Cardiovascular Risk Factors Among First-Degree Relatives of Patients with Premature Cardiovascular Disease in Malta. Baseline Findings from the CRISO Project.

Purpose: A family history of premature atherosclerotic cardiovascular disease (ASCVD) confers a greater risk of developing ASCVD. However, the prevalence of ASCVD risk factors among asymptomatic Maltese adults with parental or fraternal history of premature ASCVD is unknown. The study aimed to evaluate and compare their risk with the general population. Patients and Methods: Posters to market the project were distributed in cardiac rehabilitation areas. Patients with premature cardiovascular disease facilitated recruitment by informing their relatives about the project. Medical doctors and cardiac rehabilitation nurses referred first-degree relatives. Posters were put up in community pharmacies, and an explanatory video clip was shared on social media for interested individuals to contact researchers. Those eligible were enrolled in a preventive cardiology lifestyle intervention. Their data were compared with the risk in the general population. Results: Many first-degree relatives had a suboptimal risk profile, with 60% (N = 89) having a total cholesterol level of >5.0 mmol/L; 54% having a low-density lipoprotein-cholesterol level of >3 mmol/L; 70.5% being overweight/obese, with 62% having a waist circumference greater than the recommended values; 34.8% having hypertension; 56.2% being inadequately adherent to the Mediterranean diet; 62% being underactive, with 18% being sedentary; and 25.8% being smokers. First-degree relatives had significantly higher proportions of underactive lifestyle (p = 0.00016), high body mass index (>25kg/m2) (p = 0.006), and systolic blood pressure (p = 0.001) than the general population, with 30% having metabolic syndrome. Conclusion: This study determined the prevalence of lifestyle, biochemical, physiological, and anthropometric cardiovascular risk factors among asymptomatic first-degree relatives of Maltese patients with premature ASCVD. First-degree relatives had considerable prevalences of an underactive lifestyle, hypertension, and obesity, suggesting better screening and early risk factor intervention are needed to modify their risk of ASCVD.

This study was done to evaluate factors that can increase the risk of heart disease in siblings and offspring of Maltese patients who developed atherosclerotic cardiovascular disease (ASCVD) at a young age. Relatives were invited to meetings during which a risk evaluation was performed. The researchers found that relatives had a high prevalence of cardiometabolic risk factors, meaning they were at increased risk of developing the disease. The researchers have concluded that reducing the risk of ASCVD in individuals at increased risk requires developing and testing potentially sustainable risk factor modification strategies.

Sleep measures and cardiovascular disease in type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to assess whether poor sleep is independently associated with cardiovascular disease in people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was performed in subjects with T2DM aged between 40 and 80 years. Sleep assessment was achieved by actigraphy and Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: The study population comprised 108 subjects with T2DM. The mean age was 64.9 years, the median diabetes duration was 6 years and 73.1% were men. No association was shown between sleep parameters as assessed by actigraphy and T2DM-associated micro- and macrovascular complications. However, sleep quality as assessed by PSQI was significantly associated with macrovascular disease in univariate analysis. Multivariate logistic regression analysis showed red blood cell distribution width (RDW) (odds ratio (OR) 1.79, p=0.018) and good sleep quality (OR 0.35, p=0.017) to be independently associated. Binary logistic regression analysis revealed that body mass index (BMI) (OR 1.11, p=0.024), RDW (OR 1.95, p=0.007) and Center for Epidemiologic Studies Depression score (OR 1.06, p=0.012] were independently associated with abnormal carotid intima-media thickness (CIMT). CONCLUSIONS: Poor sleep quality and higher RDW levels are associated with macrovascular disease in a T2DM population. Increased BMI as well as depression also appear to have an independent role in subclinical atherosclerosis, as assessed by CIMT.

