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Contains fulltext : 251339.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To compare CollaboRATE and SDM-Q-9 questionnaires when appreciating patient-perceived level of shared decision-making (SDM) in doctor-patient consultations. METHODS: Data were harvested from five separate studies on SDM, conducted in three university and one large community hospital in the Netherlands, using Dutch versions of both questionnaires. CollaboRATE and SDM-Q-9 scores were expressed as percentages. Correlation was assessed using Spearman's Rho coefficient. Bland&Altman analysis was used to assess the degree of agreement. Top scores were calculated to assess possible ceiling effects. RESULTS: The five studies included 442 patients. Median CollaboRATE scores (88.9%, IQR 81.5-100%) were significantly higher (p

Background Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-established, there is no clear framework for the communication of the evidence between physicians and patients. For this reason, we developed an evidence-based shared-decision making assistant (SDM-assistant) that presents high-quality evidence from network meta-analysis on the efficacy and side-effect profile of antipsychotics and can be used as a basis for shared-decision making between physicians and patients when selecting antipsychotic medications. Methods The planned matched-pair cluster-randomised trial will be conducted in acute psychiatric wards (n = 14 wards planned) and will include adult inpatients with schizophrenia or schizophrenia-like disorders (N = 252 participants planned). On the intervention wards, patients and their treating physicians will use the SDM-assistant, whenever a decision on choosing an antipsychotic is warranted. On the control wards, antipsychotics will be chosen according to treatment-as-usual. The primary outcome will be patients’ perceived involvement in the decision-making during the inpatient stay as measured with the SDM-Q-9. We will also assess therapeutic alliance, symptom severity, side-effects, treatment satisfaction, adherence, quality of life, functioning and rehospitalizations as secondary outcomes. Outcomes could be analysed at discharge and at follow-up after three months from discharge. The analysis will be conducted per-protocol using mixed-effects linear regression models for continuous outcomes and logistic regression models using generalised estimating equations for dichotomous outcomes. Barriers and facilitators in the implementation of the intervention will also be examined using a qualitative content analysis. Discussion This is the first trial to examine a decision assistant specifically designed to facilitate shared-decision making for choosing antipsychotic medications, i.e., SDM-assistant, in acutely ill inpatients with schizophrenia. If the intervention can be successfully implemented, SDM-assistant could advance evidence-based medicine in schizophrenia by putting medical evidence on antipsychotics into the context of patient preferences and values. This could subsequently lead to a higher involvement of the patients in decision-making and better therapy decisions. Trial registration German Clinical Trials Register (ID: DRKS00027316, registration date 26.01.2022).

Purpose Central serous chorioretinopathy (CSCR) has been associated with oxidative stress–related risk factors. The objective of this study was to optimize an analytical method for evaluating the oxidative stress biomarker malondialdehyde (MDA) in human tears and determine its level in the tears of patients with CSCR. Methods In this pilot study, tear samples were obtained from 34 healthy donors and 31 treatment-naïve CSCR male patients (eight with acute CSCR and 23 with chronic CSCR). Two analytical methods based on high-performance liquid chromatography followed by fluorescence detection were evaluated, with either 2-thiobarbituric derivative (TBA) or 2-aminoacridone (2-AA). Activity of CSCR was defined by the serous retinal detachment (SRD) height, which was measured by two independent observers on spectral-domain optical coherence tomography. Results The 2-AA method showed higher sensitivity and precision compared to the TBA method. When the 2-AA method was applied to tears from healthy donors, the levels of MDA were statistically significantly higher in men compared to women (mean ± standard deviation, SD: 9,914 nM ± 6,126 versus 4,635 nM ± 1,173, p = 0.006). No difference was found in tear MDA levels between male patients with CSCR and age-matched control men (p = 0.17). However, MDA levels were statistically significantly higher in acute compared to chronic CSCR cases (mean ± SD: 12,295 nM ± 8,495 versus 6,790 ± 3,969 nM, p = 0.03). Additionally, there was a correlation between MDA levels and RPE leakage, quantified by the height of the serous retinal detachment (p = 0.02, r = 0.40). Conclusions Levels of MDA in tears, measured with an optimized analytical method, correlate with RPE leakage in CSCR.

The construction of prefabricated buildings is an effective and efficient approach to improving construction processes and productivity. However, there are practical problems in this approach, such as listing, safety risk levels, and quality control. This study aims to develop a systematic approach for determining the key factors affecting prefabricated building projects’ quality and safety risk and assessing this risk. Based on the literature review, a structured questionnaire was distributed to 408 China-based construction organizations. Considering the factors of safety risk evaluation systems for construction, the safety risk model of prefabricated buildings is established and combined with structural equation modeling (SEM) and a system dynamic model (SDM). A detailed case study was conducted to verify the empirical findings. The results show that pre-construction, during-construction, and after-construction significantly influence the quality risk (from high to low). The final comprehensive score is 92.71, indicating that the construction safety of the residential building is generally controllable and the quality is guaranteed. Furthermore, the investment risk of such projects can be assessed using SEM and SDM. This study contributes to the literature by considering quality-risk-influencing factors in this field. Furthermore, the findings provide an understanding of implementation and quality risk control for prefabricated building projects and provide valuable information to departments in charge of improving the safety risk performance of such projects.

Background Social robots (SRs) have been used for improving anxiety in children in stressful clinical situations, such as during painful procedures. However, no studies have yet been performed to assess their effect in children while waiting for emergency room consultations. Objective This study aims to assess the impact of SRs on managing stress in children waiting for an emergency room procedure through the assessment of salivary cortisol levels. Methods This was an open randomized clinical trial in children attending a pediatric emergency department. Children accessing the emergency room were randomized to 1 of 3 groups: (1) playing with a NAO SR, (2) playing with a study nurse, or (3) waiting with parents. The salivary cortisol levels of all children were measured through a swab. Salivary cortisol levels before and after the intervention were compared in the 3 groups. We calculated the effect size of our interventions through the Cohen d-based effect size correlation (r). Results A total of 109 children aged 3-10 years were enrolled in the study, and 94 (86.2%) had complete data for the analyses. Salivary cortisol levels significantly decreased more in the group exposed to robot interaction than in the other two groups (r=0.75). Cortisol levels decreased more in girls (r=0.92) than in boys (r=0.57). Conclusions SRs are efficacious in decreasing stress in children accessing the emergency room and may be considered a tool for improving emotional perceptions of children and their families in such a critical setting. Trial Registration ClinicalTrials.gov NCT04627909; https://clinicaltrials.gov/ct2/show/study/NCT04627909

Objective: Ready for SDM was developed in Norway as a comprehensive modularized curriculum for health care providers (HCP). The current study evaluated the efficacy of one of the modules, a 2-hour interprofessional SDM training designed to enhance SDM competencies. Methods: A cluster randomized controlled trial was conducted with eight District Psychiatric Centres randomized to wait-list control (CG) or intervention group (IG). Participants and trainers were not blinded to their allocation. The IG received a 2-hour didactic and interactive training, using video examples. The primary outcome was the agreement between the participants’ and an expert assessment of patient involvement in a video recorded consultation. The SDM-knowledge score was a secondary outcome. Results: Compared to the CG (n = 65), the IG (n = 69) judged involvement behavior in a communication example more accurately (mean difference of weighted T, adjusted for age and gender:=− 0.098, p = 0.028) and demonstrated better knowledge (mean difference=− 0.58; p = 0.014). A sensitivity analysis entering a random effect for cluster turned out not significant. Conclusion: The interprofessional group training can improve HCPs’ SDM-competencies. Practice implications: Addressing interprofessional teams using SDM communication training could supplement existing SDM training approaches. More research is needed to evaluate the training module’s effects as a component of large-scale implementation of SDM.

The reliance of number processing on sensorimotor mechanisms involved in hand action has been extensively documented by behavioural studies. Nonetheless, where and how the computations of number and hand action interact in the brain has received limited attention. In this study we investigated the brain networks underlying symbolic number comparison and the hand action of reaching and grasping, capitalizing on functional imaging studies meta-analyzed with the seed-based d mapping with permutation of subject images meta-analytic method (SDM-PSI). The main objective was to test whether and to what extent symbolic number processing recruits the same sensorimotor network involved in the hand action of reaching and grasping. We included 42 studies (756 participants) adopting symbolic number comparison tasks and 58 studies (867 participants) investigating hand reaching and hand grasping. The conjunction analysis of brain networks common to number processing, reaching, and grasping revealed spatial convergence over frontoparietal areas. Specifically, four clusters were identified, in and around the left and right intraparietal sulci, in the left precentral gyrus, and in the supplementary motor area. The degree of overlap was extensive, since the reach/grasp network mostly included the number areas. A qualitative analysis of functional characterization capitalizing on the Neurosynth database depicted a strong multifunctionality of the regions of overlap between numbers and hand action: these brain areas were also associated to a variety of functions within the domains of memory and imagery, visuospatial attention, and language. Overall, these results characterize the neuroanatomical substrate of the interaction between reaching, grasping, and symbolic number comparison.

Machine learning methods have now become an optional technique in Earth science research, and such data-driven solutions have also made tremendous progress in weather forecasting and climate prediction in recent years. Since climate data are typically time series, the neural network layers, which can identify the intrinsic connections between the points of the sequence and features in two-dimensional data, perform particularly well for climate prediction. The North Atlantic Oscillation (NAO) is a prominent atmospherical mode in the northern hemisphere, with the frequency change characteristic of sea level pressure (SLP) in the North Atlantic sector. One of the reasons why NAO prediction is still challenging is that NAO is also proven to be influenced by other climate circulations, the most significant of which is the interaction between El Niño-Southern Oscillation (ENSO) and NAO. Therefore, sea surface temperature (SST) in the Pacific Ocean used to characterize ENSO is also one of the factors that contribute to the evolution of NAO and can be used as an input factor to predict the NAO. In this paper, the seasonal lag correlation between ENSO and NAO is explored and analyzed. The interaction has been considered in both short-term forecasting and midterm prediction of the NAO variability. The monthly NAO index (NAOI) fluctuation is predicted using the Niño indices based on the RF-Var model, and the accuracy achieves 68% when the lead time is about three months. In addition, integrating multiple physical variables directly related to the NAO and Pacific SST, the short-term NAO forecasting is conducted using a multi-channel neural network named AccNet with trajectory gated recursive unit (TrajGRU) layer. AccNet has the ability to identify the mechanism of the high-frequency variation in several days, and the NAO variability is indicated by SLP. The loss function of AccNet is set to anomaly correlation coefficient (ACC), which is the indicator that verifies spatial correlation in geoscience. Forecasting extreme events of NAO between 2010 and 2021, AccNet presents higher flexibility compared against other structures that can capture spatial-temporal features.

