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Routine depression screening and subsequent treatment in post-myocardial infarction (MI) patients may lead to improved cardiac outcomes. However, screening for depression is not a standard of post-MI care. Though the American Heart Association (AHA) published an advisory recommending routine depression screening in post-MI patients, there is conflicting evidence on the benefit that routine depression screening has on cardiovascular outcomes. The purpose of this study is to compare the occurrence of cardiovascular-related readmissions in post-MI patients diagnosed with depression versus post-MI patients not diagnosed with depression. This retrospective cohort study analyzed the incidence of cardiovascular-related readmissions and mortality in adult post-MI patients diagnosed with depression within 1 year compared to those not diagnosed with depression within a year. Those diagnosed with depression were more likely to experience a subsequent cardiovascular-related hospitalization within 2 years of MI than those not diagnosed with depression (52.6% vs 28.7%; odds ratio [OR], 3.19; 95% CI 2.33-4.38). There was no difference between groups in the incidence of in-hospital mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, we describe the complete mitochondrial genome of Diopatra cuprea (Bosc, 1802). The mitogenome was found to contain 14,990 base pairs (67.53% A + T content), with a total of 37 genes (13 protein coding, 22 transfer RNAs, and 2 ribosomal RNAs). This study also examined mitogenome phylogenetics relationships of closely related species and recovered that D. cuprea is closely related to eunicids. This work has added to the genetic resources for furthering evolutionary studies of Annelida., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that segregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. With overwhelming evidence of the involvement of aberrant Transforming Growth Factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in the relationship between connective tissue disorders and their associated cardiovascular complications. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, the heritable connective tissue syndromes related to aberrant TGF-β signaling, and will discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system., (© 2021. Springer Nature Switzerland AG.)

Though older adults are more sensitive to the effects of medications than their younger counterparts, they are often excluded from manufacturer-based clinical studies. Practice-based research is a practical method to identify medication-related effects in older patients. This research also highlights the role of a pharmacist in improving care in this population. A single study rarely has strong enough evidence to change geriatric practice, unless it is a large-scale, multisite, randomized controlled trial that specifically targets older adults. It is important to design studies that may be used in systematic reviews or meta-analyses that build a stronger evidence base. Recent literature has documented a gap in advanced pharmacist training pertaining to research skills. In this paper, we hope to fill some of the educational gaps related to research in older adults. We define best practices when deciding on the type of study, inclusion and exclusion criteria, design of the intervention, how outcomes are measured, and how results are reported. Well-designed studies increase the pool of available data to further document the important role that pharmacists have in optimizing care of older patients.

Rates of death because of asphyxia in motor vehicle crashes have been previously estimated using county and statewide data sets, but national estimates have not been reported. The literature regarding asphyxia in motor vehicle crashes primarily involves discussions about clinical findings, and crash-related variables have been sparsely reported. The current study calculated a nationwide fatality rate for asphyxia in motor vehicle crashes of 1.4%. Seventeen case studies of asphyxia were also reported providing crash-, vehicle-, and occupant-related variables. These included type of accident, crash severity, seat belt use, containment status, extent of occupant compartment intrusion, height, weight, and injury pattern. The data presented can be used to better understand the injury mechanism, identify risk factors, develop possible protective countermeasures, and create situational awareness for emergency responders and investigators.

Background: Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood., Methods and Results: Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age., Conclusions: These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system.

