Cytochrome P450 Inhibition by Antimicrobials and Their Mixtures in Rainbow Trout Liver Microsomes In Vitro

Antimicrobials are ubiquitous in the environment and can bioaccumulate in fish. In the present study, we determined the half-maximal inhibitory concentrations (IC50) of 7 environmentally abundant antimicrobials (ciprofloxacin, clarithromycin, clotrimazole, erythromycin, ketoconazole, miconazole, and sulfamethoxazole) on the cytochrome P450 (CYP) system in rainbow trout (Oncorhynchus mykiss) liver microsomes, using 7-ethoxyresorufin O-deethylation (EROD, CYP1A) and 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD, CYP3A) as model reactions. Apart from ciprofloxacin and sulfamethoxazole, all antimicrobials inhibited either EROD or BFCOD activities or both at concentrationsPeer reviewe

Vaaka- ja pystysuuntaisten siirtymien mittaukset jokiuomassa

Tiivistelmä. Tämän kandintyön tavoitteena oli luoda laajempaa kuvaa siitä, miten vaaka- ja pystysiirtymämittaukset on mahdollista toteuttaa jokiuomassa. Työssä on tutkittu, millaisia haasteita jokiuomassa työskennellessä ilmenee ja miten eri mittausmenetelmiä voidaan hyödyntää tällaisessa kohteessa. Siirtymien mittauksilla voidaan arvioida jokiuoman vakautta ja ennakoida tulevia muutoksia. Työssä on perehdytty erilaisiin menetelmiin ja laitteisiin, joita voidaan käyttää siirtymien mittaamiseen, sekä käsitellään siirtymien mittauksiin liittyviä käytännön haasteita. Koska suomenkielistä kirjallisuutta on niukasti saatavilla tästä aiheesta, aikomuksena oli myös luoda helpommin lähestyttävää materiaalia. Tutkimus on toteutettu kirjallisuusselvityksenä ja siinä on esitelty, miten vaaka- ja pystysiirtymämittaukset onnistuvat jokiuomassa. Osa aineistosta on peräisin todellisista hankkeista, joiden avulla selviää, miten mittauksia on käytännössä toteutettu. Tässä työssä on mukana kaksi esimerkkiä, mutta erilaisia tapoja mitata on useampia. Työn teoriaosuudessa käydään läpi eri mittausmenetelmiä ja niiden toimintatapoja. Teoriaosuudessa tarkastellaan myös niiden etuja ja rajoituksia, jotka saattavat vaikuttaa mitattaessa siirtymiä jokiympäristössä. Näiden avulla myös vertaillaan menetelmien soveltumista erityyppisiin tarpeisiin. Yhteenvetona voidaan todeta, että vaaka- ja pystysuuntaisten siirtymien mittaukset jokiuomassa ovat tärkeitä jokiuoman vakauden arvioinnin ja tulevien muutosten ennakoimisen kannalta. Työ antaa lukijalle käsityksen siitä, millaisilla laitteilla ja menetelmillä on mahdollista monitoroida jokiuoman luiskan vaaka- että pystysuuntaisia siirtymiä.Measurement of horizontal and vertical displacements in a riverbed. Abstract. The aim of this bachelor’s thesis was to provide a broader understanding of how horizontal and vertical displacement measurements can be carried out in a riverbed. The study examines the challenges that arise when working in a riverbed and how different measurement methods can be utilized in such environments. Displacement measurements can be used to assess the stability of the riverbed and predict future changes. The thesis explores various methods and devices used for displacement measurements, as well as practical challenges associated with these measurements. Due to limited availability of Finnish literature on this topic, the intention was also to create more accessible material. The research was conducted as a literature review, presenting how horizontal and vertical displacement measurements can be successfully implemented in a riverbed. Some of the data used in this work is derived from real projects, which illustrate practical implementation of the measurements. Two examples are included in this thesis, but there are several other ways to perform the measurements. The theoretical part of the thesis covers different measurement methods and their operational principles. The advantages and limitations of these methods are also examined, considering their applicability in measuring displacements in a river environment. This enables a comparison of the suitability of the methods for different needs. In conclusion, horizontal and vertical displacement measurements in a river channel are important for assessing the stability of the river channel and predicting future changes. The thesis provides the reader with an understanding of the devices and methods that can be used to monitor both horizontal and vertical displacements of the river slope

Reduced Frontal Nogo-N2 With Uncompromised Response Inhibition During Transcutaneous Vagus Nerve Stimulation—More Efficient Cognitive Control?