The article presents the methodology of preparing a cosmetic sample for analysi, and the creation of a dataset for teaching artificial intelligence to recognize specific species of microorganisms in cosmetic samples in terms of compliance with the ISO standard document, to develop of the Microorganism Detection System (SDM).Methodology of preparation a cosmetic sample for testing covers the steps from taking a cosmetic sample to obtaining separated living microorganisms through staining to photos, which in the final stage are used for analysis of the purity of cosmetics by SDM, as well as for learning and testing of the deep convolutional neural network (CNN) for detecting and classifying cells of specific species of bacteria, fungi and yeast in cosmetics, according to the document of standard PN-EN ISO 17516-2014:11.A new techique was devised for preparing a cosmetic sample for the development of Microorganism Detection System (SDM) software, and artificial intelligence learning to recognize specific microbial species. Based on metod demonstrated, the Intelligent algorithms of SDM proved to be effective in counting and recognizing specific microorganisms (average accuracy for Candida albicans - 97%, Escherichia coli - 76%, Pseudomonas aeruginosa - 70%, Staphylococcus aureus - 85%), which are the most important species for the assessment of the purity of cosmetics. In addition, the reproducibility of the developed method was verified, and the results obtained were comparable to the breeding methods currently used, based on specific standards.The experiments confirmed the high sensitivity and specificity of the SDM method, its repeatability and, above all, the comparability of the results with clasic methods of European standards.

The Microorganism Detection System (SDM) is a new solution using artificial intelligence, unique on the international scale, to correctly identify and count microorganisms, with particular emphasis on specificlisted microorganisms (Document of Standard PN-EN ISO 17516-2014:11) - Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus. SDM enables the use of algorithms for microscopic image interpretation in the microbiological assessment of the cosmetics in accordance with the standard, providing an answer to whether the tested product complies with the standard. Apart from the software part of SDM, an integral part of the system is an innovative methodology for preparing a cosmetic sample for testing. The experiments confirm the high sensitivity and specificity of the SDM method, its repeatability and, above all, the comparability of the results with the methods of European standards.

Acridine cell-penetrating peptide conjugates are an extremely important family of compounds in antitumor chemotherapy. These conjugates are not so widely analysed in antimicrobial therapy, although bioactive peptides could be used as nanocarriers to smuggle antimicrobial compounds. An octaarginine conjugate of an imidazoacridinone derivative (Compound 1-R8) synthetized by us exhibited high antifungal activity against reference and fluconazole-resistant clinical strains (MICs ≤ 4 μg mL−1). Our results clearly demonstrate the qualitative difference in accumulation of the mother compound and Compound 1-R8 conjugate into fungal cells. Only the latter was transported and accumulated effectively. Microscopic and flow cytometry analysis provide some evidence that the killing activity of Compound 1-R8 may be associated with a change in the permeability of the fungal cell membrane. The conjugate exhibited low cytotoxicity against human embryonic kidney (HEK-293) and human liver (HEPG2) cancer cell lines. Nevertheless, the selectivity index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted in a high antifungal effect.

Electrochemical DNA sensors offer unique opportunities for the sensitive detection of specific DNA interactions. In this work, a voltametric DNA sensor is proposed on the base of glassy carbon electrode modified with carbon black, adsorbed acridine yellow and DNA for highly sensitive determination of doxorubicin antitumor drug. The signal recorded by cyclic voltammetry was attributed to irreversible oxidation of the dye. Its value was altered by aggregation of the hydrophobic dye molecules on the carbon black particles. DNA molecules promote disaggregation of the dye and increased the signal. This effect was partially suppressed by doxorubicin compensate for the charge of DNA in the intercalation. Sensitivity of the signal toward DNA and doxorubicin was additionally increased by treatment of the layer with dimethylformamide. In optimal conditions, the linear range of doxorubicin concentrations determined was 0.1 pM–1.0 nM, and the detection limit was 0.07 pM. No influence of sulfonamide medicines and plasma electrolytes on the doxorubicin determination was shown. The DNA sensor was tested on two medications (doxorubicin-TEVA and doxorubicin-LANS) and showed recoveries of 102–105%. The DNA sensor developed can find applications in the determination of drug residues in blood and for the pharmacokinetics studies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This research was funded by the Russian Science Foundation (A.P., grant no. 17-73-20024, investigations of DNA adsorption DMF influence and DNA-doxorubicin interactions) and the Russian Foundation for Basic Research (G.E., grant no. 20-03-00207, investigation of the AY electrochemical properties and its transfer on the electrode interface).

This study aims to test the psychometric properties of the Malay, English, and Chinese 9-Item Shared Decision Making Questionnaire (SDM-Q-9) in breast cancer patients making treatment decisions. The original German SDM-Q-9 was translated to Malay using the back-translation method. A total of 222 newly diagnosed breast cancer patients making treatment decisions were sampled conveniently from three breast clinics between August 2015 and February 2016. A total of 66 patients answered the SDM-Q-9 in Malay, 87 in English, and 69 in Chinese. Data were analyzed using SPSS and AMOS software. SDM-Q-9 demonstrated good reliability in the three translations. All the items correlated well except for Item 1 in English. The factor loadings were within acceptable range except for Item 1 in Malay, Items 1 and 2 in English, and Items 7 and 9 in Chinese SDM-Q-9. However, no items were deleted in accordance with experts’ opinions and the previous SDM-Q-9 validation studies. The Malay, English, and Chinese SDM-Q-9 demonstrated good reliability and validity.

An intriguing challenge in the human–robot interaction field is the prospect of endowing robots with emotional intelligence to make the interaction more genuine, intuitive, and natural. A crucial aspect in achieving this goal is the robot’s capability to infer and interpret human emotions. Thanks to its design and open programming platform, the NAO humanoid robot is one of the most widely used agents for human interaction. As with person-to-person communication, facial expressions are the privileged channel for recognizing the interlocutor’s emotional expressions. Although NAO is equipped with a facial expression recognition module, specific use cases may require additional features and affective computing capabilities that are not currently available. This study proposes a highly accurate convolutional-neural-network-based facial expression recognition model that is able to further enhance the NAO robot’ awareness of human facial expressions and provide the robot with an interlocutor’s arousal level detection capability. Indeed, the model tested during human–robot interactions was 91% and 90% accurate in recognizing happy and sad facial expressions, respectively, 75% accurate in recognizing surprised and scared expressions, and less accurate in recognizing neutral and angry expressions. Finally, the model was successfully integrated into the NAO SDK, thus allowing for high-performing facial expression classification with an inference time of 0.34 ± 0.04 s.

Shared decision making (SDM) is on the international healthcare agenda among patient advocacy groups and decision makers in healthcare worldwide [1–5]. In Denmark, implementation of SDM with all ca...

To quantify the synaptic vesicle glycoprotein 2A (SV2A) changes in the whole central nervous system (CNS) under pathophysiological conditions, a high affinity SV2A PET radiotracer with improved in vivo stability is desirable to minimize the potential confounding effect of radiometabolites. The aim of this study was to develop such a PET tracer based on the molecular scaffold of UCB-A, and evaluate its pharmacokinetics, in vivo stability, specific binding, and nonspecific binding signals in nonhuman primate brains, in comparison with [The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) and its two enantiomers were synthesized and assayed for in vitro binding affinities to human SV2A. We synthesized the enantiopure [SDM-16 was synthesized in 3 steps with 44% overall yield and has the highest affinity (KWe have successfully synthesized a novel SV2A PET tracer [

Understanding local conformations of DNA at the level of individual nucleic acid bases and base pairs is important for elucidating molecular processes that depend on DNA sequence. Here, we apply linear absorption and circular dichroism measurements to the study of local DNA conformations, using the guanine base analog 6-methyl isoxanthopterin (6-MI) as a structural probe. We show that the spectroscopic properties of this probe can provide detailed information about the average local base and basepair conformations as a function of the surrounding DNA sequence. Based on these results we apply a simple theoretical model to calculate the circular dichroism spectra of 6-MI-substituted DNA constructs and show that our model can be used to extract information about how the local conformations of the 6-MI probe are influenced by the local base or basepair environment. We also use this probe to examine the pathway for the insertion (intercalation) of a tethered acridine ligand (9-amino-6-chloro methoxyacridine) into duplex DNA. We show that this model intercalator interacts with duplex DNA by a “displacement insertion intercalation” mechanism, whereby the acridine moiety is inserted into the DNA structure and displaces the base located opposite its attachment site. These findings suggest that site-specifically positioned base analog probes can be used to characterize the molecular and structural details of binding ligand effects on local base stacking and unstacking reactions in single- and double-stranded DNA and thus may help to define the molecular mechanisms of DNA-protein interactions that involve the site-specific intercalation of aromatic amino acid side chains into genomic DNA.