Background: Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilation that progresses to rupture if left undetected and untreated. If detected, patients with TAA are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging because no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAVs), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). In addition, altered microRNA (miR) expression levels have also been reported in TAAs compared with normal aortic tissue. The objective of our study was to identify circulating factors within plasma that could serve as potential biomarkers for distinguishing etiologic subtypes of aneurysm disease., Methods: Ascending TAA tissue and plasma specimens were obtained from patients with BAV (n = 21) and TAV (n = 21) at the time of surgical resection. The protein abundance of key MMPs (1, 2, 3, 8, and 9), TIMPs (1, 2, 3, and 4), and miRs (1, 21, 29a, 133a, 143, and 145) was examined using a multianalyte protein profiling system or by quantitative polymerase chain reaction, respectively. Results were compared with normal aortic tissue and plasma obtained from patients without aortic disease (n = 10)., Results: Significant (P < .05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis revealed significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMP-1, TIMP-3, and TIMP-4 (P < .05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, MMP-2, and MMP-7, and for decreased MMP-8 and MMP-9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and MMP-9., Conclusions: Taken together, these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized strategies to distinguish between etiologic subtypes of TAAs in patients with aneurysm disease., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The Southeastern United States (US) has a rapidly growing Latino population, yet little is known about HIV-infected Latinos in the region. To help inform future prevention studies, we compared sociodemographic, clinical, and behavioral characteristics between immigrant and US-born HIV-infected Latinos using face-to-face interviews conducted at three clinics in North Carolina. Questions encompassed HIV testing, acculturation, sexual- and substance-related behaviors, and migration history. Behavioral data were compared with 451 black and white clinic patients. Differences were tested using Pearson's and Kruskal-Wallis tests. Participants (n = 127) were primarily male (74%) and immigrants (82%). Most immigrants were Mexican (67%), had low acculturation scores (92%), and were diagnosed a median of 8 years (IQR 0-12) following immigration. Compared with US-born Latinos, immigrants had lower CD4 counts at clinic entry (median 187 vs. 371 cells/mm(3)) and were less likely to have graduated high school (49% vs. 78%) or have insurance (9% vs. 52%; all P <0.05). Most immigrants identified as heterosexual (60%) and reported fewer lifetime partners than US-born Latinos (median 6 vs. 20; P = 0.001). Immigrant men were less likely to report sex with men than US-born men (43% vs. 81%; P = 0.005). Immigrant men also had similar risk behaviors to black men, and US-born Latino men exhibited behaviors that were more similar to white men in our clinic. At the time of survey, >90% of participants were receiving antiretroviral therapy (ART) and most had achieved HIV RNA <50 copies/mL (62% immigrants vs. 76% US-born; P = 0.32). In conclusion, Latino immigrants were more likely to present with advanced disease, identify as heterosexual, and report different risk behaviors than US-born Latinos, yet receipt and response to ART were similar between the two groups. Prevention strategies should prioritize finding innovative methods to reach Latino immigrants for routine early testing regardless of risk stratification and include programs targeted toward the different needs of immigrant and US-born Latinos.

This article discusses the incidence, geographic differences, and risk factors for the 2 most common cancers of the esophagus: squamous cell and adenocarcinoma., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Glutathione (GSH) transferases (GSTs) catalyze the conjugation of small haloalkanes with GSH. In the case of dihalomethanes and vic-1,2-dihaloalkanes, the reaction leads to the formation of genotoxic GSH conjugates. A generally established feature of the reaction of the mammalian theta-class GSTs, which preferentially catalyze these reactions, is the lack of saturability of the rate with regard to the substrate concentration. However, the bacterial GST DM11 catalyzes the same reactions with a relatively low K(m). Recently, DM11 has been shown to exhibit burst kinetics, with a rate-determining k(off) rate for product (Stourman et al. (2003) Biochemistry 42, 11048-11056). We examined rat GST 5-5 and human GST T1-1 and did not detect any burst kinetics in the conjugation of C(2)H(5)Cl, CH(2)Br(2), or CH(2)Cl(2), distinguishing these enzymes from GST DM11. The kinetic results were fit to a minimal mechanism in which the rate-limiting step is halide displacement. The differences in the steady state kinetics of conjugations catalyzed by bacterial GST DM11 and the mammalian GSTs 5-5 and T1-1 are concluded to be the result of differences in the rate-limiting steps and not to inherent enzyme affinity for the haloalkanes. The results may be interpreted in the context of a model in which the halide order affects the rate of carbon-halogen bond cleavage of all such reactions catalyzed by the GSTs. With GST DM11, the halide order is manifested in the K(m) parameter but not k(cat). With mammalian GSTs, the high K(m) is difficult to estimate. With all of the GSTs, the halide order is seen in the enzyme efficiency, k(cat)/K(m), with C-Br cleavage approximately 10-fold faster than C-Cl cleavage. The ratio k(cat)/K(m) is the most relevant parameter for issues of risk assessment.

