Magnetic nanoparticles coated with materials having unique properties, such as ordered pore structures and large surface areas, hold great potential for multimodal therapies. This study reports on ...the biocompatibility of composites of maghemite nanoparticles embedded in an ordered mesoporous silica-matrix to form magnetic microspheres (MMS), and on their ability to conduct magnetic hyperthermia upon exposure to a low-frequency alternating magnetic field (AMF). MMS particles were efficiently internalized by human A549, Saos-2 and HepG2 cells, and were excluded from the nuclear compartment. MMS treatment did not interfere with morphological features or metabolic activities of the cells, indicating good biocompatibility of the material. MMS did not affect the endogenous heat-shock response of a HeLa-derived cell line that precisely reports the intensity of thermal stresses through changes in the activities of a stably integrated hsp70B promoter and a constitutive viral promoter. Maximum temperature in MMS suspensions increased to a range above 42
°C as a function of the amounts of particles exposed to AMF. Cell culture experiments showed that, by adjusting the amount of MMS and the time of exposure to AMF, heat treatments of mild to very high intensities could be achieved. Cell viability dropped as a function of the intensity of the heat treatment achieved by MMS and AMF exposures. The possibility of fine-tuning the heating power output, together with efficient uptake by tumor cells in vitro, makes MMS a promising agent by which to provide hyperthermia treatments aimed toward remission of solid tumors.
•Three months of aerobic exercise training (AET) improves fitness in PD patients.•Effects of AET on cognitive and motor skills in PD were evaluated concurrently.•Some executive functions and ...procedural learning capacity improved after AET.•AET can be used as a non-pharmacological intervention to improve functioning in PD.
Background: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson’s disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. Objective: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. Methods: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12weeks). Exercise prescription started at 20min (+5min/week up to 40min) based on participant’s maximal aerobic power. Before and after AET, EF tests assessed participants’ inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. Results: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. Conclusion: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.
Thermal plasma gasification is considered as an attractive technology to produce high quality syngas from municipal solid waste (MSW). It is imperative to study the effect of operating parameters on ...syngas quality and find a practical way to predict syngas characteristics. This paper compiled 112 research cases to develop quantitative models for 8 kinds of syngas characteristics and explored the simultaneous effects of input parameters during the plasma gasification by applying stepwise linear regression (SLR) and artificial neural network (ANN) methods. The SLR model has a higher predictive accuracy than the ANN model for gas yield, volume fraction of CH4 and CO2, as well as mechanical gasification efficiency (MGE), with Rtesting2 = 0.659–0.916. The ANN model demonstrates better performance than the SLR model for low heating value (LHV), dry gas ratio, volume fraction of H2 and CO, with Rtesting2 = 0.807–0.939. According to the importance analysis, flow rates of the work gas-N2, feedstock type, flow rates of the work gas-steam, and input power are the most critical parameters for LHV, gas yield, and volume fraction of CH4 and H2, respectively. Input power and specific energy requirements (SER) are the most important factors affecting volume fractions of H2 (25.7–57.3 vol%) and input power plays a dominant role. The models developed in this study could enhance understanding of plasma gasification and are unique to considering multiple input parameters together.
Display omitted
•Mathemetical statistics methods has been applied for plasma gasification.•Artificial neural network model is more accurate for LHV, H2 and CO proportion.•The Rtesting2 of final optimal models ranges from 0.659 to 0.939.•Input power plays a dominant role in H2 proportion.
Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence ...of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored.
In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL).
20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task.
Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity.
Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.
Zaire ebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more ...serious or fatal outcomes. The 2013-16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4
or CD8
T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.
