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Background Pyronaridine-artesunate (PA) is a registered artemisinin-based combination therapy, potentially useful for mass drug administration campaigns. However, further data are needed to evaluate its efficacy, safety and tolerability as full or incomplete treatment in asymptomatic Plasmodium falciparum-infected individuals. Methods This phase II, multi-center, open label, randomized clinical trial was conducted in The Gambia and Zambia. Participants with microscopically confirmed asymptomatic P. falciparum infection were randomly assigned (1:1:1) to receive a 3-day, 2-day, or 1-day treatment regimen of PA (180:60 mg), dosed according to bodyweight. The primary efficacy outcome was polymerase chain reaction (PCR)-adjusted adequate parasitological response (APR) at day 28 in the per-protocol population. Results A total of 303 participants were randomized. Day 28 PCR-adjusted APR was 100% for both the 3-day (98/98) and 2-day regimens (96/96), and 96.8% (89/94) for the 1-day regimen. Efficacy was maintained at 100% until day 63 for the 3-day and 2-day regimens but declined to 94.4% (84/89) with the 1-day regimen. Adverse event frequency was similar between the 3-day (51.5% [52/101]), 2-day (52.5% [52/99]), and 1-day (54.4% [56/103]) regimens; the majority of adverse events were of grade 1 or 2 severity (85% [136/160]). Asymptomatic, transient increases (>3 times the upper limit of normal) in alanine aminotransferase/aspartate aminotransferase were observed for 6/301 (2.0%) participants. Conclusions PA had high efficacy and good tolerability in asymptomatic P. falciparum-infected individuals, with similar efficacy for the full 3-day and incomplete 2-day regimens. Although good adherence to the 3-day regimen should be encouraged, these results support the further investigation of PA for mass drug administration campaigns. Clinical Trials Registration NCT03814616., This randomized study in The Gambia and Zambia evaluated pyronaridine-artesunate as full or incomplete treatment in individuals with asymptomatic Plasmodium falciparum infection. High efficacy and good tolerability suggest that pyronaridine-artesunate could be useful in mass drug administration campaigns in Africa.

Attention Deficit/Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder in children. ADHD has a multifactorial origin, combining genetic and environmental factors. Several studies suggested an influence of early parent-child relationships on the symptomatic expression of ADHD. In this review, we examine the studies that have investigated the links between attachment and ADHD in children. We searched for studies published between January 2000 and November 2019 on PsychInfo, PubMed, and Scopus. Selected studies included a theoretically based measure of attachment and an explicit measure of ADHD symptoms or an ADHD diagnosis. Studies that included children from adoption, institutionalization, or mistreatment were not included. We found only 26 studies meeting the inclusion criteria. Almost all these studies indicated a link between the attachment type and the presence of attentional difficulties and hyperactivity. However, associations were better explained, in several studies, by confounding factors such as comorbidities, cognitive difficulties, or contextual factors. The method used to assess attachment and parental mental health also had an impact. An increasing number of studies show a link between the type of attachment and the presence of attentional difficulties and hyperactivity in children. However, the nature of this link remains unclear. Implications for future research are discussed., info:eu-repo/semantics/published

Real-world experience is typically multimodal. Evidence indicates that the facilitation in the detection of multisensory stimuli is modulated by the perceptual load, the amount of information involved in the processing of the stimuli. Here, we used a realistic virtual reality environment while concomitantly acquiring Electroencephalography (EEG) and Galvanic Skin Response (GSR) to investigate how multisensory signals impact target detection in two conditions, high and low perceptual load. Different multimodal stimuli (auditory and vibrotactile) were presented, alone or in combination with the visual target. Results showed that only in the high load condition, multisensory stimuli significantly improve performance, compared to visual stimulation alone. Multisensory stimulation also decreases the EEG-based workload. Instead, the perceived workload, according to the “NASA Task Load Index” questionnaire, was reduced only by the trimodal condition (i.e., visual, auditory, tactile). This trimodal stimulation was more effective in enhancing the sense of presence, that is the feeling of being in the virtual environment, compared to the bimodal or unimodal stimulation. Also, we show that in the high load task, the GSR components are higher compared to the low load condition. Finally, the multimodal stimulation (Visual-Audio-Tactile—VAT and Visual-Audio—VA) induced a significant decrease in latency, and a significant increase in the amplitude of the P300 potentials with respect to the unimodal (visual) and visual and tactile bimodal stimulation, suggesting a faster and more effective processing and detection of stimuli if auditory stimulation is included. Overall, these findings provide insights into the relationship between multisensory integration and human behavior and cognition.

