A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes

MicroRNAs (miRNAs) are small non-coding RNAs that control expression of complementary target mRNAs. A growing number of miRNAs has been implicated in the pathogenesis of cardiac diseases, mostly based not on functional data, but on the observation that they are dysregulated in diseased myocardium. Consequently, our knowledge regarding a potential cardiac role of the majority of miRNAs is limited. Here, we report the development of an assay format that allows the simultaneous analysis of several hundred molecules with regard to their phenotypic effect on primary rat cardiomyocytes. Using automated microscopy and an edge detection algorithm, this assay achieved high reproducibility and a robust assessment of cardiomyocyte size as a key parameter. Screening a library of synthetic miRNAs revealed several miRNAs previously not recognized as pro- or anti-hypertrophic. Out of these, we selected nine miRNAs and confirmed the pro-hypertrophic potential of miR-22, miR-30c, miR-30d, miR-212, miR-365 and the anti-hypertrophic potential of miR-27a, miR-27b and miR-133a. Quantitative analysis of the expression level of pro-hypertrophic miRNAs in primary cardiomyocytes indicated a rather low level of correlation of the phenotypic effects of individual miRNAs and their expression level. This assay allows the automated determination of cell size in primary cardiomyocytes and permitted the identification of a set of miRNAs capable of regulating cardiomyocyte hypertrophy. Elucidating their mechanism of action should provide insight into mechanisms underlying the cardiomyocyte hypertrophic response. This article is part of a Special Issue entitled 'Possible Editorial'.     

Help-seeking behaviour,barriers to care and experiences of care among persons with depression in Eastern Cape,South Africa

Background

Little is known about the help-seeking behaviour and barriers to care among people with depression in poor resource settings in Sub-Saharan Africa.

Methods

This is a cross-sectional population-based study including 977 persons aged 18-40 living in the Eastern Cape Province in South Africa. The prevalence of depression was investigated with the help of a questionnaire (the Mini International Neuropsychiatric Interview). Several socio-economic variables, statements on help-seeking and perceptions of earlier mental health care were included. Data collection was performed from March to July 2012.

Results

The prevalence of depression was 31.4%. People aged 18-29 and those with no or low incomes were less likely to seek help. Promotive factors for help-seeking included having social support and tuberculosis comorbidity. Of all people with depression in this sample, 57% did not seek health care at all even though they felt they needed it. Of the variety of barriers identified, those of most significance were related to stigma, lack of knowledge of their own illness and its treatability as well as financial constraints.

Limitation

Recall bias may be present and the people identified with depression were asked if they ever felt so emotionally troubled that they felt they should seek help; however, we do not know if they had depression at the time they referred to.

Conclusions

Depression is highly prevalent among young adults in the Eastern Cape Province, South Africa; however, many do not seek help. Health planners should increase mental health literacy in the communities and improve the competence of the health staff.     

Influence of computer navigation on TKA revision rates

Purpose

We performed this study to determine whether the use of imageless navigation reduces revision rates after total knee arthroplasty (TKA).

Methods

Data of 1,121 consecutive primary TKA with a follow-up of one to six years were retrospectively analysed. Following the conversion of the standard technique from conventional to navigated procedures, these data included the last 342 conventional and first 779 navigated procedures performed in our clinic. Demographic and perioperative covariates were recorded. All patients were asked by post to report instances of revisions.

Results

Data of 1,054 patients (94 %) were complete. Mean follow-up was 3.9 years for conventional and 2.4 years for navigated operations. Cumulative revision rate averaged 4.7 % for conventional and 2.3 % for navigated procedures. Cox’s proportional hazard model was used to assess the effect of covariates on survival, resulting in significantly lower revision rates for older patients (p < 0.001) and for the navigated technique (p = 0.012). The reduced revision rate for navigated operations was mainly caused by a significantly reduced rate of aseptic implant loosening (1.9 % vs. 0.1 %, p = 0.024).

Conclusions

Our study showed lower revision rates when computer navigation was used. However, due to the retrospective uncontrolled design, further prospective trials will be necessary to further evaluate this effect.     

Impact of Protein Intake during Weight Loss on Preservation of Fat-Free Mass,Resting Energy Expenditure,and Physical Function in Overweight Postmenopausal Women: A Randomized Controlled Trial

IntroductionWeight loss in old age increases the risk of sarcopenia caused by the age-related reduction of fat-free mass (FFM). Due to the strong correlation between FFM and resting energy expenditure (REE), the maintenance of this must also be considered. Besides, the physical function (PF) must be maintained.ObjectiveThe impact of protein intake on changes in FFM, REE, and PF during weight loss in overweight postmenopausal women was investigated.MethodsFifty-four postmenopausal women (BMI 30.9 ± 3.4; age 59 ± 7 years) were randomized into 2 groups receiving energy-restricted diets with either 0.8 g (normal protein; NP) or 1.5 g protein/kg body weight (high protein; HP) for 12 weeks, followed by a 6-month follow-up phase with an ad libitum food intake. FFM, REE, and PF (strength, endurance, and balance) were measured at baseline, after weight loss, and after follow-up.ResultsForty-six women completed the weight loss intervention and 29 were followed up. The weight loss was −4.6 ± 3.6 kg (HP) and −5.2 ± 3.4 kg (NP; both p < 0.001) and the weight regain during follow-up was 1.3 ± 2.8 kg (HP; p = 0.03) and 0.4 ± 2.5 kg (NP; p = 0.39), with no differences between groups. Similar decreases in FFM (−0.9 ± 1.1 [HP] vs. −1.0 ± 1.3 kg [NP]) and REE (−862 ± 569 [HP] vs. −1,000 ± 561 kJ [NP]; both p < 0.001) were observed in both groups. During follow-up, no changes in FFM were detected in either group, whereas in the NP group the REE increased again (+138 ± 296; p = 0.02). The main determinants of FFM loss were the energy deficit and the speed of weight loss. In the NP group, the Short Physical Performance Battery score improved with weight loss (+0.6 ± 0.8; p < 0.001) and handgrip strength decreased (−1.7 ± 3.4 kg; p < 0.001), whereas no changes were observed in the HP group.ConclusionsAn HP weight-loss diet without exercise had no impact on preservation of FFM and REE but may help to maintain muscle strength in postmenopausal women.     

Association of regional white matter hyperintensities with hypertension and cognition in the population-based 1000BRAINS study

Background

White matter hyperintensities of presumed vascular origin (WMH) are frequent in cerebral magnetic resonance imaging of older people. They are promoted by vascular risk factors, especially hypertension, and are associated with cognitive deficits at the group level. It has been suggested that not only the severity, but also the location, of lesions might critically influence cognitive deficits and represent different pathologies.

Methods

In 560 participants (65.2 ± 7.5 years, 51.4% males) of the population-based 1000BRAINS study, we analyzed the association of regional WMH using Fazekas scoring separately for cerebral lobes, with hypertension and cognition.

Results

WMH most often affected the frontal lobe (83.7% score >0), followed by the parietal (75.8%), temporal (32.7%), and occipital lobe (7.3%). Higher Fazekas scores in the frontal, parietal, and temporal lobe were associated with higher blood pressure and antihypertensive treatment in unadjusted ordinal regression models and in models adjusted for age, sex, and vascular risk factors (e.g., age- and sex-adjusted odds ratio = 1.14, 95% confidence interval = 1.03–1.25 for the association of frontal lobe WMH Fazekas score with systolic blood pressure [SBP] [per 10 mm Hg]; 1.13 [1.02–1.23] for the association of parietal lobe score with SBP; 1.72 [1.19–2.48] for the association of temporal lobe score with antihypertensive medications). In linear regressions, higher frontal lobe scores were associated with lower performance in executive function and non-verbal memory, and higher parietal lobe scores were associated with lower performance in executive function, verbal-, and non-verbal memory.

Conclusions

Hypertension promotes WMH in the frontal, parietal, and temporal lobe. WMH in the frontal and parietal lobe are associated with reduced executive function and memory.