OBJECTIVEIndividuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients.RESEARCH DESIGN AND METHODSTLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects (n = 23) and type 2 diabetic subjects (n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays.RESULTSType 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects (P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment–insulin resistance (HOMA-IR), glucose, A1C, Nε-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-κB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-κB signaling resulted in elevated levels of cytokines (P < 0.05), but increased interleukin (IL)-1β, interferon (IFN)-γ, and endotoxin were not significant when adjusted for BMI.CONCLUSIONSIn this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.

The authors propose that there are 2 different mechanisms whereby spatial cues capture attention. The voluntary mechanism is the strategic allocation of perceptual resources to the location most likely to contain the target. The involuntary mechanism is a reflexive orienting response that occurs even when the spatial cue does not indicate the probable target location. Voluntary attention enhances the perceptual representation of the stimulus in the cued location relative to other locations. Hence, voluntary attention affects performance in experiments designed around both accuracy and reaction time. Involuntary attention affects a decision as to which location should be responded to. Because involuntary attention does not change the perceptual representation, it affects performance in reaction time experiments but not accuracy experiments. The authors obtained this pattern of results in 4 different versions of the spatial cuing paradigm.

The single-bundle reconstruction produced graft forces, knee laxities, and coupled tibial rotations that were closest to normal. Adding a posterolateral graft to an anteromedial graft tended to reduce laxities and tibial rotations, but the reductions were accompanied by markedly higher forces in the posterolateral graft near 0 degrees that occasionally caused it to fail during tests with internal torque or anterior tibial force.

Reduction or elimination of the pivot-shift sign is an important goal for anterior cruciate ligament reconstruction. In our model, the results show that a single-bundle reconstruction was sufficient to restore intact knee kinematics during a simulated pivot-shift event. The higher graft forces with some double-bundle graft-tensioning protocols reduced the coupled rotations and displacements from an applied valgus moment to less than the intact levels. This overcorrection should theoretically make the knee less likely to pivot but could have unknown clinical consequences.

The Baumann angle of the humerus has been commonly used as an outcome measure for supracondylar fractures in children. However, there is limited or no information about the reliability of this measurement. The purpose of this study was to determine the inter-observer reliability (IEOR) and intra-observer reliability (IAOR) of the Baumann angle of the humerus. The Baumann angle of the humerus was measured by five observers on the anteroposterior radiographs of 35 children’s elbows, all of which had sustained a nondisplaced supracondylar humeral fracture. The values of IEOR and IAOR were calculated using a Pearson coefficient of correlation. Ranges of differences in the measurement of the Baumann angle of the humerus were established, and the percentage of agreement between observers was then calculated using those ranges. The Baumann angle of the humerus is a simple, repeatable and reliable measurement that can be used for the determination of the outcome of supracondylar humeral fractures in the paediatric population. An excellent IEOR was found for the measurement of the Baumann angle (r = 0.78, p = 0.0001). When the difference between observers in the reported measurement of the Baumann’s angle was calculated to be within seven degrees of each other, at least four of the five observers agreed 100% of the time. Similarly, excellent values of IAOR were found for the measurement of the Baumann’s angle (r = 0.80, p = 0.0001). Level of evidence for this study was III.

Toll-like receptors (TLRs) are key innate immune sensors of endogenous damage signals and play an important role in inflammatory diseases like diabetes and atherosclerosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been reported to be an antiinflammatory agent. Thus, in the present study, we examined the antiinflammatory effects of PIO on TLR2 and TLR4 expression in human monocytes exposed to Pam3CSK4 (Pam; TLR2 ligand) and purified lipopolysaccharide (LPS; TLR4 ligand) using flow cytometry and real-time RT-PCR. Monocytes were isolated from healthy human volunteers and pretreated with PIO (1 microM) followed by Pam (170 ng/ml) and LPS (160 ng/ml) challenge. PIO significantly decreased Pam- and LPS-induced TLR2 (-56%) and TLR4 (-78%) expression (P < 0.05). In addition, PIO decreased TLR ligand-induced nuclear factor-kappaB activity (-63%), IL-1beta (-50%), IL-6 (-52%), monocyte chemoattractant protein-1(-83%), and TNF-alpha (-87%) compared with control. Next, PIO-treated db/db mice (n = 6/group) showed decreased TLR2 (-60%) and TLR4 (-45%) expression in peritoneal macrophages compared with vehicle control mice (P < 0.001) with associated decrease in MyD88-dependent signaling and nuclear factor-kappaB activation. Data suggest that Pam- and LPS-induced TLR2 and TLR4 expression are inhibited by PIO in human monocytes and db/db mice. Thus, we define a novel pathway by which PIO could induce antiinflammatory effects.

Colonization of fluoroquinolone resistant organisms in the rectum identifies men at high risk for infection and subsequent hospitalization from prostate biopsy, especially in those with fluoroquinolone prophylaxis only.

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