Effect of material type, torque value, and sterilization on linear displacements of a scan body: An in vitro study.

BACKGROUND There is limited knowledge on the effect of scan body (SB) material type, torque value, and sterilization on linear displacements of implant SBs. PURPOSE To evaluate the effect of material type, torque value, and sterilization on linear displacements of SBs during screw tightening by using digital image correlation (DIC) analysis. MATERIALS AND METHODS One polyetheretherketone (PEEK, Zfx Intraoral Scan Body) and one titanium SB (Ti, MPS Zimmer Scanbody R1410) were tightened with 5 Ncm torque on two implants (Zimmer TSV ⌀4.7 mm) by using a digital torque limiting device. SBs' initial spatial positions relative to the implants were recorded by using 3D DIC technique. Measurements were repeated after initially increasing torque value to 10 Ncm and then to 15 Ncm, and these steps were repeated for a total of 10 PEEK and 10 Ti SBs on both implants (n = 20). All SBs were then sterilized 25 times by using an autoclave (STATIM 5000 S G4) according to manufacturer's recommendations and all measurements were repeated. Linear displacements on three axes were calculated for each SB with increasing torque values (from 5 to 10 Ncm and from 10 to 15 Ncm) before and after sterilization. SB displacements within each torque value-sterilization pair were compared by using Mann-Whitney U test, whereas Wilcoxon signed-rank test was used to compare SB displacements within each material-torque value pair between conditions and within each material-sterilization pair between torque values (α = 0.05). RESULTS On x-axis, PEEK SBs had higher displacements than Ti SBs (p < 0.001), whereas sterilization (p ≤ 0.028) and 15 Ncm torque application (p ≤ 0.006) led to higher displacements of PEEK SBs. On y-axis, PEEK SBs had higher displacements than Ti SBs with 15 Ncm torque application (p ≤ 0.033). A total of 15 Ncm torque-applied PEEK SBs and 10 Ncm torque-applied Ti SBs had higher displacements after sterilization (p ≤ 0.028). Application of 15 Ncm torque led to higher displacements regardless of the material (p ≤ 0.002). On z-axis, PEEK SBs had higher displacements (p ≤ 0.015), except for 10 Ncm torque-applied sterilized SBs (p = 0.102). With 10 Ncm torque application, sterilization decreased the displacement values of PEEK SBs (p = 0.044). Greater displacements were observed with 10 Ncm torque-applied Ti SBs before sterilization and 15 Ncm torque-applied PEEK SBs after sterilization (p ≤ 0.033). CONCLUSIONS Axial displacement of SBs was affected by material type, torque value, and sterilization. Ti SBs mostly had lower displacements than PEEK SBs. Application of 15 Ncm torque to tested PEEK SBs should be refrained from and a calibrated tightening tool may enable the application of 10 Ncm or lower torque values for lower displacements. Sterilization generally increased PEEK SB displacements

Defining alternative recovery strategies for reuse: An analysis of multiple case studies under the reuse umbrella

This study focuses on the role of the reuse recovery approach and its strategies in the circular economy through a product design lens. While the circular economy has been widely discussed, not all recovery strategies have been thoroughly investigated and understood alike. This research differentiates between reuse and other recovery strategies and defines three distinct opportunities under the ‘reuse umbrella’ – reuse, cascade and relink. For each opportunity, possible sub-opportunities are identified and elaborated. Through a multiple case study analysis, the sub-opportunities are elaborated with a "Design for X" approach into eight different strategies of reuse, including design for direct reuse, reconfiguration, material cascading, repurposing, component reuse, creative reuse, material reclamation and adaptive reuse. The research emphasises that the appropriateness of a reuse strategy depends on various aspects such as the context, users, industries, and material flows. Also, this study stresses the importance of reuse in promoting circular product development and consumption, providing valuable implications for businesses and designers.The research project received financial backing from the UKRI National Interdisciplinary Circular Economy Research programme (NICER

TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis

Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD

NRF2 Activation Restores Disease Related Metabolic Deficiencies in Olfactory Neurosphere-Derived Cells from Patients with Sporadic Parkinson's Disease