To test the usefulness of non-invasive coronary flow reserve (CFR) by transthoracic Doppler echocardiography by comparison to invasive fractional flow reserve (FFR) and instantaneous wave-free ratio ...(IFR), a new vasodilator-free index of coronary stenosis severity, in patients with left anterior descending artery (LAD) stenosis of intermediate severity (IS) and stable coronary artery disease. 94 consecutive patients (mean age 68 ± 10 years) with angiographic LAD stenosis of IS (50–70 % diameter stenosis), were prospectively studied. IFR was calculated as a trans-lesion pressure ratio during the wave-free period in diastole; FFR as distal pressure divided by mean aortic pressure during maximal hyperemia (using 180 μg intracoronary adenosine); and CFR as hyperemic peak LAD flow velocity divided by baseline flow velocity using intravenous adenosine (140 μg/kg/min over 2 min). The mean values of IFR, FFR, and CFR were 0.88 ± 0.07, 0.81 ± 0.09, and 2.4 ± 0.6 respectively. A significant correlation was found between CFR and FFR (r = 0. 68), FFR and IFR (r = 0.6), and between CFR and IFR (r = 0.5) (all, p < 0.01). Using a ROC curve analysis, the best cut-off to detect a significant lesion based on FFR assessment (FFR ≤ 0.8, n = 31) was IFR ≤ 0.88 with a sensitivity (Se) of 74 %, specificity (Sp) of 73 %, AUC 0.81 ± 0.04, accuracy 72 %; and CFR ≤ 2 with a Se = 77 %, Sp = 89 %, AUC 0.88 ± 0.04, accuracy 85 % (all, p < 0.001). In stable patients with LAD stenosis of IS, non-invasive CFR is a useful tool to detect a significant lesion based on FFR. Furthermore, there was a better correlation between CFR and FFR than between CFR and IFR, and a trend to a better diagnostic performance for CFR versus IFR.
We present a case which developed a typical tako-tsubo-like cardiomyopathy (TTC) during dobutamine stress echocardiography (DSE). Its originality is related to several findings, which have never been ...described simultaneously in the same patient. This 63-year-old woman with normal coronary angiography and no evidence of coronary vasospasm had a biphasic response to DSE, a finding which usually occurs in coronary artery disease. Moreover, the symmetric extensive wall motion abnormalities (WMA) occurred simultaneously with the development of a systolic anterior motion of the mitral valve (SAM) and left ventricular obstruction, and was clinically asymptomatic. Although in TTC the stunning usually occurs for several days, WMA and SAM resolved within few minutes after cessation of dobutamine and administration of a beta-blocker. And finally, exercise echo performed at the same target heart rate few days later did not induce neither a SAM nor WMA, which suggests that left ventricular obstruction could have played a role in the pathogenesis of this case by supply-demand mismatch. Concomitant coronary microvascular dysfunction was also demonstrated by a reduction of the non-invasive coronary flow reserve in the distal part of the left anterior descending artery.
Nous présentons le cas d’une patiente qui a développé une cardiomyopathie de tako-tsubo (TTC) au cours d’une échographie de stress à la dobutamine (ESD). Son originalité est en rapport avec plusieurs éléments n’ayant jamais été décrits simultanément chez le même patient. Cette patiente de 63ans dont la coronarographie est normale et qui n’a pas de spasme coronaire a eu une réponse biphasique à la dobutamine, phénomène qui survient habituellement dans la maladie coronaire. De plus, le trouble de cinétique étendu, symétrique est apparu en même temps qu’un mouvement systolique antérieur de la valve mitrale (SAM) et une obstruction dynamique intra-ventriculaire gauche, et était cliniquement asymptomatique. Bien qu’habituellement dans la TTC la sidération myocardique dure plusieurs jours, le trouble de cinétique et le SAM ont disparu quelques minutes après l’arrêt de la dobutamine et l’administration d’un bêtabloquant. Et enfin, une échographie d’effort réalisée avec la même fréquence cardiaque cible quelques jours plus tard n’a pas pu induire de trouble de cinétique et de SAM, ce qui suggère que l’obstruction dynamique intra-ventriculaire gauche a pu jouer un rôle dans la pathogénie de ce cas par non-congruence besoins-apports. Une dysfonction concomitante de la microcirculation coronaire a également été illustrée par la réduction de la réserve coronaire non invasive dans la partie distale de l’artère interventriculaire antérieure.
