Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization.

Heat shock proteins 90 (Hsp90) are promising therapeutic targets due to their involvement in stabilizing several aberrantly expressed oncoproteins. In cancerous cells, Hsp90 expression is elevated, thereby exerting antiapoptotic effects, which is essential for the malignant transformation and tumor progression. Most of the Hsp90 inhibitors (Hsp90i) under investigation target the ATP binding site in the N-terminal domain of Hsp90.

Antibody-Mediated Screening of Peptide Inhibitors for Monoamine Oxidase-B (MAO-B) from an Autodisplayed F Library.

Inhibitors for monoamine oxidase-B (MAO-B) were screened from an F library with a randomized complementarity-determining region 3 (CDR3) region using a monoclonal antibody against dopamine. As the first step, the F library was expressed on the outer membrane of by site-directed mutagenesis of the randomized CDR3 region. Among the F library, variants with a binding affinity to monoclonal antibodies against dopamine were screened and cloned.

variants of cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway.

encodes for casein kinase II subunit beta (CK2β), the regulatory subunit of casein kinase II (CK2), which is known to mediate diverse cellular pathways. Variants in this gene have been recently identified as a cause of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), but functional evidence is sparse. Here, we report five unrelated individuals: two of them manifesting POBINDS, while three are identified to segregate a new intellectual disability-craniodigital syndrome (IDCS), distinct from POBINDS.

Mice Lacking Wnt9a or Wnt4 Are Prone to Develop Spontaneous Osteoarthritis With Age and Display Alteration in Either the Trabecular or Cortical Bone Compartment.

Osteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype.

Effectiveness of diagnosing pulpitis: A systematic review.

Background: The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and well-executed clinical trials on the diagnosis of the true status of the pulp.

Objectives: Three PICO questions were formulated and agreed a priori by the European Society of Endodontology to evaluate the clinical tests for sensibility testing, determination of biomarkers and pulp bleeding with regard to their suitability to correctly diagnose the condition of the pulp tissue for the development of S3-Level guidelines.

Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (K3.1) channels .

Expression of the Ca activated potassium channel 3.1 (K3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival.

The "WWHow" Concept for Prospective Categorization of Post-operative Severity Assessment in Mice and Rats.

The prospective severity assessment in animal experiments in the categories' non-recovery, mild, moderate, and severe is part of each approval process and serves to estimate the harm/benefit. Harms are essential for evaluating ethical justifiability, and on the other hand, they may represent confounders and effect modifiers within an experiment. Catalogs and guidelines provide a way to assess the experimental severity prospectively but are limited in adaptation due to their nature of representing particular examples without clear explanations of the assessment strategies.

Knowledge about Hand Hygiene and Related Infectious Disease Awareness among Primary School Children in Germany.

Hand hygiene is a cornerstone of infection prevention. However, few data are available for school children on their knowledge of infectious diseases and their prevention. The aim of the study was to develop and apply a standardized questionnaire for children when visiting primary schools to survey their knowledge about infectious diseases, pathogen transmission and prevention measures.

Requirements for an app from the perspective of patients in plastic and reconstructive surgery.

Background: Along with the higher availability of Internet, worldwide access and the use of cell phones, the demands of patients for digitalized medical care have increased.

Methods: A questionnaire-based prospective study of 405 patients was conducted to investigate their expectations and requirements of app-based "mHealth" applications.

Results: "Behavioral guidance after surgery," "overview of personal findings," and "contact with the treating physician" were the most important factors.

Screening of Fv Antibodies with Specific Binding Activities to Monosodium Urate and Calcium Pyrophosphate Dihydrate Crystals for the Diagnosis of Gout and Pseudogout.

To date, medical diagnosis of gout and pseudogout has been performed by observing the crystals in the joint fluid of patients under a polarized microscope. Conventional diagnostic methods using a polarized microscope have disadvantages, such as time-consuming analysis, a high false negative rate, and difficulty in distinguishing gout with monosodium urate (MSU) crystals and pseudogout with calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluids. In this study, a chromogenic assay for the diagnosis of gout and pseudogout, without the requirement of a polarized microscope and trained experts, was proposed using Fv antibodies with specific binding activities to MSU and CPPD crystals.

Results of the prospective multicenter SoLKiD cohort study indicate bio-psycho-social outcome risks to kidney donors 12 months after donation.

The outcome after living kidney donation was assumed to be comparable to that of the general population. However, recent register studies reveal negative changes in kidney function, quality of life and fatigue. Avoiding methodological issues of previous studies, the Safety of the Living Kidney Donor (SoLKiD) cohort study analyzed the outcome of donors in a multicenter and interdisciplinary fashion.

2-(2-Hydroxyethyl)piperazine derivatives as potent human carbonic anhydrase inhibitors: Synthesis, enzyme inhibition, computational studies and antiglaucoma activity.

Targeting Carbonic Anhydrases (CAs) represents a strategy to treat several diseases, from glaucoma to cancer. To widen the structure-activity relationships (SARs) of our series of piperazines endowed with potent human carbonic anhydrase (hCA) inhibition, a new series of chiral piperazines carrying a (2-hydroxyethyl) group was prepared. The Zn-binding function, the 4-sulfamoylbenzoyl moiety, was connected to one piperazine N-atom, while the other nitrogen was decorated with alkyl substituents.

