A Potential Role of the Inferior Frontal Gyrus and Anterior Insula in Cognitive Control, Brain Rhythms, and Event-Related Potentials

In the present paper, we review evidence for of a model in which the inferior frontal gyrus/anterior insula (IFG/AI) area is involved in elaborate attentional and working memory processing and we present the hypothesis that this processing may take different forms and may have different effects, depending on the task at hand: (1) it may facilitate fast and accurate responding, or (2) it may cause slow responding when prolonged elaborate processing is required to increase accuracy of responding, or (3) it may interfere with accuracy and speed of next-trial (for instance, post-error) performance when prolonged elaborate processing interferes with processing of the next stimulus. We present our viewpoint that ventrolateral corticolimbic control pathways, including the IFG/AI, and mediodorsal corticolimbic control pathways, including dorsal anterior cingulate cortex areas, play partly separable, but interacting roles in adaptive behavior in environmental conditions that differ in the level of predictability: compared to dorsal feed-forward control, the ventral corticolimbic control pathways implement control over actions through higher responsiveness to momentary environmental stimuli. This latter control mode is associated with an attentional focus on stimuli that are urgent or close in time and space, while the former control mode is associated with a broader, more global focus in time and space. Both control pathways have developed extensively through evolution, and both developed their own “cognitive controls,” such that neither one can be properly described as purely “cognitive” or “emotional.” We discuss literature that suggests that the role of IFG/AI in top-down control is reflected in cortical rhythms and event-related potentials. Together, the literature suggests that the IFG/AI is an important node in brain networks that control cognitive and emotional processing and behavior

Brain Substrates of Behavioral Programs Associated with Self-Regulation

The present paper proposes that four neuromodulator systems underpin highly generalized behavioral sets, but each targets either dorsomedial or ventrolateral cortical systems, where it produces its effects in either a proactive or reactive orientation to the environment. This way systems are discriminated that control reactive approach (dopaminergic), reactive avoidance (cholinergic), proactive behavior (noradrenergic), and withdrawal (serotonergic). This model is compared with models of temperament, affect, personality, and so-called two-system models from psychology. Although the present model converges with previous models that point to a basic scheme underlying temperamental and affective space, at the same time it suggest that specific additional discriminations are necessary to improve descriptive fit to data and solve inconsistencies and confusions. We demonstrate how proactive and reactive actions and controls can be confused, and that this has many potential implications for psychology and neurobiology. We uncover conceptual problems regarding constructs such as effortful control, positive affect, approach-avoidance, extraversion, impulsivity, impulse-control, and goal-directedness of behavior. By delineating those problems, our approach also opens up ways to tackle them

Oxytocin Receptor Gene Associated with the Efficiency of Social Auditory Processing

Oxytocin has been shown to facilitate social aspects of sensory processing, thereby enhancing social communicative behaviors and empathy. Here we report that compared to the AA/AG genotypes, the presumably more efficient GG genotype of an oxytocin receptor gene polymorphism (OXTR rs53576) that has previously been associated with increased sensitivity of social processing is related to less self-reported difficulty in hearing and understanding people when there is background noise. The present result extends associations between oxytocin and social processing to the auditory and vocal domain. We discuss the relevance of our findings for autistic spectrum disorders (ASD), as ASD seems related to specific impairments in the orienting to, and selection of speech sounds from background noise, and some social processing impairments in patients with ASD have been found responsive to oxytocin treatment

EWSR1—The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review

EWSR1 belongs to the FET family of RNA-binding proteins including also Fused in Sarcoma (FUS), and TATA-box binding protein Associated Factor 15 (TAF15). As consequence of the multifunctional role of EWSR1 leading to a high frequency of transcription of the chromosomal region where the gene is located, EWSR1 is exposed to aberrations such as rearrangements. Consecutive binding to other genes leads to chimeric proteins inducing oncogenesis. The other TET family members are homologous. With the advent of widely used modern molecular techniques during the last decades, it has become obvious that EWSR1 is involved in the development of diverse benign and malignant tumors with mesenchymal, neuroectodermal, and epithelial/myoepithelial features. As oncogenic transformation mediated by EWSR1-fusion proteins leads to such diverse tumor types, there must be a selection on the multipotent stem cell level. In this review, we will focus on the wide variety of soft tissue and bone entities, including benign and malignant lesions, harboring EWSR1 rearrangement. Fusion gene analysis is the diagnostic gold standard in most of these tumors. We present clinicopathologic, immunohistochemical, and molecular features and discuss differential diagnoses.</jats:p

The role of long-term mechanical circulatory support in patients with advanced heart failure

In patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be considered. LVADs can be implanted as a bridge to transplantation or as an alternative to heart transplantation: destination therapy. In the Netherlands, long-term LVAD therapy is gaining importance as a result of increased prevalence of heart failure together with a low number of heart transplantations due to shortage of donor hearts. As a result, the difference between bridge to transplantation and destination therapy is becoming more artificial since, at present, most patients initially implanted as bridge to transplantation end up receiving extended LVAD therapy. Following LVAD implantation, survival after 1, 2 and 3 years is 83%, 76% and 70%, respectively. Quality of life improves substantially despite important adverse events such as device-related infection, stroke, major bleeding and right heart failure. Early referral of potential candidates for long-term MCS is of utmost importance and positively influences outcome. In this review, an overview of the indications, contraindications, patient selection, clinical outcome and optimal time of referral for long-term MCS is given

Chronic care for heart failure patients: who to refer back to the general practitioner?: Experiences of the Dutch integrated heart failure care model

ObjectiveThe number of patients with heart failure (HF) and corresponding burden of the healthcare system will increase significantly. The Dutch integrated model, 'Transmural care of HF Patients' was based on the European Society of Cardiology (ESC) guidelines and initiated to manage the increasing prevalence of HF patients in primary and secondary care and stimulate integrated care. It is unknown how many HF patients are eligible for back-referral to general practitioners (GPs), which is important information for the management of chronic HF care. This study aims to evaluate clinical practice of patients for whom chronic HF care can be referred from the cardiologist to the GP based on the aforementioned chronic HF care model.Design and MethodsA retrospective case record-based study was conducted, which included all chronic HF patients registered in the cardiology information systems of two different hospitals. Subsequently, 200 patients were randomly selected for evaluation. The following patients were considered eligible for referral to the GP: 1/Stable HF patients with reduced left ventricular ejection fraction (LVEF), 2/Stable HF patients with a recovered LVEF and 3/Stable HF patients with a preserved LVEF, 4/HF, palliative setting.ResultsOf the 200 patients, 17% was considered eligible for referral to the GP. This group consisted of 5% patients with a reduced LVEF, 10.5% patients with recovered LVEF and 1.5% patients with a preserved LVEF. Main indicators for HF care by cardiologists were active cardiac disease other than HF (39.5%), recent admission for HF (29.5%) or a recent adjustment in HF medication (7.5%).ConclusionApplying the chronic HF care model of the 'Transmural care of HF patients' and the ESC-guidelines, results in an important opportunity to further optimise HF integrated care and to deal with the increasing number of HF patients referred to the hospital

Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy

This study aimed to determine the prevalence of APC-associated familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) in a large cohort, taking into account factors as adenoma count and year of diagnosis. All application forms used to send patients in for APC and MUTYH variant analysis between 1992 and 2017 were collected (n = 2082). Using the data provided on the application form, the APC and biallelic MUTYH prevalence was determined and possible predictive factors were examined using multivariate multinomial logistic regression analysis in SPSS. The prevalence of disease causing variants in the APC gene significantly increases with adenoma count while MAP shows a peak prevalence in individuals with 50–99 adenomas. Logistic regression analysis shows significant odds ratios for adenoma count, age at diagnosis, and, interestingly, a decline in the chance of finding a variant in either gene over time. Moreover, in 22% (43/200) of patients with FAP-related extracolonic manifestations a variant was identified. The overall detection rates are above 10% for patients with >10 adenomas aged 20 adenomas aged T variant in the tumor or a first-degree relative with >10 adenomas. Therefore, APC and MUTYH testing in patients with >10 adenomas aged 20 adenomas aged <70 is advised. Almost all FAP and MAP patients not meeting these criteria showed other characteristics that can be used as an indication to prompt genetic testing

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are—at least to some extent—nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline

Acute left ventricular dysfunction secondary to right ventricular septal pacing in a woman with initial preserved contractility: a case report

<p>Abstract</p> <p>Introduction</p> <p>Right ventricular apical pacing-related heart failure is reported in some patients after long-term pacing. The exact mechanism is not yet clear but may be related to left ventricular dyssynchrony induced by right ventricular apical pacing. Right ventricular septal pacing is thought to deteriorate left ventricular function less frequently because of a more normal left ventricular activation pattern.</p> <p>Case presentation</p> <p>We report the case of a 55-year-old Tunisian woman with preserved ventricular function, implanted with a dual-chamber pacemaker for complete atrioventricular block. Right ventricular septal pacing induced a major ventricular dyssynchrony, severe left ventricular ejection fraction deterioration and symptoms of congestive heart failure. Upgrading to a biventricular device was associated with a decrease in the symptoms and the ventricular dyssynchrony, and an increase of left ventricular ejection fraction.</p> <p>Conclusion</p> <p>Right ventricular septal pacing can induce reversible left ventricular dysfunction and heart failure secondary to left ventricular dyssynchrony. This complication remains an unpredictable complication of right ventricular septal pacing.</p