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.
Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging ...effects of the regimen in patients with operable PDA.
Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine.
A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine.
These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.
The performance of deposit feeders in integrated multi-trophic aquaculture (IMTA) was analysed through the application of mathematical models. Loading of organic particulates to the benthos as a ...result of finfish cage culture and shellfish suspended culture was analysed by means of a deposition model (ORGANIX), and an individual model for growth and environmental effects was developed for the California sea cucumber Parastichopus californicus. Following validation, the model was combined with existing models for finfish, shellfish, and macroalgae into a framework for simulation of IMTA interactions at the local scale. Several scenarios for different culture combinations and densities were simulated using the Farm Aquaculture Resource Management (FARM) model, using a layout which reflects typical stocking densities and spatial occupation in Europe and North America. The model allows an analysis of the different sources and fate of particulate organic matter associated with distinct culture groups. Our results illustrate the production enhancement for deposit feeders cultivated below both finfish (600%) and shellfish (150%). Furthermore, sea cucumbers are responsible for a significant removal of the particulate organic carbon loading to the bottom, reducing the gross load by up to 86% for finfish culture and 99% for shellfish culture. The role of cultivated seaweeds in reducing the dissolved nitrogen concentration in the farm area was also examined—no significant reduction in ambient nutrient concentration was observed, but the added nitrogen provides a clear stimulus (22% increase) to kelp production. By contrast, shellfish grown in suspended culture in the vicinity of finfish cages show very little change in individual growth or harvestable biomass. This work helps to analyse the ecological and economic potential of various forms of IMTA, and the role of co-cultivation in direct extraction and re-use of materials and energy at both the local (farm) and system (bay, estuary) scales.
Analysis of the ecological and economic potential of various forms of IMTA, and the relevance of co-cultivation in direct extraction and re-use of materials and energy at both the local (farm) and system (bay, estuary) scales. FARM model framework applied to understand the roles of suspended bivalve culture and benthic deposit-feeder culture in mitigating the negative externalities of finfish culture.
•Analyse ecological and economic potential of IMTA, and the role of co-culture in extraction and re-use of nutrients.•Develop models for organic loading from cage culture, and deposit-feeder (sea cucumber) growth and environmental effects.•Combine individual and population models to analyse the role of co-cultured species in mitigating finfish culture impacts.•Deposit-feeders below finfish and shellfish structures increase production and remove particulate organic loading to the bottom.•Suspended shellfish culture close to finfish cages show very little change in individual growth or harvestable biomass.
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.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The study's aim was to apply Gaussian process ...classification (GPC) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD).
Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. In addition, voxel-based morphometry (VBM) analysis tested for traditional univariate group level differences in GM.
The pattern of GM correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. The discriminating GM patterns showed higher classification weights for ADHD in earlier developing ventrolateral/premotor fronto-temporo-limbic and stronger classification weights for healthy controls in later developing dorsolateral fronto-striato-parieto-cerebellar networks. Several regions were also decreased in GM in ADHD relative to healthy controls in the univariate VBM analysis, suggesting they are GM deficit areas.
The study provides evidence that pattern recognition analysis can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed GM patterns with 79.3% accuracy and that this is disorder-specific relative to ASD. Findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD.
Fish growth is strongly influenced by environmental and nutritional factors and changing culture conditions can help optimize it. The importance of early-life experience on the muscle phenotype later ...in life is well known. Here, we study the effects of 5 weeks of moderate and sustained swimming activity (5 BL s
−1
) in gilthead sea bream during early development. We analysed growth and body indexes, plasma IGF-I and GH levels, feed conversion, composition proximate and isotopic (
15
N/
13
C) and metabolic key enzymes (COX, CS, LDH, HOAD, HK, ALAT, ASAT) of white muscle. Moderate and continuous exercise in fingerlings of gilthead sea bream increased plasma IGF-I, whereas it reduced plasma GH. Under these conditions, growth rate improved without any modification to feed intake through an increase in muscle mass and a reduction in mesenteric fat deposits. There were no changes in the content and turnover of muscle proteins and lipid reserves. Glycogen stores were maintained, but glycogen turnover was higher in white muscle of exercised fish. A lower LDH/CS ratio demonstrated an improvement in the aerobic capacity of white muscle, while a reduction in the COX/CS ratio possibly indicated a functional adaptation of mitochondria to adjust to the tissue-specific energy demand and metabolic fuel availability in exercised fish. We discuss the synergistic effects of dietary nutrients and sustained exercise on the different mitochondrial responses.
The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the ...neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM).
A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys.
Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects.
The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two common childhood disorders that exhibit genetic and behavioural overlap and have abnormalities in similar ...brain systems, in particular in frontal and cerebellar regions. This study compared the two neurodevelopmental disorders to investigate shared and disorder-specific structural brain abnormalities.
Forty-four predominantly medication-naïve male adolescents with ADHD, 19 medication-naïve male adolescents with ASD and 33 age-matched healthy male controls were scanned using high-resolution T1-weighted volumetric imaging in a 3-T magnetic resonance imaging (MRI) scanner. Voxel-based morphometry (VBM) was used to test for group-level differences in structural grey matter (GM) and white matter (WM) volumes.
There was a significant group difference in the GM of the right posterior cerebellum and left middle/superior temporal gyrus (MTG/STG). Post-hoc analyses revealed that this was due to ADHD boys having a significantly smaller right posterior cerebellar GM volume compared to healthy controls and ASD boys, who did not differ from each other. ASD boys had a larger left MTG/STG GM volume relative to healthy controls and at a more lenient threshold relative to ADHD boys.
The study shows for the first time that the GM reduction in the cerebellum in ADHD is disorder specific relative to ASD whereas GM enlargement in the MTG/STG in ASD may be disorder specific relative to ADHD. This study is a first step towards elucidating disorder-specific structural biomarkers for these two related childhood disorders.
Cancer during pregnancy is a challenge for multi- and interdisciplinary collaboration due to the diagnostic, prognostic and therapeutic implications, the need for an integrated harmonization of ...medical action for the pregnant patient and the embryo or foetus and the characteristics of each gestational period, which will determine the protocol to be proposed and its limitations. For this reason, a group of experts appointed by participating scientific societies, which includes the Spanish Society of Medical Oncology (
Sociedad Española de Oncología Médica
—SEOM), the Spanish Association of Surgeons (
Asociación Española de Cirujanos
—AEC), the Spanish Society of Gynaecology and Obstetrics (
Sociedad Española de Ginecología y Obstetricia
—SEGO), the Spanish Society of Nuclear Medicine and Molecular Imaging (
Sociedad Española de Medicina Nuclear e Imagen Molecular
—SEMNIM), the Spanish Society of Oncological Radiotherapy (
Sociedad Española de Oncología Radioterápica
—SEOR) and the Spanish Society of Medical Radiology (
Sociedad Española de Radiología Médica
—SERAM), have worked together to establish consensus recommendations that allow the harmonization of management and ultimately the optimization of the healthcare of pregnant patients with cancer. When cancer is detected in a pregnant woman, the week of gestation in which the diagnosis is made must be considered, as well as the characteristics of the tumour. It is strongly recommended that a multidisciplinary team assesses the situation and guides the patient and her family during the informing, diagnosis and treatment process. Likewise, the foetus should be monitored and managed by specialized obstetricians who are part of a multidisciplinary cancer committee.
Exercise training in fish leads to enhanced growth, mostly in salmonids, but also in gilthead sea bream (Sparus aurata). Most of the published studies have involved juveniles or adult fish, but ...little is known about the effects of exercise on early stages of fish growth. Our study aimed to examine the effect of sustained swimming on the growth of gilthead sea bream fingerlings, by analysing white muscle cellularity and capillarisation. Two groups of fingerlings were compared: the exercise group (EX), forced to swim at five body lengths·s−1, and the control group (CT), maintained under still water flow and showing only voluntary swimming. After 5 weeks the EX group had a significantly higher body weight (CT: 17.5 ± 0.46; EX: 20.3 ± 0.38 g, p < .001) without significant differences in muscle-somatic index (CT: 34.9%; EX: 37.3%). The white muscle of EX fish showed significant reductions in fibre cross-sectional area (FCSA) and fibre perimeter (FPER), by 21% (p < .05) and 10% (p < .0.5) respectively, with no differences in fibre circularity. The number of small fibres (with FCSA <2000 μm2) was significantly (p < .05) higher in the EX than in the CT group. Therefore, the distribution of FCSA demonstrated an increase in hyperplasic processes in EX fish. Total muscle capillary density (CD) and the capillarisation of individual fibres (expressed as the number of capillaries per unit FCSA) of the EX group also increased significantly (p < .05 and p < .001, respectively). In summary, sustained aerobic exercise in the early stages of life of gilthead sea bream enhances body growth, increasing total muscle mass by hyperplasia and determining a more aerobic muscle phenotype by increasing individual fibre capillarisation.
•Gilthead seabream fingerlings enhance growth and total muscle mass under moderate and sustained exercise.•In exercised muscle, a greater number of small fibres base early growth on hyperplasia processes.•Sustained swimming increases white muscle fibre capillarization
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