We have previously shown invasive vagus nerve stimulation to improve attention and working memory and alter emotion-attention interaction in patients with refractory epilepsy, suggesting that VNS might be useful in the treatment of cognitive impairment. The current research focuses on whether non-invasive, transcutaneous vagus nerve stimulation (tVNS) has similar effects to VNS. Furthermore, we aimed to assess whether tVNS has an impact on cognitive control in general or on underlying brain physiology in a task that mimics everyday life demands where multiple executive functions are engaged while encountering intervening emotional stimuli. Event-related potentials (ERP) evoked in such a task, specifically centro-parietal P3 and frontal N2 were used as biomarkers for attention allocation and cognitive control required to carry out the task. A single-blinded, sham-controlled, within-subject study on healthy subjects (n = 25) was conducted using Executive Reaction Time Test (RT-test), a Go/NoGo task engaging multiple executive functions along with intervening threat-related distractors while EEG was recorded. tVNS at the left tragus and sham stimulation at the left ear lobe was alternately delivered throughout the task. To assess the impact of tVNS on neural activity underlying attention and cognitive control, centro-parietal P3 and frontal N2 peak amplitudes were measured in Go and NoGo conditions. Task performance was assessed with RTs and different error types reflecting cognitive control in general and distinct executive functions, such as working memory and response inhibition.No significant effects due to tVNS on performance in the Executive RT-test were observed. For N2 there was a main effect of stimulator status and a significant interaction of trial type (Go, NoGo) and stimulator status. Post hoc analysis revealed that tVNS resulted in a significant reduction of frontal N2 only in the NoGo condition. No significant effects were observed for P3 nor were there any effects of emotion. Diminished NoGo-N2 potential along with unaltered task performance during tVNS suggests fewer cognitive control resources were required to successfully withhold a prepotent response. Though caution is warranted, we suggest that tVNS may lead to more efficient neural processing with fewer resources needed for successful cognitive control, providing promise for its potential use in cognitive enhancement.Peer reviewe

Enhancing Peer Interaction in Early Childhood Special Education: Chains of Children’s Initiatives, Adults’ Responses and Their Consequences in Play

This article focuses on the initiatives taken by children and the responses given by professional adults with regard to the pedagogy of enhancing peer interaction among diverse learners. The study took place in four integrated special groups of public early childhood education. In groups of this kind, typically developing children and those with special educational needs (SEN) spent time together on a daily basis. We analysed 12 videotaped play sessions with 33 (3- to 6-year-old) children and 10 adults to examine the children’s initiatives, the adults’ responses, and the consequences that ensued. The study revealed verbal and nonverbal initiatives followed by a variety of responses scaffolding the children’s interaction and participation. However, the nonverbal or faint initiatives, especially those taken by the children with SEN, were at risk of being unnoticed or ignored. These findings call for professional reflection on pedagogical sensitivity in recognizing and responding to the initiatives of children.</p

What do children with social, emotional and behavioural difficulties think about themselves in early childhood?

The aim of this study was to discover what kind of perceptions young children in need of social, emotional, and behavioural support have about themselves. The interest was especially in social and emotional self-perceptions. For this study, ten children attending Finnish early childhood education and care were interviewed in spring 2016 and the material was analysed by using thematic analysis. Several developmental characteristics, typical for children aged 4–7 years, were found in the analysis such as general positivity of self-perceptions. However, the children’s perceptions also included atypical and negative features which manifested in various ways. Based on these features, four self-perception types were formed to describe the levels of positivity and negativity as well as the different features typical for each child and for each self-perception type. The results and possible explanations of the findings are discussed.</p

The Anti-Inflammatory Effects of Lipoxygenase and Cyclo-Oxygenase Inhibitors in Inflammation-Induced Human Fetal Glia Cells and the Aβ Degradation Capacity of Human Fetal Astrocytes in an Ex vivo Assay

Chronic inflammation is a common phenomenon present in the background of multiple neurodegenerative diseases, including Alzheimer's disease (AD). The arachidonic acid pathway overproduces proinflammatory eicosanoids during these states and glial cells in the brain gradually lose their vital functions of protecting and supporting neurons. In this study, the role of different key enzymes of the eicosanoid pathway mediating inflammatory responses was examined in vitro and ex vivo using human fetal glial cells. Astrocytes and microglia were exposed to proinflammatory agents i.e., cytokines interleukin 1-beta (IL-1 beta) and tumor necrosis factor (TNF-alpha). ELISA assays were used to examine the effects of inhibitors of key enzymes in the eicosanoid pathway. Inhibitors for 5-lipoxygenase (5-LOX) and cyclo-oxygenase 2 (COX-2) in both cell types and 5-, 12-, and 15-LOX-inhibitor in astrocytes reduced significantly IL-6 secretion, compared to exposed glial cells without inhibitors. The cytokine antibody array showed that especially treatments with 5, -12, and -15 LOX inhibitor in astrocytes, 5-LOX inhibitor in microglia and COX-2 inhibitor in both glial cell types significantly reduced the expression of multiple proinflammatory cytokines. Furthermore, human fetal astrocytes and microglia were cultured on top of AD-affected and control human brain sections for 30h. According to the immunochemical evaluation of the level of total A beta, astrocytes were very efficient at degrading A beta from AD-affected brain sections ex vivo; simultaneously added enzyme inhibitors did not increase their A beta degradation capabilities. Microglia were not able to reduce the level of total A beta during the 30h incubation time

Internet-Delivered Cognitive Behavioral Therapy for Generalized Anxiety Disorder in Nationwide Routine Care : Effectiveness Study

Background: Therapist-supported, internet-delivered cognitive behavioral therapy (iCBT) is efficacious for generalized anxiety disorder (GAD), but few studies are yet to report its effectiveness in routine care. Objective: In this study, we aim to examine whether a new 12-session iCBT program for GAD is effective in nationwide routine care. Methods: We administered a specialized, clinic-delivered, therapist-supported iCBT for GAD in 1099 physician-referred patients. The program was free of charge for patients, and the completion time was not predetermined. We measured symptoms with web-based questionnaires. The primary measure of anxiety was the GAD 7-item scale (GAD-7); secondary measures were, for pathological worry, the Penn State Worry Questionnaire and, for anxiety and impairment, the Overall Anxiety Severity and Impairment Scale. Results: Patients completed a mean 7.8 (SD 4.2; 65.1%) of 12 sessions, and 44.1% (485/1099) of patients completed all sessions. The effect size in the whole sample for GAD-7 was large (Cohen d=0.97, 95% CI 0.88-1.06). For completers, effect sizes were very large (Cohen d=1.34, 95% CI 1.25-1.53 for GAD-7; Cohen d=1.14, 95% CI 1.00-1.27 for Penn State Worry Questionnaire; and Cohen d=1.23, 95% CI 1.09-1.37 for Overall Anxiety Severity and Impairment Scale). Noncompleters also benefited from the treatment. Greater symptomatic GAD-7–measured relief was associated with more completed sessions, older age, and being referred from private or occupational care. Of the 894 patients with a baseline GAD-7 score ≥10, approximately 421 (47.1%) achieved reliable recovery. Conclusions: This nationwide, free-of-charge, therapist-supported HUS Helsinki University Hospital–iCBT for GAD was effective in routine care, but further research must establish effectiveness against other treatments and optimize the design of iCBT for GAD for different patient groups and individual patients.Background: Therapist-supported, internet-delivered cognitive behavioral therapy (iCBT) is efficacious for generalized anxiety disorder (GAD), but few studies are yet to report its effectiveness in routine care. Objective: In this study, we aim to examine whether a new 12-session iCBT program for GAD is effective in nationwide routine care. Methods: We administered a specialized, clinic-delivered, therapist-supported iCBT for GAD in 1099 physician-referred patients. The program was free of charge for patients, and the completion time was not predetermined. We measured symptoms with web-based questionnaires. The primary measure of anxiety was the GAD 7-item scale (GAD-7); secondary measures were, for pathological worry, the Penn State Worry Questionnaire and, for anxiety and impairment, the Overall Anxiety Severity and Impairment Scale. Results: Patients completed a mean 7.8 (SD 4.2; 65.1%) of 12 sessions, and 44.1% (485/1099) of patients completed all sessions. The effect size in the whole sample for GAD-7 was large (Cohen d=0.97, 95% CI 0.88-1.06). For completers, effect sizes were very large (Cohen d=1.34, 95% CI 1.25-1.53 for GAD-7; Cohen d=1.14, 95% CI 1.00-1.27 for Penn State Worry Questionnaire; and Cohen d=1.23, 95% CI 1.09-1.37 for Overall Anxiety Severity and Impairment Scale). Noncompleters also benefited from the treatment. Greater symptomatic GAD-7–measured relief was associated with more completed sessions, older age, and being referred from private or occupational care. Of the 894 patients with a baseline GAD-7 score ≥10, approximately 421 (47.1%) achieved reliable recovery. Conclusions: This nationwide, free-of-charge, therapist-supported HUS Helsinki University Hospital–iCBT for GAD was effective in routine care, but further research must establish effectiveness against other treatments and optimize the design of iCBT for GAD for different patient groups and individual patients.Peer reviewe

Occupational Burnout Is Linked with Inefficient Executive Functioning, Elevated Average Heart Rate, and Decreased Physical Activity in Daily Life - Initial Evidence from Teaching Professionals

Burnout is becoming a global pandemic jeopardizing brain health, with a huge impact on quality of life, available workforce, and the economy. Knowledge of the impact of burnout on cognition, physiology, and physical activity (PA) in daily life allows for an improved understanding of the health consequences and everyday ramifications of burnout. Twenty-eight volunteers participated in a three-day recording of daily physiology and PA, including heart rate (HR) and daily steps, with a wearable device. They filled in questionnaires screening for burnout (BBI-15), depression (BDI), and executive functions (EFs) in daily life (BRIEF-A). The subjects with burnout had more challenges in EFs, higher average HRs and lower numbers of steps in daily life than those without it. The BBI-15 scores correlated positively with the BDI scores and BRIEF-A indices and negatively with the awake HR variability (HRV) and daily steps. The metacognition index correlated negatively with the HRV. In conclusion, burnout is linked with compromised EFs along with alterations in cardiac physiology and PA in daily life. Such alterations may be easily detected with wearable devices, opening possibilities for novel biomarkers of burnout and other neuropsychiatric disorders. We suggest that physical activity and heart and brain health are intimately intertwined and that burnout interacts with each of them bidirectionally.publishedVersionPeer reviewe

Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells

Conclusions: JZL184 decreased the proinflammatory reactions of microglia and reduced the total A beta burden and its precursors in the APdE9 mouse model. It also reduced the proinflammatory responses of microglia and astrocytes isolated from adult mice.</p

Swift follow-up observations of candidate gravitational-wave transient events

We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors and their candidate sky locations were observed by the Swift observatory. Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge". With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25, published 2012 November 21, in ApJS, 203, 28 ( http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables; LIGO-P1100038; Science summary at http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003