Sleep measures and cardiovascular disease in type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to assess whether poor sleep is independently associated with cardiovascular disease in people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was performed in subjects with T2DM aged between 40 and 80 years. Sleep assessment was achieved by actigraphy and Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: The study population comprised 108 subjects with T2DM. The mean age was 64.9 years, the median diabetes duration was 6 years and 73.1% were men. No association was shown between sleep parameters as assessed by actigraphy and T2DM-associated micro- and macrovascular complications. However, sleep quality as assessed by PSQI was significantly associated with macrovascular disease in univariate analysis. Multivariate logistic regression analysis showed red blood cell distribution width (RDW) (odds ratio (OR) 1.79, p=0.018) and good sleep quality (OR 0.35, p=0.017) to be independently associated. Binary logistic regression analysis revealed that body mass index (BMI) (OR 1.11, p=0.024), RDW (OR 1.95, p=0.007) and Center for Epidemiologic Studies Depression score (OR 1.06, p=0.012] were independently associated with abnormal carotid intima-media thickness (CIMT). CONCLUSIONS: Poor sleep quality and higher RDW levels are associated with macrovascular disease in a T2DM population. Increased BMI as well as depression also appear to have an independent role in subclinical atherosclerosis, as assessed by CIMT.

Sensorimotor feedback loops are selectively sensitive to reward.

Although it is well established that motivational factors such as earning more money for performing well improve motor performance, how the motor system implements this improvement remains unclear. For instance, feedback-based control, which uses sensory feedback from the body to correct for errors in movement, improves with greater reward. But feedback control encompasses many feedback loops with diverse characteristics such as the brain regions involved and their response time. Which specific loops drive these performance improvements with reward is unknown, even though their diversity makes it unlikely that they are contributing uniformly. We systematically tested the effect of reward on the latency (how long for a corrective response to arise?) and gain (how large is the corrective response?) of seven distinct sensorimotor feedback loops in humans. Only the fastest feedback loops were insensitive to reward, and the earliest reward-driven changes were consistently an increase in feedback gains, not a reduction in latency. Rather, a reduction of response latencies only tended to occur in slower feedback loops. These observations were similar across sensory modalities (vision and proprioception). Our results may have implications regarding feedback control performance in athletic coaching. For instance, coaching methodologies that rely on reinforcement or 'reward shaping' may need to specifically target aspects of movement that rely on reward-sensitive feedback responses.

Short duration event related cerebellar TDCS enhances visuomotor adaptation.

BACKGROUND: Transcranial direct current stimulation (TDCS) is typically applied before or during a task, for periods ranging from 5 to 30 min. HYPOTHESIS: We hypothesise that briefer stimulation epochs synchronous with individual task actions may be more effective. METHODS: In two separate experiments, we applied brief bursts of event-related anodal stimulation (erTDCS) to the cerebellum during a visuomotor adaptation task. RESULTS: The first study demonstrated that 1 s duration erTDCS time-locked to the participants' reaching actions enhanced adaptation significantly better than sham. A close replication in the second study demonstrated 0.5 s erTDCS synchronous with the reaching actions again resulted in better adaptation than standard TDCS, significantly better than sham. Stimulation either during the inter-trial intervals between movements or after movement, during assessment of visual feedback, had no significant effect. Because short duration stimulation with rapid onset and offset is more readily perceived by the participants, we additionally show that a non-electrical vibrotactile stimulation of the scalp, presented with the same timing as the erTDCS, had no significant effect. CONCLUSIONS: We conclude that short duration, event related, anodal TDCS targeting the cerebellum enhances motor adaptation compared to the standard model. We discuss possible mechanisms of action and speculate on neural learning processes that may be involved.

Predictors of subclinical atherosclerosis and microalbuminuria in middle-aged women: a cross-sectional study.

