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The serotonin receptor subtype 1A (5-HT1AR), one of the G-protein-coupled receptor (GPCR) family, has been implicated in several neurological conditions. Understanding the activation and inactivation mechanism of 5-HT1AR at the molecular level is critical for discovering novel therapeutics in many diseases. Recently there has been a growing appreciation for the role of external electric fields (EFs) in influencing the structure and activity of biomolecules. In this study, we used molecular dynamics (MD) simulations to examine conformational features of active states of 5-HT1AR and investigate the effect of an external static EF with 0.02 V/nm applied on the active state of 5-HT1AR. Our results showed that the active state of 5-HT1AR maintained the native structure, while the EF led to structural modifications in 5-HT1AR, particularly inducing the inward movement of transmembrane helix 6 (TM6). Furthermore, it disturbed the conformational switches associated with activation in the CWxP, DRY, PIF, and NPxxY motifs, consequently predisposing an inclination towards the inactive-like conformation. We also found that the EF led to an overall increase in the dipole moment of 5-HT1AR, encompassing TM6 and pivotal amino acids. The analyses of conformational properties of TM6 showed that the changed secondary structure and decreased solvent exposure occurred upon the EF condition. The interaction of 5-HT1AR with the membrane lipid bilayer was also altered under the EF. Our findings reveal the molecular mechanism underlying the transition of 5-HT1AR conformation induced by external EFs, which offer potential novel insights into the prospect of employing structure-based EF applications for GPCRs.

Research has shown that external relative to internal focus (IF) instructions may improve motor performance as well as cognitive function (e.g., attentional stability and task-focus). The aim of the study was to examine the influence of attentional focus instructions on skill acquisition and learning of an aiming task in individuals with hearing impairments. The participants (N = 39, Mage = 17.87 ± 1.88 years) performed a bowling task with their dominant hand to knock down as many pins as possible. On day 1, they were randomly divided into three attentional focus groups; IF (focus on your throwing hand), external focus (EF) (focus on the pins), and control (no-focus) instructions. Each participant performed 36 trials, divided into 3 blocks of 12 trials. Attentional focus instructions were given before each block, with a brief reminder provided after each 3 trials. On day 2, retention and transfer (further distance) tests were performed. Results showed that while there were no significant differences between groups in the pre-test, the EF group outperformed both IF and control groups in retention and transfer tests. No significant difference was found between the control and IF. The findings suggest that the advantages of the external relative to the IF and no-focus instructions may generalize to individuals with hearing impairments.

BACKGROUND: Baseline right ventricular (RV) function derived from 3-dimensional analyses has been demonstrated to be predictive in patients undergoing transcatheter tricuspid valve repair (TTVR). The complex nature of these cumbersome analyses makes patient selection based on established imaging methods challenging. Artificial intelligence (AI)-driven computed tomography (CT) segmentation of the RV might serve as a fast and predictive tool for evaluating patients prior to TTVR.
METHODS: Patients suffering from severe tricuspid regurgitation underwent full cycle cardiac CT. AI-driven analyses were compared to conventional CT analyses. Outcome measures were correlated with survival free of rehospitalization for heart-failure or death after TTVR as the primary endpoint.
RESULTS: Automated AI-based image CT-analysis from 100 patients (mean age 77 ± 8 years, 63% female) showed excellent correlation for chamber quantification compared to conventional, core-lab evaluated CT analysis (R 0.963-0.966; p < 0.001). At 1 year (mean follow-up 229 ± 134 days) the primary endpoint occurred significantly more frequently in patients with reduced RV ejection fraction (EF) <50% (36.6% vs. 13.7%; HR 2.864, CI 1.212-6.763; p = 0.016). Furthermore, patients with dysfunctional RVs defined as end-diastolic RV volume > 210 ml and RV EF <50% demonstrated worse outcome than patients with functional RVs (43.7% vs. 12.2%; HR 3.753, CI 1.621-8.693; p = 0.002).
CONCLUSIONS: Derived RVEF and dysfunctional RV were predictors for death and hospitalization after TTVR. AI-facilitated CT analysis serves as an inter- and intra-observer independent and time-effective tool which may thus aid in optimizing patient selection prior to TTVR in clinical routine and in trials.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.
METHODS: A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.
CONCLUSIONS: This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.
BACKGROUND: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

