Hypoesthesia after anterior cruciate ligament reconstruction: The relationship between proprioception and vibration perception deficits in individuals greater than one year post-surgery

Background

While surgical reconstruction restores mechanical stability following anterior cruciate ligament (ACL) rupture, many experience early-onset osteoarthritis despite surgery. Neurophysiological changes are hypothesized to contribute to knee osteoarthritis progression. Proprioceptive deficits have been reported following ACL injury/reconstruction; however, vibration perception threshold (VPT) has been less studied. This study explored relationships between pain, VPT, proprioception, function, and strength following ACL-reconstruction.

Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes

Recognition of Gram-positive bacteria by Toll-like receptor 2 (TLR2) induces activation of proinflammatory pathways. In mice, sensitization with the Gram-positive Propionibacterium acnes followed by a challenge with the TLR4 ligand, lipopolysaccharide (LPS), results in fulminant hepatic failure. Here, we investigated the role of TLR2 in liver sensitization to LPS-induced injury. Stimulation of Chinese hamster ovary cells and peritoneal macrophages with heat-killed P. acnes required expression of TLR2 but not of TLR4, suggesting that P. acnes was a TLR2 ligand. Cell activation by P. acnes was myeloid differentiation primary-response protein 88 (MyD88)-dependent, and it was augmented by coexpression of CD14 in mouse peritoneal macrophages. In vitro, P. acnes behaved as a TLR2 ligand and induced TLR4 hetero- and TLR2 homotolerance in peritoneal macrophages. In vivo priming of wild-type mice with P. acnes, but not with the selective TLR2 ligands peptidoglycan and lipotheicoic acid, resulted in hepatocyte necrosis, hyperelevated serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, interferon-gamma (IFN-gamma), and IL-12 (p40/p70), and increased RNA expression of proinflammatory cytokines (IL-12p40, IL-1alpha, IL-6, IL-1beta, IL-18, IFN-gamma) in the liver after a LPS challenge. Furthermore, P. acnes priming sensitized TLR2-deficient (TLR2-/-) but not MyD88-/- mice to LPS-induced injury, evidenced by hepatocyte necrosis, increased levels of serum TNF-alpha, IFN-gamma, IL-6, and liver proinflammatory cytokine mRNA expression. IFN-gamma, a cytokine sensitizing to endotoxin, was induced by P. acnes in splenocytes of TLR2-/- and TLR9-/- but not MyD88-/- mice. These results suggest that although P. acnes triggers TLR2-mediated cell activation, TLR2-independent but MyD88-dependent mechanisms mediate in vivo sensitization by P. acnes for LPS-induced liver injury.     

Acute ethanol consumption synergizes with trauma to increase monocyte tumor necrosis factor α production late postinjury

The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor (TNF) production during the very early postinjury (0–3 days) period. However, TNF production by these alcoholexposed patients' monocytes (MØ) became hyperelevated late postinjury (>9 days). Consequently, these massively elevated MØ TNF levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen,Staphylococcus enterotoxin B (SEB), results in a preferential induction of cellassociated MØ TNF production, described as characteristic of immunosuppressed trauma patients. Acutein vitro ethanol treatment down-regulated the elevated TNF production by trauma patients' MØ after either SEB, muramyl-dipeptide (MDP), interferon- plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS-induced TNF mRNA induction was inhibited by acute alcohol treatment in normal MØ, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor production in trauma patients' activated MØ.     

GyrB Polymorphisms Accurately Assign Invasive Viridans Group Streptococcal Species

Viridans group streptococci (VGS) are a heterogeneous group of medically important bacteria that cannot be accurately assigned to a particular species using conventional phenotypic methods. Although multilocus sequence analysis (MLSA) is considered the gold standard for VGS species-level identification, MLSA is not yet feasible in the clinical setting. Conversely, molecular methods, such as sodA and 16S rRNA gene sequencing, are clinically practical but not sufficiently accurate for VGS species-level identification. Here, we present data regarding the use of an ∼400-nucleotide internal fragment of the gene encoding DNA gyrase subunit B (GyrB) for VGS species-level identification. MLSA, internal gyrB, sodA, full-length, and 5′ 16S gene sequences were used to characterize 102 unique VGS blood isolates collected from 2011 to 2012. When using the MLSA species assignment as a reference, full-length and 5′ partial 16S gene and sodA sequence analyses failed to correctly assign all strains to a species. Precise species determination was particularly problematic for Streptococcus mitis and Streptococcus oralis isolates. However, the internal gyrB fragment allowed for accurate species designations for all 102 strains. We validated these findings using 54 VGS strains for which MLSA, 16S gene, sodA, and gyrB data are available at the NCBI, showing that gyrB is superior to 16S gene and sodA sequence analyses for VGS species identification. We also observed that specific polymorphisms in the 133-amino acid sequence of the internal GyrB fragment can be used to identify invasive VGS species. Thus, the GyrB amino acid sequence may offer a more practical and accurate method for classifying invasive VGS strains to the species level.     