BACKGROUND: Cardiovascular disease is of increasing concern in women. The aim was to assess the role of clinical and anthropometric measures in the development of subclinical atherosclerosis. METHODS: A cross-sectional study in 203 Europid females to determine the prevalence of abnormal carotid intima-media thickness (CIMT) and associated clinical parameters. RESULTS: The study population had a mean age of the 38.3±5.4 years, a median Body Mass Index of 29.25 (IQR 25.06-36.11) kg/m2 and median waist index (WI) of 1.15 (IQR 1.06-1.34). Increased CIMT was present in 169 (83.25%) participants. Linear regression analysis revealed WI to be the sole predictor of increased CIMT (ß=24.387, P<0.001). Post-hoc ROC analysis revealed a WI of 1.12 has 62% sensitivity and 53% specificity for predicting increased CIMT (AUC 0.63, 95% CI 0.55-0.72, P=0.016). The median urinary albumin-creatinine ratio (ACR) was 4.4 mg/g, and the prevalence of microalbuminuria was 8.9%; serum triglycerides were the only independent predictor of ACR. CONCLUSIONS: Atherosclerosis, as detected by abnormal CIMT, is very prevalent in middle-aged women. Waist index is the major predictor of subclinical atherosclerosis in a contemporary premenopausal female population. A WI of 1.12 exhibits relatively good sensitivity and specificity in predicting the presence of atherosclerosis in this patient population.

The dissociable effects of reward on sequential motor behavior.

Reward has consistently been shown to enhance motor behavior; however, its beneficial effects appear to be largely unspecific. For example, reward is associated with both rapid and training-dependent improvements in performance, with a mechanistic account of these effects currently lacking. Here we tested the hypothesis that these distinct reward-based improvements are driven by dissociable reward types: monetary incentive and performance feedback. Whereas performance feedback provides information on how well a motor task has been completed (knowledge of performance), monetary incentive increases the motivation to perform optimally without providing a performance-based learning signal. Experiment 1 showed that groups who received monetary incentive rapidly improved movement times (MTs), using a novel sequential reaching task. In contrast, only groups with correct performance-based feedback showed learning-related improvements. Importantly, pairing both maximized MT performance gains and accelerated movement fusion. Fusion describes an optimization process during which neighboring sequential movements blend together to form singular actions. Results from experiment 2 served as a replication and showed that fusion led to enhanced performance speed while also improving movement efficiency through increased smoothness. Finally, experiment 3 showed that these improvements in performance persist for 24 h even without reward availability. This highlights the dissociable impact of monetary incentive and performance feedback, with their combination maximizing performance gains and leading to stable improvements in the speed and efficiency of sequential actions.NEW & NOTEWORTHY Our work provides a mechanistic framework for how reward influences motor behavior. Specifically, we show that rapid improvements in speed and accuracy are driven by reward presented in the form of money, whereas knowledge of performance through performance feedback leads to training-based improvements. Importantly, combining both maximized performance gains and led to improvements in movement quality through fusion, which describes an optimization process during which sequential movements blend into a single action.

Coronary risk reduction intervention for siblings and offspring of patients with premature coronary heart disease: the CRISO study protocol for a randomised controlled pilot study.

BACKGROUND: Research has consistently demonstrated that preventive cardiology programs have limited success, and healthy practices among high-risk individuals remain suboptimal. Furthermore, there are no current programmes in Malta that offer support to first-degree relatives of patients with premature coronary heart disease. This internal pilot study will determine the feasibility, acceptability, and potential effectiveness of a preventative intervention. METHODS/DESIGN: We are conducting a 12-month single-centre, two-armed group randomised controlled trial (RCT), recruiting a sample of 100 asymptomatic first-degree relatives of patients with premature coronary heart disease (CHD). The study seeks to test an evidence-based intervention to reduce modifiable risk and determine its feasibility and acceptability. The Intervention will be delivered at an outpatient office based in a large acute academic hospital. It will comprise risk communication using an online risk calculator, a counselling style adapted from motivational interviewing, and 12 weekly telephone goal reinforcement calls (3 months). Control subjects will receive verbal lifestyle advice only. Feasibility will be assessed through recruitment and retention. Qualitative evaluation interviews will be conducted with a subsample of 24 purposefully selected participants at 12 months. Assessment for risk factor changes will be measured at pre-intervention and 6 and 12 months. Associations between variables will also be assessed descriptively. DISCUSSION: Preventive cardiology guidelines highlighted the importance of lifestyle interventions, and lifestyle intervention adherence was proven to reduce atherosclerotic cardiovascular disease (ASCVD) risk, regardless of the individual's genetic risk. Preventive cardiology programmes may fail to adequately support persons in modifying risky behaviours, and research demonstrates that healthy practices among high-risk individuals can remain suboptimal. Siblings and offspring of patients with premature CHD are at increased risk of ASCVD. Despite this, there is no process in place for routine screening and support to modify risk. It is hypothesised that participants assigned to the intervention arm will show more cardio-protective lifestyle-related improvement from the baseline than those in the control group. To date, this is the first trial being conducted amongst Maltese first-degree relatives. This study addresses the needed research, and the results will inform a definitive trial. The funding institution is the University of Malta. TRIAL REGISTRATION: ISRCTN, ISRCTN21559170 ; Registered 06/08/2020.

Motivational interviewing to support modifiable risk factor change in individuals at increased risk of cardiovascular disease: A systematic review and meta-analysis.

BACKGROUND: Programmes using motivational interviewing show potential in facilitating lifestyle change, however this has not been well established and explored in individuals at risk of, yet without symptomatic pre-existent cardiovascular disease. The objective of this systematic review and meta-analysis was to determine the effectiveness of motivational interviewing in supporting modifiable risk factor change in individuals at an increased risk of cardiovascular disease. METHODS: Systematic review and meta-analysis with results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Health-related databases were searched for randomised controlled trials from 1980 to March 2020. Criteria for inclusion included; preventive programmes, motivational interviewing principles, modification of cardiovascular risk factors in adults of both genders, different ethnicities and employment status, and having at least 1 or more modifiable cardiovascular risk factor/s. Two reviewers independently extracted data and conducted a quality appraisal of eligible studies using an adapted Cochrane framework. The Cochrane framework supports to systematically identify, appraise and synthesize all the empirical evidence that meets the pre-specified eligibility criteria to answer a specific question. FINDINGS: A total of 12 studies met the inclusion criteria. While completeness of intervention reporting was found to be adequate, the application of motivational interviewing was found to be insufficiently reported across all studies (mean overall reporting rate; 68%, 26% respectively). No statistical difference between groups in smoking status and physical activity was reported. A random effects analysis from 4 studies was conducted, this determined a synthesized estimate for standardised mean difference in weight of -2.00kg (95% CI -3.31 to -0.69 kg; p = 0.003), with high statistical heterogeneity. Pooled results from 4 studies determined a mean difference in LDL-c of -0.14mmol/l (5.414mg/dl), which was non-significant. The characteristics of interventions more likely to be effective were identified as: use of a blended approach delivered by a nurse expert in motivational interviewing from an outpatient-clinic. The application of affirmation, compassion and evocation, use of open questions, summarising, listening, supporting and raising ambivalence, combining education and barrier change identification with goal setting are also important intervention characteristics. CONCLUSIONS: While motivational interviewing may support individuals to modify their cardiovascular risk through lifestyle change, the effectiveness of this approach remains uncertain. The strengths and limitations of motivational interviewing need to be further explored through robust studies.

Reward-driven enhancements in motor control are robust to TMS manipulation.

