The fracture strength and the failure mode of lithium disilicate or resin nano ceramics as a crown, overlay, or endocrown restoration on endodontically treated teeth.

Introduction: Different materials and restorative concepts have been proposed over the years to restore endodontically treated teeth (ETT). Monolithic ceramic and composite restoration can be lute to the tooh, without the use of a post. However, little is known how the material stiffness and presence of a composite core will affect the survival and failure mode.

Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery.

Efficient and targeted delivery of therapeutic agents remains a bottleneck in modern medicine. Here, biochemical engineering approaches to advance the repurposing of extracellular vesicles (EVs) as drug delivery vehicles are explored. Targeting ligands such as the sugar GalNAc are displayed on the surface of EVs using a HaloTag-fused to a protein anchor that is enriched on engineered EVs.

Orthogonal proteomics methods warrant the development of Duchenne muscular dystrophy biomarkers.

Background: Molecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, their translation to clinical use is difficult due to the lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy was developed and used to assess the reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD).

A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring.

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity.

Experiences of Stress - A Focus Group Interview Study Among Swedish Adolescents During the COVID-19 Pandemic.

Adolescence can be a stressful period in life. The period contains challenges associated with the transition from childhood to adulthood (body changes, changes in interpersonal relationships, and identity changes). The aim was to investigate experiences of stress among adolescents in addition to stress related to the COVID-19 pandemic.

Circadian Genes as Exploratory Biomarkers in DMD: Results From Both the Mouse Model and Patients.

Duchenne muscular dystrophy (DMD) is a rare genetic disease due to dystrophin gene mutations which cause progressive weakness and muscle wasting. Circadian rhythm coordinates biological processes with the 24-h cycle and it plays a key role in maintaining muscle functions, both in animal models and in humans. We explored expression profiles of circadian circuit master genes both in Duchenne muscular dystrophy skeletal muscle and in its animal model, the mdx mouse.

Bond strength between titanium and polymer-based materials adhesively cemented.

The aim was to evaluate the bond strength between titanium and polymer-based materials for prosthetic restorations, cemented with different adhesive cement systems. Eight groups with 13 specimens in each group were included. Each specimen consisted of two parts: a cylinder of titanium resembling a titanium base, and a cylinder of one of two polymer-based materials Micro Filled Hybrid (MFH) or Telio CAD and cemented with one of four adhesive cement systems, namely Multilink Hybrid Abutment, Panavia V5, RelyX Ultimate and G-Cem LinkAce.

Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein.

Accuracy of 3D printed polymers intended for models and surgical guides printed with two different 3D printers.

The purpose of the study was to evaluate the accuracy: trueness and precision of photopolymers used for dental models and surgical guides printed with two different digital light processing (DLP) printers. Forty specimens of four materials; E-dentstone, E-shell, NextDent™ Model, NextDent™ SG, and two designs; models A and B (n=5), were manufactured (DDDP, EvoDent). Trueness was evaluated by comparing values for 26 parameters with the CAD models' reference values and precision through standard deviation.

Development of an ObLiGaRe Doxycycline Inducible Cas9 system for pre-clinical cancer drug discovery.

The CRISPR-Cas9 system has increased the speed and precision of genetic editing in cells and animals. However, model generation for drug development is still expensive and time-consuming, demanding more target flexibility and faster turnaround times with high reproducibility. The generation of a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene and its use in targeted ObLiGaRe results in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse.

Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy.

Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD.

Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a fatal disease for which no cure is available. Clinical trials have shown to be largely underpowered due to inter-individual variability and noisy outcome measures. The availability of biomarkers able to anticipate clinical benefit is highly needed to improve clinical trial design and facilitate drug development.

The effects of dual PPAR/ agonism compared with ACE inhibition in the BTBRob/ob mouse model of diabetes and diabetic nephropathy.

The leptin-deficient BTBRob/ob mouse develops progressive albuminuria and morphological lesions similar to human diabetic nephropathy (DN), although whether glomerular hyperfiltration, a recognized feature of early DN that may contribute to renal injury, also occurs in this model is not known. Leptin replacement has been shown to reverse the signs of renal injury in this model, but in contrast, the expected renoprotection by angiotensin-converting enzyme (ACE) inhibition in BTBRob/ob mice seems to be limited. Therefore, to investigate the potential renal benefits of improved metabolic control in this model, we studied the effect of treatment with the dual peroxisome proliferator-activated receptor (PPAR) / agonist AZD6610 and compared it with the ACE inhibitor enalapril.