Aim: SNPs in miRNA machinery genes may affect miRNA function by impacting their biogenesis. Here, we investigated the association between three SNPs in miRNA machinery genes ( DICER rs1057035, DROSHA rs10719 and XPO5 rs11077) and bicuspid aortic valve (BAV). Materials & methods: Three polymorphisms were analyzed in 177 BAV patients and 414 healthy subjects by using a TaqMan®SNP assay. Results: The frequencies of XPO5 rs11077 genotype were significantly different between BAV patients and controls (p = 0.022). On multivariate logistic regression analysis, the XPO5 rs11077 C allele resulted a significant predictor of BAV (odds ratioadjusted = 0.65; CI: 0.42–0.98; p = 0.047). Conclusion: The XPO5 rs11077 SNP was associated with a decreased BAV risk supporting the causative role of miRNAs in aortic valve development.

Background Aging of the workforce challenges European countries. Keeping aged workers healthy and productive, through health promotion, is a key goal of European labour policy. The aim of the present study was to collect experiences of workplace health promotion for older workers (WHPOW) conducted in 10 representative countries of Central Europe, Eastern Europe and the Mediterranean. Methods A literature review of activities of WHPOW was conducted through a comprehensive search of major scientific databases and on the website of the major European Agencies on worker health promotion. The search was restricted to papers published in English from 2000 to 2015. Companies were asked for additional documentation about WHPOW programmes in a survey conducted with SurveyMonkey. Results A total of 756 initiatives regarding WHPOW were identified. 134 of these were guidelines, regulations, or review studies. The remaining 622 activities were intervention studies performed or promoted in the workplace and targeted at older workers or at the aging of the workforce. Most of the programs were carried out in Central Europe (295, 47.4%), less in East Europe (193, 31.0%) and in Mediterranean countries (134, 21.6%). Conclusion Our study shows that there are only a limited number of WHPOW actions throughout the 10 selected European Countries. While in Central Europe widespread interest in issues of aging workforce has resulted in national policies to encourage WHPO, not all the countries of Eastern Europe are equally well equipped. Lastly, in Southern Europe health promotion activities are largely inadequate compared to needs.

Four single-arm, prospective, clinical studies of pyronaridine-artesunate efficacy in uncomplicated Plasmodium falciparum or Plasmodium vivax malaria were conducted in Myanmar between 2017 and 2019. Eligible subjects were aged at least 6 years, with microscopically confirmed P. falciparum (n = 196) or P. vivax mono-infection (n = 206). Patients received pyronaridine-artesunate once daily for 3 days with follow-up until day 42 for P. falciparum or day 28 for P. vivax. For the primary efficacy analysis, adequate clinical and parasitological response (ACPR) in the per-protocol population at day 42 for P. falciparum malaria was 100% (88/88; 95% CI: 95.9, 100) in northern Myanmar (Kachin State and northern Shan State), and 100% (101/101; 95% CI: 96.4, 100) in southern Myanmar (Tanintharyi Region and Kayin State). Plasmodium falciparum day-3 parasite clearance was observed for 96.9% (190/196) of patients. Mutations in the P. falciparum Kelch propeller domain (K13) were detected in 39.0% (69/177) of isolates: F446I (14.7% [26/177]), R561H (13.0% [23/177]), C580Y (10.2% [18/177]), and P574L (1.1% [2/177]). For P. vivax, the day-28 ACPR was 100% (104/104; 95% CI: 96.5, 100) in northern Myanmar and 100% (97/97; 95% CI: 96.3, 100) in southern Myanmar. Across both P. vivax studies, 100% (206/206) of patients had day-3 parasite clearance. There were no adverse events. Pyronaridine-artesunate had excellent efficacy in Myanmar against P. falciparum and P. vivax and was well tolerated. This study supports the inclusion of pyronaridine-artesunate in national malaria treatment guidelines for Myanmar.

Meperidine and fentanyl are opioids currently used in addition to midazolam for sedation and analgesia during colonoscopy in Italy. The aim of the study was to assess the impact of patients' psychological state before elective colonoscopy on the efficacy of the sedation regimens. Eighty outpatients who underwent an elective colonoscopy were included in our study. The Hospital Anxiety and Depression Scale questionnaire was self-administered to evaluate basal anxiety and depression state. The rate of baseline discomfort was evaluated by a standard 100-mm visual analog scale. Sedation was obtained alternatively with a midazolam-meperidine or midazolam-fentanyl combination. There were no statistically significant differences between the fentanyl and meperidine groups on body mass index, age, and gender composition. Patients in the meperidine group reported less pain during colonoscopy than patients in the fentanyl group. There were statistically significant positive correlations in the meperidine group with the distress, anxiety, and depression. Our study has pointed out greater effectiveness of the midazolam plus meperidine regimen, equal recovery times, and no significant differences in the duration of the endoscopic examinations. The evaluation of patients' psychological status seems to predict the efficacy of sedation when the nociceptive component of pain is well controlled.

