Cardiopulmonary exercise testing in severe osteoarthritis: a crossover comparison of four exercise modalities.

Cardiopulmonary exercise testing is performed increasingly for cardiorespiratory fitness assessment and pre-operative risk stratification. Lower limb osteoarthritis is a common comorbidity in surgical patients, meaning traditional cycle ergometry-based cardiopulmonary exercise testing is difficult. The purpose of this study was to compare cardiopulmonary exercise testing variables and subjective responses in four different exercise modalities. In this crossover study, 15 patients with osteoarthritis scheduled for total hip or knee arthroplasty (mean (SD) age 68 (7) years; body mass index 31.4 (4.1) kg.m-2 ) completed cardiopulmonary exercise testing on a treadmill, elliptical cross-trainer, cycle and arm ergometer. Mean (SD) peak oxygen consumption was 20-30% greater on the lower limb modalities (treadmill 21.5 (4.6) (p < 0.001); elliptical cross-trainer (21.2 (4.1) (p < 0.001); and cycle ergometer (19.4 (4.2) ml.min-1 .kg-1 (p = 0.001), respectively) than on the arm ergometer (15.7 (3.7) ml.min-1 .kg-1 ). Anaerobic threshold was 25-50% greater on the lower limb modalities (treadmill 13.5 (3.1) (p < 0.001); elliptical cross-trainer 14.6 (3.0) (p < 0.001); and cycle ergometer 10.7 (2.9) (p = 0.003)) compared with the arm ergometer (8.4 (1.7) ml.min-1 .kg-1 ). The median (95%CI) difference between pre-exercise and peak-exercise pain scores was greater for tests on the treadmill (2.0 (0.0-5.0) (p = 0.001); elliptical cross-trainer (3.0 (2.0-4.0) (p = 0.001); and cycle ergometer (3.0 (1.0-5.0) (p = 0.001)), compared with the arm ergometer (0.0 (0.0-1.0) (p = 0.406)). Despite greater peak exercise pain, cardiopulmonary exercise testing modalities utilising the lower limbs affected by osteoarthritis elicited higher peak oxygen consumption and anaerobic threshold values compared with arm ergometry.

Perspectives on the Implementation of Screening and Treatment for Depression and Alcohol Use Disorder in Primary Care in Colombia.

Depression and alcohol use disorder (AUD) greatly contribute to the burden of disease worldwide, and have large impact on Colombia's population. In this study, a qualitative analysis evaluates the implementation of a technology-supported model for screening, decision support, and digital therapy for depression and AUD in Colombian primary care clinics. Patient, provider, and administrator interviews were conducted, exploring attitudes towards depression and AUD, attitudes towards technology, and implementation successes and challenges. Researchers used qualitative methods to analyze interview themes. Despite stigma around depression and AUD, the model improved provider capacity to diagnose and manage patients, helped patients feel supported, and provided useful prevalence data for administrators. Challenges included limited provider time and questions about sustainability. The implementation facilitated the identification, diagnosis, and care of patients with depression and AUD. There is ongoing need to decrease stigma, create stronger networks of mental health professionals, and transition intervention ownership to the healthcare center.

Storm-induced sea-ice breakup and the implications for ice extent.

The propagation of large, storm-generated waves through sea ice has so far not been measured, limiting our understanding of how ocean waves break sea ice. Without improved knowledge of ice breakup, we are unable to understand recent changes, or predict future changes, in Arctic and Antarctic sea ice. Here we show that storm-generated ocean waves propagating through Antarctic sea ice are able to transport enough energy to break sea ice hundreds of kilometres from the ice edge. Our results, which are based on concurrent observations at multiple locations, establish that large waves break sea ice much farther from the ice edge than would be predicted by the commonly assumed exponential decay. We observed the wave height decay to be almost linear for large waves--those with a significant wave height greater than three metres--and to be exponential only for small waves. This implies a more prominent role for large ocean waves in sea-ice breakup and retreat than previously thought. We examine the wider relevance of this by comparing observed Antarctic sea-ice edge positions with changes in modelled significant wave heights for the Southern Ocean between 1997 and 2009, and find that the retreat and expansion of the sea-ice edge correlate with mean significant wave height increases and decreases, respectively. This includes capturing the spatial variability in sea-ice trends found in the Ross and Amundsen-Bellingshausen seas. Climate models fail to capture recent changes in sea ice in both polar regions. Our results suggest that the incorporation of explicit or parameterized interactions between ocean waves and sea ice may resolve this problem.

Compounds with Potential Activity against Mycobacterium tuberculosis.

The high acquisition rate of drug resistance by Mycobacterium tuberculosis necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high-throughput screening of compounds against thiol-deficient Mycobacterium smegmatis strains and subsequent validation with thiol-deficient M. tuberculosis strains revealed that ΔegtA and ΔmshA mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); ΔegtB and ΔegtE mutants had increased susceptibility to bacitracin (Ba); and ΔegtA, ΔmshA, and ΔegtB mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress in M. tuberculosis This study reports the activities of Aza, Su, Fu, and Ba against M. tuberculosis and provides a rationale for further investigations.

Gamma-glutamylcysteine protects ergothioneine-deficient Mycobacterium tuberculosis mutants against oxidative and nitrosative stress.

Mycobacterium tuberculosis (M.tb.), the causative agent of tuberculosis (TB), cannot synthesize GSH, but synthesizes two major low molecular weight thiols namely mycothiol (MSH) and ergothioneine (ERG). Gamma-glutamylcysteine (GGC), an intermediate in GSH synthesis, has been implicated in the protection of lactic acid bacteria from oxidative stress in the absence of GSH. In mycobacteria, GGC is an intermediate in ERG biosynthesis, and its formation is catalysed by EgtA (GshA). GGC is subsequently used by EgtB in the formation of hercynine-sulphoxide-GGC. In this study, M.tb. mutants harbouring unmarked, in-frame deletions in each of the fives genes involved in ERG biosynthesis (egtA, egtB, egtC, egtD and egtE) or a marked deletion of the mshA gene (required for MSH biosynthesis) were generated. Liquid chromatography tandem mass spectrometry analyses (LC-MS) revealed that the production of GGC was elevated in the MSH-deficient and the ERG-deficient mutants. The ERG-deficient ΔegtB mutant which accumulated GGC was more resistant to oxidative and nitrosative stress than the ERG-deficient, GGC-deficient ΔegtA mutant. This implicates GGC in the detoxification of reactive oxygen and nitrogen species in M.tb.

The functional interplay of low molecular weight thiols in Mycobacterium tuberculosis.

BACKGROUND: Three low molecular weight thiols are synthesized by Mycobacterium tuberculosis (M.tb), namely ergothioneine (ERG), mycothiol (MSH) and gamma-glutamylcysteine (GGC). They are able to counteract reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). In addition, the production of ERG is elevated in the MSH-deficient M.tb mutant, while the production of MSH is elevated in the ERG-deficient mutants. Furthermore, the production of GGC is elevated in the MSH-deficient mutant and the ERG-deficient mutants. The propensity of one thiol to be elevated in the absence of the other prompted further investigations into their interplay in M.tb. METHODS: To achieve that, we generated two M.tb mutants that are unable to produce ERG nor MSH but are able to produce a moderate (ΔegtD-mshA) or significantly high (ΔegtB-mshA) amount of GGC relative to the wild-type strain. In addition, we generated an M.tb mutant that is unable to produce GGC nor MSH but is able to produce a significantly low level of ERG (ΔegtA-mshA) relative to the wild-type strain. The susceptibilities of these mutants to various in vitro and ex vivo stress conditions were investigated and compared. RESULTS: The ΔegtA-mshA mutant was the most susceptible to cellular stress relative to its parent single mutant strains (ΔegtA and ∆mshA) and the other double mutants. In addition, it displayed a growth-defect in vitro, in mouse and human macrophages suggesting; that the complete inhibition of ERG, MSH and GGC biosynthesis is deleterious for the growth of M.tb. CONCLUSIONS: This study indicates that ERG, MSH and GGC are able to compensate for each other to maximize the protection and ensure the fitness of M.tb. This study therefore suggests that the most effective strategy to target thiol biosynthesis for anti-tuberculosis drug development would be the simultaneous inhibition of the biosynthesis of ERG, MSH and GGC.

Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife.

BACKGROUND/OBJECTIVES: Endothelial dysfunction predicts mortality but it is unknown whether childhood obesity predicts adult endothelial dysfunction. The aim of this study was to determine whether anthropometric indices of body fat in childhood, adolescence and early midlife are associated with endothelial dysfunction in early midlife. SUBJECTS/METHODS: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We assessed anthropometric indices of obesity at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38 years. We tested associations between endothelial function assessed by peripheral arterial tonometry (PAT) at age 38 and; age 38 cardiovascular risk factors; age 3 body mass index (BMI); and four BMI trajectory groups from childhood to early midlife. RESULTS: Early midlife endothelial dysfunction was associated with BMI, large waist circumference, low high-density lipoprotein cholesterol, low cardiorespiratory fitness and increased high-sensitivity C-reactive protein. After adjustment for sex and childhood socioeconomic status, 3-year-olds with BMI 1 s.d. above the mean had Framingham-reactive hyperemia index (F-RHI) ratios that were 0.10 below those with normal BMI (ß=-0.10, 95% confidence interval (CI) -0.17 to -0.03, P=0.007) at age 38. Cohort members in the 'overweight', 'obese' and 'morbidly obese' trajectories had F-RHI ratios that were 0.08 (ß=-0.08, 95% CI -0.14 to -0.03, P=0.003), 0.13 (ß=-0.13, 95% CI -0.21 to -0.06, P<0.001) and 0.17 (ß=-0.17, 95% CI -0.33 to -0.01, P=0.033), respectively, below age-peers in the 'normal' trajectory. CONCLUSIONS: Childhood BMI and the trajectories of BMI from childhood to early midlife predict endothelial dysfunction evaluated by PAT in early midlife.

Comparison of three targeted approaches to screening for abdominal aortic aneurysm based on cardiovascular risk.

BACKGROUND: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. METHODS: The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. RESULTS: A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). CONCLUSION: Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.

Variation in Arterial Access for Invasive Coronary Procedures in New Zealand: A National Analysis (ANZACS-QI 5).

BACKGROUND: Radial arterial access (RA) and femoral arterial access (FA) rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. METHODS AND RESULTS: Patient characteristics, procedural details, and inpatient outcome data were collected in the All New Zealand Acute Coronary Syndrome - Quality Improvement (ANZACS-QI) registry on consecutive patients undergoing ICA over five months. Of the 5894 ICAs 81% were via RA. Hospitals averaged 25 - 176 procedures/month (46.5% - 96.4% via RA). Operators averaged 17 procedures/month. Those performing more than 20 ICAs/month had RA rates between 61% - 99%. Of the 75 operators, 69% met the ESC recommendation. After multivariable adjustment higher operator (RR 1.12, CI 1.09 - 1.30) and hospital (RR 1.21, CI 1.15 - 1.28) volume were independent predictors of RA. Those with prior CABG (RR 0.51, CI 0.45 - 0.57), STEMI <12h (RR 0.91, CI 0.87 - 0.96), and female sex (RR 0.96, CI 0.94 - 0.99) were less likely to receive RA. CONCLUSIONS: New Zealand has a high RA rate for ICAs. Rates vary substantially between both operators and centres. Radial arterial was highest amongst the highest volume operators and centres.

Prevalence of abdominal aortic aneurysm in patients referred for transthoracic echocardiography.

