 41.0 MPa (p ≤ 0.05). After 150 days of storage with thermocycling, the air-abraded group showed the most durable TBS (34.8 MPa), while the silicon carbide bur group showed a significant reduction in TBS (21.2 MPa); in the polished control group, specimens all debonded spontaneously during storage (p ≤ 0.05). CONCLUSION: Repair of zirconia ceramic after chipping of its veneers showed durable TBS when surface conditioning with air abrasion or roughening of the zirconia surface with a silicon carbide bur was provided.


Subject(s)
Dental Bonding , Resin Cements , Dental Etching , Dental Stress Analysis , Materials Testing , Methacrylates , Surface Properties , Tensile Strength , Zirconium
9.
J Adhes Dent ; 19(3): 221-228, 2017.
Article in English | MEDLINE | ID: mdl-28597007

ABSTRACT

PURPOSE: To test the bond strength and durability after artificial aging of so-called universal primers and universal multimode adhesives to lithium disilicate or zirconia ceramics. MATERIALS AND METHODS: A total of 240 ceramic plates, divided into two groups, were produced and conditioned: 120 acid-etched lithium disilicate plates (IPS e.max CAD) and 120 air-abraded zirconia plates (Zenostar T). Each group was divided into five subgroups (n = 24), and a universal restorative primer or multimode universal adhesive was used for each subgroup to bond plexiglas tubes filled with a composite resin to the ceramic plate. The specimens were stored in water at 37°C for 3 days without thermal cycling, or for 30 or 150 days with 7500 or 37,500 thermal cycles between 5°C and 55°C, respectively. All specimens then underwent tensile bond strength testing. RESULTS: Initially, all bonding systems exhibited high TBS, but some showed a significant reduction after 30 and 150 days of storage. After 3, 30, and 150 days, Monobond Plus, which contains silane and phosphate monomer, showed significantly higher bond strengths than the other universal primer and adhesive systems. CONCLUSIONS: The bond strength to lithium disilicate and zirconia ceramic is significantly affected by the bonding system used. Using a separate primer containg silane and phosphate monomer provides more durable bonding than do silanes incorporated in universal multimode adhesives. Only one of five so-called universal primers and adhesives provided durable bonding to lithium disilicate and zirconia ceramic.


Subject(s)
Dental Bonding , Resin Cements , Ceramics , Dental Cements , Dental Porcelain , Materials Testing , Surface Properties , Tensile Strength , Zirconium
10.
Article in German | MEDLINE | ID: mdl-26696409

ABSTRACT

BACKGROUND: In 2003, the German Federal Center for Health Education (BZgA) initiated a national Cooperation Network named "Equity in Health" to address scientific results, focusing on the association between social inequalities and health. The main goal is to support setting approaches aimed at reducing these health inequalities. RESULTS AND KEY ACTIVITIES: In the autumn of 2015 the Cooperation Network comprised a total of 65 (institutional) cooperation partners, e.g., from prevention and health promotion, from the medical profession, from the welfare associations, and from the municipal umbrella organziations. The website www.gesundheitliche-chancengleichheit.de was created to present the information available on all activities and structures. Further, Coordination Centers for Health Equity were established in all federal states of Germany to advise, coordinate and provide support for all those who are actively engaged in the key issues for each state. These Coordination Centers are sponsored by the statutory sickness funds and the Health Ministry of the respective states. They also support continuous quality improvement, based on the good practice criteria developed by the Cooperation Network. Since 2011, the local partner process "Health for All" (until November 2015 "Growing Up Healthily for All") has assisted the municipalities in developing their own integrated health strategies oriented toward the different stages in the life course ("prevention chains"). PERSPECTIVES: The results and structures that have emerged from the Cooperation Network form a good basis for the implementation of the new national Prevention Law passed by German Parliament in July 2015, to expand and develop further, on a country-wide basis and in the various states, living-space-oriented prevention and health promotion consolidating activities. The paper also discusses the present and future challenges of the Cooperation Network.


