The constant internal monitoring of speech is a crucial feature to ensure the fairly error-free process of speech production. It has been argued that internal speech monitoring takes place through ...detection of conflict between different response options or “speech plans”. Speech errors are thought to occur because two (or more) competing speech plans become activated, and the speaker is unable to inhibit the erroneous plan(s) prior to vocalization. A prime example for a speech plan that has to be suppressed is the involuntary utterance of a taboo word. The present study seeks to examine the suppression of involuntary taboo word utterances. We used the “Spoonerisms of Laboratory Induced Predisposition” (SLIP) paradigm to elicit two competing speech plans, one being correct and one embodying either a taboo word or a non-taboo word spoonerism. Behavioral data showed that inadequate speech plans generally were effectively suppressed, although more effectively in the taboo word spoonerism condition. Event-related potential (ERP) analysis revealed a broad medial frontal negativity (MFN) after the target word pair presentation, interpreted as reflecting conflict detection and resolution to suppress the inadequate speech plan. The MFN was found to be more pronounced in the taboo word spoonerism compared to the neutral word spoonerism condition, indicative of a higher level of conflict when subjects suppressed the involuntary utterance of taboo words.
Motor and vocal tics are the main symptom of Gilles de la Tourette-syndrome (GTS). A particular complex vocal tic comprises the utterance of swear words, termed coprolalia. Since taboo words are ...socially inappropriate, they are normally suppressed by people, which implies cognitive control processes.
To investigate the control of the unintentional pronunciation of taboo words and the associated processes of conflict monitoring, we used the "Spoonerisms of Laboratory Induced Predisposition" (SLIP) paradigm. Participants read multiple inductor word pairs with the same phonemes, followed by pronouncing a target pair with inverse phonemes. This led to a conflict between two competing speech plans: the correct word pair and the word pair with inverted phonemes. Latter speech error, a spoonerism, could result in a neutral or taboo word. We investigated 19 patients with GTS and 23 typically developed controls (TDC) and measured participants' electroencephalography (EEG) during the SLIP task.
At the behavioral level less taboo than neutral word spoonerisms occurred in both groups without significant differences. Event-related brain potentials (ERP) revealed a difference between taboo and neutral word conditions in the GTS group at the midline electrodes in a time range of 250-400 ms after the speech prompt, which was not found in the TDC group. The extent of this effect depended on the number of inductor word pairs, suggesting an increasing level of cognitive control in the GTS group.
The differences between taboo and neutral word conditions in patients with GTS compared to TDC suggest an altered recruitment of cognitive control processes in GTS, likely enlisted to suppress taboo words.
Abstract
Persons with Tourette syndrome show altered social behaviours, such as echophenomena and increased personal distress in emotional situations. These symptoms may reflect an overactive mirror ...neuron system, causing both increased automatic imitation and a stronger tendency to share others’ emotions. To test this, we measured the individual level of echophenomena with a video protocol and experimentally induced empathy for pain in 21 participants with Tourette syndrome and 25 matched controls. In the empathy for pain paradigm, pictures of hands and feet in painful or neutral situations were presented, while we measured participants’ EEG and skin conductance response. Changes in somatosensory mu suppression during the observation of the pictures and pain ratings were compared between groups, and correlations were calculated with the occurrence of echophenomena, self-reported empathy and clinical measures. Our Tourette syndrome sample showed significantly more echophenomena than controls, but the groups showed no behavioural differences in empathic abilities. However, controls, but not patients with Tourette syndrome, showed the predicted increased mu suppression when watching painful compared to neutral actions. While echophenomena were present in all persons with Tourette syndrome, the hypothesis of an overactive mirror neuron system in Tourette syndrome could not be substantiated. On the contrary, the Tourette syndrome group showed a noticeable lack of mu attenuation in response to pain stimuli. In conclusion, we found a first hint of altered processing of others’ emotional states in a brain region associated with the mirror neuron system.
Weiblen et al. report intact behavioural empathy for pain in Tourette syndrome, accompanied by reduced neural differentiation between painful and neutral stimuli. They find no evidence for the hypothesis of an overactive mirror neuron system as the cause of echophenomena and altered social behaviours in Tourette syndrome.
Graphical Abstract
Graphical Abstract
When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. ...But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88-116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43-56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36-52 kya, after the Out of Africa migrations around 60 kya.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex ...differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.
A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.
Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.
As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing ...percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.
The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of ...this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.
Mucosa‐associated invariant T (MAIT) cells are unconventional T lymphocytes defined by their innate‐like characteristics and broad antimicrobial responsiveness. Whether MAIT cells are part of the ...tissue‐resident defense in the oral mucosal barrier is unknown. Here, we found MAIT cells present in the buccal mucosa, with a tendency to cluster near the basement membrane, and located in both epithelium and the underlying connective tissue. Overall MAIT cell levels were similar in the mucosa compared to peripheral blood, in contrast to conventional T cells that showed an altered representation of CD4+ and CD8+ subsets. The major mucosal MAIT cell subset displayed a tissue‐resident and activated profile with high expression of CD69, CD103, HLA‐DR, and PD‐1, as well as a skewed subset distribution with higher representation of CD4–/CD8– double‐negative cells and CD8αα+ cells. Interestingly, tissue‐resident MAIT cells had a specialized polyfunctional response profile with higher IL‐17 levels, as assessed by polyclonal stimulus and compared to tissue nonresident and circulating populations. Furthermore, resident buccal MAIT cells were low in perforin. Together, these data indicate that MAIT cells form a part of the oral mucosal T cell compartment, where they exhibit a tissue‐resident‐activated profile biased toward IL‐17 production.
MAIT cells are part of the human buccal mucosal immune defenses. Buccal MAIT cells are enriched in the CD4–CD8– phenotypic subset and can be further sub‐divided based on tissue residency markers CD103 and CD69. The buccal MAIT cells have distinct polyfunctional response profiles with high IL‐17 and low IFN‐γ production.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is ...absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.
Display omitted
•Lysosome-rich enterocytes (LREs) internalize and digest dietary protein intracellularly•LREs are conserved between zebrafish and mammals•Cubn, Amn, and Dab2 mediate high-capacity protein uptake in LREs•Loss of LRE function impairs growth and survival in zebrafish and mice
Lysosome-rich enterocytes (LREs) are highly endocytic enterocytes found in pre-weaning mammals and stomachless fishes. Park et al. report that LREs mediate dietary protein absorption in the immature vertebrate gut via a multi-ligand endocytic machinery, composed of Cubilin, Amnionless, and Dab2, and a large lysosomal vacuole where dietary proteins are digested.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
PDF