The correct technique for accurate upper gastrointestinal endoscopy has some key points: preparation of the patient, use of anti-peristaltic agents and mapping of the entire stomach. Systematic protocols to explore the entire gastric mucosa have been proposed to reduce the risk of missing lesions, but a worldwide standardized protocol is still lacking. For a correct diagnosis of superficial neoplastic lesions, white light imaging (WLI) together with chromoendoscopy showed a higher accuracy compared to WLI alone. High-definition endoscopy with the combination of narrow band imaging has been used to better characterize early lesions. However, biopsy specimens and histological examination remain essential for assessing the presence of pre-neoplastic lesions or early gastric adenocarcinoma and guaranteeing the correct therapeutic pathway. Moreover, due intra-tumor heterogeneity also in the case of advanced gastric cancer a biopsy protocol should be conceptualized in order to obtain the most accurate tumor representation, crucial in an era of target therapy. A well-performed endoscopy is instrumental for both an accurate diagnosis and appropriate treatment.

Accurate detection of driving fatigue is helpful in significantly reducing the rate of road traffic accidents. Electroencephalogram (EEG) based methods are proven to be efficient to evaluate mental fatigue. Due to its high non-linearity, as well as significant individual differences, how to perform EEG fatigue mental state evaluation across different subjects still keeps challenging. In this study, we propose a Label-based Alignment Multi-Source Domain Adaptation (LA-MSDA) for cross-subject EEG fatigue mental state evaluation. Specifically, LA-MSDA considers the local feature distributions of relevant labels between different domains, which efficiently eliminates the negative impact of significant individual differences by aligning label-based feature distributions. In addition, the strategy of global optimization is introduced to address the classifier confusion decision boundary issues and improve the generalization ability of LA-MSDA. Experimental results show LA-MSDA can achieve remarkable results on EEG-based fatigue mental state evaluation across subjects, which is expected to have wide application prospects in practical brain-computer interaction (BCI), such as online monitoring of driver fatigue, or assisting in the development of on-board safety systems.

International audience; Air Traffic Control (ATC) has been classified as the fourth most stressful job. In this regard, sixteen controllers were asked to perform ecological ATC simulation during which behavioral (Radio Communications with pilots - RCs), subjective (stress perception) and neurophysiological signals (brain activity and skin conductance - SC) were collected. All the considered parameters reported significant changes under high stress conditions. In particular, the theta, alpha, and beta brain rhythms increased significantly (all p

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65–89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid–femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10 −3 ; P =0.009); only the latter remained significant after adjustment for confounders ( P =0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P =0.006; P =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 + cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa −1 ; P =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 + cells, and preserved carotid distensibility. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01725178.

Objective: To investigate the evolution of maternal representations (ie, the way parents perceive their child in term of temperament, character, behaviors, etc) of children with a cleft at 3 major milestones: before/after reconstructive surgeries and at school age. Parenting style was also analyzed and compared with parents of children born without a cleft. Design and participants: The sample was composed of 30 mothers of children with an orofacial cleft and 14 mothers of children without a cleft. Maternal representations were assessed when the child was 2 months (before surgery), 12 months (after surgery), and 5 years of age (when starting school) using semistructured interviews that were transcribed and coded according to the subscales of the Working Model of the Child Interview and the Parental Development Interview. At the 5-year appointment, mothers also completed a questionnaire about parenting style. Results: Results showed no difference across groups (cleft/noncleft) in maternal representations at the 2-month, 12-month, and 5-year assessments. In the cleft group, significant differences were shown between 2 and 12 months in caregiving sensitivity, perceived infant difficulty, fear for the infant’s safety, and parental pride, all factors being higher at 12 months. Those differences in parental representations over time were not found in the noncleft group. Additionally, mothers of the cleft group were significantly more authoritarian than mothers of children without a cleft. Conclusion: The absence of differences across cleft and noncleft groups suggests that having a child with a cleft does not affect maternal representations and emotions between 2 months and 5 years of the child’s age. However, parenting style seems to be influenced by the presence of a cleft in the present sample.