BACKGROUND: Previous studies have documented the prevalence of abdominal aortic aneurysm (AAA) during transthoracic echocardiography, but the effect of such screening on subsequent vascular interventions remains unclear. AIM: This study aimed to determine the utility of opportunistic selective screening for AAA in a contemporary large series of patients having transthoracic echocardiography. METHODS: Subjects aged 50 years or older having transthoracic echocardiography had scanning of the infrarenal aorta in a consecutive series of 10 403 men and women. RESULTS: The study subjects had a mean age of 70.2 ± 10.7 years, and 54.1% were men. There was a 3.5% (95% confidence interval (CI) 3.2-3.9%) prevalence of AAA with a median diameter of 39 mm (interquartile range 32 mm-48 mm). In males ≥ 65 years the prevalence of newly diagnosed AAA was 6.2% (95% CI 5.5-7.0%). Of those with newly diagnosed AAA, 39.7% underwent AAA repair. Age and male gender were associated with AAA prevalence. After adjustment for age and gender, echocardiographic variables associated with AAA were left ventricular end diastolic dimension (odds ratio (OR) 1.02, 95%CI 1.01-1.04), interventricular septum thickness (OR 1.11, 95% CI 1.06-1.17), left ventricular posterior wall thickness (OR 1.09, 95% CI 1.03-1.15), left atrial diameter (OR 1.04, 95% CI 1.02-1.07) and aortic root diameter (OR 1.09, 95% CI 1.06-1.11). CONCLUSIONS: This study revealed a high prevalence of newly diagnosed AAA in a group of older men having cardiac evaluation. There was a relationship of increasing age with AAA, and a significant proportion of newly diagnosed subjects were not suitable for AAA repair.

Intra-individual changes of active matrix metalloproteinase-9 are associated with clinical in-stent restenosis of bare metal stents.

OBJECTIVES: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. METHODS: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. RESULTS: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. CONCLUSIONS: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.

Progression of initially mild hepatic fibrosis in patients with chronic hepatitis C infection.

A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.

Autoantibodies in chronic hepatitis C virus infection and their association with disease profile.

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

The inner world of cell adhesion: integrin cytoplasmic domains.

Many of the interactions between cells and their environment are mediated by the integrin family of heterodimeric transmembrane receptors. The past decade has been a broad-based effort to decipher the rules by which integrins function. Integrins bind both intracellular and extracellular ligands and thus transfer signals across the membrane in both directions. The cytoplasmic domains of these receptors play a key role in this bidirectional flow of information and in the formation of direct physical linkages between protein structures on the inside and outside of the cell.

Resource expenditure not resource allocation: response to McDougall on cloning and dignity.

This paper offers some comments on bioethical debates about resource allocation in healthcare. It is stimulated by Rosalind McDougall's argument that it is an affront to the human dignity of people with below "liberties-level" health to fund human reproductive cloning. McDougall is right to underline the relevance of resource prioritisation to the ethics of research and provision of new biomedical technologies. This paper argues that bioethicists should be careful when offering comments about such issues. In particular, it emphasises the need to represent accurately the reality of the situation-especially when we are passing judgement on technologies that are in their infancy and whose practical application is yet to be confirmed. The paper also emphasises the importance of the actual context to bioethical debate, and note that it would be better to talk about resource expenditure rather than resource allocation when it comes to discussing the rights and wrongs of how money is spent. It also reiterates the claims made by other writers that social and political philosophy need to have a transparent and considered role in debates about resources.

Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels.

The ATP-binding cassette A1 (ABCA1) protein regulates plasma high-density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low-HDL individuals and 102 high-HDL individuals. Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C-564T, G-407C, G-278C, and C-14T) identified the C-14T SNP and the TCCT haplotype to be over-represented in low-HDL individuals. The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels.

Canine lymphoproliferative disease characterized by lymphocytosis: immunophenotypic markers of prognosis.

