Therapy refractory hypertension in adults: aortic coarctation has to be ruled out

In patients with unexplained hypertension, especially in combination with a cardiac murmur, the presence of an aortic coarctation should always be ruled out given the high morbidity and mortality. However, particularly patients with an isolated coarctation often remain asymptomatic for years and the defect may be unnoticed even until the fifth or sixth decade of life. In the present article, we describe two patients with late detected coarctation to illustrate the clinical consequences, diagnostic clues for earlier detection and current therapeutic options to achieve optimal treatment. The key sign of an aortic coarctation, a difference in arterial blood pressure measured between the upper and lower extremities, should always be examined, followed by echocardiography. We conclude that even in case of a late detected severe coarctation, surgical or percutaneous repair has proven to be feasible and substantially effective, improving quality of life and lowering the risk of further hypertension-associated problems

Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications

<p>Abstract</p> <p>Background</p> <p>Autoantibodies against glutamate decarboxylase-65 (GAD₆₅Abs) are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD₆₅Abs are a sensitive and specific marker for type 1 diabetes (T1D). These autoantibodies can also be found in 6-10% of patients classified with type 2 diabetes (T2D), as well as in 1-2% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD₆₅Abs is only about 0.3%. It has, therefore, been suggested that the antibody binding to GAD₆₅in these three different GAD₆₅Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD₆₅(ROS-GAD₆₅) is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD₆₅(ROS-GAD₆₅Abs) and quantitative assays in T1D associated complications.</p> <p>Results</p> <p>From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD₆₅as compared to native GAD₆₅(N-GAD₆₅). Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD₆₅. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC) indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10^-6M) followed by nephropathic (1.81 × 10^-6M) and uncomplicated (3.11 × 10^-7M) T1D patients for ROS-GAD₆₅compared to N-GAD₆₅.</p> <p>Conclusion</p> <p>Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD₆₅that induce increased production of ROS-GAD₆₅Abs. Hence regulation of ROS-GAD₆₅Abs could offer novel tools for analysing and possibly treating T1D complications.</p

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

The Effects of Acute Tryptophan Depletion on Reactive Aggression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Healthy Controls

Background: The neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. Methodology/Principal Findings: Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRPbalanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD

14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila

Post-translational modifications of histone proteins modulate the binding of transcription regulators to chromatin. Studies in Drosophila have shown that the phosphorylation of histone H3 at Ser10 (H3S10ph) by JIL-1 is required specifically during early transcription elongation. 14-3-3 proteins bind H3 only when phosphorylated, providing mechanistic insights into the role of H3S10ph in transcription. Findings presented here show that 14-3-3 functions downstream of H3S10ph during transcription elongation. 14-3-3 proteins localize to active genes in a JIL-1–dependent manner. In the absence of 14-3-3, levels of actively elongating RNA polymerase II are severely diminished. 14-3-3 proteins interact with Elongator protein 3 (Elp3), an acetyltransferase that functions during transcription elongation. JIL-1 and 14-3-3 are required for Elp3 binding to chromatin, and in the absence of either protein, levels of H3K9 acetylation are significantly reduced. These results suggest that 14-3-3 proteins mediate cross-talk between histone phosphorylation and acetylation at a critical step in transcription elongation

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration