Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies

Inherited cardiomyopathies caused by pathological genetic variants include multiple subtypes of heart disease. Advances in next-generation sequencing (NGS) techniques have allowed for the identification of numerous genetic variants as pathological variants. However, the disease penetrance varies among mutated genes. Some can be associated with more than one disease subtype, leading to a complex genotype-phenotype relationship in inherited cardiomyopathies. Previous studies have demonstrated disrupted metabolism in inherited cardiomyopathies and the importance of metabolic adaptations in disease onset and progression. In addition, genotype- and phenotype-specific metabolic alterations, especially in lipid metabolism, have been revealed. In this mini-review, we describe the metabolic changes that are associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which account for the largest proportion of inherited cardiomyopathies. We also summarize the affected expression of genes involved in fatty acid oxidation (FAO) in DCM and HCM, highlighting the potential of PPARA-targeting drugs as FAO modulators in treating patients with inherited cardiomyopathies

Familiarity between patient and general practitioner does not influence the content of the consultation

<p>Abstract</p> <p>Background</p> <p>Personal continuity in general practice is considered to be a prerequisite of high quality patient care based on shared knowledge and mutual understanding. Not much is known about how personal continuity is reflected in the content of GP – patient communication. We explored whether personal continuity of care influences the content of communication during the consultation.</p> <p>Methods</p> <p>Personal continuity was defined as the degree of familiarity between GP and patient, rated by both the GP and the patient. 394 videotaped consultations between GPs and patients aged 18 years and older were analyzed. GP – patient communication was evaluated with an observation checklist, which rated the following topics of conversation: (1) medical issues, (2) psychological themes, and (3) the social environment of the patient. For each of these topics we coded whether or not it received attention, and was built upon prior knowledge. Data were analyzed using multilevel logistic regression analyses.</p> <p>Results</p> <p>No relationship was found between GP – patient familiarity and the discussion of medical issues, psychological themes, or the social environment of the patient. But if the patient and the GP knew each other very well, the GP more often displayed prior knowledge with the topic in question. Few patient and GP characteristics were associated with differences in content of communication.</p> <p>Conclusion</p> <p>Given the relatively small sample size, we carefully conclude that familiarity between a GP and a patient does not influence the content of the communication (medical issues, psychological themes nor topics relating to the social environment). This is remarkable because we expected that familiarity would 'open up the communication' for more psychological and social themes. GPs seem to have the communication skills to put both familiar and non-familiar patients at ease enabling them to freely raise any issue they think necessary.</p

The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology

Patient Safety in Radiology

AbstractMedical imaging (in short radiology) includes diagnostic and interventional procedures and has an essential role in the diagnosis and treatment of diseases. The objective in this field of medicine is focused on providing diagnostic and therapeutic benefit to the patients along with protecting them from the possible hazards associated with the procedures. By continuously upgrading imaging technologies and improving imaging modalities, such as ultrasound imaging, X-ray-based imaging (radiography, fluoroscopy, and computed tomography), magnetic resonance imaging (MRI), and interventional radiology, safety has become more and more crucial. The potential hazards in radiology for the patients and the staff are multidimensional and will be discussed in the chapter

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Pragmatic skills predict online counterfactual comprehension:Evidence from the N400

Counterfactual thought allows people to consider alternative worlds they know to be false. Communicating these thoughts through language poses a social-communicative challenge because listeners typically expect a speaker to produce true utterances, but counterfactuals per definition convey information that is false. Listeners must therefore incorporate overt linguistic cues (subjunctive mood, such as in If I loved you then) in a rapid way to infer the intended counterfactual meaning. The present EEG study focused on the comprehension of such counterfactual antecedents and investigated if pragmatic ability—the ability to apply knowledge of the social-communicative use of language in daily life—predicts the online generation of counterfactual worlds. This yielded two novel findings: (1) Words that are consistent with factual knowledge incur a semantic processing cost, as reflected in larger N400 amplitude, in counterfactual antecedents compared to hypothetical antecedents (If sweets were/are made of sugar). We take this to suggest that counterfactuality is quickly incorporated during language comprehension and reduces online expectations based on factual knowledge. (2) Individual scores on the Autism Quotient Communication subscale modulated this effect, suggesting that individuals who are better at understanding the communicative intentions of other people are more likely to reduce knowledge-based expectations in counterfactuals. These results are the first demonstration of the real-time pragmatic processes involved in creating possible worlds