Neuroimaging and biomarker evidence of neurodegeneration in asthma

Background: Epidemiological studies have shown that Alzheimer’s disease and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. // Objective: To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (p-Tau181), neurodegeneration (NfL) and glial activation (GFAP). // Methods: dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration and glial activation, indexed by plasma p-Tau181, NfL and GFAP respectively. Additional relationships were tested with cognitive function. // Results: Asthma participants had widespread and large magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and robustly associated with GFAP and to a lesser extent, with NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn, were associated with slower processing speed, a test of cognitive performance. // Conclusion: These data suggest that asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration and may be a potential risk factor for neural injury and cognitive dysfunction. The results suggest a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects

Persistent peri-Heptacene: Synthesis and In Situ Characterization

n-peri-Acenes (n-PAs) have gained interest as model systems of zigzag-edged graphene nanoribbons for potential applications in nanoelectronics and spintronics. However, the synthesis of n-PAs larger than peri-tetracene remains challenging because of their intrinsic open-shell character and high reactivity. Presented here is the synthesis of a hitherto unknown n-PA, that is, peri-heptacene (7-PA), in which the reactive zigzag edges are kinetically protected with eight 4-tBu-C6H4 groups. The formation of 7-PA is validated by high-resolution mass spectrometry and in situ FT-Raman spectroscopy. 7-PA displays a narrow optical energy gap of 1.01 eV and exhibits persistent stability (t1/2≈25 min) under inert conditions. Moreover, electron-spin resonance measurements and theoretical studies reveal that 7-PA exhibits an open-shell feature and a significant tetraradical character. This strategy could be considered a modular approach for the construction of next-generation (3 N+1)-PAs (where N≥3). © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH Gmb

Spleen Vagal Denervation Inhibits the Production of Antibodies to Circulating Antigens

BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA) does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS), activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production

The impact of delayed development on the quality of life of adults with end-stage renal disease since childhood

Little is known about the impact of the course of life of children with end-stage renal disease (ESRD) on their quality of life in adulthood. We therefore assessed the course of life of adult patients with onset of ESRD at an age of <15 years between 1972 and 1992 and compared it with that of the general population. Furthermore, we explored how course of life is associated with quality of life (QoL) in young adulthood. A total of 75 young adult patients who had had ESRD since childhood, aged between 20 years and 30 years, completed the RAND-36 Health Survey and a questionnaire, which retrospectively assesses the achievement of development milestones. Patients achieved fewer milestones than peers with respect to autonomy, social, and psycho-sexual development, and displayed less risk behaviour. Patients who achieved fewer social milestones while growing up experienced more emotional problems and less vitality, and they had a lesser overall mental quality of life. Paediatric nephrologists should pay more attention to the development of social and independent functioning of children with ESRD in order to prepare them for active participation in society in adult life. © IPNA 2006

Relatively higher norms of blood flow velocity of major intracranial arteries in North-West Iran

<p>Abstract</p> <p>Background</p> <p>Transcranial Doppler (TCD) is a noninvasive, less expensive and harmless hemodynamic study of main intracranial arteries. The aim of this study was to assess normal population values of cerebral blood flow velocity and its variation over age and gender in a given population.</p> <p>Findings</p> <p>Eighty healthy volunteers including 40 people with an age range of 25-40 years (group1) and 40 persons with an age range of 41-55 years (group2) were studied. In each group 20 males and 20 females were enrolled. Peak systolic, end diastolic and mean velocities of nine main intracranial arteries were determined using TCD. Mean age of the studied volunteers was 31.6 ± 4.50 years in group one and 47.2 ± 4.3 years in group two. Mean age among males was 40 years and among females it was 39. Mean blood flow velocity in middle, anterior and posterior cerebral arteries, vertebral and basilar arteries was 60 ± 8, 52 ± 9, 42 ± 6, 39 ± 8 and 48 ± 8 cm/sec respectively. Cerebral blood flow velocities among females were relatively higher than males. Cerebral blood flow velocity of left side was relatively higher than right side.</p> <p>Conclusion</p> <p>Compared to previous studies, cerebral blood flow velocity in this population was relatively higher.</p

