Development and Validation of Apolipoprotein AI-Associated Lipoprotein Proteome Panel for the Prediction of Cholesterol Efflux Capacity and Coronary Artery Disease

BACKGROUND: Cholesterol efflux capacity (CEC) is a measure of HDL function that, in cell-based studies, has demonstrated an inverse association with cardiovascular disease. The cell-based measure of CEC is complex and low-throughput. We hypothesized that assessment of the lipoprotein proteome would allow for precise, high-throughput CEC prediction. METHODS: After isolating lipoprotein particles from serum, we used LC-MS/MS to quantify 21 lipoprotein-associated proteins. A bioinformatic pipeline was used to identify proteins with univariate correlation to cell-based CEC measurements and generate a multivariate algorithm for CEC prediction (pCE). Using logistic regression, protein coefficients in the pCE model were reweighted to yield a new algorithm predicting coronary artery disease (pCAD). RESULTS: Discovery using targeted LC-MS/MS analysis of 105 training and test samples yielded a pCE model comprising 5 proteins (Spearman r = 0.86). Evaluation of pCE in a case-control study of 231 specimens from healthy individuals and patients with coronary artery disease revealed lower pCE in cases (P = 0.03). Derived within this same study, the pCAD model significantly improved classification (P < 0.0001). Following analytical validation of the multiplexed proteomic method, we conducted a case-control study of myocardial infarction in 137 postmenopausal women that confirmed significant separation of specimen cohorts in both the pCE (P = 0.015) and pCAD (P = 0.001) models. CONCLUSIONS: Development of a proteomic pCE provides a reproducible high-throughput alternative to traditional cell-based CEC assays. The pCAD model improves stratification of case and control cohorts and, with further studies to establish clinical validity, presents a new opportunity for the assessment of cardiovascular health

Does self-monitoring reduce blood pressure? Meta-analysis with meta-regression of randomized controlled trials

Introduction. Self-monitoring of blood pressure (BP) is an increasingly common part of hypertension management. The objectives of this systematic review were to evaluate the systolic and diastolic BP reduction, and achievement of target BP, associated with self-monitoring. Methods. MEDLINE, Embase, Cochrane database of systematic reviews, database of abstracts of clinical effectiveness, the health technology assessment database, the NHS economic evaluation database, and the TRIP database were searched for studies where the intervention included self-monitoring of BP and the outcome was change in office/ambulatory BP or proportion with controlled BP. Two reviewers independently extracted data. Meta-analysis using a random effects model was combined with meta-regression to investigate heterogeneity in effect sizes. Results. A total of 25 eligible randomized controlled trials (RCTs) (27 comparisons) were identified. Office systolic BP (20 RCTs, 21 comparisons, 5,898 patients) and diastolic BP (23 RCTs, 25 comparisons, 6,038 patients) were significantly reduced in those who self-monitored compared to usual care (weighted mean difference (WMD) systolic −3.82 mmHg (95% confidence interval −5.61 to −2.03), diastolic −1.45 mmHg (−1.95 to −0.94)). Self-monitoring increased the chance of meeting office BP targets (12 RCTs, 13 comparisons, 2,260 patients, relative risk = 1.09 (1.02 to 1.16)). There was significant heterogeneity between studies for all three comparisons, which could be partially accounted for by the use of additional co-interventions. Conclusion. Self-monitoring reduces blood pressure by a small but significant amount. Meta-regression could only account for part of the observed heterogeneity

Myocarditis related to Campylobacter jejuni infection: A case report

BACKGROUND: Myocarditis can develop as a complication of various infections and is most commonly linked to enterovirus infections. Myocarditis is rarely associated with bacterial infections; salmonellosis and shigellosis have been the most frequently reported bacterial cause. We report a case of myocarditis related to Campylobacter jejuni enteritis. CASE PRESENTATION: A 30-year-old previously healthy man presented with a history of prolonged chest pain radiating to the jaw and the left arm. Five days prior to the onset of chest pain, he developed bloody diarrhea, fever and chills. Creatine kinase (CK) and CK-MB were elevated to 289 U/L and 28.7 μg/L. Troponin I was 30.2 μg/L. The electrocardiogram (ECG) showed T wave inversion in the lateral and inferior leads. The chest pain resolved within 24 hours of admission. The patient had a completely normal ECG stress test. The patient was initiated on ciprofloxacin 500 mg po bid when Campylobacter jejuni was isolated from the stool. Diarrhea resolved within 48 hours of initiation of ciprofloxacin. The diagnosis of Campylobacter enteritis and related myocarditis was made based on the clinical and laboratory results and the patient was discharged from the hospital in stable condition. CONCLUSION: Myocarditis can be a rare but severe complication of infectious disease and should be considered as a diagnosis in patients presenting with chest pain and elevated cardiac enzymes in the absence of underlying coronary disease. It can lead to cardiomyopathy and congestive heart failure. There are only a few reported cases of myocarditis associated with Campylobacter infection

