Cardiac troponin in ischemic cardiomyocytes: Intracellular decrease before onset of cell death

Aim

Cardiac troponin I (cTnI) and T (cTnT) are the most important biomarkers in the diagnosis of acute myocardial infarction (AMI). Nevertheless, they can be elevated in the absence of AMI. It is unclear if such elevations represent irreversible cardiomyocyte-damage or leakage from viable cardiomyocytes. Our objective is to evaluate whether cTn is released from viable cardiomyocytes in response to ischemia and to identify differences in the release of cTn and its molecular forms.

Methods and results

HL-1 cardiomyocytes (mouse) were subjected to ischemia (modeled by anoxia with glucose deprivation). The total contents and molecular forms of cTn were determined in culture media and cell lysates. Cell viability was assessed from the release of lactate dehydrogenase (LDH). Before the release of LDH, the intracellular cTn content in ischemic cells decreased significantly compared to control (52% for cTnI; 23% for cTnT) and was not matched by a cTn increase in the medium. cTnI decreased more rapidly than cTnT, resulting in an intracellular cTnT/cTnI ratio of 25.5 after 24 h of ischemia. Western blots revealed changes in the relative amounts of fragmented cTnI and cTnT in ischemic cells.

Conclusions

HL-1 cardiomyocytes subjected to simulated ischemia released cTnI and cTnT only in combination with the release of LDH. We find no evidence of cTn release from viable cardiomyocytes, but did observe a significant decrease in cTn content, before the onset of cell death. Intracellular decrease of cTn in viable cardiomyocytes can have important consequences for the interpretation of cTn values in clinical practice.     

Parental longevity correlates with offspring’s optimism in two cohorts of community-dwelling older subjects

Dispositional optimism and other positive personality traits have been associated with longevity. Using a familial approach, we investigated the relationship between parental longevity and offspring’s dispositional optimism among community-dwelling older subjects. Parental age of death was assessed using structured questionnaires in two different population-based samples: the Leiden Longevity Study (n = 1,252, 52.2% female, mean age 66 years, SD = 4) and the Alpha Omega Trial (n = 769, 22.8% female, mean age 69 years, SD = 6). Adult offspring’s dispositional optimism was assessed with the Life Orientation Test—Revised (LOT-R). The association between parental age of death and levels of optimism in the offspring was analysed using linear regression analysis within each sample and a meta-analysis for the overall effect. In both samples, the parental mean age of death was positively associated with optimism scores of the offspring. The association remained significant after adjustment for age, gender, living arrangement, body mass index, smoking status, education and self-rated health of the offspring. The pooled B coefficient (increase in LOT-R score per 10-year increase in parental mean age of death) was 0.30 (SE = 0.08, p < 0.001). In conclusion, parental longevity was positively associated with optimism in adult offspring, suggesting a partial linked heritability of longevity and optimism.     

Reflections of Caretakers on the Process of Implementation of Life Space Crisis Intervention at a Therapeutic Centre for Youngsters with Emotional and Behavioural Disorders

Life space crisis intervention (LSCI) is a therapeutic and verbal strategy used to intervene when children are in crisis. It has its roots in the work of Aichorn, Redl, Wineman and Bettelheim, and is part of the milieu-therapeutic tradition. In 2000, LSCI was introduced at the Orthopedagogical Observation and Treatment Centre, a school and day unit for 60 children with emotional and behavioural disorders affiliated with the Department of Orthopedagogy at Ghent University (Belgium). The particular position of orientation towards ‘therapeutic environments’ in the department’s history has encouraged the integration of LSCI in the daily activities of the departments’ school (Broekaert et al., Int J Ther Communities 30(2):122–145, 2009). In 2003, LSCI was implemented and studied in several Flemish Institutes. Positive effects were found on school results, attendance in the classroom and number of conflicts. In this article, the reflections of the caretakers are taken into account. Analyses of these reflections resulted in 4 major themes: content of job and tasks, the youth in the centre, working with the youth in the centre, and cooperation with colleagues and other teams. The results of this analysis will be discussed.     

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery.

Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach.

Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.     