Uptake and depuration of gold nanoparticles in Daphnia magna

This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics and animal body burdens. 10 and 30 nm Au NP with different stabilizing agents [citrate (CIT) and mercaptoundecanoic acid (MUDA)] were tested in concentrations around 0.5 mg Au/L. Fast initial uptake was observed for all studied Au NP, with CIT stabilized Au NP showing similar rates independent of size and MUDA showing increased uptake for the smaller Au NP (MUDA 10 nm > CIT 10 nm, 30 nm > MUDA 30 nm). However, upon transfer to clean media no clear trend on depuration rates was found in terms of stabilizing agent or size. Independent of stabilizing agent, 10 nm Au NP resulted in higher residual whole-animal body burdens after 24 h depuration than 30 nm Au NP with residual body burdens about one order of magnitude higher of animals exposed to 10 nm Au NP. The presence of food (P. subcapitata) did not significantly affect the body burden after 24 h of exposure, but depuration was increased. While food addition is not necessary to ensure D. magna survival in the presented short-term test design, the influence of food on uptake and depuration kinetics is essential to consider in long term studies of ENP where food addition is necessary. This study demonstrates the feasibility of a short-term test design to assess the uptake and depuration of ENP in D. magna. The findings underlines that the assumptions behind the traditional way of quantifying bioconcentration are not fulfilled when ENPs are studied.Peer reviewed: YesNRC publication: Ye

Excitability of the Motor Cortex Ipsilateral to the Moving Body Side Depends on Spatio-Temporal Task Complexity and Hemispheric Specialization

Unilateral movements are mainly controlled by the contralateral hemisphere, even though the primary motor cortex ipsilateral (M1ipsi) to the moving body side can undergo task-related changes of activity as well. Here we used transcranial magnetic stimulation (TMS) to investigate whether representations of the wrist flexor (FCR) and extensor (ECR) in M1ipsi would be modulated when unilateral rhythmical wrist movements were executed in isolation or in the context of a simple or difficult hand-foot coordination pattern, and whether this modulation would differ for the left versus right hemisphere. We found that M1ipsi facilitation of the resting ECR and FCR mirrored the activation of the moving wrist such that facilitation was higher when the homologous muscle was activated during the cyclical movement. We showed that this ipsilateral facilitation increased significantly when the wrist movements were performed in the context of demanding hand-foot coordination tasks whereas foot movements alone influenced the hand representation of M1ipsi only slightly. Our data revealed a clear hemispheric asymmetry such that MEP responses were significantly larger when elicited in the left M1ipsi than in the right. In experiment 2, we tested whether the modulations of M1ipsi facilitation, caused by performing different coordination tasks with the left versus right body sides, could be explained by changes in short intracortical inhibition (SICI). We found that SICI was increasingly reduced for a complex coordination pattern as compared to rest, but only in the right M1ipsi. We argue that our results might reflect the stronger involvement of the left versus right hemisphere in performing demanding motor tasks

Long-Term Memory for Pavlovian Fear Conditioning Requires Dopamine in the Nucleus Accumbens and Basolateral Amygdala

The neurotransmitter dopamine (DA) is essential for learning in a Pavlovian fear conditioning paradigm known as fear-potentiated startle (FPS). Mice lacking the ability to synthesize DA fail to learn the association between the conditioned stimulus and the fear-inducing footshock. Previously, we demonstrated that restoration of DA synthesis to neurons of the ventral tegmental area (VTA) was sufficient to restore FPS. Here, we used a target-selective viral restoration approach to determine which mesocorticolimbic brain regions receiving DA signaling from the VTA require DA for FPS. We demonstrate that restoration of DA synthesis to both the basolateral amygdala (BLA) and nucleus accumbens (NAc) is required for long-term memory of FPS. These data provide crucial insight into the dopamine-dependent circuitry involved in the formation of fear-related memory