Background In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine–artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. Methods and findings This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine–artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine–artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine–artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. Conclusions Pyronaridine–artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine–artesunate as an operationally useful addition to the management of acute uncomplicated malaria. Trial registration ClinicalTrials.gov NCT03201770., Gaston Tona Lutete and co-workers report on safety and effectiveness of the antimalarial drug pyronaridine-artesunate in African countries., Author summary Why was this study done? Pyronaridine–artesunate has shown high efficacy and an acceptable safety profile in randomized controlled clinical trials for the treatment of acute uncomplicated Plasmodium falciparum malaria. Transient, asymptomatic, mostly mild-to-moderate increases in liver aminotransferases have been observed with pyronaridine–artesunate in some patients. We assessed pyronaridine–artesunate hepatic safety, tolerability, and effectiveness in adults and children for the treatment of acute uncomplicated malaria under real-world conditions in Africa, including patients with elevated baseline liver aminotransferases. What did the researchers do and find? In a single-arm, open-label, cohort event monitoring study conducted across 5 African countries, patients of any age, weighing >5 kg with acute uncomplicated malaria received fixed-dose pyronaridine–artesunate once daily for 3 days. Patient exclusion and inclusion criteria were consistent with the approved prescribing information, and patients with elevated baseline liver enzymes could be treated under the protocol. The study included 8,560 malaria episodes, 158 of which occurred in patients with baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) abnormalities. There were no hepatic events following pyronaridine–artesunate treatment. Tolerability was as reported in previous studies, and treatment effectiveness at day 28 was 98.6% in patients with acute uncomplicated P. falciparum malaria. What do these findings mean? Pyronaridine–artesunate was an operationally effective and well-tolerated antimalarial therapy in this unselected population of patients from 5 African countries.

Occupational radiation exposure may impact the reproductive outcome of male workers in the cardiac catheterization laboratory (cath Lab) who receive a dose of ~1-10 mSv/year. An increased copy number variation (CNV) in azoospermia factor region c (AZFc) of the Y chromosome is a marker of spermatogenic failure, previously associated with radiation exposure. This study sought to investigate the association between paternal exposure in the Cath Lab and adverse reproductive outcomes as well as to assess the induction of CNV in the AZFc region. In a case-control study, we enrolled 193 catheterization lab workers (Group I) and 164 age-matched unexposed controls (Group II). Reproductive outcomes were assessed through a structured questionnaire. Two sequence-tagged sites (SY1197 and SY579) in AZFc region were evaluated by qRT-PCR in 83 exposed and 47 unexposed subjects. Exposed workers had a higher prevalence of low birth weight in offspring (Group I = 13% vs. II = 5.3%, P = 0.02; ORadjusted = 2.7; 95% CI: 1.1-6.3; P = 0.02). The mean of CNV (microdeletion and microduplication) for SY1197 was significantly higher in the exposed workers (Group I = 1.53 ± 0.85 vs. Group II = 1.02 ± 0.41; P = 0.0005). Despite the study design limitations, our findings show that chronic occupational radiation exposure of male workers is correlated with higher prevalence of low birth weight in offspring and instability in the Y chromosome AZFc region. Environ. Mol. Mutagen. 61:361-368, 2020. © 2019 Wiley Periodicals, Inc.

Unilateral hearing loss constitutes a field of growing interest in the scientific community. In fact, this kind of patients represent a unique and physiological way to investigate how neuroplasticity overcame unilateral deafferentation by implementing particular strategies that produce apparently next- to- normal hearing behavioural performances. This explains why such patients have been underinvestigated for a long time. Thanks to the availability of techniques able to study the cerebral activity underlying the mentioned behavioural outcomes, the aim of the present research was to elucidate whether different electroencephalographic (EEG) patterns occurred in unilateral hearing loss (UHL) children in comparison to normal hearing (NH) controls during speech-in-noise listening. Given the intrinsic lateralized nature of such patients, due to the unilateral side of hearing impairment, the experimental question was to assess whether this would reflect a different EEG pattern while performing a word in noise recognition task varying the direction of the noise source. Results showed a correlation between the period of deafness and the cortical activity asymmetry toward the hearing ear side in the frontal, parietal and occipital areas in all the experimental conditions. Concerning alpha and beta activity in the frontal and central areas highlighted that in the NH group, the lateralization was always left-sided during the Quiet condition, while it was right-sided in noise conditions; this evidence was not, however, detected also in the UHL group. In addition, focusing on the theta and alpha activity in the frontal areas (Broca area) during noise conditions, while the activity was always left-lateralized in the NH group, it was ipsilateral to the direction of the background noise in the UHL group, and of a weaker extent than in NH controls. Furthermore, in noise conditions, only the UHL group showed a higher theta activity in the temporal areas ipsilateral to the side where the background noise was directed to. Finally, in the case of bilateral noise (background noise and word signal both coming from the same two sources), the theta and alpha activity in the frontal areas (Broca area) was left-lateralized in the case of the NH group and lateralized towards the side of the better hearing ear in the case of the UHL group. Taken together, this evidence supports the establishment of a particular EEG pattern occurrence in UHL children taking place in the frontal (Broca area), temporal and parietal lobes, probably physiologically established in order to deal with different sound and noise source directions.