Alcohol-Induced Regulation of Nuclear Regulatory Factor-Kβ in Human Monocytes

Acute ethanol exposure has the capacity to modulate immune functions, particularly, to down regulate monocyte production of inflammatory cytokines. However, the intracellular mechanisms for these effects of ethanol are yet to be understood. Considering that nuclear regulatory factor-kβ (NF-KB)/Rel is a common regulatory element of the promoter region of the inflammatory cytokine genes, herein, we tested the hypothesis that acute ethanol affects NF-kB activation in human monocytes. Adherence-isolated monocytes showed constitutive DNA binding activity of NF-kB. A clinically relevant dose (25 mM) of acute ethanol treatment in vitro increased NF-kB binding activity in monocytes with a preferential induction of the inhibitory, p50/p50, NF-kB/Rel homodimer, and resulted in no induction of the p65/p50 heterodimer. In contrast, lipopolysaccharide stimulation primarily induced the p65/p50 heterodimer that has been shown to result in gene activation. Thus, such unique activation of the inhibitory p50/p50 homodimer by acute ethanol treatment may result in inhibition rather than activation of NF-kB-regulated inflammatory cytokine genes. Consequently, these results suggest that physiologically relevant concentrations of ethanol may affect production of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 by disrupting NF-kB signaling in monocytes.     

Comparison of three newer generation freely available intraocular lens power calculation formulae across all axial lengths

Purpose:The aim of this study is to evaluate the accuracy of three newer generation formulae (Barrett Universal II, EVO, Hill-RBF 2.0) for calculation of power of two standard IOLs—the Acrysof IQ and Tecnis ZCB00 across all axial lengths.Methods:In this retrospective series, 206 eyes of 206 patients, operated for cataract surgery with above two IOLs over the last 6 months, were included in the study. Preoperative biometry measurements were obtained from LenstarLS900. By using recommended lens constants, the mean error for each formula was calculated and compared. Then, the optimized IOL constants were calculated to reduce the mean error to zero. Mean and median absolute errors were calculated for all eyes and separately for short (AL<22.5 mm), medium (22.5–24.5 mm), and long eyes (>24.5 mm). Absolute errors and percentages of eyes within prediction errors of ±0.25 D, ±0.50 D, ±0.75 D, and ±1.00 D were compared.Results:Prediction error with using recommended lens constants was significantly lower in the Barrett Universal II formula as compared to the other two formulae. However, after optimizing lens constants, there were no significant differences in the absolute errors between the three formulae. The formulae ranked by mean absolute error were as follows: Barrett Universal II (0.304 D), EVO (0.317 D), and Hill-RBF (0.322) D. There were no significant differences between absolute errors in the three formulae in each of the short-, medium-, and long-eye subgroups.Conclusion:With proper lens constant optimization, the Barrett Universal II, EVO, and Hill-RBF 2.0 formulae were equally accurate in predicting IOL power across the entire range of axial lengths.     

Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen.     

Additive inhibition of dendritic cell allostimulatory capacity by alcohol and hepatitis C is not restored by DC maturation and involves abnormal IL-10 and IL-2 induction

Background: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity. Methods: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV‐DC) and controls (N‐DC) with IL‐4 plus granulocyte‐macrophage colony stimulating factor (GM‐CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA. Results: Allostimulatory capacity of HCV‐DCs was reduced compared to N‐DCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol‐treated N‐DCs. DC phenotypic markers and apoptosis were comparable between HCV‐DCs and N‐DCs irrespective of alcohol treatment. However, HCV‐DCs and alcohol‐treated N‐DCs exhibited elevated IL‐10 and reduced IL‐12 production. Reduced MLR with HCV‐DCs and its further inhibition by alcohol coexisted with decreasing IL‐2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol‐treated or alcohol‐naïve HCV‐DCs (p < 0.018). Conclusions: Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL‐10, reduce IL‐12 and IL‐2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells.     

RSA 2004: combined basic research satellite symposium - session four: hepatitis virus and alcohol interactions in immunity and liver disease

This article summarizes the proceedings of the RSA 2004 Combined Basic Research Satellite Meeting convened at the Westin Bayshore Resort and Marina, Vancouver, CA. The session "Hepatitis virus and alcohol interactions in immunity and liver disease" featured four speakers and was chaired by Drs. Diane Lucas and Samuel French. The presentations were 1) Mitochondrial effects of HCV proteins and alcohol by Steve Weinman, 2) Chronic alcohol consumption accelerates viral hepatitis and T-cell hepatitis via dysregulation of cytokine signaling by Bin Gao 3) Interactions between alcohol, hepatitis C virus and innate defense pathways by Steve Polyak and 4) Scavenger Receptor-mediated modulation of the innate and adaptive immune responses following chronic ethanol consumption by Geoffrey Thiele.     

Increased lipopolysaccharide sensitivity in alcoholic fatty livers is independent of leptin deficiency and toll-like receptor 4 (TLR4) or TLR2 mRNA expression

BACKGROUND: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-kappaB and pro-inflammatory pathways that are activated in AFL and NAFL. METHODS: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels; hepatic NF-kappaB activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. RESULTS: Increased LPS sensitivity in AFL and NAFL was characterized by elevated serum TNF-alpha and IL-6 induction. However, there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob livers at baseline and after acute or chronic alcohol treatment. LPS increased TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS increased serum ALT and TNF-alpha levels in lean but not in ob/ob mice compared with pair-fed controls. Hepatic NF-kappaB activation was increased in both ob/ob and lean mice after chronic alcohol feeding compared with pair-fed controls. Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective protein, were higher in ob/ob compared with lean mice after chronic alcohol feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in ob/ob compared with lean mice. CONCLUSION: These results imply that the increased sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective mechanisms.