Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers.

Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7-14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients’ outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure

Cardiac Resynchronization Therapy in Patients with Mild Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

# The Author(s) 2011. This article is published with open access at Springerlink.com Objective This review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage. Methods Randomized controlled trials of CRT in patients with New York Heart Association (NYHA) Class I or II heart failure were identified. The effects of CRT on worsening heart failure hospitalization, all-cause mortality, and overall adverse events were meta-analyzed, and the effects of CRT on left ventricular (LV) were systematically reviewed and meta-analyzed. Results Eight studies were identified with a total of 4,302 patients. CRT was associated with a substantial improvement in LVend-systolic volume (WMD −39, 95%CI −41.56 to −36.45). CRT also had a marked effect in reducing new hospitalizations for worsening heart failure by 31 % (RR 0.69, 95%CI 0.60 to 0.79). In addition, CRTsignificantly decreased all-cause mortality by 21 % (RR 0.79, 95%CI 0.67 to 0.93). However, complications in patients with CRT increased by 74 % (RR 1.74, 95%CI 1.44 to 2.11). Conclusions This meta-analysis suggests that CRT could improve the prognosis in patients with mild heart failure and ventricular dyssynchrony, but these improvements are accompanied by more adverse events. Since most patients in the included trials had received ICD therapy, our analysis suggests that CRT could offer an additional benefit. Key words Heart failure. Cardiac resynchronization therapy. Meta-analysi

Rethink reporting of evaluation results in AI

[EN] Artificial intelligence (AI) systems have begun to be deployed in high-stakes contexts, including autonomous driving and medical diagnosis. In contexts such as these, the consequences of system failures can be devastating. It is therefore vital that researchers and policymakers have a full understanding of the capabilities and weaknesses of AI systems so that they can make informed decisions about where these systems are safe to use and how they might be improved.We are grateful to J. Pineau and S. Russell for their feedback on the manuscript and to M. Brundage and L. Ahmad for helpful discussions about the need for instance-by-instance results for foundation models. Funding support was provided by the Future of Life Institute under grant RFP2-152 (J.H.O. and J.B.); US Defense Advanced Research Projects Agency HR00112120007 (RECoG-AI) (J.H.O., L.C., R.B., J.B., and D.K.); grant PID2021-122830OB-C42 (SFERA) funded by MCIN/AEI/10.13039/501100011033 and ERDF A way of making Europe (J.H.O., F.M.P., and W.S.); INNEST/2021/317 [Project cofunded by the European Union with the Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER) de la Comunitat Valenciana 2014-2020 ] (J.H.O. and W.S.); and UPV (Vicerrectorado de Investigación) grant PAI-10-21 (J.H.O. and W.S.).Burnell, R.; Schellaert, WWM.; Burden, J.; Ullman, TD.; Martínez-Plumed, F.; Tenenbaum, JB.; Rutar, D.... (2023). Rethink reporting of evaluation results in AI. Science. 380(6641):136-138. https://doi.org/10.1126/science.adf6369136138380664

PET and SPECT imaging in ADHD

ADHD is a clinically heterogeneous neuropsychiatric disorder with a childhood onset and is often accompanied by comorbidities. Symptoms consisting of inattention with or without hyperactivity or impulsivity may result from disturbances of higher cognitive control, involving multiple regions of the brain which are functionally connected. Although the value of PET and SPECT in establishing diagnosis is limited, it has added to understanding the neurobiological basis of ADHD. Investigations of cerebral perfusion and glucose metabolism during resting conditions and specific tasks have led ADHD to be associated with reduced functionality of the prefrontal cortex and the anterior cingulate cortex, as well as the basal ganglia, cerebellum and parietal lobe. In addition, there is a growing body of literature assessing the dopamine transporter, endogenous levels of dopamine, response to treatment with methylphenidate and the relationship with genotypes in ADHD with few studies having assessed serotonergic and noradrenergic functioning.</p

Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients with diabetes mellitus and in patients with renal failure. Through the formation of collagen crosslinks, and by interaction with the AGE-receptor, which impairs calcium handling and increases fibrosis, AGE-accumulation has pathophysiologically been associated with the development of diastolic and renal dysfunction. Interestingly, diastolic dysfunction is a frequent finding in elderly patients, diabetic patients and in patients with renal failure. Taken together, this suggests that AGEs are related to the development and progression of diastolic HF and renal failure. In this review, the role of AGEs as a possible pathophysiological factor that link the development and progression of heart and renal failure, is discussed. Finally, the role of AGE intervention as a possible treatment in HF patients will be discussed

Sleep and immune function

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations

Loss of Caveolin-1 Accelerates Neurodegeneration and Aging

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease