Moderate elevations of cardiac troponin (Tn) T, up to levels presumably diagnostic for minor myocardial damage, are suspected to be false positive in nearly 0.3 of end-stage renal disease (ESRD) ...patients undergoing haemodialysis (HD). It is not clear whether cardiac TnI is superior to TnT in those patients, if differences between ESRD and pre-ESRD occur, and what the prognostic meaning of these troponin elevations might be.
We examined 40 chronic renaldisease patients 56.4 SD 13.9 years; 22 male, 18 female) without evidence of an acute coronary syndrome (ACS) for at least 28 days prior to the investigation. Cardiac status was determined by history, physical examination, ECG and echocardiography. Patients were divided into subgroups with HD (n = 20) and without HD (n = 20). Patients without HD had a mean creatinine clearance (CC) of 13.45 ml/min. Tn were measured by immunoassay techniques. TnT was compared to two different TnI tests (TnID, TnIB), CK/CKMB activity and myoglobin (MYO) concentrations. In all patients, a 9-month follow-up for acute myocardial infarction, re-hospitalization, and death was completed.
None of the troponins significantly predicted patient outcome. Tn did not correlate with CC (r<0.6). Applying the lowest reported threshold values for all tests in the HD group, 0.3 patients were positive for TnT, 0.55 patients were positive for TnID, and 0.15 for TnIB. In the group without HD, 0.2 patients were positive for TnT and TnID and 0.1 for TnIB.
Moderate elevations of cardiac troponins are common in clinically stable patients with renal disease and are neither diagnostic for an acute coronary syndrome nor predictive of outcome. It is concluded that increased troponins in asymptomatic renal patients are of questionable value for risk stratification, most probably due to unspecific elevations.
Summary
Background and Objectives
Anagrelide represents a treatment option for essential thrombocythemia patients. It lowers platelet counts through inhibition of megakaryocyte maturation and ...polyploidization, although the basis for this effect remains unclear. Based on its rapid onset of action, we assessed whether, besides blocking megakaryopoiesis, anagrelide represses proplatelet formation (PPF) and aimed to clarify the underlying mechanisms.
Methods and Results
Exposure of cord blood‐derived megakaryocytes to anagrelide during late stages of culture led to a dose‐ and time‐dependent inhibition of PPF and reduced proplatelet complexity, which were independent of the anagrelide‐induced effect on megakaryocyte maturation. Whereas anagrelide was shown to phosphorylate cAMP‐substrate VASP, two pharmacologic inhibitors of the cAMP pathway were completely unable to revert anagrelide‐induced repression in megakaryopoiesis and PPF, suggesting these effects are unrelated to its ability to inhibit phosphodiesterase (PDE) 3. The reduction in thrombopoiesis was not the result of down‐regulation of transcription factors which coordinate PPF, while the myosin pathway was identified as a candidate target, as anagrelide was shown to phosphorylate the myosin light chain and the PPF phenotype was partially rescued after inhibition of myosin activity with blebbistatin.
Conclusions
The platelet‐lowering effect of anagrelide results from impaired megakaryocyte maturation and reduced PPF, both of which are deregulated in essential thrombocythemia. These effects seem unrelated to PDE3 inhibition, which is responsible for anagrelide′s cardiovascular side‐effects and antiplatelet activity. Further work in this field may lead to the potential development of drugs to treat thrombocytosis in myeloproliferative disorders with an improved pharmacologic profile.
Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely ...role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m
), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.
•Among American Society of Hematology CRTI applicants, URM applicants received significantly lower scores than non-URM applicants.•Impact of the reviewer’s sex and URM status on application scores ...changed over time.
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The American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. There was no significant difference in scores according to applicant sex. URM applicants had significantly worse scores than non-URM applicants (mean standard error 67.9 1.56 vs 71.4 0.63; P = .0355). There were significant interactions between reviewer sex and time (P = .0030) and reviewer URM status and time (P = .0424); thus, results were stratified by time. For the 2 earlier time periods, male reviewers gave significantly worse scores than did female reviewers; this difference did not persist for the most recent time period. The URM reviewers did not give significantly different scores across time periods. URM applicants received significantly lower scores than non-URM applicants. The impact of reviewer sex and URM status changed over time. Although male reviewers gave lower scores in the early periods, this effect did not persist in the late period. Efforts are required to mitigate the impact of applicant URM status on application scores.
The desire for social distance towards individuals with obesity as part of the stigmatization process has not been investigated. The aims of this study include: (a) determining the prevalence of ...social distance and its domains in a population-based sample; (b) reporting levels of emotional response; and (c) investigating the association of BMI, emotional response and social distance. The data were derived from a large population based telephone survey in Germany (total n = 3,003, this sub-sample n = 1008). Emotional response to individuals with obesity was assessed for the emotions discomfort, pity, insecurity, amusement, sympathy, help and incomprehension (5-point Likert scale). Social distance was measured on a 5-point Likert scale covering different areas of social interaction. This served as the dependent variable for a linear regression model and mediation models that included BMI and emotional response. Social distance was highest for job recommendation, introduction to a friend, someone with obesity marrying into the family and renting out a room. Means of emotional responses were highest for pity (Mean = 2.58), sympathy (Mean = 2.87) and wanting to help (M = 2.76). In regression analyses, incomprehension (b = 1.095, p < 0.001) and sympathy (b = −0.833, p < 0.001) and the respondents' own BMI (b = −0.145, p < 0.001) were significantly associated to the overall amount of social distance. Mediation models revealed a significant mediation effect of BMI through sympathy (b = −0.229, % of total effect through mediation = 10.3%) and through incomprehension (b = −0.057, % of total effect through mediation = 27.5%) on social distance.
Social distance towards individuals with obesity is prevalent in the general public in Germany and it is associated with emotional responses. Altering the emotional responses may, therefore, be a starting point in anti-stigma interventions. Evoking sympathy and lowering incomprehension may result in lower overall social distance.
•Population-based prevalence rates of social distance towards obesity are provided.•Prevalence rates are compared to other illnesses, such as mental disorders.•Emotional responses to individuals with obesity are described.•Personal Interaction, sympathy and understanding affect social distance.
Resilience describes good adaptation to adversity and is a significant factor for well-being in old age. Initial studies indicate a high relevance of social resources. So far, only few studies have ...investigated resilience patterns in the elderly population. Therefore, the present study aims to investigate sociodemographic and social correlates of resilience in a large population-based sample aged 65 years and older.
Analyses were conducted on n = 2410 people aged 65 years and older from the follow-up survey of the LIFE-Adult-Study. The survey included the variables resilience (Resilience Scale - RS-11), social support (ENRICHD Social Support Inventory - ESSI), and social network (Lubben Social Network Scale - LSNS-6). The association of sociodemographic and social variables with resilience was analyzed using multiple linear regression analysis.
The age of 75 years and older was associated with lower resilience compared with the age of 65-74 years. Further, widowed marital status was related to higher resilience. Better social support and a larger social network were significantly associated with higher resilience. No association was found for gender and education.
The results reveal sociodemographic correlates of resilience in the elderly population that can help identify at-risk groups with lower resilience. Social resources are significant in older age for resilient adaptation and represent a starting point for deriving preventive measures. Social inclusion of older people should be promoted to strengthen resilience in this population and provide favorable conditions for successful aging.
Studies have shown that dementia and cognitive impairment can increase mortality, but less is known about the association between subjectively perceived cognitive deficits (subjective cognitive ...decline, SCD) and mortality risk.
In this study, we analyzed mortality in non-demented individuals with SCD in a general population sample aged 75+ years.
Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan-Meier survival method to estimate survival times of individuals with and without SCD and multivariable Cox proportional hazards regression to assess the association between SCD and mortality risk, controlled for covariates.
Out of 953 non-demented individuals at baseline, 117 (12.3% ) expressed SCD. Participants with SCD showed a significantly higher case-fatality rate per 1,000 person-years (114.8, 95% CI = 90.5-145.7 versus 71.7, 95% CI = 64.6-79.5) and a significantly shorter mean survival time than those without (5.4 versus 6.9 years, p < 0.001). The association between SCD and mortality remained significant in the Cox analysis; SCD increased mortality risk by about 50% (adjusted Hazard Ratio = 1.51) during the study period. Besides SCD, older age, male gender, diabetes mellitus, stroke, and lower global cognitive functioning were also significantly associated with increased mortality.
Our findings suggest an increased mortality risk in non-demented older individuals with SCD. Even though further studies are required to analyze potential underlying mechanisms, subjective reports on cognitive deficits may be taken seriously in clinical practice not only for an increased risk of developing dementia and AD but also for a broader range of possible adverse health outcomes.
Background
The number of people living with dementia worldwide is increasing rapidly. Preventive approaches constitute a promising strategy to counter the dementia epidemic, and growing numbers of ...lifestyle interventions are conducted around the globe. Gender differences with respect to modifiable risk factors for dementia have been reported, however, little is known about gender-specific effectiveness of lifestyle trials against cognitive decline and dementia. A systematic review and meta-analysis was conducted to assess evidence on gender-specific design and effectiveness of randomized controlled trials against cognitive decline.
Methods
Systematic literature searches were conducted in MEDLINE, PsycINFO, Web of Science, Cochrane Central and ALOIS. Studies assessing global and/or domain-specific cognitive function in older adults free from dementia were eligible for the systematic review. We assessed between-group effect sizes using random-effects meta-analysis. Methodological quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN)-checklist.
Results
The systematic review and meta-analysis included 34 and 31 studies, respectively. Effects of lifestyle-interventions on global cognition were non-significant overall (g =.27; 95% CI: −.01;.56) and in male subsamples (g = −.05; 95% CI: −.55;.45), and small for female subsamples (g =.38; 95% CI:.05;.72). Small beneficial effects were found for memory (overall: g =.38; 95% CI =.17;.59). Stratified by gender, significant effects were observed only in women (g =.39; 95% CI =.13;.65; men: g =.37; 95% CI:.00;.73). Aspects of gender in study design and conduct were discussed in a small minority of studies. Comparable results were observed for executive function and verbal fluency. Methodological quality was deemed high in 17.6% of studies, acceptable and low quality in 52.9% and 29.4%, respectively.
Discussion
We found evidence for small differences in the effectiveness of lifestyle interventions on global cognition and memory in favor of women. However, small numbers of trials 1) targeting men and 2) reporting gender-specific results for older adults with mild cognitive impairment warrant further attention. Assessing differences in modifiable risk factors for dementia in men and women and systematically addressing aspects of gender in trial conduction and recruitment in future studies might increase knowledge on gender-specific effectiveness of lifestyle trials against cognitive decline.
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