Lack of patients? – a hypothesis for understanding discrepancies between hospital resources and productivity

BACKGROUND: Despite a substantial increase in hospital resources, increased hospital admissions and out-patient visits, long waiting lists have been a significant problem in Norwegian health care. A detailed analysis of the development in resource allocation and productivity at St. Olavs University Hospital in central Norway was therefore undertaken. METHODS: Resource allocation and patient volume was analysed during the period 1995 to 2001. Data were analysed both for emergency and elective admissions as well as outpatient visits specified into new referrals and follow-up consultations. RESULTS: Full time employee equivalents for doctors and nurses increased by 36.6% and 25.9%, respectively, and all employees by 28.1%. However, admitted patients, outpatient consultations and surgical procedures only increased by 10%, 15% and 8.3%, respectively. Thus, the productivity for each hospital employee, defined as operations pr. surgeon, outpatient consultations pr. doctor etc. was significantly reduced. A striking finding was that although the number of outpatient consultations increased, the number of new referrals actually went down and the whole increase in activity at the outpatient clinics could be explained by a substantial increase in follow-up consultations. This trend was more evident in the surgical departments, where some departments actually showed a reduction in total outpatient consultations. CONCLUSION: In view of the slow increase in hospital activity in spite of a significant increase in resources, it can be speculated that patient volume might be a limiting factor for hospital activity. The health market (patient population) might not be big enough in relation to the investments in increased production capacity (equipment and manpower)

Does community-based education increase students' motivation to practice community health care? - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Community-based education has been introduced in many medical schools around the globe, but evaluation of instructional quality has remained a critical issue. Community-based education is an approach that aims to prepare students for future professional work at the community level. Instructional quality should be measured based on a program's outcomes. However, the association between learning activities and students' attitudes is unknown. The purpose of this study was to clarify what learning activities affect students' attitudes toward community health care.</p> <p>Methods</p> <p>From 2003 to 2009, self-administered pre- and post-questionnaire surveys were given to 693 fifth-year medical students taking a 2-week clinical clerkship. Main items measured were student attitudes, which were: "I think practicing community health care is worthwhile" ("worthwhile") and "I am confident about practicing community health care" ("confidence") using a visual analogue scale (0-100). Other items were gender, training setting, and learning activities. We analyzed the difference in attitudes before and after the clerkships by paired <it>t </it>test and the factors associated with a positive change in attitude by logistic regression analysis.</p> <p>Results</p> <p>Six hundred forty-five students (93.1%), 494 (76.6%) male and 151(23.4%) female, completed the pre- and post-questionnaires. The VAS scores of the students' attitudes for "worthwhile" and "confidence" after the clerkship were 80.2 ± 17.4 and 57.3 ± 20.1, respectively. Both of the scores increased after the clerkship. Using multivariate logistic regression analysis, "health education" was associated with a positive change for both attitudes of "worthwhile" (adjusted RR: 1.71, 95% CI: 1.10-2.66) and "confidence" (1.56, 1.08-2.25).</p> <p>Conclusions</p> <p>Community-based education motivates students to practice community health care. In addition, their motivation is increased by the health education activity. Participating in this activity probably produces a positive effect and improves the instructional quality of the program based on its outcomes.</p

Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009

<p>Abstract</p> <p>Background</p> <p>In 2009, an outbreak of dengue caused high fatality in Sri Lanka. We conducted 5 autopsies of clinically suspected myocarditis cases at the General Hospital, Peradeniya to describe the histopathology of the heart and other organs.</p> <p>Methods</p> <p>The diagnosis of dengue was confirmed with specific IgM and IgG ELISA, HAI and RT-PCR techniques. The histology was done in tissue sections stained with hematoxylin and eosin.</p> <p>Results</p> <p>Of the 319 cases of dengue fever, 166(52%) had severe infection. Of them, 149 patients (90%) had secondary dengue infection and in 5 patients, DEN-1 was identified as the causative serotype. The clinical diagnosis of myocarditis was considered in 45(27%) patients. The autopsies were done in 5 patients who succumbed to shock (3 females and 2 males) aged 13- 31 years. All had pleural effusions, ascites, bleeding patches in tissue planes and histological evidence of myocarditis. The main histological findings of the heart were interstitial oedema with inflammatory cell infiltration and necrosis of myocardial fibers. One patient had pericarditis. The concurrent pulmonary abnormalities were septal congestion, pulmonary haemorrhage and diffuse alveolar damage; one case showed massive necrosis of liver.</p> <p>Conclusions</p> <p>The histology supports occurrence of myocarditis in dengue infection.</p

Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies

<p>Abstract</p> <p>Background</p> <p>Physicians experience workplace stress and draw on different coping strategies. The primary goal of this paper is to use interview data to explore physicians' self reported coping strategies. In addition, questionnaire data is utilized to explore the degree to which the coping strategies are used and are associated with feelings of emotional exhaustion, a key symptom of burnout.</p> <p>Methods</p> <p>This mixed methods study explores factors related to physician wellness within a large health region in Western Canada. This paper focuses on the coping strategies that physicians use in response to work-related stress. The qualitative component explores physicians' self reported coping strategies through open ended interviews of 42 physicians representing diverse medical specialties and settings (91% response rate). The major themes extracted from the qualitative interviews were used to construct 12 survey items that were included in the comprehensive quantitative questionnaire. Questionnaires were sent to all eligible physicians in the health region with 1178 completed surveys (40% response rate.) Questionnaire items were used to measure how often physicians draw on the various coping strategies. Feelings of burnout were also measured in the survey by 5 items from the Emotional Exhaustion subscale of the revised Maslach Burnout Inventory.</p> <p>Results</p> <p>Major themes identified from the interviews include coping strategies used at work (e.g., working through stress, talking with co-workers, taking a time out, using humor) and after work (e.g., exercise, quiet time, spending time with family). Analysis of the questionnaire data showed three often used workplace coping strategies were positively correlated with feeling emotionally exhausted (i.e., keeping stress to oneself (r = .23), concentrating on what to do next (r = .16), and going on as if nothing happened (r = .07)). Some less often used workplace coping strategies (e.g., taking a time out) and all those used after work were negatively correlated with frequency of emotional exhaustion.</p> <p>Conclusions</p> <p>Physicians' self reported coping strategies are not all created equal in terms of frequency of use and correlation with feeling emotionally exhausted from one's work. This knowledge may be integrated into practical physician stress reduction interventions.</p

Modulation of phosphofructokinase (PFK) from Setaria cervi, a bovine filarial parasite, by different effectors and its interaction with some antifilarials

<p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively less attention has been paid towards its characterization from filarial parasites. Furthermore, the information about the response of filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view of these facts, PFK from <it>Setaria cervi</it>, a bovine filarial parasite having similarity with that of human filarial worms, was isolated, purified and characterized.</p> <p>Results</p> <p>The <it>S. cervi </it>PFK was cytosolic in nature. The adult parasites (both female and male) contained more enzyme activity than the microfilarial (Mf) stage of <it>S. cervi</it>, which exhibited only 20% of total activity. The <it>S. cervi </it>PFK could be modulated by different nucleotides and the response of enzyme to these nucleotides was dependent on the concentrations of substrates (F-6-P and ATP). The enzyme possessed wide specificity towards utilization of the nucleotides as phosphate group donors. <it>S. cervi </it>PFK showed the presence of thiol group(s) at the active site of the enzyme, which could be protected from inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by pretreatment with cysteine or β-ME. The sensitivity of PFK from <it>S. cervi </it>towards antifilarials/anthelmintics was comparatively higher than that of mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher than PFK from <it>S. cervi</it>.</p> <p>Conclusions</p> <p>The results indicate that the activity of filarial PFK may be modified by different effectors (such as nucleotides, thiol group reactants and anthelmintics) in filarial worms depending on the presence of varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It may possess thiol group at its active site responsible for catalysis. Relatively, 40 times higher sensitivity of filarial PFK towards suramin as compared to the analogous enzyme from the mammalian system indicates that this enzyme could be exploited as a potential chemotherapeutic target against filariasis.</p

Candida dubliniensis: An Appraisal of Its Clinical Significance as a Bloodstream Pathogen

A nine-year prospective study (2002–2010) on the prevalence of Candida dubliniensis among Candida bloodstream isolates is presented. The germ tube positive isolates were provisionally identified as C. dubliniensis by presence of fringed and rough colonies on sunflower seed agar. Subsequently, their identity was confirmed by Vitek2 Yeast identification system and/or by amplification and sequencing of the ITS region of rDNA. In all, 368 isolates were identified as C. dubliniensis; 67.1% came from respiratory specimens, 11.7% from oral swabs, 9.2% from urine, 3.8% from blood, 2.7% from vaginal swabs and 5.4% from other sources. All C. dubliniensis isolates tested by Etest were susceptible to voriconazole and amphotericin B. Resistance to fluconazole (≥8 µg/ml) was observed in 2.5% of C. dubliniensis isolates, 7 of which occurred between 2008–2010. Of note was the diagnosis of C. dubliniensis candidemia in 14 patients, 11 of them occurring between 2008–2010. None of the bloodstream isolate was resistant to fluconazole, while a solitary isolate showed increased MIC to 5-flucytosine (>32 µg/ml) and belonged to genotype 4. A review of literature since 1999 revealed 28 additional cases of C. dubliniensis candidemia, and 167 isolates identified from blood cultures since 1982. In conclusion, this study highlights a greater role of C. dubliniensis in bloodstream infections than hitherto recognized