A wealth of evidence describes the strong positive impact that reward has on motor control at the behavioural level. However, surprisingly little is known regarding the neural mechanisms which underpin these effects, beyond a reliance on the dopaminergic system. In recent work, we developed a task that enabled the dissociation of the selection and execution components of an upper limb reaching movement. Our results demonstrated that both selection and execution are concommitently enhanced by immediate reward availability. Here, we investigate what the neural underpinnings of each component may be. To this end, we aimed to alter the cortical excitability of the ventromedial prefrontal cortex and supplementary motor area using continuous theta-burst transcranial magnetic stimulation (cTBS) in a within-participant design (N = 23). Both cortical areas are involved in determining an individual's sensitivity to reward and physical effort, and we hypothesised that a change in excitability would result in the reward-driven effects on action selection and execution to be altered, respectively. To increase statistical power, participants were pre-selected based on their sensitivity to reward in the reaching task. While reward did lead to enhanced performance during the cTBS sessions and a control sham session, cTBS was ineffective in altering these effects. These results may provide evidence that other areas, such as the primary motor cortex or the premotor area, may drive the reward-based enhancements of motor performance.

Reward-Based Improvements in Motor Control Are Driven by Multiple Error-Reducing Mechanisms.

Reward has a remarkable ability to invigorate motor behavior, enabling individuals to select and execute actions with greater precision and speed. However, if reward is to be exploited in applied settings, such as rehabilitation, a thorough understanding of its underlying mechanisms is required. In a series of experiments, we first demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Specifically, reward promoted the selection of the correct action in the presence of distractors, while also improving execution through increased speed and maintenance of accuracy. These results led to a shift in the speed-accuracy functions for both selection and execution. In addition, punishment had a similar impact on action selection and execution, although it enhanced execution performance across all trials within a block, that is, its impact was noncontingent to trial value. Although the reward-driven enhancement of movement execution has been proposed to occur through enhanced feedback control, an untested possibility is that it is also driven by increased arm stiffness, an energy-consuming process that enhances limb stability. Computational analysis revealed that reward led to both an increase in feedback correction in the middle of the movement and a reduction in motor noise near the target. In line with our hypothesis, we provide novel evidence that this noise reduction is driven by a reward-dependent increase in arm stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate motor performance without compromising accuracy.SIGNIFICANCE STATEMENT While reward is well-known for enhancing motor performance, how the nervous system generates these improvements is unclear. Despite recent work indicating that reward leads to enhanced feedback control, an untested possibility is that it also increases arm stiffness. We demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Furthermore, we show that punishment has a similar positive impact on performance. Importantly, by combining computational and biomechanical approaches, we show that reward leads to both improved feedback correction and an increase in stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate performance without compromising accuracy. This work suggests that stiffness control plays a vital, and underappreciated, role in the reward-based imporvemenets in motor control.

Living and Dying in Malta During the Horrible Summer of 1837.

Cholera reached the Maltese Archipelago for the first time ever in June 1837. It found a poor and destitute population that was not prepared for the epidemic. Many doctors feared contagion while others believed it was contracted from bad air or miasma. The first cases of cholera in Malta broke out at a hospital for the elderly and the infirm, the Ospizio in Floriana on 9th June 1837, reached a peak in the week between 12 July to 18 July and dwindled by the end of August 1837. The epidemic saw a death toll of 4252 from 8785 registered cholera cases when the Maltese population was 120,000. Contemporary foreign residents on the islands witnessed and recorded stories of heartlessness and harshness of terrified people. This degenerative behaviour, however, did not reach the callousness of rioting and murder that were observed in other countries. Also, during this dark time, there were people who showed compassion, kindness and selfless devotion to the sick and the dying. In the chaos that reigned during that summer, the inhabitants of one small town in the north of Malta organized themselves better than the rest with good results.

Dopamine-Dependent Loss Aversion during Effort-Based Decision-Making.