Subject(s)
Health Promotion/organization & administration , Health Services Research/organization & administration , Healthcare Disparities/organization & administration , Models, Organizational , National Health Programs/organization & administration , Resource Allocation/organization & administration , Germany , Health Status Disparities , Social Determinants of Health
11.
Dig Dis Sci ; 60(2): 485-91, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25344905

ABSTRACT

BACKGROUND: Non-invasive monitoring of inflammatory bowel disease is an unmet clinical need as patients in clinical remission may have residual mucosal inflammation preceding clinical relapse. AIMS: We aimed to assess the value of fecal calprotectin and standardized clinical activity scoring to monitor disease activity in ulcerative colitis under medical treatment. METHODS: Forty-one patients with ulcerative colitis were included in a prospective observational study. Medical treatment was guided by clinical judgement of treating physicians. Fecal calprotectin and the clinical activity index (CAI) were measured blinded to treating physicians every 2 months until the end of follow-up. Twenty-six patients received colonoscopy for clinical reason. RESULTS: As defined by the CAI, patients were in clinical remission (63.4 %), having mild (26.8 %) or moderate (11.2 %) disease activity. Of those in clinical remission (CAI ≤ 4), 86.4 % showed residual endoscopic activity (Mayo Score ≥1). Calprotectin levels were higher in endoscopically active disease (779.0 vs 331.5 µg/g, P = 0.034) and calprotectin testing identified more patients with endoscopic disease activity (86.4 %) than the CAI (45.5 %, P = 0.034). Medical treatment was escalated in 90.2 % during the study. Values of the CAI and calprotectin correlated with therapy escalation (OR 3.94 and 3.22, respectively). Only for calprotectin, changes between two measurements were related to intensified medical treatment (OR 1.39). CONCLUSION: Fecal calprotectin was similarly useful to the CAI to monitor disease activity of ulcerative colitis during medical treatment but identified endoscopic disease activity far more reliably. Changes of calprotectin values between measurements might indicate clinical relapse earlier than the CAI.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Feces/chemistry , Gastrointestinal Agents/therapeutic use , Leukocyte L1 Antigen Complex/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/metabolism , Colonoscopy , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , Prospective Studies , Recurrence , Remission Induction , Reproducibility of Results , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
12.
Int J Cancer ; 135(5): 1153-64, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-24500882

ABSTRACT

Adoptive T cell therapy is an important additional treatment option for malignant diseases resistant to chemotherapy. Using a murine high-grade B cell lymphoma model, we have addressed the question whether the B cell differentiation antigen CD19 can act as rejection antigen. CD19(-/-) mice inoculated with CD19(+) B cell lymphoma cells showed higher survival rates than WT mice and were protected against additional tumor challenge. T cell depletion prior to tumor transfer completely abolished the protective response. By heterotypic vaccination of CD19(-/-) mice against murine CD19, survival after tumor challenge was significantly increased. To define protective epitopes within the CD19 molecule, T cells collected from mice that had survived the tumor transfer were analyzed for IFNγ secretion in response to CD19-derived peptides. The majority of mice exhibited a CD4(+) T cell response to CD19 peptide 27, which was the most dominant epitope after CD19 vaccination. A peptide 27-specific CD4(+) T cell line protected CD19(-/-) mice against challenge with CD19(+) lymphoma and also cured a significant proportion of WT mice from recurrent disease in a model of minimal residual disease after chemotherapy. In conclusion, our data highlight CD19-specific CD4(+) T cells for adoptive T cell therapy of B cell lymphomas.


Subject(s)
Antigens, CD19/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunotherapy, Adoptive/methods , Lymphoma, B-Cell/therapy , Animals , Antigens, CD19/genetics , Interferon-gamma/immunology , Interferon-gamma/metabolism , Lymphocyte Depletion , Lymphoma, B-Cell/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neoplasm Transplantation , Tumor Cells, Cultured
13.
BMC Gastroenterol ; 14: 57, 2014 Mar 29.
Article in English | MEDLINE | ID: mdl-24679065

ABSTRACT

BACKGROUND: European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria have been developed to increase diagnostic yield, but their predictive value is limited. We investigated the incremental diagnostic value of faecal calprotectin to EPAGE criteria. METHODS: In a post-hoc analysis of a prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal complaints at the Division of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin values. RESULTS: Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median calprotectin levels were higher (81.5 µg/g, interquartile range 26-175, vs. 10 µg/g, IQR 10-22, P < 0.001) and testing was more often positive (>50 µg/g) in patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and in colonoscopy (57.3% vs. 7.4%, P < 0.001). The use of faecal calprotectin in addition to EPAGE criteria improved the risk reclassification of patients by endoscopic findings. The calculated net reclassification index was 37.8% (P = 0.002) for EGD and 110.9% (P <0.001) for colonoscopy, thus improving diagnostic yield to 56.8% and 70.2%, respectively. CONCLUSIONS: The use of faecal calprotectin in addition to EPAGE criteria improved diagnostic yield in patients with abdominal complaints.


Subject(s)
Endoscopy, Digestive System/methods , Feces/chemistry , Gastrointestinal Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Adenoma/diagnosis , Aged , Carcinoma/diagnosis , Colitis/diagnosis , Colonoscopy/methods , Colonoscopy/standards , Colorectal Neoplasms/diagnosis , Endoscopy, Digestive System/standards , Enzyme-Linked Immunosorbent Assay , Esophagitis, Peptic/diagnosis , Europe , Female , Humans , Inflammatory Bowel Diseases/diagnosis , Male , Middle Aged , Practice Guidelines as Topic , Predictive Value of Tests , Prospective Studies , Stomach Neoplasms/diagnosis , Stomach Ulcer/diagnosis
14.
Nat Commun ; 15(1): 1844, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418509

ABSTRACT

The synthesis of complex sugars is a key aspect of microbial biology. Cyclic ß-1,2-glucan (CßG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CßG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein. So far, its structure as well as the mechanism underlining the synthesis have not been clarified. Here we use cryo-electron microscopy (cryo-EM) and functional approaches to study Cgs from A. tumefaciens. We determine the structure of this complex protein machinery and clarify key aspects of CßG synthesis, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain. Our research opens possibilities for combating pathogens that rely on polysaccharide virulence factors and may lead to synthetic biology approaches for producing complex cyclic sugars.


Subject(s)
Agrobacterium tumefaciens , Glucosyltransferases , beta-Glucans , Humans , Agrobacterium tumefaciens/metabolism , Brucella abortus/metabolism , Cryoelectron Microscopy , beta-Glucans/metabolism , Glucans/metabolism , Sugars/metabolism
15.
Materials (Basel) ; 17(2)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38255594

ABSTRACT

This laboratory study was conducted to evaluate and compare the resin bond strength of different adhesive resin systems in different combinations and the durability of their bonds with zirconia ceramic. MATERIALS AND METHODS: One hundred and twenty-eight specimens were milled from 3Y-TZP zirconia ceramic. The bonding surfaces of all disks were wet polished, steam cleaned, airborne-particle abraded and ultrasonically cleaned in 99% isopropanol. The specimens were randomly divided into four main groups according to the applied resin system; two conventional and two self-adhesive systems were used. Each group was further subdivided into two subgroups; the first was conditioned with the specified primer for conventional luting resins or not conditioned for the self-adhesive systems, whereas the second subgroup of each was conditioned with the same phosphate monomer-containing primer (Alloy Primer). The zirconia specimens were adhesively bonded, using the allocated luting resin, to plexiglass tubes filled with self-curing composite resin (Clearfil FII). Half of the specimens of each subgroup were stored in distilled water at 37 °C for 3 days, whereas the other half were subjected to artificial aging, 150 days of storage and additional thermal cycling. Thereafter, all specimens were subjected to TBS testing using a universal testing machine. Statistical analysis was conducted using two-way ANOVA followed by separate one-way ANOVAs. The Games-Howell post-hoc test was applied for pairwise comparisons. RESULTS: All specimens survived storage with thermal cycling. The mean TBS values ranged from a minimum of 43.4 ± 5.0 MPa to a maximum of 66.4 ± 3.5 after 3 days and from a minimum of 13.6 ± 2.5 MPa to a maximum of 50.1 ± 9.4 MPa after 150 days. CONCLUSIONS: Artificial aging had a significantly negative effect on all test groups. The chosen adhesive-resin system had a significant effect on the resulting TBS values. The highest TBS values were achieved for the self-adhesive luting resin G-Cem One but were statistically comparable to the results obtained for the dual-cure luting resin G-Cem LinkForce.