Our groups have had a long-term interest in utilizing bacterial systems in the characterization of bioactivation and detoxication reactions catalyzed by cytochrome P450 (P450) and glutathione transferase (GST) enzymes. Bacterial systems remain the first choice for initial screens with new chemicals and have advantages, including high-throughput capability. Most human P450s of interest in toxicology have been readily expressed in Escherichia coli with only minor sequence modification. These enzymes can be readily purified and used in assays of activation of chemicals. Bicistronic systems have been developed in order to provide the auxiliary NADPH-P450 reductase. Alternative systems involve these enzymes expressed together within bacteria. In one approach, a lac selection system is used with E. coli and has been applied to the characterization of inhibitors of P450s 1A2 and 1B1, as well as in basic studies involving random mutagenesis. Another approach utilizes induction of the SOS (umu) response in Salmonella typhimurium, and systems have now been developed with human P450s 1A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4, which have been used to report responses from heterocyclic amines. S. typhimurium his reporter systems have also been used with GSTs, first to demonstrate the role of rat GST 5-5 in the activation of dihalomethanes. These systems have been used to compare these GSTs with regard to activation of dihaloalkanes and potential toxicity.

Bile acid CoA ligase (BAL) is responsible for catalyzing the first step in the conjugation of bile acids with amino acids. Sequencing of putative rat liver BAL cDNAs identified a cDNA (rBAL-1) possessing a 51 nucleotide 5'-untranslated region, an open reading frame of 2,070 bases encoding a 690 aa protein with a molecular mass of 75,960 Da, and a 138 nucleotide 3'-nontranslated region followed by a poly(A) tail. Identity of the cDNA was established by: 1) the rBAL-1 open reading frame encoded peptides obtained by chemical sequencing of the purified rBAL protein; 2) expressed rBAL-1 protein comigrated with purified rBAL during SDS-polyacrylamide gel electrophoresis; and 3) rBAL-1 expressed in insect Sf9 cells had enzymatic properties that were comparable to the enzyme isolated from rat liver. Evidence for a relationship between fatty acid and bile acid metabolism is suggested by specific inhibition of rBAL-1 by cis-unsaturated fatty acids and its high homology to a human very long chain fatty acid CoA ligase. In summary, these results indicate that the cDNA for rat liver BAL has been isolated and expression of the rBAL cDNA in insect Sf9 cells results in a catalytically active enzyme capable of utilizing several different bile acids as substrates.

A primary route of metabolism of dihalomethanes occurs via glutathione (GSH) transferase-catalyzed conjugation. Mammalian theta class GSH transferases and a group of bacterial dichloromethane dehalogenases are able to catalyze the hydrolytic dehalogenation of dihalomethanes via GSH conjugation and subsequent formation of HCHO. Dihalomethanes have been shown to induce revertants in Salmonella typhimurium TA 1535 expressing theta class GSH transferases. Two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and the bacterial dehalogenase DM11 were compared in the in vitro conjugation of CH(3)Cl and using in vitro assays (HCHO formation) and the S. typhimurium mutagenesis assay with the dihalomethanes CH(2)Cl(2), CH(2)Br(2), CH(2)BrCl, CH(2)ICl, CH(2)I(2), and CH(2)ClF. GSTs 5-5 and T1 had similar characteristics and exhibited first-order rather than Michaelis-Menten kinetics for HCHO formation over the range of dihalomethane concentrations tested. In contrast, the DM11 enzyme displayed typical hyperbolic Michaelis-Menten kinetics for all of the compounds tested. A similar pattern was observed for the conjugation of CH(3)Cl. The reversion tests with S. typhimurium expressing DM11 or GST 5-5 showed a concentration-dependent increase in revertants for most of the dihalomethanes, and DM11 produced revertants at dihalomethane concentrations lower than GST 5-5. Collectively, the results indicate that rates of conversion of dihalomethanes to HCHO are not correlated with mutagenicity and that GSH conjugates are genotoxic. The results are compared with the conjugation and genotoxicity of haloethanes in the preceding paper in this issue [Wheeler, J. B., Stourman, N. V., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide order appears most important in the dihalomethane conjugation reactions catalyzed by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate-limiting steps.

Glutathione (GSH) transferases are generally involved in the detoxication of xenobiotic chemicals. However, conjugation can also activate compounds and result in DNA modification. Activation of 1,2-dihaloethanes (BrCH(2)CH(2)Br, BrCH(2)CH(2)Cl, and ClCH(2)CH(2)Cl) was investigated using two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial dichloromethane dehalogenase (DM11). Although the literature suggests that the bacterial dehalogenase does not catalyze reactions with CH(3)Cl, ClCH(2)CH(2)Cl, or CH(3)CHCl(2), we found a higher enzyme efficiency for DM11 than for the mammalian GSH transferases in conjugating CH(3)Cl, CH(3)CH(2)Cl, and CH(3)CH(2)Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535 systems expressing each of these GSH transferases were used to determine mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases correlated with the mutagenicity determined in the reversion assays for the three 1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH] containing either F, Cl, or Br (as the leaving group) were tested for their abilities to induce revertants in S. typhimurium, and rates of hydrolysis were also determined. GSH transferases do not appear to be involved in the breakdown of the half-mustard intermediates. A halide order (Br > Cl) was observed for both GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from 1,2-dihaloethanes, with the single exception (both assays) of BrCH(2)CH(2)Cl reaction with DM11, which was unexpectedly high. The lack of substrate saturation seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases.

Objective: To assess the potential for cervical muscle injury from a rear-end automobile collision., Design: Experimental design in which human subjects were exposed to low-speed rear-end collisions. The influence of independent variable (gender, speed change, muscle group, and motion phase) on dependent variables (kinematic response, muscle onset and muscle activation level) was examined using repeated-measures analysis of variance., Background: Injuries to various tissues of the cervical spine have been proposed, yet little attention has been focused on the cervical muscles as a site of injury., Methods: 42 subjects (21 males, 20-40 yr) were exposed to collisions of 4 and 8 km/h speed change while measuring kinematic response of the head and torso and electromyography of the sternocleidomastoid and cervical paraspinal muscles., Results: Muscle activation occurred earlier in females and in the 8 km/h speed change. Sternocleidomastoid onset preceded paraspinal onset. Muscle activation level varied significantly with speed change, motion phase and muscle group. Initial rearward retraction of the head relative to the torso resulted in lengthening of the activated sternocleidomastoid, consistent with a contraction-induced muscle injury., Conclusions: The cervical muscles contract rapidly in response to impact and the potential exists for muscle injury due to lengthening contractions., Relevance: The clinician should recognize the role of cervical retraction in the mechanism of whiplash injury and avoid aggressive motion in that plane during diagnosis and treatment. An understanding of whiplash injury mechanisms should improve patient education and preventative measures.

Recent experiments have produced a linked data set of clinical and kinematic responses for human subjects exposed to controlled low-speed rear-end collisions. The purpose of this paper was to examine this paired data set and determine whether the presence or absence of clinical symptoms could be predicted from the peak linear and angular kinematic response of the head and neck. The data were generated using 42 male and female human subjects seated normally in the front passenger seat of a stationary vehicle struck from behind to produce vehicle speed changes of 4 and 8 km/h. Pre- and post-test clinical examinations documented the presence, severity and duration of whiplash-associated disorders (WAD). Logistic regression and backward elimination of independent variables were used to develop the prediction model. The analysis yielded a 16 parameter model that was significantly related (odds ratio = 21.2; P = 0.0069) to the presence or absence of transient whiplash symptoms. The model correctly predicted symptom presence in 13 of 23 tests (sensitivity 57%) and symptom absence in 49 of 52 tests (specificity 94%) in a population of 75 with a symptom prevalence of 31%. The model's positive predictive value was 81% and its negative predictive value was 83%. Despite statistical significance, the model did not discriminate between the presence and absence of symptoms in all tests, and indicated that factors other than the selected peak kinematic responses influenced symptom production.

Prior two-way analyses of variance showed that the peak kinematic response of the head and neck of subjects exposed to low-speed rear-end collisions was related to speed change and gender, however potential reasons for this gender dependence were not determined. Using multiple linear regression, this study further examined these response data to determine the relative influence of specific factors, including subject anthropometry, neck strength, cervical range of motion, seated posture and head restraint position, which may have been responsible for the previously-observed gender dependence. The results of this analysis showed that vehicle speed change and relative head restraint position explained the largest proportion of the observed variation in peak occupant kinematic response. Seated posture measures also explained some of the variation in kinematic response. The current analysis prioritizes which variables to explore more thoroughly in future research and which variables should be carefully controlled in future studies.

