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Tubulointerstitial nephritis is a cardinal renal manifestation in leptospirosis and LipL32, the major lipoprotein component of leptospiral outer membrane proteins (OMPs), induces a robust inflammatory response in cultured renal proximal tubule cells through a nuclear factor-kappaB-related pathway. Here, we investigated whether Toll-like receptor (TLR), known to play a pivotal role in innate immunity, could mediate the inflammatory response induced by leptospiral OMPs in renal proximal tubule cells. TLR expression was analyzed by flow cytometry and indirect immunofluorescence in cultured mouse proximal tubule (pyruvate kinase simian virus 40-proximal straight (PKSV-PR)) cells. Reverse transcription-competitive polymerase chain reaction and enzyme-linked immunosorbent assay were undertaken to analyze the inducible effects of inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1 also termed CCL2) by pathogenic and non-pathogenic leptospiral OMPs and recombinant lipoproteins in either PKSV-PR cells or TLR-transfected human embryonic kidney (HEK) 293 cells. Anti-TLR antibodies were used for blocking experiments. Leptospira santarosai serovar Shermani OMPs and LipL32 induced a significant increase in TLR2 but not TLR4 expression in PKSV-PR cells. The increase in iNOS and CCL2/MCP-1 mRNA expressions could be prevented by an anti-TLR2 antibody, but not by an anti-TLR4 antibody. Furthermore, leptospiral OMPs stimulated both CCL2/MCP-1 mRNA and secreted protein in transfected HEK 293 cells with a TLR2-expressing plasmid, but had no effect in cells with a TLR4-expressing plasmid. In conclusion, these findings indicate that the stimulation of iNOS and CCL2/MCP-1 caused by pathogenic leptospiral OMPs, in particular LipL32, in proximal tubule cells requires TLR2 for the early inflammatory response.

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The air pollutants NO₂, SO₂, O₃, and PM₁₀ increase the chances of outpatient visits for nonspecific conjunctivitis and have no evident lag effects.

The use of an mesial-occlusal-distal (MOD) restoration in repairing a large carious lesion depends on many factors. Biomechanical performance is one of the most important. It has been recognized that resistance to restoration failure is not solely a biological concern (e.g. toxicity), but that the cavity shape, dimensions, and the state of stress must all be taken into account. In the present study, a newly developed auto-mesh program was used to generate 30 three-dimensional (3D) finite element (FE) models simulating the biomechanics for multiple factorial design of the MOD gold restoration in a maxillary second premolar. Stress levels were related to individual design factors (e.g. pulpal wall depth [P], isthmus width [W] and interaxial thickness [T]) and to their interactions under the worst physiological scenario: a concentrated bite force acting on lingual cusp with debonded interfaces between cavity walls and restorations. The results showed that enlarging the volume of the MOD cavity significantly increased stresses in enamel but did not intentionally affect stresses in dentin. The alternation of individual design parameters significantly changed the peak stresses (P < 0.05). For all three parameters, except for the width, the peak stress increased as the cavity dimension increased. Stress elevation rate (termed as 'volumetric stress rate'--stress elevation by increasing one unit volume of the restored materials) was different among three design factors. Depth was the most critical factor governing the stress elevation in enamel (1.76 MPa mm(-3)) while length (interaxial thickness) was the most important parameter in dentin (0.49 MPa mm(-3)). Width was the least compromising factor to the remaining tooth, 0.32 MPa mm(-3) for enamel and -0.23 MPa mm(-3) for dentin. The findings, at its core, did not fully agree with the traditional concept that the preservation of tooth substances will reduce risk of tooth fracture. This study leaves open possibility for the structural optimization of the MOD restoration.

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Background Systemic tranexamic acid can decrease blood loss and rates of transfusion in patients undergoing total hip arthroplasty (THA). However, the efficacy of topical tranexamic acid in THA has only recently been characterized in a small number of studies. Questions/purposes The purpose of this study was to compare (1) the greatest hemoglobin decrease after surgery;(2) transfusion rates; and (3) symptomatic thromboembolic events among patients undergoing THA who did and did not receive topical tranexamic acid.