Tissue factor serum levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study

INTRODUCTION: Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS: We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS: In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION: High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.     

“When He Asks for Sex,You Will Never Refuse”: Transactional Sex and Adolescent Pregnancy in Zambia

Pregnancy among adolescent girls in Zambia is a significant concern on its own and as a factor in school dropout and early marriage, with one‐third of girls aged 15–19 having experienced pregnancy. Using qualitative and quantitative data from the Adolescent Girls Empowerment Program, we explore transactional sex as a driver of adolescent pregnancy. In qualitative interviews, transactional sex was repeatedly discussed as the main driver of pregnancy, as respondents indicated that when a girl feels that she “owes” a man sex, it prevents her from declining sex or using condoms. In addition, multivariate Cox proportional hazards models using four rounds of longitudinal data from a sample of unmarried and never pregnant adolescent girls (n=1,853) show that girls who have engaged in transactional sex face a hazard of first premarital pregnancy almost 30 percent greater than their peers who have not, independent of the effect of other risk‐related sexual behaviors such as condom use and number of sexual partners. Identifying and understanding the role of transactional sex in adolescent pregnancy is important for designing effective curricula and programs that delay pregnancy, and highlights the importance of addressing access to economic resources in adolescent health outcomes.     

Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1

The ras family of small GTP-binding proteins exerts powerful effects upon cell structure and function. One member of this family, rac, induces actin cytoskeletal reorganization in nonmuscle cells and hypertrophic changes in cultured cardiomyocytes. To examine the effect of rac1 activation upon cardiac structure and function, transgenic mice were created that express constitutively activated rac1 specifically in the myocardium. Transgenic rac1 protein was expressed at levels comparable to endogenous rac levels, with activation of the rac1 signaling pathway resulting in two distinct cardiomyopathic phenotypes: a lethal dilated phenotype associated with neonatal activation of the transgene and a transient cardiac hypertrophy seen among juvenile mice that resolved with age. Neither phenotype showed myofibril disarray and hypertrophic hearts were hypercontractilein working heart analyses. The rac1 target p21-activated kinase translocated from a cytosolic to a cytoskeletal distribution, suggesting that rac1 activation was inducing focal adhesion reorganization. Corroborating results showed altered localizations of src in dilated cardiomyopathy and paxillin in both cardiomyopathic phenotypes. This study, the first examination of rac1-mediated cardiac effects in vivo, demonstrates that dilation and hypertrophy can share a common molecular origin and presents evidence that both timing and concurrent signaling from multiple pathways can influence cardiac remodeling.     

Specialized neuromuscular training to improve neuromuscular function and biomechanics in a patient with quiescent juvenile rheumatoid arthritis

BACKGROUND AND PURPOSE: The purpose of this case report is to describe a novel multidisciplinary approach for evaluating and preparing a patient with quiescent juvenile rheumatoid arthritis (JRA) for safe sports participation. CASE DESCRIPTION: The patient was a 10-year-old girl with a history of bilateral knee arthritis who desired to participate in soccer and basketball. Range of motion and manual muscle testing of the lower extremity were within normal limits. Neuromuscular testing included kinematic and kinetic testing, isokinetic assessment, and postural stability testing. The patient's gait was near normal; however, she had narrowed step width and increased knee flexion at heel-strike. Landing analysis during a box drop vertical jump task showed increased and imbalanced (right versus left lower extremity) peak impact forces. The testing was followed by specialized neuromuscular training (SNT). OUTCOMES: Following SNT, heel-strike and step width were within normal limits, peak impact forces on the box drop test decreased by 31%, imbalance decreased by 46%, and vertical jump increased 15%. The isokinetic strength ratio between knee flexors and extensors and the overall balance measures were within normal limits and equal bilaterally. DISCUSSION: Patients with quiescent JRA may have abnormal biomechanics, which could place them at increased risk for injury or future articular cartilage damage. Specialized neuromuscular training may have helped to decrease the patient's risk for future injury or disease progression.     

Biocompatibility of white cell filters as evaluated by complement activation

The biocompatibility of nine different white cell filters was examined by analysis of complement activation in plasma specimens obtained from blood components before and after filtration. Filters for both red cell (RBC) concentrates and platelet concentrates (PCs) were tested. It was found in all of the filters tested that the postfiltration levels of complement activation products were not higher than the prefiltration levels in RBC concentrates and PCs. One exception was the filtration of multiple PCs with Imugard IG-500, in which case a rise in C3 activation products was seen. Moreover, there was a significant rise in C3 activation products, but not the terminal complement complex, when plasma was filtered through Imugard E, which contrasted with results with the other filters. High initial and storage time-dependent levels, especially of C3 activation products, were observed in the PCs, probably due to their processing at room temperature. It can be concluded that the majority of the filters tested do not activate complement.     