Objective: Forty-two persons were exposed to controlled low-speed rear-end automobile collisions to assess the relation between both gender and impact severity and the presence, severity, and duration of whiplash-associated disorders (WAD). Individual measures were also assessed for their potential to predict the onset of WAD., Design: Experimental study subjecting individuals to a speed change of 4 km/h and 8 km/h and utilizing pretest and posttest physical examinations (immediately after and 24 hours after impact) to quantify subjects' clinical response., Results: Approximately 29% and 38% of the subjects exposed to the 4 km/h and 8 km/h speed changes, respectively, experienced WAD symptoms, with cervical symptoms and headaches predominating. Objective clinical deficits consistent with WAD were measured in both men and women subjects at both 4 km/h and 8 km/h. At 4 km/h, the duration of symptoms experienced by women was significantly longer when compared with that in men (p < .05). There were no significant differences in the presence and severity of WAD between men and women at 4 km/h and 8 km/h or in the duration of WAD at 8 km/h. There was also no significant difference in the presence, severity, and duration of WAD between 4 km/h and 8 km/h. No preimpact measures were predictive of WAD., Conclusion: The empirical findings in this study contribute to establishing a causal relationship between rear-end collisions and clinical signs and symptoms.

In the present study, using the C24 bile acid chenodeoxycholic acid as substrate, rat liver bile acid CoA ligase activity (rBAL) was purified 200-fold from detergent-solubilized microsomes using a combination of Q-Sepharose anion exchange, hydroxyapatite, and CM-Sepharose chromatography. Purified rBAL had a molecular weight of 65 kDa by SDS-PAGE analysis. Gel filtration of purified rBAL indicated that rBAL activity forms a complex with other proteins with an apparent aggregate molecular weight of 243 kDa. A monoclonal antibody raised against the 65-kDa protein and covalently coupled to 6B-Sepharose completely absorbed rBAL activity from a semipurified preparation of rat liver microsomes. Western blot analysis confirmed the elution of the 65-kDa protein from the affinity phase at low pH. Optimum rBAL activity was found at pH 8.5, and activity was dependent on the divalent cation Mg2+. In the presence of 50 microM CoA and 2.5 mM MgCl2, kinetic analysis revealed that the apparent K(m)s of ATP and chenodeoxycholic acid of the purified enzyme were 548 +/- 247 and 18.0 +/- 6.2 microM, respectively, and the apparent Vmax was 9.53 +/- 2.0 nmol min-1 mg protein-1. The formation of chenodeoxycholyl-CoA by rBAL was strongly inhibited by hydrophobic bile acids (the C24 monohydroxy bile acid lithocholic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid, the C27 homolog of cholic acid), but only weakly by cholic acid. Chenodeoxycholyl-CoA and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-27-oyl-CoA were confirmed as reaction products of purified rBAL by HPLC-electrospray ionization mass spectrometry.

The principal demand on the body during cycling is on the lower extremities as they are responsible for producing a majority of the energy imparted to the bike. As a result the legs, due to high reactive forces between the foot and pedal, experience high loads on the joints. These loads may adversely affect joint tissues and contribute to overuse injuries, e.g. knee pain. The mechanical link between the leg and the bike is the shoe/pedal interface. This transmission site, by design, can either create smooth transfer of energy or abnormally high repetitive loads which are potentially injurious to the body. Incidence of lower extremity injury in cycling is high, and historically biomechanical analyses of this activity have focused their attention on either the rider or the bike, but not the link between the two. Recently, pedal designs have changed in response to complaints of sore knees with the development of pedals allowing varying degrees of float. This form of transmission is intended to enhance power transfer from rider to bike as well as minimise trauma to the legs by permitting the foot to rotate during the pedalling cycle in a toe-in/heel-out or heel-in/toe-out movement pattern. Recent evidence suggests this type of pedal design does reduce trauma and maintains power output. This article reviews common lower extremity overuse injuries and biomechanical factors during the pedalling cycle with the primary focus on the shoe/pedal interface. We will summarise information available on lower extremity kinematics and kinetics as well as recent data specifically related to shoe/pedal interface kinetics, evaluation of different pedal types-specifically comparison between clipless 'fixed' and clipless 'float' systems-and discuss their resultant effect on lower extremity dynamics and their implications for injury.