Introduction The benefits of thrombectomy for occlusion of M2 segments remain controversial. The aim of this study is to assess thrombectomy’s efficacy and safety in patients with M2 segment occlusion and associations between occlusion sites and anatomic variations of M1 division. Materials and methods A prospective series of 30 patients with acute ischemic stroke (AIS) resulting from M2 segment occlusion of the middle cerebral artery (MCA) who underwent thrombectomy was analyzed. The primary endpoint was assessed by the Extended Treatment in Cerebral Infarction scale (eTICI). The secondary endpoints were the incidence of symptomatic hemorrhagic transformation (sICH), mortality and good functional outcome at three months. Results The mean patient age was 69.2 years. The mean National Institutes Health Stroke Scale score (NIHSS) upon hospital admission was 16. The recanalization rates were eTICI 2b/3 in 90% and 2c/3 in 60% of the patients. Total recanalization of the M2 branch was achieved in 53% of patients. sICH incidence was 6.6%, the mortality rate was 30%, and a good functional outcome (mRS ≤2) was observed in 50% of the patients. Twenty-seven patients (90%) had a dominant M2 branch and all were occluded. Regarding the site of M2 occlusions, 74% of patients had proximal M2 occlusions. Conclusions Thrombectomy appears to be a safe and effective method for the treatment of acute M2 segment occlusions of the MCA. Most of the cases had a dominant M2 branch, and all of them were occluded. Larger studies are needed to verify the benefits of thrombectomy for different settings of M2 occlusions.

Objective: Physical activity (PA) may influence acute stress reactivity in children differently depending on their weight. This randomized controlled trial investigated the impact of acute PA and of BMI status (overweight/obese (OB/OW) and normal weight (NW) on stress reactivity. Method: 50 prepubertal children (24 OW/OB and 26 NW) were randomly assigned to the PA or sedentary arm (SED) for 30 min followed by a stress task. Salivary cortisol, blood pressure (BP), and heart rate (HR) were measured. Results: An interaction effect between the randomization arms and weight status on salivary cortisol was found after the stress task (p = 0.04). Cortisol increased in the SED, but not in the PA arm (p = 0.004 for differences in time course) of NW children. Time course did not differ between both arms in OW/OB children (p = 0.7). OW/OB SED children had a flat cortisol course, and levels were reduced compared to the NW SED or the OW/OB PA children (p ≤ 0.03). Systolic BP increased only in the SED arm (p = 0.01). HR was higher in the PA than in the SED arm during stress (p < 0.001) and showed different time courses (p = 0.006). Conclusion: PA impacted on acute stress reactivity and influenced stress reactivity differently in NW and OW/OB children.

The sample size is a crucial concern in scientific research and even more in behavioural neurosciences, where besides the best practice it is not always possible to reach large experimental samples. In this study we investigated how the outcomes of research change in response to sample size reduction. Three indices computed during a task involving the observations of four videos were considered in the analysis, two related to the brain electroencephalographic (EEG) activity and one to autonomic physiological measures, i.e., heart rate and skin conductance. The modifications of these indices were investigated considering five subgroups of sample size (32, 28, 24, 20, 16), each subgroup consisting of 630 different combinations made by bootstrapping n (n = sample size) out of 36 subjects, with respect to the total population (i.e., 36 subjects). The correlation analysis, the mean squared error (MSE), and the standard deviation (STD) of the indexes were studied at the participant reduction and three factors of influence were considered in the analysis: the type of index, the task, and its duration (time length). The findings showed a significant decrease of the correlation associated to the participant reduction as well as a significant increase of MSE and STD (p &lt, 0.05). A threshold of subjects for which the outcomes remained significant and comparable was pointed out. The effects were to some extents sensitive to all the investigated variables, but the main effect was due to the task length. Therefore, the minimum threshold of subjects for which the outcomes were comparable increased at the reduction of the spot duration.

In several fields, the need for a joint analysis of brain activity and eye activity to investigate the association between brain mechanisms and manifest behavior has been felt. In this work, two levels of attentional demand, elicited through a conjunction search task, have been modelled in terms of eye blinks, brain activity, and brain network features. Moreover, the association between endogenous neural mechanisms underlying attentional demand and eye blinks, without imposing a time-locked structure to the analysis, has been investigated. The analysis revealed statistically significant spatial and spectral modulations of the recorded brain activity according to the different levels of attentional demand, and a significant reduction in the number of eye blinks when a higher amount of attentional investment was required. Besides, the integration of information coming from high-density electroencephalography (EEG), brain source localization, and connectivity estimation allowed us to merge spectral and causal information between brain areas, characterizing a comprehensive model of neurophysiological processes behind attentional demand. The analysis of the association between eye and brain-related parameters revealed a statistically significant high correlation (R > 0.7) of eye blink rate with anterofrontal brain activity at 8 Hz, centroparietal brain activity at 12 Hz, and a significant moderate correlation with the participation of right Intra Parietal Sulcus in alpha band (R = -0.62). Due to these findings, this work suggests the possibility of using eye blinks measured from one sensor placed on the forehead as an unobtrusive measure correlating with neural mechanisms underpinning attentional demand &nbsp

Fatigued driving is one of the main causes of traffic accidents. The electroencephalogram (EEG)-based mental state analysis method is an effective and objective way of detecting fatigue. However, as EEG shows significant differences across subjects, effectively “transfering” the EEG analysis model of the existing subjects to the EEG signals of other subjects is still a challenge. Domain-Adversarial Neural Network (DANN) has excellent performance in transfer learning, especially in the fields of document analysis and image recognition, but has not been applied directly in EEG-based cross-subject fatigue detection. In this paper, we present a DANN-based model, Generative-DANN (GDANN), which combines Generative Adversarial Networks (GAN) to enhance the ability by addressing the issue of different distribution of EEG across subjects. The comparative results show that in the analysis of cross-subject tasks, GDANN has a higher average accuracy of 91.63% in fatigue detection across subjects than those of traditional classification models, which is expected to have much broader application prospects in practical brain–computer interaction (BCI).

Single-nucleotide polymorphisms in miRNA-machinery genes may alter the biogenesis of miRNAs affecting disease susceptibility. In this case–control study, we aimed to evaluate the impact of three single-nucleotide polymorphisms (DICER rs1057035, DROSHA rs10719, and XPO5 rs11077) and their combined effect in a genetic risk score model on congenital heart disease (CHD) risk. A total of 639 participants was recruited, including 125 patients with CHD (65 males; age 9.2 ± 10 years) and 514 healthy controls (289 males; age 15.8 ± 18 years). Genotyping of polymorphisms in miRNA-machinery genes was performed using a TaqMan®SNP genotyping assay. A genetic risk score was calculated by summing the number of risk alleles of selected single-nucleotide polymorphisms. There was a significantly increased risk of CHD in patients with XPO5 rs11077 CC genotype as compared to AC heterozygote and AA homozygote patients (ORadjusted = 1.7; 95% CI: 1.1–2.8; p = 0.018). A clear tendency to significance was also found for DROSHA rs10719 AA genotype and CHD risk for both codominant and recessive models (ORadjusted = 1.8; 95% CI: 0.91–3.8; p = 0.09 and ORadjusted = 1.9; 95% CI: 0.92–4; p = 0.08, respectively). The resulting genetic risk score predicted a 1.73 risk for CHD per risk allele (95% CI: 1.2–2.5; p = 0.002). Subjects in the top tertile of genetic risk score were estimated to have more than three-fold increased risk of CHD compared with those in the bottom tertile (ORadjusted = 3.52; 95% CI: 1.4–9; p = 0.009). Our findings show that the genetic variants in miRNA-machinery genes might participate in the development of CHD.

Scents have the ability to affect peoples’ mental states and task performance with to different extents. It has been widely demonstrated that the lemon scent, included in most all-purpose cleaners, elicits stimulation and activation, while the lavender scent elicits relaxation and sedative effects. The present study aimed at investigating and fostering a novel approach to evaluate users’ experience with respect to scents’ effects through the joint employment of Virtual Reality and users’ neurophysiological monitoring, in particular Electroencephalography. In particular, this study, involving 42 participants, aimed to compare the effects of lemon and lavender scents on the deployment of cognitive resources during a daily life experience consisting in a train journey carried out in virtual reality. Our findings showed a significant higher request of cognitive resources during the processing of an informative message for subjects exposed to the lavender scent with respect to the lemon exposure. No differences were found between lemon and lavender conditions on the self-reported items of pleasantness and involvement, as this study demonstrated, the employment of the lavender scent preserves the quality of the customer experience to the same extent as the more widely used lemon scent.

