Genetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population

Abstract

The purpose of this study is to identify microRNA (miRNA) related polymorphism, including single nucleotide variants (SNVs) in mature miRNA-encoding sequences or in miRNA-target sites, and their association with cardiovascular disease (CVD) risk factors in African-American population. To achieve our objective, we examined 1900 African-Americans from the Atherosclerosis Risk in Communities study using SNVs identified from whole-genome sequencing data. A total of 971 SNVs found in 726 different mature miRNA-encoding sequences and 16,057 SNVs found in the three prime untranslated region (3′UTR) of 3647 protein-coding genes were identified and interrogated their associations with 17 CVD risk factors. Using single-variant-based approach, we found 5 SNVs in miRNA-encoding sequences to be associated with serum Lipoprotein(a) [Lp(a)], high-density lipoprotein (HDL) or triglycerides, and 2 SNVs in miRNA-target sites to be associated with Lp(a) and HDL, all with false discovery rates of 5%. Using a gene-based approach, we identified 3 pairs of associations between gene NSD1 and platelet count, gene HSPA4L and cardiac troponin T, and gene AHSA2 and magnesium. We successfully validated the association between a variant specific to African-American population, NR_039880.1:n.18A>C, in mature hsa-miR-4727-5p encoding sequence and serum HDL level in an independent sample of 2135 African-Americans. Our study provided candidate miRNAs and their targets for further investigation of their potential contribution to ethnic disparities in CVD risk factors.

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Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact

ABSTRACT

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

The aMICRA score was used to assess impact, including distress, uncertainty and positivity (reversed scored) of the genetic test results on the parents. On average, the aMICRA was 12 points higher (more negative impact) in parents who interpreted the results as positive and seven points higher for those who interpreted the results as uncertain compared to those who interpreted the results as negative (p<0.0001, p=0.02). Overall the majority of parents correctly interpreted their child's exome sequencing results. Parental misinterpretation occurred most frequently when the clinician interpreted the results as uncertain.

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Bilateral deficit of spring-like behaviour during hopping in sprinters

Abstract

Purpose

Unilateral leg stiffness is a key contributor to sprint running speed, thereby great bilateral deficit (BLD) of leg stiffness would be expected to be observed in sprinters. However, it remains clear only BLD of leg stiffness at the preferred hopping frequency in non-sprinters. The purpose of this study was to clarify the BLD of spring-like behaviour in hopping at various frequencies and the effect of chronic adaptation via sprint running experience on BLD during the hopping.

Methods

Fifteen male experienced sprinters and 12 male novices participated in this study. They were instructed to hop in place at three frequencies (2.0, 2.5, and 3.0 Hz), and to perform hopping with maximal effort. Ground reaction forces (GRF) of both legs during the hopping were recorded using two force plates.

Results

At higher hopping frequencies during the unilateral and bilateral hopping, smaller peak value of vertical GRF (F _max) and greater leg stiffness (K _leg) were significantly observed. The BLD index of F _max and the BLD index of K _leg were significantly smaller at higher hopping frequencies. No significant differences of BLD index of F _max and BLD index of K _leg were observed between sprinters and novices.

Conclusion

Our results demonstrate that neuromuscular inhibition in the contralateral leg changes during the hopping based on hopping frequency. This suggests that plyometric training in the beginning of rehabilitation should involve bilateral jumping at a high frequency. In experienced sprinters, detailed mechanics of chronic neuromuscular adaptation via unilateral facilitation of spring-like behaviour should be assessed by measuring electromyographic activity.

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Event-related potentials of attentional bias toward faces in the dot-probe task: A systematic review

Abstract

The dot-probe task is a common task to assess attentional bias toward different stimuli and how groups differ (e.g., attentional bias in anxiety disorders). However, measuring reaction time has been suggested to be unreliable. Neuroimaging methods such as fMRI were shown to be more reliable in assessing attentional bias, but fMRI has poor temporal resolution and therefore cannot assess timing of attention. ERPs have been used to examine the time course of attentional bias. Although ERP research may be more reliable than reaction time, there have been inconsistencies in the literature. This review systematically searched for articles that used the dot-probe task with facial expressions and measured neural correlates with ERP. We found that some of the inconsistencies might be the cause of methodological differences (e.g., timing of stimuli), differences in emotional expression, and/or sample differences (e.g., sex, age, etc.). Suggestions on how future research could address the issues presented in this review were discussed.

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Spatial versus temporal inhibition in dystonia

Dystonia is a motor disorder characterized by involuntary muscle contractions, frequently causing twisted postures. A pathophysiological hallmark of dystonia is reduced motor inhibition at multiple levels of the central nervous system including the spinal cord, brainstem and cortex. In addition, it is widely accepted that the sensory system is involved in dystonia. A well-known and fascinating phenomenon is the sensory trick. Touching a body part, usually at a location close to where dystonia occurs such as the neck or face in cervical dystonia or blepharospasm, alleviates dystonia symptoms.

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The implant effect after intracranial electrode placement: is transient clinical improvement explained by post-implantation electrophysiological changes?

It has been repeatedly observed that implanting electrodes in the brain or on the brain is occasionally associated with a transient improvement in seizure control. This improvement was observed with responsive neurostimulation (Morrell et al., 2011), deep brain stimulation (Velasco et al., 2006; Fisher et al., 2010; Valentin et al., 2013), and even diagnostic intracranial electrode implantation (Schulze-Bonhage et al., 2010; Roth et al., 2012; Kovac et al., 2014). In the pivotal trial of anterior thalamic stimulation, there was a 21-22% median seizure frequency reduction in the first month after implantation, prior to randomization (Fisher et al., 2010).

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Restoration of metabolic health by decreased consumption of branched-chain amino acids

Abstract

Obesity and diabetes are increasing problems around the world, and while even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. Here, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21. Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs to the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance.

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