Transitive inference (TI) is a critical capacity involving the integration of relevant information into prior knowledge structure for drawing novel inferences on unobserved relationships. To date, the neural correlates of TI remain unclear due to the small sample size and heterogeneity of various experimental tasks from individual studies. Here, the meta-analysis on 32 fMRI studies was performed to detect brain activation patterns of TI and its three paradigms (spatial inference, hierarchical inference, and associative inference). We found the hippocampus, prefrontal cortex (PFC), putamen, posterior parietal cortex (PPC), retrosplenial cortex (RSC), supplementary motor area (SMA), precentral gyrus (PreCG), and median cingulate cortex (MCC) were engaged in TI. Specifically, the RSC was implicated in the associative inference, whereas PPC, SMA, PreCG, and MCC were implicated in the hierarchical inference. In addition, the hierarchical inference and associative inference both evoked activation in the hippocampus, medial PFC, and PCC. Although the meta-analysis on spatial inference did not generate a reliable result due to insufficient amount of investigations, the present work still offers a new insight for better understanding the neural basis underlying TI.

Objective Shared decision making integrates health care provider expertise with patient values and preferences. The MAPPIN’SDM is a recently developed measurement instrument that incorporates physician, patient, and observer perspectives during medical consultations. This review sought to critically appraise the development, sensibility, reliability, and validity of the MAPPIN’SDM and to determine in which settings it has been used. Methods This critical appraisal was performed through a targeted review of the literature. Articles outlining the development or measurement property assessment of the MAPPIN’SDM or that used the instrument for predictor or outcome purposes were identified. Results Thirteen studies were included. The MAPPIN’SDM was developed by both adapting and building on previous shared decision making measurement instruments, as well as through creation of novel items. Content validity, face validity, and item quality of the MAPPIN’SDM are adequate. Internal consistency ranged from 0.91 to 0.94 and agreement statistics from 0.41 to 0.92. The MAPPIN’SDM has been evaluated in several populations and settings, ranging from chronic disease to acute oncological settings. Limitations include high reading levels required for self-administered patient questionnaires and the small number of studies that have employed the instrument to date. Conclusion The MAPPIN’SDM generally shows adequate development, sensibility, reliability, and validity in preliminary testing and holds promise for shared decision making research integrating multiple perspectives. Further research is needed to develop its use in other patient populations and to assess patient understanding of complex item wording.

The effects of potato and traditional staple foods (corn, wheat and rice) on physiology and gut microbiota were investigated by feeding ICR mice for 12 months. Compared with traditional staple foods, potato significantly improved the food and water intake and survival rate, and inhibited the swelling of viscera of mice, accompanied by a decreased white blood cell count and urine bilirubin content. Furthermore, potato significantly increased the relative abundance of Bacteroides and Faecalibacterium, which are short-chain fatty acid producing bacteria and play very important roles in the maintenance of human health. Meanwhile, potato significantly decreased the relative abundance of spoilage bacteria Pseudomonas and Thiobacillus. Analysis of putative metagenomes indicated that the potato diet upregulated the gene abundance of glycan biosynthesis and metabolism, digestive system and immune system. These findings indicated that potato has the potential to be an excellent substitute for traditional staple foods owing to its good physiological function and favorable gut microbiota modulation.

Multi‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits.