16.
Nature ; 446(7134): 440-3, 2007 Mar 22.
Article in English | MEDLINE | ID: mdl-17322905

ABSTRACT

Cyclic nucleotide-gated (CNG) ion channels mediate sensory signal transduction in photoreceptors and olfactory cells. Structurally, CNG channels are heterotetramers composed of either two or three homologue subunits. Although it is well established that activation is a cooperative process of these subunits, it remains unknown whether the cooperativity is generated by the ligand binding, the gating, or both, and how the subunits interact. In this study, the action of homotetrameric olfactory-type CNGA2 channels was studied in inside-out membrane patches by simultaneously determining channel activation and ligand binding, using the fluorescent cGMP analogue 8-DY547-cGMP as the ligand. At concentrations of 8-DY547-cGMP < 1 microM, steady-state binding was larger than steady-state activation, whereas at higher concentrations it was smaller, generating a crossover of the steady-state relationships. Global analysis of these relationships together with multiple activation time courses following cGMP jumps showed that four ligands bind to the channels and that there is significant interaction between the binding sites. Among the binding steps, the second is most critical for channel opening: its association constant is three orders of magnitude smaller than the others and it triggers a switch from a mostly closed to a maximally open state. These results contribute to unravelling the role of the subunits in the cooperative mechanism of CNGA2 channel activation and could be of general relevance for the action of other ion channels and receptors.


Subject(s)
Cyclic GMP/metabolism , Cyclic GMP/pharmacology , Ion Channel Gating/drug effects , Ion Channels/metabolism , Animals , Cyclic GMP/analogs & derivatives , Ion Channels/agonists , Ion Channels/chemistry , Ion Channels/genetics , Ligands , Models, Biological , Oocytes/metabolism , Patch-Clamp Techniques , Xenopus laevis
17.
Dent Mater ; 39(7): 634-639, 2023 07.
Article in English | MEDLINE | ID: mdl-37183157

ABSTRACT

OBJECTIVES: The purpose of this study was to investigate the survival rate, the debonding resistance, and the failure modes of different occlusal veneer designs when used as a retainer for posterior cantilever, resin-bonded fixed dental prostheses (RBFDPs) at two tooth wear levels. METHODS: Four test groups were assigned: two groups with occlusal-proximal preparation (PT1 and PT2 for grade 2 and 3 wear), and two groups for occlusal-proximal and lingual preparation (PLT1 and PLT2 for grade 2 and 3 wear) Monolithic zirconia ceramic (3Y-TZP) RBFDPs were luted with an adhesive bonding system (Panavia V5). The specimens underwent a chewing simulation for 1.200.000 cycles with a load of 5 kg and thermocycling for 7500 cycles between 5 °C and 55 °C. The surviving restorations were debonded under quasi-static conditions. The results were analyzed with ANOVA. RESULTS: The specimens exhibited a 100 % survival rate after thermomechanical fatigue loading. The debonding resistance was statistically significant higher for group PLT1 than for group PT1 (P = 0.004), and higher for group PT2 than group PT1 (P ≤ 0.001). However, the debonding resistance showed no statistically significant difference between groups PT2 and PLT2 (P = 0.343), and groups PLT1 and PLT2 (P = 0.222). Groups PT1 and PT2 showed favorable failure modes in 62.5 % and 0.00 % of the specimens, respectively. While groups PLT1 and PLT2 presented 25 % favorable failure modes. SIGNIFICANCE: Occlusal veneers showed promising results as a retainer for cantilever RBFDPs. The lingual extension might increase debonding resistance. Nevertheless, conservative designs with lingual and proximal bevels are to be recommended, irrespective of the level of tooth wear.


