Distribution and coexistence of myoclonus and dystonia as clinical predictors of SGCE mutation status: a pilot study

Introduction: Myoclonus-dystonia (M-D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria, identification of patients most likely to have an SGCE mutation remains difficult. Methods: Forty consecutive patients meeting pre-existing diagnostic clinical criteria for M-D underwent a standardized clinical examination (20 SGCE mutation positive and 20 negative). Each video was reviewed and systematically scored by two assessors blinded to mutation status. In addition, the presence and coexistence of myoclonus and dystonia was recorded in four body regions (neck, arms, legs, and trunk) at rest and with action. Results: Thirty-nine patients were included in the study (one case was excluded owing to insufficient video footage). Based on previously proposed diagnostic criteria, patients were subdivided into 24 "definite," 5 "probable," and 10 "possible" M-D. Motor symptom severity was higher in the SGCE mutation-negative group. Myoclonus and dystonia were most commonly observed in the neck and upper limbs of both groups. Truncal dystonia with action was significantly seen more in the mutation-negative group (p <0.05). Coexistence of myoclonus and dystonia in the same body part with action was more commonly seen in the mutation-negative cohort (p <0.05). Conclusion: Truncal action dystonia and coexistence of myoclonus and dystonia in the same body part with action might suggest the presence of an alternative mutation in patients with M-D

Acute Effects of Decaffeinated Coffee and the Major Coffee Components Chlorogenic Acid and Trigonelline on Glucose Tolerance

OBJECTIVE: Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. RESEARCH DESIGN AND METHODS: We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men. RESULTS Chlorogenic acid and trigonelline ingestion significantly reduced glucose (−0.7 mmol/l, P = 0.007, and −0.5 mmol/l, P = 0.024, respectively) and insulin (−73 pmol/l, P = 0.038, and −117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo. CONCLUSIONS: Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT

Natural course of Myoclonus-Dystonia in adulthood: stable motor signs but increased psychiatry

Myoclonus‐dystonia (M‐D) is a rare hyperkinetic movement disorder characterized by upper body–predominant myoclonus and dystonia.1 A large proportion of cases are caused by autosomal‐dominant inherited mutations in the SGCE gene. In addition to the motor manifestations, psychiatric disorders are frequently reported.2 Several studies have suggested that they may form a primary component of the M‐D phenotype.3, 4 This study represents the first long‐term follow‐up study of both motor and psychiatric symptomatology in adults with M‐D (SGCE mutation), providing further insights into the natural history of M‐D and enabling more prognostic information

Parental experiences of rapid exome sequencing in cases with major ultrasound anomalies during pregnancy

BACKGROUND: Adding rapid Exome Sequencing (rES) to conventional genetic tests improves the diagnostic yield of pregnancies showing ultrasound abnormalities but also carries a higher chance of unsolicited findings. We evaluated how rES, including pre- and post-test counseling, was experienced by parents investigating its impact on decision-making and experienced levels of anxiety. METHODS: A mixed-methods approach was adopted. Participating couples (n=46) were asked to fill in two surveys (pre-test and post-test counseling) and 11 couples were approached for an additional interview. RESULTS: All couples accepted the rES test-offer with the most important reason for testing emphasizing their hope of finding an underlying diagnosis that would aid decision-making. The actual impact on decision-making was low, however, since most parents decided to terminate the pregnancy based on the major and multiple fetal ultrasound anomalies and did not wait for their rES results. Anxiety was elevated for most participants and decreased over time. CONCLUSION: Major congenital anomalies detected on ultrasound seem to have more impact on prenatal parental decision-making and anxiety then the offer and results of rES. However, the impact of rES on reproductive decision-making and experienced anxiety requires further investigation, especially in pregnancies where less (severe) fetal anomalies are detected on ultrasound. This article is protected by copyright. All rights reserved

Psychiatric disorders, myoclonus dystonia and SGCE:An international study

OBJECTIVE: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder, typically alcohol-responsive upper body myoclonus and dystonia. The majority of autosomal dominant familial cases are caused by epsilon-sarcoglycan gene (SGCE) mutations. Previous publications have observed increased rates of psychiatric disorders amongst SGCE mutation-positive populations. We analyzed the psychiatric data from four international centers, forming the largest cohort to date, to further determine the extent and type of psychiatric disorders in M-D.METHODS: Psychiatric data from SGCE mutation-positive M-D cohorts, collected by movement disorder specialists in the Netherlands, United Kingdom, United States, and Germany, were analyzed. These data were collected using standardized, systematic questionnaires allowing classification of symptoms according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Based on motor findings and SGCE mutation analysis, participants were classified into one of three groups: manifesting carriers, nonmanifesting carriers and noncarriers.RESULTS: Data from 307 participants were evaluated (140 males, 167 females, mean age at examination: 42.5 years). Two-thirds of motor affected mutation carriers (n = 132) had ≥1 psychiatric diagnosis, specific, and social phobias being most common followed by alcohol dependence and obsessive-compulsive disorder (OCD). Compared to familial controls, affected mutation carriers had significantly elevated overall rates of psychiatric disorders (P &lt; 0.001). The most significant differences were observed with alcohol dependence (P &lt; 0.001), OCD (P &lt; 0.001), social and specific phobias (P &lt; 0.001).INTERPRETATION: M-D due to SGCE mutations is associated with specific psychiatric disorders, most commonly OCD, anxiety-related disorders, and alcohol dependence. These suggest either a potential pleiotropic function for SGCE within the central nervous system or a secondary effect of the motor disorder.</p