Typical tako-tsubo cardiomyopathy (TTC) mimics acute anterior myocardial infarction (AMI) and the differential diagnosis is challenging before coronary angiography (CA) is performed; it demonstrates ...reduced or absent antegrade flow in the left anterior descending artery (LAD) in AMI, whereas there is no such flow limiting in TTC. At the acute phase, we tested the usefulness of the distal LAD flow visualization by transthoracic Doppler echocardiography (TDE) to distinguish between these two diseases. For this purpose, we prospectively enrolled 28 consecutive patients with TTC (75 ± 10 years, 93% females) who were compared with 28 consecutive patients with AMI treated successfully by primary angioplasty (66 ± 12 years, 79% females). All the patients underwent the assessment of the distal LAD flow just before CA, using colour and pulsed-wave TDE. In addition, the symmetric involvement of wall motion abnormalities (WMAs) based on the extent of the disease far beyond one coronary territory in TTC was searched by TDE. Non-invasive coronary flow reserve (CFR) by TDE, in the distal LAD, was also performed within 1 day after admission.
Before CA, the distal LAD flow was visible in 38 of 56 cases (68%) in the whole population, in all cases with TTC and in 10 cases with AMI (36%). The sensitivity (Se) and specificity (Sp) of the LAD flow visualization for the diagnosis of TTC were 100 and 64%, respectively, with a diagnostic accuracy of 82%. In comparison, the pattern of WMA yielded a Se of 75% and Sp of 86%, and a diagnostic accuracy of 80%. With the combination of both tools, the Se and Sp to detect TTC were 75 and 96% respectively, with a diagnostic accuracy of 86%. After CA, the acute CFR was less severely impaired in the TTC group when compared with the AMI group (2.2 ± 0.5 vs. 1.7 ± 0.6, P < 0.01) despite a worse LV systolic dysfunction.
Non-invasive evaluation of the distal LAD flow could be helpful to differentiate TTC from AMI, and its combination with the pattern of WMA improved slightly its diagnostic accuracy. Furthermore, the acute CFR is less severely impaired in TTC compared with AMI despite poorer LV systolic dysfunction, suggesting that other mechanisms than direct microcirculatory damage are also involved in the pathogenesis of WMAs in TTC.
Behavioral, cognitive and functional particularities in autism differ according to autism subgroups and might be associated with domain-specific cognitive strengths. It is unknown whether structural ...changes support this specialization. We investigated the link between cortical folding, its maturation and cognitive strengths in autism subgroups presenting verbal or visuo-spatial peaks of abilities.
We measured gyrification, a structural index related to function, in 55 autistic participants with (AS-SOD, N = 27) or without (AS-NoSOD, N = 28) a speech onset delay (SOD) with similar symptom severity but respectively perceptual and verbal cognitive strengths, and 37 typical adolescents and young adults matched for intelligence and age. We calculated the local Gyrification Index (lGI) throughout an occipito-temporal region of interest and independently modeled age and peak of ability effects for each group.
Unique gyrification features in both autistic groups were detected in localized clusters. When comparing the three groups, gyrification was found lower in AS-SOD in a fusiform visual area, whereas it was higher in AS-NoSOD in a temporal language-related region. These particular areas presented age-related gyrification differences reflecting contrasting local maturation pathways in AS. As expected, peaks of ability were found in a verbal subtest for the AS-NoSOD group and in the Block Design IQ subtest for the AS-SOD group.
Irrespective of their direction, regional gyrification differences in visual and language processing areas respectively reflect AS-SOD perceptual and AS-NoSOD language-oriented peaks. Unique regional maturation trajectories in the autistic brain may underline specific cognitive strengths, which are key variables for understanding heterogeneity in autism.
•Subgrouping the autism spectrum (AS) partly accounts for its heterogeneity.•AS individuals with a speech onset delay (SOD) show perceptual cognitive strengths.•AS individuals without a SOD show language-related cognitive strengths.•AS subgroups show unique gyrification patterns in areas related to their strengths.•Cortical structural maturation may be related to domain-specific strengths in AS.
PDF