Subject(s)
Dental Bonding , Dental Implants , Dentition , Dental Restoration Failure , Ceramics , Dental Porcelain , Dental Stress Analysis
18.
BMC Gastroenterol ; 12: 5, 2012 Jan 10.
Article in English | MEDLINE | ID: mdl-22233279

ABSTRACT

BACKGROUND: The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort. METHODS: In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values. RESULTS: Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 µg/g, IQR 43-185) than in patients without (N = 326, 10 µg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 µg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165). CONCLUSION: In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.


Subject(s)
Abdominal Pain/etiology , Feces/chemistry , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Adult , Aged , Biomarkers/analysis , Biomarkers/metabolism , Endoscopy, Gastrointestinal , Female , Gastric Mucosa/pathology , Gastrointestinal Diseases/metabolism , Humans , Leukocyte L1 Antigen Complex/metabolism , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Severity of Illness Index
19.
Digestion ; 86 Suppl 1: 1-5, 2012.
Article in English | MEDLINE | ID: mdl-23051719

ABSTRACT

The monitoring of inflammatory bowel disease (IBD) based on clinical symptoms and activity scores alone has major drawbacks. Despite clinical remission, in many patients with ongoing low-grade inflammation and activity scores, there is a tendency to underestimate IBD activity as parameters depend on the subjective symptoms of the patients. C-reactive protein might identify patients with low-grade inflammation, especially in Crohn's disease, but sensitivity remains limited. Recently, fecal markers of inflammation have been shown to correlate well with endoscopic disease activity and to predict relapse. However, data on serial measurements to guide therapy are scarce. The role of anti-TNF-α antibodies and plasma TNF-α concentrations in IBD therapy is currently unclear and needs to be defined further. The goal of improving disease outcome has not been demonstrated for any noninvasive biomarker so far.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drug Monitoring/methods , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Biomarkers/metabolism , Biopsy , C-Reactive Protein/metabolism , Colonoscopy , Feces/chemistry , Humans , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/pathology , Leukocyte L1 Antigen Complex/metabolism , Severity of Illness Index , Treatment Outcome
20.
Dent Mater ; 38(2): 444-450, 2022 02.
Article in English | MEDLINE | ID: mdl-34998602

ABSTRACT

OBJECTIVES: To evaluate the bonding durability after artificial aging provided by a self-etching and a no-etching ceramic primer compared to primers, which are applied by the etch and rinse method. METHODS: Lithium disilicate blocks were bonded to a composite resin (Clearfill Core, Kuraray) using 5 bonding methods (N = 24). Specimens of group MEP were bonded using a self-etching primer and the corresponding luting resin (Monobond Etch&Prime/Variolink Esthetic, Ivoclar Vivadent) Specimens of group UBE were bonded using a two-bottle silane solution (Universal Primer/Estecem, Tokuyama) without hydrofluoric acid ceramic etching. Specimens of the other 3 groups were bonded using etch and rinse bonding systems with prior hydrofluoric acid ceramic etching (MPV: Monobond Plus/Variolink Esthetic, Ivoclar Vivadent; SUR: Scotchbond Universal/RelyX Ultimate, 3 M; GML: G-Multi Primer/G-CEM LinkForce, GC). Each group was divided into 3 subgroups (n = 8) according to the storage conditions (3 days water storage (37 °C), 30 days water storage, 7,500 thermal cycles (5-55 °C) and 150 days water storage, 37,500 thermal cycles). The tensile bond strength (TBS) was measured and the data was statistically analyzed. RESULTS: After 3 days the median TBS ranged from 14.6 to 41.7 MPa, after 30 days from 4.2 to 39.0 MPa and after 150 days from 0 to 29.7 MPa. Both bonding systems utilizing a self-etching primer showed a significantly lower TBS than group MPV using a conventional ceramic bonding system. SIGNIFICANCE: Especially after long-term storage with additional thermal cycling the bonding systems using primers without hydrofluoric acid ceramic etching do not provide a high bond strength.


Subject(s)
Dental Bonding , Ceramics , Dental Bonding/methods , Dental Porcelain/chemistry , Hydrofluoric Acid , Materials Testing , Resin Cements/chemistry , Silanes , Surface Properties , Tensile Strength
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