International audience; Objective: The aim of this study was to investigate attachment behavior in a population of infants with infantile spasms (ISs) using the Strange Situation Procedure (SSP) and to explore factors associated with the infants' attachment behavior.Methods: The SSP was assessed in a population of 29 children with ISs during the second year of life. In mothers, we assessed anxiety, depression, maternal emotions, and perception of the temperament of the child, and sociodemographic characteristics. In children, we assessed epilepsy characteristics, response to antiepileptic drugs (AEDs) at the time of the SSP, and the child's outcome at 3 years of age, in terms of intellectual disability (ID), and autism spectrum disorder (ASD).Results: Insecure attachment was higher than in the general population (68% versus 32%). It was associated with maternal anxiety, sadness, and maternal representation of the child at 12 months but with none of the child characteristics including ID, ASD, response to AEDs, or ISs etiology.Significance: Nonspecific dimensions were more important than disease characteristics for the infants' attachment behavior. In conclusion, we propose that interventions targeting mother-child interaction could prevent attachment insecurity and the developmental consequences of early epilepsy.

Electroencephalogram (EEG) is an effective indicator for the detection of driver fatigue. Due to the significant differences in EEG signals across subjects, and difficulty in collecting sufficient EEG samples for analysis during driving, detecting fatigue across subjects through using EEG signals remains a challenge. EasyTL is a kind of transfer-learning model, which has demonstrated better performance in the field of image recognition, but not yet been applied in cross-subject EEG-based applications. In this paper, we propose an improved EasyTL-based classifier, the InstanceEasyTL, to perform EEG-based analysis for cross-subject fatigue mental-state detection. Experimental results show that InstanceEasyTL not only requires less EEG data, but also obtains better performance in accuracy and robustness than EasyTL, as well as existing machine-learning models such as Support Vector Machine (SVM), Transfer Component Analysis (TCA), Geodesic Flow Kernel (GFK), and Domain-adversarial Neural Networks (DANN), etc.

AimsTo identify whether staff from the PATH Early Intervention in Psychosis (EIP) Service routinely ask female service users of child bearing age about their plans for pregnancy, whether risks of medication in pregnancy are routinely discussed and whether contraception is routinely discussed.MethodIn May 2019, a report was run capturing all female PATH service users of child bearing age (16-50 years) who were on the pathway at this time. This totalled 177 service users, all of whom were included in the sample. We used the search terms “pregnant”, “pregnancy”, “having children”, “contraception”, “conceive”, “baby”, “conception”, “miscarriage”, “abortion”, “IVF”, “still born” to interrogate the patient records . Auditors searched case notes, clinic letters, recent physical health assessment and recent wellbeing plan for evidence as to whether staff had asked about pregnancy plans, contraception, offered a referral to the Community Perinatal Team, and discussed risks about medication in pregnancy.ResultOf the 177 service users, 34 were asked whether they had plans for pregnancy (19%). Of the 177 service users, 28 were given advice regarding contraception (16%). Of the 34 service users who were asked about pregnancy plans, 27 did have plans for pregnancy. Of these 27 service users, 15 were offered a referral to the Community Perinatal Team (56%). Of the 27 service users who did have plans for pregnancy, 12 received advice and or information about risks of antipsychotic medication in pregnancy (44%).ConclusionIt is clear that PATH staff are not routinely having discussions with female service users of child bearing age about their plans for pregnancy or contraception; this audit has identified that this occurs in less than 20% of cases. Of service users that did have plans for pregnancy, only 56% were offered a referral to the Community Perinatal Team; we should strive for this to be 100% so service users can access specialist support and advice. Work is underway to include information on pregnancy in the PATH service information leaflet to ensure women referred to PATH expect staff to ask them about their plans for pregnancy and contraception. Questions about pregnancy planning and contraception are to be embedded in the Trust's Physical Health Assessment care document to act as a prompt for staff. Finally, the topics of pregnancy and contraception in women with psychosis have been incorporated into the PATH physical health training programme which will be delivered with support from the Community Perinatal Team.

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype. Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.