Effects of exercise training programs on walking competency after stroke: a systematic review

To determine the effectiveness of training programs that focus on lower-limb strengthening, cardiorespiratory fitness, or gait-oriented tasks in improving gait, gait-related activities, and health-related quality of life after stroke. Randomized controlled trials (RCTs) were searched for in the databases of Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, Physiotherapy Evidence Database (PEDro), EMBASE, Database of the Dutch Institute of Allied Health Care, and CINAHL. Databases were systematically searched by two independent researchers. The following inclusion criteria were applied: (1) participants were people with stroke, older than 18 yrs; (2) one of the outcomes focused on gait-related activities; (3) the studies evaluated the effectiveness of therapy programs focusing on lower-limb strengthening, cardiorespiratory fitness, or gait-oriented training; and (4) the study was published in English, German, or Dutch. Studies were collected up to November 2005, and their methodological quality was assessed using the PEDro scale. Studies were pooled and summarized effect sizes were calculated. Best-evidence synthesis was applied if pooling was impossible. Twenty-one RCTs were included, of which five focused on lower-limb strengthening, two on cardiorespiratory fitness training (e.g., cycling exercises), and 14 on gait-oriented training. Median PEDro score was 7. Meta-analysis showed a significant medium effect of gait-oriented training interventions on both gait speed and walking distance, whereas a small, nonsignificant effect size was found on balance. Cardiorespiratory fitness programs had a nonsignificant medium effect size on gait speed. No significant effects were found for programs targeting lower-limb strengthening. In the best-evidence synthesis, strong evidence was found to support cardiorespiratory training for stair-climbing performance. Although functional mobility was positively affected, no evidence was found that activities of daily living, instrumental activities of daily living, or health-related quality of life were significantly affected by gait-oriented training. This review shows that gait-oriented training is effective in improving walking competency after stroke.     

Return to work after major trauma

OBJECTIVE: To quantify the prevalence of return to work after major trauma, and to investigate the determinants of postinjury work status. DESIGN: Prospective cohort study. SETTING: University Medical Centre Utrecht, a level 1 trauma centre in the Netherlands. METHOD: All severely injured (ISS > 16) adult (age = 16+) trauma survivors admitted from January 1999 to December 2000 who were full-time employed at the time of the injury were selected for follow-up (n = 214). Response rate was 93%. Outcome was assessed at a mean of 15 months (SD = 1.5) after injury. Multivariate logistic regression analyses identified determinants at hospital discharge and at follow-up. RESULTS: Following injury 58.4% of the patients (n = 125) were able to return to full-time employment, 21.5% had a part-time job, and 20.1% did not return to work. Univariate analysis yielded the following significant determinants of postinjury work status: age, comorbidity, injury severity score, brain injury, spinal cord injury, length of stay in an intensive care unit, hospital stay, discharge destination, percentage of permanent impairment (according to the fourth American Medical Association guide (AMA)), limitations in activities of daily living and cognitive complaints. Logistic regression analyses (23% explained variance) identified spinal cord injury, duration of hospital stay, discharge destination and age as determinants of return to work at hospital discharge. At follow-up, determinants of return to work included AMA, activities of daily living, cognitive complaints and being discharged home (51% explained variance). CONCLUSIONS: Around 60% of the patients returned to their pre-injury work status after major trauma. The return to work rate was only partly explained by disability at follow-up. Independent determinants of return to work differ with the time of assessment.     

Predictors of successful and unsuccessful quit attempts among smokers motivated to quit

Introduction

Despite their positive motivation to quit, many smokers do not attempt to quit or relapse soon after their quit attempt. This study investigated the predictors of successful and unsuccessful quit attempts among smokers motivated to quit smoking.

Methods

We conducted secondary data analysis among respondents motivated to quit within 6 months, randomized to the control group (N = 570) of a Web-based smoking cessation intervention study. Using chi-square tests and ANOVA with Tukey post hoc comparisons, we investigated baseline differences by smoking status (successful quitter/relapse/persistent smoker) assessed after 6 weeks (N = 214). To identify independent predictors of smoking status, multivariate multinomial logistic regression analyses were conducted.

Results

Successful quitters at 6-week follow-up (26%) had reported significantly higher baseline levels of self-efficacy than relapsers (45%) and persistent smokers (29%). Furthermore, both successful quitters and relapsers had reported a significantly higher baseline intention to quit than persistent smokers and successful quitters had reported significantly more preparatory planning at baseline than persistent smokers. Results from regression analyses showed that smokers' baseline intention to quit positively predicted quit attempts reported after 6 weeks, while self-efficacy positively predicted quit attempt success.

Conclusions

Different factors appear to play a role in predicting quit attempts and their success. Whereas intention to quit only appeared to play a role in predicting quit attempts, self-efficacy was the main factor predicting quit attempt success. More research is needed to determine the role of preparatory planning and plan enactment and to investigate whether these findings can be replicated on the long term.     

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term

Purpose

An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8–1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term.

Methods

At term age, 3 and 6 months post-term, ferritin (μg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated.

Results

Iron was supplemented to 71.7 % of HM-fed and 83.7 % of IFF-fed infants between term age and 3 months post-term and to 13 % of HM-fed and 0 % of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 μg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8 % and 26.3 vs. 9.5 %, P < 0.02).

Conclusion

This observational study demonstrates that ferritin <12 μg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8–1.0 mg iron/100 ml), as they achieve ferritin ≥12 μg/l without additional iron supplements between 3 and 6 months post-term.