The use of humanoid robots as assistants in therapy processes is not new. Several projects in the past several years have achieved promising results when combining human-robot interaction with standard techniques. Moreover, there are multiple screening systems for autism; one of the most used systems is the Quantitative Checklist for Autism in Toddlers (Q-CHAT-10), which includes ten questions to be answered by the parents or caregivers of a child. We present Q-CHAT-NAO, an observation-based autism screening system supported by a NAO robot. It includes the six questions of the Q-CHAT-10 that can be adapted to work in a robotic context; unlike the original system, it obtains information from the toddler instead of from an indirect source. The detection results obtained after applying machine learning models to the six questions in the Autistic Spectrum Disorder Screening Data for Toddlers dataset were almost equivalent to those of the original version with ten questions. These findings indicate that the Q-CHAT-NAO could be a screening option that would exploit all the benefits related to human-robot interaction.

Semen Ziziphus jujube (SZJ) has been widely consumed because it is recognized as edible in China to treat insomnia disorders. However, the underlying mechanisms and potential therapeutic targets remain obscure. SZJ-I and SZJ-II with a saponin content of 52.10% and 75.20%, respectively, were extracted from SZJ. LC-MS analysis presented quite different chemical profiles of SZJ-I and SZJ-II. Mice with p-chlorophenylalanine (PCPA)-induced insomnia were used to comparatively and systematically test the sedative-hypnotic activities of SZJ-I and SZJ-II. In vivo behavioral tests revealed that SZJ-I and SZJ-II significantly shortened the immobility time and potentiated sodium pentobarbital-induced sleep. SZJ-II with a higher saponin content showed greater potency than SZJ-I. SZJ-I and SZJ-II also protected against PCPA-triggered neuropathological damages in the brain. Concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NE), glutamate (Glu), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitric oxide (NO) and prostaglandin D2 (PGD2) in plasma were significantly affected by SZJ-I and SZJ-II application. SZJ-I and SZJ-II also exhibited differential modulation of 5-hydroxytryptamine 1A (5-HT1A), 5-hydroxytryptamine 2A (5-HT2A), GABAA receptor α2 (GABAARα2), GABAA receptor α3 (GABAARα3), glutamic acid decarboxylase (GAD) 65/67, IL-6 and IL-1β expression in the hypothalamus and hippocampus. SZJ-I and SZJ-II might exert excellent sedative-hypnotic effects through multiple mechanisms that worked simultaneously. SZJ-I and especially SZJ-II are promising candidates for relieving insomnia.

Background Among the studied antitumor acridinone derivatives developed in our laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic and antitumor properties against several cancer types and were selected to be evaluated in preclinical and early-phase clinical trials. In the present work, we investigated the impact of C-1305 and C-1311 on UDP-glucuronosyltransferase (UGT) activity. Methods Enzyme activity modulation was studied using HPLC by analyzing standard UGT substrate metabolism in the presence and absence of antitumor drugs. The investigations were performed in two model systems: (i) under noncellular conditions, including human liver microsomes (HLM) and recombinant UGT1A1, 1A9 and 1A10 isoenzymes and (ii) in tumor cells. Results There was observed a slight impact of studied drugs on enzyme activity. Only UGT1A1 action was altered by both compounds. The modulatory effects of UGT activity in cellular systems depended on the tumor cell type. In the case of HepG2, C-1305 and C-1311 strongly induced UGT activity, particularly for C-1311, at concentrations significantly lower than the EC 50 . This effect contradicted irinotecan mediated UGT inhibition. HT29 colon tumor cells were less sensitive than HepG2 to enzyme modulation in the presence of the studied compounds, particularly C-1305, where enzymatic inhibition similar to that of irinotecan was observed. Conclusions The results demonstrated that UGT activity modulation should be expected in the case of antitumor therapy with C-1305 or/and C-1311. Analysis of the results indicated that these modulations would occur via cellular regulatory pathways not by direct drug-enzyme interactions.

