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Removable prosthodontics are often associated with mechanical troubles in daily use, such as fracture or deformation. These troubles render prostheses unusable and reduce wearers' QOL. Various reinforcements are used to prevent such problems, but consensus on reinforcement has not been reached. This review aimed to summarise the effects of reinforcement and to propose favourable reinforcement based on material, design and position in the prostheses. Initially, 139 articles were selected by electronic and manual searches. After exclusion of 99 articles based on the exclusion criteria, 40 articles were finally included in the review. Electronic searches were performed for articles published from 2005 to 2015 in PubMed, EMBASE, MEDLINE and Cochrane Library, and manual searches were performed in 10 journals relevant to the topic of removable prosthodontics. For in vitro studies, certain dental alloys and fibres were mainly used. Their forms were different, including complicated forms in dental alloys and various forms in fibres. The materials were examined for mechanical properties like fracture strength, flexural strength and elastic modulus and compared with one another or without reinforcement. There were a few clinical studies and one longitudinal study. Cast metal reinforcement seemed to be most favourable in terms of fracture toughness and stiffness. The most favourable forms differed depending on the prostheses, but placement around thin and deformable areas was effective. However, randomised or longitudinal clinical reports and comparative clinical studies on the use of reinforcement were still lacking and such studies are necessary in the future. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine a longitudinal clinical performance of magnetic attachments used for natural overdenture abutments. The study included 131 patients who had used removable prostheses (complete overdentures 31%, partial dentures 69%) more than 5 years (40-90 years old) with 211 magnetic attachments on natural abutments (Magfit 400 or 600; Aichi Steel co., Aichi, Japan) treated in 15 clinics using a standardized protocol. Analyses were performed on the degree of patient satisfaction regarding retention, complications of magnets (corrosion, detachment from denture base), abutments (pain during mastication, periodontal pocket formation, inflammation, mobility), and dentures (fracture etc.). Ninety-seven percent of patients were satisfied with the retention and stability of their dentures. No corrosion of magnet was observed, and 19 magnets were detached. Most frequent complication of abutments was periodontal pocket formation (52%), followed by the inflammation (29%), increase in mobility (27%) and pain (4%). Magnetic attachment on natural tooth abutments provided a viable and long-term treatment option. [ABSTRACT FROM AUTHOR]

The Myb protein was first identified as an oncogene that causes leukemia in chickens. Since then, it has been widely associated with different types of cancers and studied in detail in myeloid leukemias. However, despite these studies, its role in the induction, pathogenesis and maintenance of AML, and other blood disorders, is still not well understood. Recent efforts to uncover its plethora of transcriptional targets have provided key insights into understanding its mechanism of action. This review evaluates our current knowledge of the role of Myb in leukemia, with a particular focus on AML, from the vast literature spanning three decades, highlighting key studies that have influenced our understanding. We discuss recent insights into its role in leukemogenesis and how these could be exploited for the therapeutic targeting of Myb, its associated co-regulators or its target genes, in order to improve outcomes in the treatment of a wide range of hematopoietic malignancies. [ABSTRACT FROM AUTHOR]

Recently, a newly developed magnetic attachment with stress breaker was used in retentive components in overdentures. Excessive lateral stress has a more harmful effect on natural teeth than axial stress, and the magnetic attachment with stress breaker is expected to reduce lateral forces on abutment teeth and protect it teeth from excessive stress. However, the properties of this retainer have not yet been determined experimentally. This study compares the lateral forces on abutment teeth for three retainers under loading on the denture base in a model study. A mandibular simulation model is constructed to measure lateral stress. Three types of retentive devices are attached to the canine root. These devices include the conventional root coping, the conventional magnetic attachment and the new magnetic attachment with stress breaker. For each retentive device, load is generated on the occlusal table of the model overdenture, and the lateral stress on the canine root and the displacement of the overdenture measured. The magnetic attachment with stress breaker does not displace the denture and exhibits lower lateral stress in the canine root than conventional root coping and magnetic attachments. [ABSTRACT FROM AUTHOR]