Retinoid-related orphan receptor γ (RORγ) adult induced knockout mice develop lymphoblastic lymphoma.

RORγ is a nuclear hormone receptor which controls polarization of naive CD4 T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORγ has therapeutic potential for autoimmune diseases; however, this mechanism may potentially carry target-related safety risks, as mice deficient in Rorc, the gene encoding RORγ, develop T-cell lymphoma with 50% frequency. Due to the requirement of RORγ during development, the Rorc knockout (KO) animals lack secondary lymphoid organs and have a dysregulation in the generation of CD4+ and CD8+ T cells.

The discovery of a selective and potent A2a agonist with extended lung retention.

Although the anti-inflammatory role of the A2a receptor is well established, controversy remains with regard to the therapeutic value for A2a agonists in treatment of inflammatory lung diseases, also as a result of unwanted A2a-mediated cardiovascular effects. In this paper, we describe the discovery and characterization of a new, potent and selective A2a agonist (compound 2) with prolonged lung retention and limited systemic exposure following local administration. To support the lead optimization chemistry program with compound selection and profiling, multiple in vitro and in vivo assays were used, characterizing compound properties, pharmacodynamics (PD), and drug concentrations.

Fracture strength of monolithic all-ceramic crowns made of high translucent yttrium oxide-stabilized zirconium dioxide compared to porcelain-veneered crowns and lithium disilicate crowns.

Objective: The aim of the study was to provide data on the fracture strength of monolithic high translucent Y-TZP crowns and porcelain-veneered high translucent Y-TZP crown cores and to compare that data with the fracture strength of porcelain-veneered Y-TZP crown cores and monolithic lithium disilicate glass-ceramic crowns.

Materials And Methods: Sixty standardized crowns divided into six groups (n = 10) were fabricated: monolithic high translucent Y-TZP crowns, brand A, monolithic high translucent Y-TZP crowns, brand B, veneered high translucent Y-TZP crown cores, brand A, veneered high translucent Y-TZP crown cores, brand B, heat-pressed monolithic lithium disilicate crowns and veneered Y-TZP crown cores. All crowns were thermocycled, cemented onto dies, cyclically pre-loaded and finally loaded to fracture.

Decreased IgA antibody production in the stomach of gastric adenocarcinoma patients.

Gastric adenocarcinoma is closely associated with Helicobacter pylori infection. It is also much more frequent in patients with common variable immunodeficiency or selective IgA-deficiency than in the general population. To investigate a possible link between local antibody production and gastric tumors, we studied gastric B cell infiltration and local IgA production in patients with H.

Chinese nurses' ethical concerns in a neurological ward.

Our aim was to describe Chinese nurses' experiences of workplace distress and ethical dilemmas on a neurological ward. Qualitative interviews were performed with 20 nurses. On using latent content analysis, themes emerged in four content areas: ethical dilemmas, workplace distress, quality of nursing and managing distress.

Comparison of different routes of vaccination for eliciting antibody responses in the human stomach.

Determination of optimal routes to induce mucosal immune responses locally in the stomach and duodenum are important steps in the development of vaccines against Helicobacter pylori infection. In this study, we immunized H. pylori-infected individuals either nasally or rectally with a model antigen, i.

Oral immunization with a Salmonella enterica serovar typhi vaccine induces specific circulating mucosa-homing CD4(+) and CD8(+) T cells in humans.

The kinetics and homing characteristics of T-cell responses in humans after mucosal immunizations have not been well characterized. Therefore, we have investigated the magnitude and duration of such responses as well as the homing receptor expression of antigen-specific peripheral blood T cells by using an oral model vaccine, i.e.

Sensitive microplate assay for detection of bactericidal antibodies to Vibrio cholerae O139.

A microplate assay for the detection of bactericidal antibodies to Vibrio cholerae O139 is described. The assay is sensitive, highly reproducible, specific, and convenient to perform. It has been used to demonstrate the induction of serum bactericidal antibodies in Vietnamese recipients of an oral, inactivated, bivalent O1/O139 vaccine, as well as in Bangladeshi patients with O139 disease.