BACKGROUND: Canine lymphoproliferative disease often presents with lymphocytosis and is immunophenotypically diverse. HYPOTHESIS: Immunophenotype predicts prognosis in canine lymphoproliferative disorders involving circulating lymphocytosis. ANIMALS: Dogs that had peripheral blood evaluation performed by flow cytometry by the Clinical Immunology Service at Colorado State University between 2003 and 2005. METHODS: Outcome data regarding treatment and survival were sought on patients with lymphocytosis comprising a single lymphocyte subset. Ninety-six patients that met the inclusion criteria had sufficient follow-up information to be included in the study. RESULTS: Four main phenotypic classifications were found: CD8+ T-cell, CD21+ B-cell, CD4-8-5+ (aberrant T-cell phenotype), and CD34+ (undifferentiated progenitor). Expression of CD34 predicted poor outcome with median survival of 16 days (P < .0001) compared with other phenotypes. Within the CD8+ phenotype, dogs presenting with a lymphocytosis >30,000 lymphocytes/muL had significantly shorter median survival (131 days) than those presenting with <30,000 lymphocytes/muL (1098 days, P < .0008). Within the T-cell leukemias, there was no difference in outcome between dogs with CD4-8-5+ leukemia and dogs with the CD8+ T-cell phenotype nor was the loss of expression of the pan-leukocyte marker CD45 associated with decreased survival time. A CD21+ lymphocytosis composed of large cells was associated with shorter survival time (129 days) than those with smaller circulating cells (median survival not reached, P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Immunophenotyping provides an objective method for determining prognosis in lymphoproliferative disorders characterized by lymphocytosis.

Generation and characterization of thiol-deficient Mycobacterium tuberculosis mutants.

Mycothiol (MSH) and ergothioneine (ERG) are thiols able to compensate for each other to protect mycobacteria against oxidative stress. Gamma-glutamylcysteine (GGC), another thiol and an intermediate in ERG biosynthesis has detoxification abilities. Five enzymes are involved in ERG biosynthesis, namely EgtA, EgtB, EgtC, EgtD and EgtE. The role of these enzymes in the production of ERG had been unclear. On the other hand, the enzyme MshA is known to be essential for MSH biosynthesis. In this manuscript, we describe the raw data of the generation and characterization of Mycobacterium tuberculosis (M.tb) mutants harbouring a deletion of the gene coding for each of these enzymes, and the raw data of the phenotypic characterization of the obtained thiol-deficient M.tb mutants. High throughput screening (HTS) of off-patent drugs and natural compounds revealed few compounds that displayed a higher activity against the thiol-deficient mutants relative to the wild-type strain. The mode of action of these drugs was further investigated. Raw data displaying these results are described here.

The Kenya cancer research and control stakeholder program: Evaluating a bilateral partnership to strengthen national cancer efforts.

Background: In response to a growing cancer burden and need for improved coordination among stakeholders in Kenya, the US National Cancer Institute and the Kenya Ministry of Health collaboratively hosted a stakeholder meeting in 2014 which identified four priority areas of need (research capacity building, pathology and cancer registries, cancer awareness and education, and health system strengthening) and developed corresponding action plans. Methods: Surveys were conducted with participants to collect input on the progress and impact of the 2014 stakeholder meeting. Findings: Of 69 eligible participants, 45 responded from academia, healthcare institutions, civil society, government, and international agencies. Of the four technical focus areas, three have continued to conduct working group meetings and two have conducted in-person meetings to review and update their respective action plans. Accomplishments linked to or enhanced by t meeting include: Kenyan and international support for expansion of population-based cancer registries, increased availability of prioritized diagnostic tests in selected regional referral hospitals, a greater focus on development of a national cancer research agenda, strategic planning for a community education strategy for cancer awareness, and improved coordination of partners through in-country technical assistance. Interpretation: The Stakeholder Program has successfully united individuals and organizations to improve cancer control planning in Kenya, and has enhanced existing efforts and programs across the country. This model of partners working in parallel on prioritized track activities has supported development of long term coordination of cancer research and control activities sustainable by the Kenyan government and Kenyan institutions.

Elevated plasma active matrix metalloproteinase-9 level is associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). METHODS AND RESULTS: A group of 158 patients with a history of ISR were compared with 128 symptom-free patients. Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro-MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. CONCLUSIONS: Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR.