Analysis of forces of ACL reconstructions at the tunnel entrance: is tunnel enlargement a biomechanical problem?

Bone tunnel enlargement is a common phenomenon following reconstruction of the anterior cruciate ligament (ACL). Biomechanical and biological factors have been reported as potential causes of this problem. However, there is no analysis of forces between the graft and bone, as the graft changes direction at the bone tunnel entrance. The purpose of this study was to study these 'redirecting forces'. Magnetic resonance images of 10 patients with an ACL reconstruction (age: 26+/-6.8 years) were used to determine the angle between graft and drill holes. Vector analysis was used to calculate the direction and magnitude of the perpendicular component of the force between the bone tunnel and the graft at the entrance of the bone tunnel. Force components were projected into the radiographically important sagittal and coronal planes. Tension of ACL reconstructions was recorded during passive knee motion in 10 cadaveric knee experiments (age: 28.9+/-10.6 years) and the tension multiplied with the force component for each plane. Results are reported for the coronal and sagittal planes, respectively: For -10 degrees of extension, the percentages of graft tension were determined to be 17+/-7 (max: 26; min: 7%) and 26+/-9 (max: 39; min: 16%) for the tibia. They were 59+/-6 (max: 66; min: 48%) and 99+/-1 (max: 1.00; min: 99%) for the femur. Force components were 14.68+/-6.54 and 25.73+/-12.96 N for the tibial tunnel. For the femoral tunnel, they were 52.48+/-19.03 and 90.77+/-32.06 N. Percentages of graft tension and force components were significantly higher for the femoral tunnel compared with the tibial tunnel. Moreover, in the sagittal direction, force components for the femoral tunnel were significantly higher compared with the coronal plane (Wilcoxon test, p < 0.01). The differences in force components calculated in this study corresponds with the amount of tunnel enlargement in the radiographic planes in the literature providing evidence that biomechanical forces play a key role in postoperative tunnel expansion.     

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).     

Mice lacking alpha/beta and gamma interferon receptors are susceptible to junin virus infection

Junin virus (JUNV) causes a highly lethal human disease, Argentine hemorrhagic fever. Previous work has demonstrated the requirement for human transferrin receptor 1 for virus entry, and the absence of the receptor was proposed to be a major cause for the resistance of laboratory mice to JUNV infection. In this study, we present for the first time in vivo evidence that the disruption of interferon signaling is sufficient to generate a disease-susceptible mouse model for JUNV infection. After peripheral inoculation with virulent JUNV, adult mice lacking alpha/beta and gamma interferon receptors developed disseminated infection and severe disease.     

Substring selection for biomedical document classification

MOTIVATION: Attribute selection is a critical step in development of document classification systems. As a standard practice, words are stemmed and the most informative ones are used as attributes in classification. Owing to high complexity of biomedical terminology, general-purpose stemming algorithms are often conservative and could also remove informative stems. This can lead to accuracy reduction, especially when the number of labeled documents is small. To address this issue, we propose an algorithm that omits stemming and, instead, uses the most discriminative substrings as attributes. RESULTS: The approach was tested on five annotated sets of abstracts from iProLINK that report on the experimental evidence about five types of protein post-translational modifications. The experiments showed that Naive Bayes and support vector machine classifiers perform consistently better [with area under the ROC curve (AUC) accuracy in range 0.92-0.97] when using the proposed attribute selection than when using attributes obtained by the Porter stemmer algorithm (AUC in 0.86-0.93 range). The proposed approach is particularly useful when labeled datasets are small.     

Length-dependent prediction of protein intrinsic disorder

Background  

Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions.     

Junín virus infection activates the type I interferon pathway in a RIG-I-dependent manner

Junín virus (JUNV), an arenavirus, is the causative agent of Argentine hemorrhagic fever, an infectious human disease with 15-30% case fatality. The pathogenesis of AHF is still not well understood. Elevated levels of interferon and cytokines are reported in AHF patients, which might be correlated to the severity of the disease. However the innate immune response to JUNV infection has not been well evaluated. Previous studies have suggested that the virulent strain of JUNV does not induce IFN in human macrophages and monocytes, whereas the attenuated strain of JUNV was found to induce IFN response in murine macrophages via the TLR-2 signaling pathway. In this study, we investigated the interaction between JUNV and IFN pathway in human epithelial cells highly permissive to JUNV infection. We have determined the expression pattern of interferon-stimulated genes (ISGs) and IFN-β at both mRNA and protein levels during JUNV infection. Our results clearly indicate that JUNV infection activates the type I IFN response. STAT1 phosphorylation, a downstream marker of activation of IFN signaling pathway, was readily detected in JUNV infected IFN-competent cells. Our studies also demonstrated for the first time that RIG-I was required for IFN production during JUNV infection. IFN activation was detected during infection by either the virulent or attenuated vaccine strain of JUNV. Curiously, both virus strains were relatively insensitive to human IFN treatment. Our studies collectively indicated that JUNV infection could induce host type I IFN response and provided new insights into the interaction between JUNV and host innate immune system, which might be important in future studies on vaccine development and antiviral treatment.