Determinants of Adherence to Treatment in Hypertensive Patients of African Descent and the Role of Culturally Appropriate Education

In Western countries, better knowledge about patient-related determinants of treatment adherence (medication and lifestyle) is needed to improve treatment adherence and outcomes among hypertensive ethnic minority patients of African descent.To identify patient-related determinants of adherence to lifestyle and medication recommendations among hypertensive African Surinamese and Ghanaian patients with suboptimal treatment results (SBP≥140) living in the Netherlands and how culturally appropriate hypertension education (CAHE) influenced those determinants.This study analysed data of 139 patients who participated in the CAHE trial. Univariate logistic regression analysis was used to measure the association between patient-related determinants (medication self-efficacy, beliefs about medication and hypertension, social support, and satisfaction with care) and treatment adherence. We also tested whether CAHE influenced the determinants.Medication self-efficacy and social support were associated with medication adherence at baseline. At six months, more medication self-efficacy and fewer concerns about medication use were associated with improved medication adherence. Self-efficacy was also associated with adherence to lifestyle recommendations at baseline. CAHE influenced patients' illness perceptions by creating more understanding of hypertension, its chronic character, and more concerns about the associated risks.In this high-risk population, health care providers can support medication adherence by paying attention to patients' medication self-efficacy, the concerns they may have about medication use and patients' perceptions on hypertension. The CAHE intervention improved patients' perception on hypertension

A multimodal regional intervention strategy framed as friendly competition to improve hand hygiene compliance

Objective: To investigate the effects of friendly competition on hand hygiene compliance as part of a multimodal intervention programDesign: Prospective observational study in which the primary outcome was hand hygiene compliance. Differences were analyzed using the Pearson χ2 test. Odds ratios (ORs) with 95% confidence interval were calculated using multilevel logistic regression. Setting: Observations were performed in 9 public hospitals and 1 rehabilitation center in Rotterdam, Netherlands. Participants: From 2014 to 2016, at 5 time points (at 6-month intervals) in 120 hospital wards, 20,286 hand hygiene opportunities were observed among physicians, nurses, and other healthcare workers (HCWs). Intervention: The multimodal, friendly competition intervention consisted of mandatory interventions: monitoring and feedback of hand hygiene compliance and optional interventions (ie, e-learning, kick-off workshop, observer training, and team training). Hand hygiene opportunities, as formulated by the World Health Organization (WHO), were unobtrusively observed at 5 time points by trained observers. Compliance data were presented to the healthcare organizations as a ranking. Results: The overall mean hand hygiene compliance at time point 1 was 42.9% (95% confidence interval [CI], 41.4–44.4), which increased to 51.4% (95% CI, 49.8–53.0) at time point 5 (P<.001). Nurses showed a significant improvement between time points 1 and 5 (P< .001), whereas the compliance of physicians and other HCWs remained unchanged. In the multilevel logistic regressions, time points, type of ward, and type of HCW showed a significant association with compliance. Conclusion: Between the start and the end of the multimodal intervention program in a friendly competition setting, overall hand hygiene compliance increased significantly

Aberrant Receptor-Mediated Endocytosis of Schistosoma mansoni Glycoproteins on Host Lipoproteins

BACKGROUND: Bilharzia is one of the major parasitic infections affecting the public health and socioeconomic circumstances in (sub) tropical areas. Its causative agents are schistosomes. Since these worms remain in their host for decades, they have developed mechanisms to evade or resist the immune system. Like several other parasites, their surface membranes are coated with a protective layer of glycoproteins that are anchored by a lipid modification. METHODS AND FINDINGS: We studied the release of glycosyl-phosphatidylinositol (GPI)-anchored proteins of S. mansoni and found them in the circulation associated with host lipoprotein particles. Host cells endocytosed schistosomal GPI-anchored proteins via their lipoprotein receptor pathway, resulting in disturbed lysosome morphology. In patients suffering from chronic schistosomiasis, antibodies attacked the parasite GPI-anchored glycoproteins that were associated with the patients' own lipoprotein particles. These immunocomplexes were endocytosed by cells carrying an immunoglobulin-Fc receptor, leading to clearance of lipoproteins by the immune system. As a consequence, neutral lipids accumulated in neutrophils of infected hamsters and in human neutrophils incubated with patient serum, and this accumulation was associated with apoptosis and reduced neutrophil viability. Also, Trypanosoma brucei, the parasite that causes sleeping sickness, released its major GPI-anchored glycoprotein VSG221 on lipoprotein particles, demonstrating that this process is generalizable to other pathogens/parasites. CONCLUSIONS: Transfer of parasite antigens to host cells via host lipoproteins disrupts lipid homeostasis in immune cells, promotes neutrophil apoptosis, may result in aberrant antigen presentation in host cells, and thus cause an inefficient immune response against the pathogen