Socially assistive robots have shown potential benefits in therapy of child and elderly patients with social and cognitive deficits. In particular, for autistic children, humanoid robots could enhance engagement and attention, thanks to their simplified toy-like appearance and the reduced set of possible movements and expressions. The recent focus on autism-related motor impairments has increased the interest on developing new robotic tools aimed at improving not only the social capabilities but also the motor skills of autistic children. To this purpose, we have designed two embodied mirroring setups using the NAO humanoid robot. Two different tracking systems were used and compared: Inertial Measurement Units and the Microsoft Kinect, a marker-less vision based system. Both platforms were able to mirror upper limb basic movements of two healthy subjects, an adult and a child. However, despite the lower accuracy, the Kinect-based setup was chosen as the best candidate for embodied mirroring in autism treatment, thanks to the lower intrusiveness and reduced setup time. A prototype of an interactive mirroring game was developed and successfully tested with the Kinect-based platform, paving the way to the development of a versatile and powerful tool for clinical use with autistic children.

The metabolism of antitumor-active 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) has been investigated widely over the last decade but some aspects of molecular mechanisms of its metabolic transformation are still not explained. In the current work, we have reported a direct and rapid analytical tool for better prediction of C-1311 metabolism which is based on electrochemistry (EC) coupled on-line with electrospray ionization mass spectrometry (ESI-MS). Simulation of the oxidative phase I metabolism of the compound was achieved in a simple electrochemical thin-layer cell consisting of three electrodes (ROXY™, Antec Leyden, the Netherlands). We demonstrated that the formation of the products of N-dealkylation reactions can be easily simulated using purely instrumental approach. Newly reported products of oxidative transformations like hydroxylated or oxygenated derivatives become accessible. Structures of the electrochemically generated metabolites were elucidated on the basis of accurate mass ion data and tandem mass spectrometry experiments. In silico prediction of main sites of C-1311 metabolism was performed using MetaSite software. The compound was evaluated for cytochrome P450 1A2-, 3A4-, and 2D6-mediated reactions. The results obtained by EC were also compared and correlated with those of reported earlier for conventional in vitro enzymatic studies in the presence of liver microsomes and in the model peroxidase system. The in vitro experimental approach and the in silico metabolism findings showed a quite good agreement with the data from EC/ESI-MS analysis. Thus, we conclude here that the electrochemical technique provides the promising platform for the simple evaluation of drug metabolism and the reaction mechanism studies, giving first clues to the metabolic transformation of pharmaceuticals in the human body.

Cisplatin analogues with an attached DNA-binding moiety represent a potentially effective class of DNA-damaging anti-tumour agents because they possess higher affinities for DNA and different DNA damage profiles compared with cisplatin. In this study, the interaction of four 9-aminoacridine carboxamide Pt complexes with purified DNA was investigated: firstly, using a fluorescent intercalator displacement (FID) assay with ethidium bromide; and secondly, with a DNA unwinding assay. The relative capacity of these compounds to perturb the fluorescence induced by DNA-bound ethidium bromide at clinically relevant drug concentrations was assessed over a 24-h period using an FID assay. All analogues were found to reduce the level of ethidium bromide-induced fluorescence in a concentration-dependent manner from the earliest time point of 10 min onwards. Cisplatin, however, showed a markedly slower reduction in ethidium bromide-induced fluorescence from 2 h onwards, producing a similar level of fluorescence reduction as that produced by the analogues from 6 h onwards. These results suggest that the altered DNA-binding modes of the DNA-targeted analogues confer a more efficient mechanism for DNA binding compared with cisplatin. Relative DNA binding coefficients were also determined for each of the compounds studied. With the DNA unwinding assay, an unwinding angle can be calculated from the coalescence point of plasmids in an agarose gel. It was found that all 9-aminoacridine carboxamide analogues had a greater unwinding angle compared with cisplatin. The knowledge obtained from these two assays has helped to further characterise the cisplatin analogues and could facilitate the development of more effective anti-tumour agents.