Case Report: Retracing Atypical Development: A Preserved Speech Variant of Rett Syndrome

The subject of the present study is the development of a girl with the preserved speech variant of Rett disorder. Our data are based on detailed retrospective and prospective video analyses. Despite achieving developmental milestones, movement quality was already abnormal during the girl's first half year of life. In addition, early hand stereotypies, idiosyncratic vocalizations, asymmetric eye opening, and abnormal facial expressions are early signs proving that this variant of the Rett complex, too, manifests itself within the first months of life.     

Patient with partial trisomy 9q and learning disability but no pyloric stenosis

Partial trisomy of the long arm of chromosome 9 represents a very rare and heterogeneous group of chromosomal aberrations. Associated clinical features include learning disability and pyloric stenosis. We present the first patient to be reported with a duplication of the chromosome region 9q22.1-->q33. The patient (female, age 17 years) presented with growth retardation, microcephaly, facial dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect, atrial septal defect II, hypothyroidism, and learning disability, but no pyloric stenosis. A review of all cases of partial trisomy 9q reported in the literature demonstrates that learning disability is a characteristic feature of this group of chromosomal aberrations. However, there are cases of duplications of the same chromosome 9 material, with and without pyloric stenosis. This study provides new information for future genetic counselling, especially in cases of prenatal diagnosis of partial trisomy 9q.     

The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

The effect of risky alcohol use and smoking on suicide risk: findings from the German MONICA/KORA-Augsburg Cohort Study

Background  

Smoking and heavy alcohol use predicts suicidal behaviour. Whether the simultaneous presentation of both conditions induces an amplified effect on risk prediction has not been investigated so far.     

Zinc and low osmolarity oral rehydration salts for diarrhoea: a?renewed call to action

In 2004, WHO and the United Nations Children’s Fund (UNICEF) released a joint statement recommending a new lower osmolarity oral rehydration salts (ORS) formulation and zinc supplementation for diarrhoea management. More than 5 years later, diarrhoea remains the second leading cause of death and few children in developing countries are receiving these life-saving interventions. Many countries are stalled in the technicalities of adapting national policy, while others struggle to find the funds for start-up activities. For nearly all countries, zinc supplements for children are not available locally; thus, zinc procurement continues to be a major obstacle. Global resources have not been sufficient to bring diarrhoea management to the forefront; thus, the introduction of these new recommendations has remained slow. Revitalizing diarrhoea management must become an international priority if we are going to reduce the burden of diarrhoea deaths and overall child mortality around the world.     

The adenosine A<Subscript>2A</Subscript> antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure

Rationale  Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Objective  Previous work showed that adenosine A_2A antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A_2A and A₁ antagonism. Materials and methods  With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Results  Haloperidol produced a dose-related (0.05–0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A_2A receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A₁ antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Conclusions  Adenosine A_2A and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders.     

Bile formation and biliary lipid composition under the influence of clofibrate and phenobarbital pretreatment in the rat

Summary The effect of the two enzyme inducing agents, clofibrate and phenobarbital, on bile formation and biliary lipid composition was compared in male rats. Clofibrate (100 mg per kg body weight per day for 14 days) and phenobarbital (at first 60 mg per kg body weight per day for 3 days, then 100 mg per kg body weight per day for 11 days) increase the spontanous bile flow, the ¹⁴C-erythritol clearance but do not alter the bile salt excretion, indicating a stimulation of the bile acid independent fraction of bile. The bile of rats pretreated with clofibrate contains less cholesterol than the bile of saline treated control animals, whereas the concentrations of bile acids, phospholipids and cholesterol are reduced in the bile of the rats of the phenobarbital group. Both drugs diminish the cholesterol saturation of bile. If the biliary bile acid concentration and excretion are augmented by an infusion of sodium taurocholate (1000 nmol per min per 100 g body weight), the biliary concentration of cholesterol remains unchanged in the clofibrate group but increases in the phenobarbital group as compared with the saline control animals. The biliary phospholipid concentration is enhanced after clofibrate as well as after phenobarbital pretreatment. These studies indicate that the biliary excretion of cholesterol and phospholipids is at least to some extent regulated by the bile acid excretion. The importance of the synthesis of cholesterol and phospholipids for their biliary excretion, however, seems to be limited: a reduced cholesterol synthesis by clofibrate results in a reduced biliary cholesterol elimination. By contrast, an increased synthesis of cholesterol by phenobarbital and of the phospholipids by both drugs, however, may enlarge the intrahepatic lipid pools and may place more lipids available for biliary secretion.