Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD

Occupational exposure to nano-TiO2 in the life cycle steps of new depollutant mortars used in construction

The present work is focused on the measurement of workers exposure to nano-TiO2 in the life cycle steps of depollutant mortars. It has been done in the framework of the SCAFFOLD project, which aims at the management of potential risks arising from the use of manufactured nanomaterials in construction. Main findings can be summarized as follows: (1) The occupational exposure to nano- TiO2 is below 0.3 mg/m3 for all measured scenarios. The highest concentrations were measured during the cleaning task (in the nano- TiO2 manufacturing process) and during the application (spraying) of depollutant coatings on a wall. (2) It was found a high release of particles above the background in several tasks as expected due to the nature of the activities performed. The maximum concentration was measured during drilling and during adding powder materials (mean total particle concentration up to 5.591E+04 particles/cm3 and 5.69E+04 particles/cm3). However, considering data on total particle concentration released, no striking differences have been observed when tasks have been performed using conventional materials in the sector (control) and when using materials doped with nano-objects.European Commission's FP

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS

First isolation report of Arcobacter cryaerophilus from a human diarrhea sample in Costa Rica

ABSTRACT Arcobacter cryaerophilus is an emerging enteropathogen and potential zoonotic agent transmitted by food and water. In Costa Rica, this bacterium has not been associated with cases of human gastroenteritis, even though it has been isolated from farm animals, especially poultry. This paper reports the first isolation of A. cryaerophilus from a human case of bloody watery diarrhea and the virulence genes associated with this isolate

Breaking bad habits by improving executive function in individuals with obesity

Background: Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Method: Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Results: Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. Conclusion: These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibil ity, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. Trial registration: The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752)

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.This work was supported by the Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).Peer reviewe

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

Background Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30). Results Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance. Conclusions The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship

Brain Structural Networks Associated with Intelligence and Visuomotor Ability

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions

MET and AKT Genetic Influence on Facial Emotion Perception

Background: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/ AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. Methods: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women) were recruited. Four single nucleotide polymorphisms (SNP) of MET (rs2237717, rs41735, rs42336, and rs1858830) and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Thorough neurocognitive functions were also assessed. Results: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration), and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5%) performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM). In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM), even when neurocognitive functions were controlled (p = 0.046 by GLM)