A critical analysis of research methods and experimental models to study the physical properties of NiTi instruments and their fracture characteristics.

The aim of this review is to provide a critical overview of the physical properties (surface hardness, cutting efficiency, bending properties, flexibility and cyclic fatigue resistance) of NiTi instruments. Frequently used experimental models regarding these aspects will be presented and discussed with regard to their strengths and weaknesses. For all these aspects, a plethora of experimental models have been described.

Quality Assurance Measures and Mortality After Stroke.

Background: Quality assurance for acute in-hospital care in Germany is based on compulsory comparisons between institutions, so-called external quality assurance (EQA). The effectiveness of EQA has not yet been adequately studied. The purpose of the QUASCH project, which is supported by the Innovation Fund of the Federal Joint Committee, is to investigate the association between EQA and health care outcomes, specifically with respect to stroke.

Long Noncoding RNA Controls Advanced Atherosclerotic Lesion Formation and Plaque Destabilization.

Background: Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript () to atherosclerosis and carotid artery disease.

Methods: We profiled differences in RNA transcript expression in patients with advanced carotid artery atherosclerotic lesions from the Biobank of Karolinska Endarterectomies.

Minimal Dentinal Tubule Penetration of Endodontic Sealers in Warm Vertical Compaction by Direct Detection via SEM Analysis.

Sealer staining using rhodamine B dye to investigate the penetration depth of endodontic sealers was proven unsuitable for this purpose. This study aimed to investigate the sealer penetration depth into dentinal tubules by scanning electron microscopy (SEM). Root canals of 52 human upper central incisors were instrumented using the ProTaper Gold NiTi system (Dentsply Sirona, York, PA, USA) up to size F3.

Effect of Core Mass and Alloy on Cyclic Fatigue Resistance of Different Nickel-Titanium Endodontic Instruments in Matching Artificial Canals.

Instrument failure during root canal preparation is still a concern among endodontists. However, it remains unclear whether the use of more martensitic alloys or the cross-sectional design parameters (i.e.

Fluorescein and Rhodamine B-Binding Domains from Autodisplayed Fv-Antibody Library.

In this study, the binding domains for fluorescent dyes were presented that could be used as synthetic peptides or fusion proteins. Fv-antibodies against two fluorescent dyes (fluorescein and rhodamine B) were screened from the Fv-antibody library, which was prepared on the outer membrane of using the autodisplay technology. Two clones with binding activities to each fluorescent dye were screened separately from the library using flow cytometry.

Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense.

This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated in vitro screen. Eight compounds exhibited selective activity against T.

Editor's Choice - Risk of Major Amputation Following Application of Paclitaxel Coated Balloons in the Lower Limb Arteries: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Objective: There have been concerns about the long term safety of paclitaxel coated devices in the lower limbs. A formal systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to examine the long term risk of major amputation using paclitaxel coated balloons in peripheral arterial disease (PAD).

Method: This systematic review was registered with PROSPERO (ID 227761).

Debunking the Concept of Dentinal Tubule Penetration of Endodontic Sealers: Sealer Staining with Rhodamine B Fluorescent Dye Is an Inadequate Method.

The aim of this study was to investigate the suitability of rhodamine B dye staining of an epoxy resin sealer (AH Plus) and calcium-silicate-based sealers (Total Fill BC Sealer, BioRoot RCS) to represent the penetration depth of the sealers into dentinal tubules after root canal obturation. In a three-step process, (1) leaching of rhodamine B from sealers into a buffer solution, (2) passive penetration of leached rhodamine B into dentinal tubules, and (3) conformity of rhodamine B penetration assessed by confocal laser scanning microscopy (CLSM), and sealer penetration assessed by scanning electron microscopy (SEM), in root-canal-filled teeth, were evaluated. Rhodamine B dye massively leached out of Total Fill BC Sealer and BioRoot RCS into the phosphate-buffered saline (PBS).

Only the Co-Transcriptional Activity of β-Catenin Is Required for the Local Regulatory Effects in Hypertrophic Chondrocytes on Developmental Bone Modeling.

In hypertrophic chondrocytes, β-catenin has two roles. First, it locally suppresses the differentiation of osteoclasts at the chondro-osseous junction by maintaining the pro-osteoclastic factor receptor activator of NF-κB ligand (RANKL) at low levels. Second, it promotes the differentiation of osteoblast-precursors from chondrocytes.

Tunnel Convergence Rate in Combined Anteromedial Portal Anterior Cruciate Ligament and Anterolateral Structure Reconstructions Is Influenced by Anterior Cruciate Ligament Knee Flexion Angle, Tunnel Position, and Direction.

Purpose: The goal of the present study was to evaluate a potential tunnel convergence in combined anterior cruciate ligament (ACL) reconstruction using the anteromedial portal technique and lateral extra-articular tenodesis (LET).

Methods: Ten fresh frozen femora were dissected and a K-wires were inserted into the middle of the ACL stump, according to an ACL reconstruction at 110° and 140° knee flexion. ACL reconstruction at 120° and 130° was simulated.