This paper presents an overview of recent hardware extensions and data analysis developments to the Wendelstein 7-X visible core spectroscopy systems. These include upgrades to prepare the in-vessel components for long-pulse operation, nine additional spectrometers, a new line of sight array for passive spectroscopy, and a coherence imaging charge exchange spectroscopy diagnostic. Progress in data analysis includes ion temperatures and densities from multiple impurity species, a statistical comparison with x-ray crystal spectrometer measurements, neutral density measurements from thermal passive Balmer-alpha emission, and a Bayesian analysis of active hydrogen emission, which is able to infer electron density and main ion temperature profiles. [ABSTRACT FROM AUTHOR]

This work reports on recent results on the search for high performance plasma scenarios at the magnetically confined stellarator fusion device Wendelstein 7-X. In four new designed scenarios, the development from transient toward stationary plasmas of improved performance has been realized. In particular, a high performance duration of up to 5 s, an energy confinement time of 0.3 s, a diamagnetic energy of 1.1 MJ, a central ion temperature of 2.2 keV, and a fusion triple product of 3.4 × 10 19 m − 3 · keV · s have been achieved, and previously observed limitations of the machine have been overcome, regarding both the performance and its duration. The two main experimental techniques for stationary high performance are neutral beam injection core fueling on the one hand and the use of a magnetic field configuration with internal islands on the other hand. Two of the developed scenarios are expected to be extendable straightforward toward a duration of several tens of seconds, making use of the long pulse operation capabilities of W7-X. [ABSTRACT FROM AUTHOR]

The MYB gene is a master regulator of hematopoiesis and contributes to leukemogenesis in several species including humans. Although it is clear that MYB can promote proliferation, suppress apoptosis and block differentiation, the identities of the MYB target genes that mediate these effects have only been partially elucidated. Several studies, including our own, have collectively identified substantial numbers of MYB target genes, including candidates for each of these activities; however, functional validation, particularly in the case of differentiation suppression, has lagged well behind. Here we show that GFI1, which encodes an important regulator of hematopoietic stem cell (HSC) function and granulocytic differentiation, is a direct target of MYB in myeloid leukemia cells. Chromatin immunoprecipitation and reporter studies identified a functional MYB-binding site in the promoter region of GFI, whereas ectopic expression and small hairpin RNA-mediated knockdown of MYB resulted in concomitant increases and decreases, respectively, in GFI1 expression. We also demonstrate that GFI1, like MYB, can block the induced monocytic differentiation of a human acute myeloid leukemia cell line, and most importantly, that GFI1 is essential for MYB's ability to block monocytic differentiation. Thus, we have identified a target of MYB that is a likely mediator of its myeloid differentiation-blocking activity, and which may also be involved in MYB's activities in regulating normal HSC function and myeloid differentiation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the influence of coping heights on the strain around the abutment teeth and at the middle part of mandibular overdentures, using strain gauges. A mandibular edentulous model with a silicone artificial mucosa of thickness 2 mm was made. Two artificial roots were embedded on both sides in the canine position. The coping had a dome-shaped upper surface at a height of 0, 2, 4 and 6 mm. On the lingual polished surface of the overdenture, three strain gauges were attached in the left canine position at the vertical level corresponding to the top of the 6, 4 and 2 mm copings and two strain gauges were attached in the middle section (upper and lower). A vertical loading of 49 N was applied on the occlusal surface of first premolar, first molar and second molar. When loading on the first premolar adjacent to an abutment, the largest tensile strain was observed on the overdenture surface close to the top of each coping, independent of coping heights. When loading on the first premolar on the opposite side, the tensile strains around the coping were remarkably smaller. In the middle part of the overdenture, the compressive strains became larger by reducing the coping height or loading on distal point. The largest tensile strain was observed on the overdenture surface close to the top of copings, independent of coping heights. [ABSTRACT FROM AUTHOR]

The Wilms’ tumour suppressor gene (WT1) encodes a zinc finger-containing nuclear protein essential for kidney and urogenital development. Initially considered a transcription factor, there is mounting evidence that WT1 has a role in post-transcriptional processing. Using the interspecies heterokaryon assay, we have demonstrated that WT1 can undergo nucleocytoplasmic shuttling. We have also mapped the region responsible for nuclear export to residues 182–324. Our data add further complexity to the role of WT1 in trancriptional and post-transcriptional regulation. [Copyright &y& Elsevier]

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelialmesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features. [ABSTRACT FROM AUTHOR]

Background: PG545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The aim of the study was to assess PG545 in various solid tumour and metastasis models.Methods: The anti-angiogenic, anti-tumour and anti-metastatic properties of PG545 were assessed using in vivo angiogenesis, solid tumour and metastasis models. Pharmacokinetic (PK) data were also generated in tumour-bearing mice to gain an understanding of optimal dosing schedules and regimens.Results: PG545 was shown to inhibit angiogenesis in vivo and induce anti-tumour or anti-metastatic effects in murine models of breast, prostate, liver, lung, colon, head and neck cancers and melanoma. Enhanced anti-tumour activity was also noted when used in combination with sorafenib in a liver cancer model. PK data revealed that the half-life of PG545 was relatively long, with pharmacologically relevant concentrations of radiolabeled PG545 observed in liver tumours.Conclusion: PG545 is a new anti-angiogenic clinical candidate for cancer therapy. The anti-metastatic property of PG545, likely due to the inhibition of heparanase, may prove to be a critical attribute as the compound enters phase I clinical trials. [ABSTRACT FROM AUTHOR]

c-Myb is an essential hematopoietic transcription factor that controls proliferation and differentiation of progenitors during blood cell development. Whereas sumoylation of the C-terminal regulatory domain (CRD) is known to have a major impact on the activity of c-Myb, no role for noncovalent binding of small ubiquitin-like modifier (SUMO) to c-Myb has been described. Based on the consensus SUMO-interacting motif (SIM), we identified and examined putative SIMs in human c-Myb. Interaction and reporter assays showed that the SIM in the in the transactivation domain of c-Myb (V267NIV) is functional. This motif is necessary for c-Myb to be able to interact noncovalently with SUMO, preferentially SUMO2/3. Destroying the SUMO-binding properties by mutation resulted in a large increase in the transactivation potential of c-Myb. Mutational analysis and overexpression of conjugation-defective SUMO argued against intramolecular repression caused by sumoylated CRD and in favor of SUMO-dependent repression in trans. Using both a myeloid cell line-based assay and a primary hematopoietic cell assay, we addressed the transforming abilities of SUMO binding and conjugation mutants. Interestingly, only loss of SUMO binding, and not SUMO conjugation, enhanced the myeloid transformational potential of c-Myb. c-Myb with the SIM mutated conferred a higher proliferative ability than the wild-type and caused an effective differentiation block. This establishes SUMO binding as a mechanism involved in modulating the transactivation activity of c-Myb, and responsible for keeping the transforming potential of the oncoprotein in check. [ABSTRACT FROM AUTHOR]

Aberrant Wnt signaling mediated by mutations affecting APC (adenomatous polyposis coli) or β-catenin initiates the majority of human colorectal cancers (CRC) and drives tumorigenesis through the activation of specific genes such as MYC. We report here a novel association whereby another oncogenic transcription factor, MYB/c-Myb, is necessary for intestinal adenoma development directed by activated Wnt signaling. APCMin/+ mice in which c-myb is haploinsufficient survive longer than wild-type APCMin/+ animals due to a delay in adenoma formation. Intestinal adenomas from APCMin/+ mice were assessed and found to have high levels of c-myc gene expression. We explored the relationship between activated Wnt signaling and MYB in regulating MYC and found activated β-catenin in combination with MYB induces robust upregulation of MYC promoter activity, as well as endogenous MYC mRNA and protein expression, in human cells. This cooperation occurred through independent binding of MYB and β-catenin to the MYC promoter. These data highlight a cooperative function for MYB in the context of activated Wnt signaling and provide a molecular basis for the expression of MYC in CRC. [ABSTRACT FROM AUTHOR]

The structural design of removable partial dentures (RPDs) is critical for preventing distortion of the prosthesis, protecting abutment teeth and residual ridges as well as for high masticatory performance. The aim of this study was to clarify the feasibility and utility of a computer-aided designing (CAD) system with finite element analysis (FEA) for molar teeth arrangement in unilateral distal extension base RPDs. The shapes of artificial teeth and residual ridge were measured and converted into point group data. Solid models were created from surface-modelled point group data in a 3D surface CAD format. An occlusal rim was created on the residual ridge mucosa and the occlusal rim - residual ridge mucosa model with FEA function was created. Stress distribution on the residual ridge mucosa was compared by changing the loading point. The artificial teeth were then arranged in locations with the lowest amount of stress. After building an artificial teeth – saddle – residual ridge mucosa model, stress distribution in the residual ridge mucosa was re-evaluated by simulating occlusal force. On the occlusal rim - residual ridge mucosa model, stress was reduced when the loading point was located around the buccal shelf where functional cusps of artificial teeth were charted. It was confirmed that stress distribution in the residual ridge mucosa was equalized on the artificial teeth – saddle – residual ridge mucosa model. This system might be clinically useful tool for designing RPDs if FEA-guided designing of retainers and connectors can be added. [ABSTRACT FROM AUTHOR]