IntroductionPreterm birth may generate significant distress among the parents, who often present with difficulties in appropriating their parental role. Parental stress and low perceived parental self-efficacy may interfere with the infant’s socioemotional and cognitive development, particularly through disrupted parent–infant interactions. Perceived parental self-efficacy represents the belief of efficacy in caring for one’s own infant and successful incarnation of the parental role, as well as the perception of one’s own abilities to complete a specified task. Interventions to support parental role, as well as infant development, are needed, and parental self-efficacy represents a useful indicator to measure the effects of such early interventions.Methods and analysisThis study protocol describes a randomised controlled trial that will test an early intervention in the neonatal intensive care unit (NICU) (JOIN: Joint Observation In Neonatology) carried out by an interdisciplinary staff team. Mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age are eligible for the study. The intervention consists of a videotaped observation by a clinical child psychologist or child psychiatrist and a study nurse of a period of care delivered to the neonate by the mother and a NICU nurse. The care procedure is followed by an interactive video guidance intended to demonstrate the neonate’s abilities and resources to his parents. The primary outcome will be the difference in the perceived maternal self-efficacy between the intervention and control groups assessed by self-report questionnaires. Secondary outcomes will be maternal mental health, the perception of the parent– infant relationship, maternal responsiveness and the neurodevelopment of the infant at 6 months corrected age.Ethics and disseminationEthical approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 496/12). Results from this study will be disseminated at national and international conferences, and in peer-reviewed journals.Trial registration numberNCT02736136, Pre-results.

Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline. Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.

Background Assessment of the impact of the thrombectomy learning curve on clinical outcomes is essential for developing healthcare system protocols. Aims The aim of this study was to assess the effect of thrombectomy case volume on procedural and clinical outcomes in a Brazilian registry. Methods A total of 645 patients with acute ischemic stroke treated by thrombectomy were included in the analysis. Patients were divided into two groups regarding the period of treatment: the early period group and the late period group. Results In the adjusted analysis, treatment in the late period was an independent predictor of recanalization (odds ratio 1.91, 95% CI 1.28–2.86) and excellent neurologic outcomes at three months (odds ratio 1.77, 95% CI 1.04–3.01). Treatment in the late period had no significant association with mortality (odds ratio 0.88, 95% CI 0.55–1.41). Conclusions An increase in thrombectomy case volume for the treatment of AIS over time was an independent predictor of recanalization and excellent neurologic outcome.

Background Acute basilar artery occlusion is a devastating life-threatening condition. Early recanalization is the therapeutic goal in patients with acute ischemic stroke. Despite the high rates of recanalization achieved with modern devices for basilar occlusions, many patients have had poor clinical outcomes. This study aimed to assess the predictors of good and poor outcomes among patients with basilar artery occlusion treated with thrombectomy. Methods A consecutive registry of 80 patients was included in this retrospective study. The primary end point was to access variables associated with neurologic outcomes defined by a modified Rankin Scale (mRS) score of 0–2, symptomatic intracranial hemorrhage (sICH), and mortality at 3 months follow-up. Results Recanalization was achieved in 86.2%, and the sICH rate was 8.7%. A good neurologic outcome (mRS score 0–2) was observed in 26.2% and a moderate outcome (mRS score 0–3) in 32.5% of patients. The mortality was 38.7% at 3 months follow-up. Conclusions After thrombectomy for posterior circulation strokes, young patients, V4–proximal basilar occlusion, (high) baseline posterior circulation Alberta Stroke Program Early CT Score, and complete recanalization were independent predictors of good neurologic outcomes. Failure to recanalize was strongly related to sICH and mortality. In addition, diabetes, atrial fibrillation, and baseline National Institutes of Health Stroke Scale scores ≥10 had an independent association with mortality. This study contributes to the knowledge required to optimize recanalization treatments for posterior circulation strokes and may help to improve future clinical studies.

Background Mental illnesses comprise a wide range of mental health (MH) conditions -prevalence 3,90%- among European (EU) countries with significant effects on quality of life, life expectancy and disability. They are also related to substantial direct and indirect costs, consequences of inpatient care - not always beneficial for those patients. The main goals of our study are: to report on geographic variations in utilization rates and quality of care for adults MH diseases among 30 EU countries and regions; to explain the determinants of such variations. Methods Different data from EUROSTAT regarding healthcare resources, activities and self-perceived health and wellbeing for the years 2013-2015 are combined in a unique database at level of EU countries and NUTS 2 regions to allow for comparisons in utilization rates, perceived conditions and service local supply for MH diseases in Europe. Results Preliminary findings show a decline in the global trend of hospitalization rates for mental diseases; however, significant variations were observed among and within countries (High-Low ratio=25 in 2015, at country level). Males were more hospitalized than females (p = 0.40). Women were more likely than men to report depressive symptoms and to access to MH consultations (p Conclusions Preliminary findings confirm the presence of wide variations in the care of mental diseases across and within EU countries. Significant correlations between utilization rates and local supply of resources might indicate that part of the variation might be explained by differences in the local organization and availability of resources rather than patients' needs. Key messages There is a wide variation in the care of mental diseases across and within EU countries which might be explained by differences in the local organization and resources instead patients’ needs. These results can help policy makers and professionals to identify unwarranted variations that need to be removed and to shift to value-based healthcare.