From psychology to economics, there has been substantial interest in how costs (e.g., delay, risk) are represented asymmetrically during decision-making when attempting to gain reward or avoid punishment. For example, in decision-making under risk, individuals show a tendency to prefer to avoid punishment rather than to acquire the equivalent reward (loss aversion). Although the cost of physical effort has recently received significant attention, it remains unclear whether loss aversion exists during effort-based decision-making. On the one hand, loss aversion may be hardwired due to asymmetric evolutionary pressure on losses and gains and therefore exists across decision-making contexts. On the other hand, distinct brain regions are involved with different decision costs, making it questionable whether similar asymmetries exist. Here, we demonstrate that young healthy human participants (females, 16; males, 6) exhibit loss aversion during effort-based decision-making by exerting more physical effort to avoid punishment than to gain a same-size reward. Next, we show that medicated Parkinson's disease (PD) patients (females, 9; males, 9) show a reduction in loss aversion compared with age-matched control subjects (females, 11; males, 9). Behavioral and computational analysis revealed that people with PD exerted similar physical effort in return for a reward but were less willing to produce effort to avoid punishment. Therefore, loss aversion is present during effort-based decision-making and can be modulated by altered dopaminergic state. This finding could have important implications for our understanding of clinical disorders that show a reduced willingness to exert effort in the pursuit of reward.SIGNIFICANCE STATEMENT Loss aversion-preferring to avoid punishment rather than to acquire equivalent reward-is an important concept in decision-making under risk. However, little is known about whether loss aversion also exists during decisions where the cost is physical effort. This is surprising given that motor cost shapes human behavior, and a reduced willingness to exert effort is a characteristic of many clinical disorders. Here, we show that healthy human individuals exert more effort to minimize punishment than to maximize reward (loss aversion). We also demonstrate that medicated Parkinson's disease patients exert similar effort to gain reward but less effort to avoid punishment when compared with healthy age-matched control subjects. This indicates that dopamine-dependent loss aversion is crucial for explaining effort-based decision-making.

Domain-Specific Working Memory, But Not Dopamine-Related Genetic Variability, Shapes Reward-Based Motor Learning.

The addition of rewarding feedback to motor learning tasks has been shown to increase the retention of learning, spurring interest in its possible utility for rehabilitation. However, motor tasks using rewarding feedback have repeatedly been shown to lead to great interindividual variability in performance. Understanding the causes of such variability is vital for maximizing the potential benefits of reward-based motor learning. Thus, using a large human cohort of both sexes (n = 241), we examined whether spatial (SWM), verbal, and mental rotation (RWM) working memory capacity and dopamine-related genetic profiles were associated with performance in two reward-based motor tasks. The first task assessed the participant's ability to follow a slowly shifting reward region based on hit/miss (binary) feedback. The second task investigated the participant's capacity to preserve performance with binary feedback after adapting to the rotation with full visual feedback. Our results demonstrate that higher SWM is associated with greater success and an enhanced capacity to reproduce a successful motor action, measured as change in reach angle following reward. In contrast, higher RWM was predictive of an increased propensity to express an explicit strategy when required to make large reach angle adjustments. Therefore, SWM and RWM were reliable, but dissociable, predictors of success during reward-based motor learning. Change in reach direction following failure was also a strong predictor of success rate, although we observed no consistent relationship with working memory. Surprisingly, no dopamine-related genotypes predicted performance. Therefore, working memory capacity plays a pivotal role in determining individual ability in reward-based motor learning.SIGNIFICANCE STATEMENT Reward-based motor learning tasks have repeatedly been shown to lead to idiosyncratic behaviors that cause varying degrees of task success. Yet, the factors determining an individual's capacity to use reward-based feedback are unclear. Here, we assessed a wide range of possible candidate predictors, and demonstrate that domain-specific working memory plays an essential role in determining individual capacity to use reward-based feedback. Surprisingly, genetic variations in dopamine availability were not found to play a role. This is in stark contrast with seminal work in the reinforcement and decision-making literature, which show strong and replicated effects of the same dopaminergic genes in decision-making. Therefore, our results provide novel insights into reward-based motor learning, highlighting a key role for domain-specific working memory capacity.

What can kinematic studies tell us about the mechanisms of dystonia?

Clinical movement disorders are classified by an algorithm implemented by a practising movement disorder specialist based on information extracted during the history and clinical examination of a patient. Most simply, dystonia, is a classifier which is reached when a predominant abnormality of posture is noted. In this chapter we summarize studies that have used a variety of techniques to probe beyond the clinical examination and study kinematic features experimentally. We also outline our experimental work in DYT1 dystonia, a group of patients that share a genetically homogenous etiology and can be considered a prototypical dystonic disorder. Our results build on previous studies, confirming that motor variability on a trial-by-trial basis is selectively increased and provide evidence that increases in variability are negatively related to forms of motor learning essential for healthy motor control. Potential neural correlates of increased motor variability are discussed and the implications such work has for the rehabilitation of patients with dystonia are also highlighted.

Gestational Glycemic Parameters and Future Cardiometabolic Risk at Medium-Term Follow Up.

OBJECTIVES: Gestational diabetes is known to be associated with increased risk for future maternal cardiovascular disease. However, it is not known which gestational glycemic parameters mediate this risk. The study's aim was to assess the relationship between gestational glycemic parameters and gestational diabetes with future cardiometabolic status. METHODS: This cohort study comprised subjects who underwent assessment for gestational diabetes by means of a 75 g oral glucose tolerance test at Mater Dei Hospital, Malta, during 2009. These patients were consequently followed up through January 2018. Carotid intima-media thickness was assessed as a marker of subclinical atherosclerosis in both common carotid arteries. RESULTS: The mean age of the study population was 38.3±5.4 years. Of the 203 participants, 43 (21.2%) had gestational diabetes. Gestational diabetes and individual glycemic parameters of intrapregnancy oral glucose tolerance tests were associated with higher glycated hemoglobin, fasting plasma glucose, low-density-cholesterol and lower high-density-cholesterol levels and with the presence of the metabolic syndrome in both univariate and multivariate analyses after a median follow up of 8 years. Neither gestational diabetes nor individual glycemic parameters of intrapregnancy oral glucose tolerance tests was associated with current carotid intima-media thickness. CONCLUSIONS: Our results suggest that there is no threshold of glycemic parameters for predicting future cardiometabolic status. Our data also suggest that the known association between gestational diabetes and cardiovascular disease is mediated, at least in part, by higher postpregnancy glycemia and worse lipid profiles, even though these metabolic parameters often remain within the normal range.

Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia.

BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group. OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions. METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls. RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions. CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study. © 2018 International Parkinson and Movement Disorder Society.

Relationship of Hyperglycaemia, Hypoglycaemia, and Glucose Variability to Atherosclerotic Disease in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. METHODS: Subjects with T2DM of <10 years duration and on stable antiglycaemic treatment underwent carotid intima-media thickness (CIMT), ankle-brachial index (ABI), albumin-creatinine ratio (ACR), and HbA1c measurement, as well as 72-hour continuous glucose monitoring. Macrovascular disease was defined as one or more of the following: history of ischaemic heart disease (IHD), cerebrovascular accident (CVA), ABI < 0.9, or abnormal CIMT. RESULTS: The study population comprised 121 subjects with T2DM (89 males : 32 females). The mean age was 62.6 years, and the mean DM duration was 3.7 years. Macrovascular disease was present in 71 patients (58.7%). In multivariate logistic regression analysis, body surface area (BSA) (OR 18.88 (95% CI 2.20-156.69), p = 0.006) and duration of blood glucose (BG) < 3.9 mmol/L (OR 1.12 (95% CI 1.014-1.228), p = 0.024) were independent predictors of macrovascular disease. BSA (OR 12.6 (95% CI 1.70-93.54), p = 0.013) and duration of BG < 3.9 mmol/L (OR 1.09 (95% CI 1.003-1.187), p = 0.041) were independent predictors of abnormal CIMT. Area under the curve for BG > 7.8 mmol/L (ß = 15.83, p = 0.005) was the sole independent predictor of albuminuria in generalised linear regression. CONCLUSIONS: This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration.