Hemodynamic profiles of functional and dysfunctional forms of repetitive thinking

Background: The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. Purpose: To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Methods: Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Results: Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Conclusions: Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease

The Role of Models and Formulations in the Management of Behaviors that Challenge in Dementia

The British Psychological Society’s Briefing Paper for Behaviors that Challenge (BtC) in dementia states that psychological formulation helps in the development of effective and well targeted treatments [1]. While not explicitly using the term psychological formulation, the 2018 NICE UK Dementia Guidelines support the use of systematic problem-solving approaches in the management of BtC. The current paper gives an overview of the content of a number of formulation models developed in this area and contrasts two established models. This article looks at two different ways of understanding people’s agitation – one which emphasizes the reasons for their behaviour in terms of the person with dementia [2] and the other called DICE [3] which puts equal emphasis on the roles of both caregivers and the environment in explaining behaviors. We suggest that, while the Newcastle Model tacitly suggests a role for caregivers and the environment in BtC, the explicit emphasis in DICE encourages a more holistic understanding of agitation

How do we decide what to do? Resting-state connectivity patterns and components of self-generated thought linked to the development of more concrete personal goals

Human cognition is not limited to the available environmental input but can consider realities that are different to the here and now. We describe the cognitive states and neural processes linked to the refinement of descriptions of personal goals. When personal goals became concrete, participants reported greater thoughts about the self and the future during mind-wandering. This pattern was not observed for descriptions of TV programmes. Connectivity analysis of participants who underwent a resting-state functional magnetic resonance imaging scan revealed neural traits associated with this pattern. Strong hippocampal connectivity with ventromedial pre-frontal cortex was common to better-specified descriptions of goals and TV programmes, while connectivity between hippocampus and the pre-supplementary motor area was associated with individuals whose goals were initially abstract but became more concrete over the course of the experiment. We conclude that self-generated cognition that arises during the mind-wandering state can allow goals to be refined, and this depends on neural systems anchored in the hippocampus

Helicobacter suis infection alters glycosylation and decreases the pathogen growth inhibiting effect and binding avidity of gastric mucins

Helicobacter suis is the most prevalent non-Helicobacter pylori Helicobacter species in the human stomach and is associated with chronic gastritis, peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. H. suis colonizes the gastric mucosa of 60-95% of pigs at slaughter age, and is associated with chronic gastritis, decreased weight gain, and ulcers. Here, we show that experimental H. suis infection changes the mucin composition and glycosylation, decreasing the amount of H. suis-binding glycan structures in the pig gastric mucus niche. Similarly, the H. suis-binding ability of mucins from H. pylori-infected humans is lower than that of noninfected individuals. Furthermore, the H. suis growth-inhibiting effect of mucins from both noninfected humans and pigs is replaced by a growth-enhancing effect by mucins from infected individuals/pigs. Thus, Helicobacter spp. infections impair the mucus barrier by decreasing the H. suis-binding ability of the mucins and by decreasing the antiprolific activity that mucins can have on H. suis. Inhibition of these mucus-based defenses creates a more stable and inhabitable niche for H. suis. This is likely of importance for long-term colonization and outcome of infection, and reversing these impairments may have therapeutic benefits

How do we decide what to do? : Resting-state connectivity patterns and components of self-generated thought linked to the development of more concrete personal goals

Human cognition is not limited to the available environmental input but can consider realities that are different to the here and now. We describe the cognitive states and neural processes linked to the refinement of descriptions of personal goals. When personal goals became concrete, participants reported greater thoughts about the self and the future during mind-wandering. This pattern was not observed for descriptions of TV programmes. Connectivity analysis of participants who underwent a resting-state functional magnetic resonance imaging scan revealed neural traits associated with this pattern. Strong hippocampal connectivity with ventromedial pre-frontal cortex was common to better-specified descriptions of goals and TV programmes, while connectivity between hippocampus and the pre-supplementary motor area was associated with individuals whose goals were initially abstract but became more concrete over the course of the experiment. We conclude that self-generated cognition that arises during the mind-wandering state can allow goals to be refined, and this depends on neural systems anchored in the hippocampus

Representing Representation : Integration between the Temporal Lobe and the Posterior Cingulate Influences the Content and Form of Spontaneous Thought

When not engaged in the moment, we often spontaneously represent people, places and events that are not present in the environment. Although this capacity has been linked to the default mode network (DMN), it remains unclear how interactions between the nodes of this network give rise to particular mental experiences during spontaneous thought. One hypothesis is that the core of the DMN integrates information from medial and lateral temporal lobe memory systems, which represent different aspects of knowledge. Individual differences in the connectivity between temporal lobe regions and the default mode network core would then predict differences in the content and form of people's spontaneous thoughts. This study tested this hypothesis by examining the relationship between seed-based functional connectivity and the contents of spontaneous thought recorded in a laboratory study several days later. Variations in connectivity from both medial and lateral temporal lobe regions was associated with different patterns of spontaneous thought and these effects converged on an overlapping region in the posterior cingulate cortex. We propose that the posterior core of the DMN acts as a representational hub that integrates information represented in medial and lateral temporal lobe and this process is important in determining the content and form of spontaneous thought

Helicobacter suis binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes

Helicobacter suis colonizes the stomach of most pigs and is the most prevalent non-Helicobacter pylori Helicobacter species found in the human stomach. In the human host, H. suis contributes to the development of chronic gastritis, peptic ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis, decreased growth and ulcers. Here, we demonstrate that the level of H. pylori and H. suis binding to human and pig gastric mucins varies between individuals with species dependent specificity. The binding optimum of H. pylori is at neutral pH whereas that of H. suis has an acidic pH optimum, and the mucins that H. pylori bind to are different than those that H. suis bind to. Mass spectrometric analysis of mucin O-glycans from the porcine mucin showed that individual variation in binding is reflected by a difference in glycosylation; of 109 oligosaccharide structures identified, only 14 were present in all examined samples. H. suis binding to mucins correlated with glycans containing sulfate, sialic acid and terminal galactose. Among the glycolipids present in pig stomach, binding to lactotetraosylceramide (Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer) was identified, and adhesion to Gal beta 3GlcNAc beta 3Gal beta 4Glc at both acidic and neutral pH was confirmed using other glycoconjugates. Together with that H. suis bound to DNA (used as a proxy for acidic charge), we conclude that H. suis has two binding modes: one to glycans terminating with Gal beta 3GlcNAc, and one to negatively charged structures. Identification of the glycan structures H. suis interacts with can contribute to development of therapeutic strategies alternative to antibiotics

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms