The effect of methylphenidate on three forms of response inhibition in boys with AD/HD

Item does not contain fulltextThe current study was aimed at (a) investigating the effect of three doses methylphenidate (MPH) and placebo on inhibition of a prepotent response, inhibition of an ongoing response, and interference control in Attention Deficit/Hyperactivity Disorder (AD/HD), and (b) studying dose-response relations for the three forms of response inhibition. To meet these aims, the following tasks were selected: two versions of the Stop Paradigm for inhibition of a prepotent response, a Circle Tracing Task and a recently developed Follow Task for inhibition of an ongoing response, and the Stroop Color-Word Test and an Eriksen Flanker Task for interference control. These tasks were administered to 23 boys with AD/HD during four treatment conditions: 5 mg MPH, 10 mg MPH, 20 mg MPH, and placebo. A pseudorandomized, multiple-blind, placebo-controlled, within-subject design was used. As hypothesized, inhibitory control in children with AD/HD improved under MPH compared to placebo. However, this effect was only significant for inhibition of a prepotent response and inhibition of an ongoing response (as measured by the Follow Task), but not for interference control. The relation between treatment condition and response was linear. However, this linear relation was due to improved inhibitory control under MPH compared to placebo, because no effects of MPH dose were observed for any of the response inhibition measures

Patients suffering from psychological impairments following critical illness are in need of information

Background: Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient's post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. Methods: In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. Results: A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). Conclusions: In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention

Cremation and Grief:Are Ways of Commemorating the Dead Related to Adjustment Over Time?

Funeral services are known to serve multiple functions for bereaved persons. There is also a common, intuitively reasonable assumption of positive associations between engaging in funeral activities and adjustment to bereavement. We examined whether restricting ceremonial cremation arrangements to a minimum has a negative association with grief over time. Bereaved persons in the United Kingdom completed questionnaires 2 to 5 months postloss and again a year later (N = 233 with complete data; dropout = 11.4%). Neither type nor elaborateness of the cremation service, nor satisfaction with arrangements (typically high), emerged as significantly related to grief; no major subgroup differences (e.g., according to income level) were found. Results suggested that it does not matter to grief whether a more minimalistic or elaborate funeral ceremony was observed. We concluded that the funeral industry represented in this investigation is offering bereaved people the range of choices regarding cremation arrangements to meet their needs. Limits to generalizability are discussed

Constructing a Periodic Table of Arguments

The existing classifications of arguments are unsatisfying in a number of ways. This paper proposes an alternative in the form of a Periodic Table of Arguments. The newly developed table can be used as a systematic and comprehensive point of reference for the analysis, evaluation and production of argumentative discourse as well as for various kinds of empirical and computational research in the field of argumentation theory

Interaction between geriatric syndromes in predicting three months mortality risk

Objectives: Capturing frailty using a quick tool has proven to be challenging. We hypothesise that this is due to the complex interactions between frailty domains. We aimed to identify these interactions and assess whether adding interactions between domains improves mortality predictability. Methods: In this retrospective cohort study, we selected all patients aged 70 or older who were admitted to one Dutch hospital between April 2015 and April 2016. Patient characteristics, frailty screening (using VMS (Safety Management System), a screening tool used in Dutch hospital care), length of stay, and mortality within three months were retrospectively collected from electronic medical records. To identify predictive interactions between the frailty domains, we constructed a classification tree with mortality as the outcome using five variables: the four VMS-domains (delirium risk, fall risk, malnutrition, physical impairment) and their sum. To determine if any domain interactions were predictive for three-month mortality, we performed a multivariable logistic regression analysis. Results: We included 4,478 patients. (median age: 79 years; maximum age: 101 years; 44.8% male) The highest risk for three-month mortality included patients that were physically impaired and malnourished (23% (95%-CI 19.0–27.4%)). Subgroups had comparable three-month mortality risks based on different domains: malnutrition without physical impairment (15.2% (96%-CI 12.4–18.6%)) and physical impairment and delirium risk without malnutrition (16.3% (95%-CI 13.7–19.2%)). Discussion: We showed that taking interactions between domains into account improves the predictability of three-month mortality risk. Therefore, when screening for frailty, simply adding up domains with a cut-off score results in loss of valuable information

Thieno[2,3- d]pyrimidine-2,4(1 H,3 H)-dione Derivative Inhibits d -Dopachrome Tautomerase Activity and Suppresses the Proliferation of Non-Small Cell Lung Cancer Cells

The homologous cytokines macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT or MIF2) play key roles in cancers. Molecules binding to the MIF tautomerase active site interfere with its biological activity. In contrast, the lack of potent MIF2 inhibitors hinders the exploration of MIF2 as a drug target. In this work, screening of a focused compound collection enabled the identification of a MIF2 tautomerase inhibitor R110. Subsequent optimization provided inhibitor 5d with an IC50 of 1.0 μM for MIF2 tautomerase activity and a high selectivity over MIF. 5d suppressed the proliferation of non-small cell lung cancer cells in two-dimensional (2D) and three-dimensional (3D) cell cultures, which can be explained by the induction of cell cycle arrest via deactivation of the mitogen-activated protein kinase (MAPK) pathway. Thus, we discovered and characterized MIF2 inhibitors (5d) with improved antiproliferative activity in cellular models systems, which indicates the potential of targeting MIF2 in cancer treatment.</p