UNASSIGNED: Eosinophilic Fasciitis (EF) is a rare disease, originally proposed as \"diffuse fasciitis with eosinophilia\" by Shulman in 1974. Symptoms of EF include peripheral eosinophilia accompanied by symmetrical inflammation of the subcutaneous fascia and muscle, usually locating in the upper arms or thighs. There is no approved standard of care treatment.
UNASSIGNED: Taking into account that eosinophils may be pathogenetically involved in EF, we performed a review on Medline focusing on anti-Interleukin-5 (IL-5) therapies in EF.
UNASSIGNED: Only one case of a patient with EF has been reported who was successfully treated with reslizumab, an anti-IL-5 therapy. The patient had EF refractory to the commonly used immunosuppressive treatment but when reslizumab was added, the patient experienced remission of her symptoms.
UNASSIGNED: The exact aetiology of EF is still unclear, and many therapeutic approaches have been tested. Commonly used immunosuppressive agents, such as corticosteroids are not always effective and associate with significant side effects. Eosinophils seem to have a role in the pathogenesis of the disease; anti-eosinophilic therapies targeting IL-5/IL-5 Receptor could be an attractive alternative for the treatment of the disease.

Changes in heart structure and function after lung resection in patients with lung cancer are challenging to manage. Therefore, a non-invasive and reliable measurement tool to gauge such changes is critical. The purpose of the present study was to compare cardiological changes before and after lung resection using tissue Doppler imaging (TDI). A total of 43 patients (19 men and 24 women) with primary non-small cell lung cancer (n=37) and metastatic cancer in the lungs (n=6) were enrolled in the study.nTDI was used to determine the thickness of the ascending aorta, the open size of the ascending valve, the anterior-oposterior diameters of the left atrium and left ventricle, and the thickness of the ventricular septum and right ventricle before and after lung resection. Left ventricular (LV) ejection fraction (EF), pulmonary valve flow rate, tricuspid annular or mitral leaflet tip early (E) peak/late (A) diastolic blood flow velocities, tricuspid regurgitation flow, the lateral mitral annulus early (e\') diastolic velocity and mitral E/e\' ratio were used to determine LV filling pressure. Results revealed no significant differences between male and female patients in terms of the open size of the ascending valve, the anterior-posterior diameter of the left ventricle and the mitral E/e\' ratio. Significant differences were found in the width of the ascending aorta, anterior-posterior diameter of the left atrium, width of the LV septum and right ventricular (RV) diameter before and after lung resection. Finally, there were significantchanges in EF and tricuspid pressure. The results indicated that TDI was useful as a non-invasive method for assessing left and right heart function following lung resection. The LV and RV dimensions were affected, but LV filling pressure was preserved after lobectomy.

Changes in the economy and human conduct have contributed to one of today\'s most urgent challenges: environmental pollution. This study\'s overarching objective is to evaluate the following Next Eleven nations (N-11) ecological footprints (EF) with their natural resources (NR), economic complexity (EC), renewable energy (RE), and foreign direct investment (FDI). The data from 1995 to 2018 are used with the panel data estimations. The complexity of an economy is found to influence the EF. For this purpose, the cross-sectional autoregressive distributed lag method is appropriate. The analysis shows that a higher degree of economic complexity was associated with a larger ecological impact. Moreover, this correlation was the highest among all the variables considered. However, the consumption of natural resources and the economies\' complexity enhance environmental conditions. The key recommendation from the study\'s conclusions is to improve R&D activities to build environmentally friendly technology and clean energy infrastructures and to change to a clean industry pattern. Meanwhile, strategic initiatives are offered to legislators depending on the stability of institutional quality.

The present study sought to inquire into the subjective experience of 156 preschoolers (age 4-6.9 years) living in an area of political violence in Israel (on the border with the Gaza Strip) during a period of massive bombing. Children were invited to draw a Person Picking an Apple from a Tree (PPAT), and were interviewed on their sense of self-potency using the CAMP, a measure of potency. Teachers were asked to report problems in executive functions using a few BRIEF scales; and mothers filled out a questionnaire for maternal distress (BSI), a measure of their child strengths and difficulties (SDQ), and were asked to provide their assessment regarding the extent to which their child was exposed to political violence. Findings reveal associations between mothers\' distress, the degree of exposure of their child to trauma, and the child\'s emotional symptoms. PPAT analysis identified four main factors: Tree Generosity, Person Agency, Vividness, and As-Real-R. Positive associations were found between self-potency and the main factors of the drawings; negative associations were found between the child\'s difficulties in executive functions and the drawing\'s four main factors; and two small negative associations were found between the child\'s emotional symptoms and Tree Generosity and As-Real-R factors. The following associations were found within each gender group: mothers\' depression degree was associated with boy\'s Tree Generosity, and mother\'s perceptions of their girl\'s exposure to trauma was related to Person Agency, Tree Generosity, and As-Real-R factors; furthermore, a significant difference was found between the narrative focus of drawings in this sample and the narrative focus of drawings of a sample of the same age group from a non-war zone. In addition, narrative focus was found to be related to children\'s self-potency. The discussion deals with the study\'s findings through the prism of developmental psychology, self-agency, object-relations, and art-therapy theories.