Platelet concentrates stored for 5 days in a reduced volume of plasma maintain hemostatic function and viability

BACKGROUND: Platelet concentrates prepared from whole blood are generally suspended in a standard volume of 50 to 60 mL of plasma and can be stored thus at 20 to 24 degrees C for up to 5 days. In vitro studies suggested that this plasma volume could be reduced to 30 to 35 mL without impairing platelet function. STUDY DESIGN AND METHODS: This study evaluated whether platelets stored for 5 days in a reduced volume (30-35 mL) of plasma maintained their in vivo viability, hemostatic function, and recovery in recipients. Paired autologous platelet survival studies were done in 20 adult volunteers to assess platelet viability. A rabbit ear bleeding-time model was used to compare the hemostatic effectiveness of human platelet concentrates stored for 5 days in the standard or reduced volume of plasma. Platelet recovery was compared in thrombocytopenic hospital patients. RESULTS: Paired platelet survival studies indicated no significant difference between the values in platelet concentrates stored for 5 days in the reduced volume of plasma and the values in those stored in the standard volume. In the animal model, there was no significant difference in the bleeding times achieved by either set of platelet concentrates. The platelet count increments in thrombocytopenic patients were measured. The platelet count increments in patients who received reduced-volume platelet concentrates were as good as the increments achieved in patients given standard-volume concentrates. CONCLUSION: The in vivo viability, recovery, and hemostatic function of platelets collected in polyvinylchloride plastic containers and stored in 30 to 35 mL of plasma for 5 days are maintained as well as those of platelets stored in 50 to 60 mL of plasma.     

Smad3‐dependent signaling underlies the TGF‐β1‐mediated enhancement in astrocytic iNOS expression

We previously demonstrated that transforming growth factor‐β1 (TGF‐β1), while having no effect alone, enhances nitric oxide (NO) production in primary, purified mouse astrocytes induced by lipopolysaccharide (LPS) plus interferon‐γ (IFN‐γ), by recruiting a latent population of astrocytes to respond, thereby enhancing the total number of cells that express Nos2. In this investigation, we evaluated the molecular signaling pathway by which this occurs. We found that purified murine primary astrocytes express mRNA for TGFβRII as well as the TGFβRI subunit activin‐like kinase 5 (ALK5), but not ALK1. Immunofluorescence microscopy confirmed the expression of TGFβRII and ALK5 protein in astrocytes. Consistent with ALK5 signaling, Smad3 accumulated in the nucleus of astrocytes as early as 30 min after TGF‐β1 (3 ng/mL) treatment and persisted upto 32 hr after TGF‐β1 administration. Addition of ALK5 inhibitors prevented TGF‐β1‐mediated Smad3 nuclear accumulation and NO production when given prior to the Nos2 induction stimuli, but not after. Finally, astrocyte cultures derived from Smad3 null mutant mice did not exhibit a TGF‐β1‐mediated increase in iNOS expression. Overall, this data suggests that ALK5 signaling and Smad3 nuclear accumulation is required for optimal enhancement of LPS plus IFNγ‐induced NO production in astrocytes by TGF‐β1. © 2010 Wiley‐Liss, Inc.     

Effects of the menstrual cycle on anterior cruciate ligament injury risk: a systematic review

Several theories have been proposed to explain the 3- to 6-fold gender difference in the incidence of anterior cruciate ligament injuries. One potential theory for the increased incidence is based on gender-related hormonal differences between men and women, especially after puberty and the onset of menses in the female athlete. The purpose of this systematic review was to compile and systematically analyze the published literature to determine if the menstrual cycle is associated with anterior cruciate ligament injury risk and to provide an objective comparison of the published results. Investigations were included in the systematic review if the report included associations between the menstrual cycle and noncontact anterior cruciate ligament injuries in female athletes. Abstracts and unpublished studies were excluded. Seven articles were identified that met the systematic review inclusion criteria. The 7 reviewed studies favored an effect of the first half, or preovulatory phase, of the menstrual cycle for increased anterior cruciate ligament injuries. The 6 studies that separated the non-oral contraceptive and oral contraceptive data also favored an effect of the first half of the menstrual cycle for increased anterior cruciate ligament injuries. The clinical relevance of this finding is that female athletes may be more predisposed to anterior cruciate ligament injuries during the preovulatory phase of the menstrual cycle. These findings may lead to potential interventions targeted toward this phase of the menstrual cycle to reduce the incidence of anterior cruciate ligament injury.     

Deficits in neuromuscular control of the trunk predict knee injury risk: a prospective biomechanical-epidemiologic study

BACKGROUND: Female athletes are at significantly greater risk of anterior cruciate ligament (ACL) injury than male athletes in the same high-risk sports. Decreased trunk (core) neuromuscular control may compromise dynamic knee stability. HYPOTHESES: (1) Increased trunk displacement after sudden force release would be associated with increased knee injury risk; (2) coronal (lateral), not sagittal, plane displacement would be the strongest predictor of knee ligament injury; (3) logistic regression of factors related to core stability would accurately predict knee, ligament, and ACL injury risk; and (4) the predictive value of these models would differ between genders. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: In this study, 277 collegiate athletes (140 female and 137 male) were prospectively tested for trunk displacement after a sudden force release. Analysis of variance and multivariate logistic regression identified predictors of risk in athletes who sustained knee injury. RESULTS: Twenty-five athletes (11 female and 14 male) sustained knee injuries over a 3-year period. Trunk displacement was greater in athletes with knee, ligament, and ACL injuries than in uninjured athletes (P < .05). Lateral displacement was the strongest predictor of ligament injury (P = .009). A logistic regression model, consisting of trunk displacements, proprioception, and history of low back pain, predicted knee ligament injury with 91% sensitivity and 68% specificity (P = .001). This model predicted knee, ligament, and ACL injury risk in female athletes with 84%, 89%, and 91% accuracy, but only history of low back pain was a significant predictor of knee ligament injury risk in male athletes. CONCLUSIONS: Factors related to core stability predicted risk of athletic knee, ligament, and ACL injuries with high sensitivity and moderate specificity in female, but not male, athletes.