The tumor suppressor Gadd45α was earlier shown to be a repressed target of sustained receptor-mediated ERK1/2 signaling. We have identified Gadd45α as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (GMR-V449E). GADD45A mRNA downregulation is also associated with FLT3-ITD+ AML. Sustained ERK1/2 signaling contributes significantly to receptor-mediated downregulation of Gadd45α mRNA in FDB1 cells expressing activated receptor mutants, and in the FLT3-ITD+ cell line MV4;11. Knockdown of Gadd45α with shRNA led to increased growth and survival of FDB1 cells and enforced expression of Gadd45α in FDB1 cells expressing FLT3-ITD or GMR-V449E resulted in reduced growth and viability. Gadd45α overexpression in FLT3-ITD+ AML cell lines also resulted in reduced growth associated with increased apoptosis and G1/S cell cycle arrest. Overexpression of Gadd45α in FDB1 cells expressing GMR-V449E was sufficient to induce changes associated with myeloid differentiation suggesting Gadd45α downregulation contributes to the maintenance of receptor-induced myeloid differentiation block. Thus, we show that ERK1/2-mediated downregulation of Gadd45α by sustained receptor signaling contributes to growth, survival and arrested differentiation in AML.Leukemia (2009) 23, 729–738; doi:10.1038/leu.2008.349; published online 8 January 2009 [ABSTRACT FROM AUTHOR]

This study investigated associations between temporomandibular joint (TMJ) sounds and occlusal force or masticatory performance stratified by posterior occlusal supports in older Japanese adults. The subjects consisted of 1646 independently living people over 60 years. Masticatory performance, occlusal force, TMJ sounds and maximal mouth opening were examined. Posterior occlusal supports were classified by the Eichner Index. The prevalence of TMJ sounds was 27·7%, limitation of mouth opening (<40 mm) was 7·9% and TMJ pain was only 1·5%. In the Eichner C group, TMJ sounds were significantly associated with lower occlusal force (OR = 3·20, P = 0·046) and lower masticatory performance (OR = 3·18, P = 0·041) after controlling for gender and age. These associations were not found in the Eichner A and B groups. Within the limitations of this study, the presence of TMJ sounds, even if they were symptomless, was associated with impairment of masticatory function in older adults with reduced occlusal support. [ABSTRACT FROM AUTHOR]

Purpose Gastrointestinal bleeding (GIB) is a common complication of LVAD therapy. Previously, we retrospectively reviewed endoscopic evaluation and outcomes of GIB in LVAD recipients in our center and proposed an endoscopic management algorithm (Figure) to eliminate low yield procedures. Herein, we aimed to prospectively validate this algorithm. Methods We prospectively tested the algorithm in LVAD recipients who presented with GIB between June 2017 and August 2018. We compared the diagnostic and therapeutic yield of endoscopy and healthcare costs between conventional GIB management to the algorithm. Results 33 LVAD pts with GIB were identified. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) pts. In total, 41 endoscopies localized a source in 23 (56%) resulting in 14 (36%) interventions at a median length-of-stay (LOS) of 8 d. Of 18 lesions identified, angiodysplasias were the most common (9, 50%) and the small bowel was the most common location (11, 48%). Despite non-adherence to the algorithm in 7 of 33 pts (21%), algorithm implementation increased the diagnostic yield by 70% (p=0.008) and therapeutic yield by 125% (p=0.01), reduced the number of procedures per pt by24% (p<0.01), LOS by 33% (p<0.01), and estimated costs by 18% (p<0.01) in comparison to our retrospective cohort (Table). Conclusion Our endoscopic management algorithm of GIB in LVAD pts is effective in reducing low yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing healthcare resource utilization. [ABSTRACT FROM AUTHOR]