Extent: 14p.Background: Without appropriate cellular models the etiology of idiopathic Parkinson’s disease remains unknown. We recently reported a novel patient-derived cellular model generated from biopsies of the olfactory mucosa (termed olfactory neurosphere-derived (hONS) cells) which express functional and genetic differences in a disease-specific manner. Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differentially expressed in Parkinson’s disease. Results: We tested the robustness of our initial findings by including additional cell lines and confirmed that hONS cells from Patients had 20% reductions in reduced glutathione levels and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium, inner salt] metabolism compared to cultures from healthy Control donors. We also confirmed that Patient hONS cells are in a state of oxidative stress due to higher production of H2O2 than Control cultures. siRNA-mediated ablation of NRF2 in Control donor cells decreased both total glutathione content and MTS metabolism to levels detected in cells from Parkinson’s Disease patients. Conversely, and more importantly, we showed that activation of the NRF2 pathway in Parkinson’s disease hONS cultures restored glutathione levels and MTS metabolism to Control levels. Paradoxically, transcriptomic analysis after NRF2 pathway activation revealed an increased number of differentially expressed mRNAs within the NRF2 pathway in L-SUL treated Patient-derived hONS cells compared to L-SUL treated Controls, even though their metabolism was restored to normal. We also identified differential expression of the PI3K/AKT signalling pathway, but only post-treatment. Conclusions: Our results confirmed NRF2 as a potential therapeutic target for Parkinson’s disease and provided the first demonstration that NRF2 function was inducible in Patient-derived cells from donors with uniquely varied genetic backgrounds. However, our results also demonstrated that the response of PD patient-derived cells was not co-ordinated in the same way as in Control cells. This may be an important factor when developing new therapeutics.Anthony L. Cook, Alejandra M. Vitale, Sugandha Ravishankar, Nicholas Matigian, Greg T. Sutherland, Jiangou Shan, Ratneswary Sutharsan, Chris Perry, Peter A. Silburn, George D. Mellick, Murray L. Whitelaw, Christine A. Wells, Alan Mackay-Sim and Stephen A. Woo

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b]-[1,3,4]thiadiazole-5-carbohydrazide

In this study, some novel 2,6-dimethyl-N'-substituted phenylmethylene-imidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazides (3a-3h) were synthesized from 2,6-dimethylimidazo-[2,1-b][1,3,4]thiadiazole-5-carbohydrazide (2). The newly synthesized compounds (3a-3h) were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. Compounds 3c and 3h which passed the criteria for activity in this assay (20-29% growth percentages) were scheduled automatically for evaluation against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate cell stability or growth. 2,6-Dimethyl-N'-(2-hydroxyphenylmethylidene)imidazo[2,1b][1,3,4]thiadiazole-5-carbohydrazide (3c) showed the most favorable cytotoxicity. This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumor cell line in vitro screen on an ovarian cancer cell line (OVCAR log(10) GI(50) value -5.51). (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved

Receptor-based 3D QSAR analysis of serotonin 5-HT1D receptor agonists

A three-dimensional quantitative structure - activity relationship study (3D QSAR) has been successfully applied to explain the binding affinities for the serotonin 5-HT1D receptor of a triptan series. The paper describes the development of a receptor-based 3D QSAR model of some known agonists and recently developed triptans on the 5-HT1D serotonergic receptor, showing a significant correlation between predicted and experimentally measured binding affinity (pIC(50)). The pIC(50) values of these agonists are in the range from 5.40 to 9.50. The ligand alignment obtained from dynamic simulations was taken as basis for a 3D QSAR analysis applying the GRID/GOLPE program. 3D QSAR analysis of the ligands resulted in a model of high quality (r(2) = 0.9895, q(LOO)(2) = 0.7854). This is an excellent result and proves both the validity of the proposed pharmacophore and the predictive quality of the 3D QSAR model for the triptan series of serotonin 5-HT1D receptor agonists

Synthesis and structure-activity relationships of 3-hydrazono-1H-2-indolinones with antituberculosis activity

A series of 3-[S-(4-substituted phenacyl)-4-substituted-isothiosemicarbazono]-1H-2-indolinones 2a-h and 3-[(3,4-disubstituted-4-thiazolin-2-ylidene)hydrazono]-1H-2-indolinones 3a-f were synthesized. These new hydrazonoindolinone derivatives and 3-(4-substituted-thiosemicarbazono)-1H/1-acetyl-2-indolinones 1a-g 3-[(2-substituted-4-thiazolidinon-2-ylid drazono]-1H-2-indolinones 4a-o, 3-[(2-substituted-4-carboxy/carbetoxy-5-methyl-4-thiazolin-2-ylidene) hydrazono]-1H-2-indolinones 5a-e and 3-substituted-hydrazono-1H-2-indolinones 6a-o which had been previously reported were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv. These compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at 12 mu g/ml against M. tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. 2a, 2c, 2f-h, 3c and 3f demonstrating activity in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv to determine the actual minimum inhibitory concentration (MIC) in CABTEC 460. The structure-activity relationships of the derivatives were investigated