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Background: Fatigue is a frequently reported and disabling symptom in multiple sclerosis (MS). Objective: To investigate the effectiveness of an individual energy conservation management (ECM) intervention on fatigue and participation in persons with primary MS-related fatigue. Methods: A total of 86 severely fatigued and ambulatory adults with a definite diagnosis of MS were randomized in a single-blind, two-parallel-arm randomized clinical trial to the ECM group or the information-only control group in outpatient rehabilitation departments. Blinded assessments were carried out at baseline and at 8, 16, 26 and 52 weeks after randomization. Primary outcomes were fatigue (fatigue subscale of Checklist Individual Strength – CIS20r) and participation (Impact on Participation and Autonomy scale – IPA). Results: Modified intention-to-treat analysis was based on 76 randomized patients (ECM, n = 36; MS nurse, n=40). No significant ECM effects were found for fatigue (overall difference CIS20r between the groups = −0.81; 95% confidence interval (CI), −3.71 to 2.11) or for four out of five IPA domains. An overall unfavourable effect was found in the ECM group for the IPA domain social relations (difference between the groups = 0.19; 95% CI, 0.03 to 0.35). Conclusion: The individual ECM format used in this study did not reduce MS-related fatigue and restrictions in participation more than an information-only control condition.

From 24 vertical jumps (eight subjects, three jumps each), calculations of forces, torques, and power per joint were combined with EMG data of eight leg muscles and with estimations of their contraction velocities. In the second part of the push-off, a high power output of 3000-4000 W was delivered in the ankle joints during plantar flexion. This is attributed to a sequential energy flow from hip to knee and ankle joints. Through coordinated actions of both the m. gluteus maximus and the m. rectus femoris as well as the m. vastus med., intermedius and lat. (mm. vasti) and the m. gastrocnemius, power delivered by the monoarticular extensors of the hip and knee joints was transported distally via the biarticular muscles to the ankle joints. During the high plantar flexion velocity at the end of the push-off, hip and knee joints showed high extension velocities resulting in relatively low contraction velocities for the biarticular muscles. As a consequence they could deliver high forces, which allowed them to transport energy in a proximodistal direction and allowed them to decelerate the angular velocities of the hip and knee joints without losses due to eccentric contractions. It is concluded that this power transport is essential in the execution of explosive movements.

Alcohol attentional bias has been pointed as a major marker of alcohol misuse. Recent evidence has revealed that brain functional connectivity (FC) may be a valuable index of the brain networks' integrity in young binge drinkers (BDs). However, there is no study to date examining the FC networks linked to the processing of alcohol-related images in this population. The present study aimed to explore the FC signatures underlying alcohol attention bias in young BDs. Thus, electroencephalographic (EEG) activity was recorded in 54 college students (55.5% females; 27 non/low-drinkers and 27 BDs) while performing a visual alcohol cue-reactivity task. We evaluated whole-brain FC profiles during the processing of alcoholic and non-alcoholic cues, as well as their potential relationship with craving and severity of alcohol use. Results showed that, at the behavioural level, BDs rated alcohol-related images as more pleasant/attractive than non/low-drinkers. Furthermore, at the electrophysiological level, BDs exhibited increased beta-band FC-particularly in the fronto-parieto-occipital network-when processing alcoholic cues. Conversely, they displayed reduced theta-band FC relatively to non/low-drinkers for non-alcoholic images. These hyper-/hypo-connectivity patterns were associated with higher alcohol craving levels. Findings are congruent with previous neurofunctional studies reporting an attentional bias towards alcohol-related information in BDs. These results may have important clinical implications as this neural reactivity to alcoholic cues may contribute to the maintenance and/or escalation of the drinking pattern. Finally, the present study constitutes the first evidence showing that FC networks may be a sensitive indicator to alcohol attentional bias in BDs. UCM-Santander, Grant/Award Number: CT18/17; European Regional Development Fund (FEDER); Fundação para a Ciência e a Tecnologia, Grant/Award Numbers: CEECIND/02979/2018, POCI01-0145-FEDER-028672, SFRH/ BD/146194/2019, UIDB/PSI/01662/2020

Alcohol use disorder (AUD) has been associated with impairments in social and emotional cognition that play a crucial role in the development and maintenance of addiction. Repeated alcohol intoxications trigger inflammatory processes and sensitise the immune system. In addition, emerging data point to perturbations in the gut microbiome as a key regulator of the inflammatory cascade in AUD. Inflammation and social cognition are potent modulators of one another. At the same time, accumulating evidence implicates the gut microbiome in shaping emotional and social cognition, suggesting the possibility of a common underlying loop of crucial importance for addiction. Here we propose an integrative microbiome neuro-immuno-affective framework of how emotional dysregulation and alcohol-related microbiome dysbiosis could accelerate the cycle of addiction. We outline the overlapping effects of chronic alcohol use, inflammation and microbiome alterations on the fronto-limbic circuitry as a convergence hub for emotional dysregulation. We discuss the interdependent relationship of social cognition, immunity and the microbiome in relation to alcohol misuse- from binge drinking to addiction. In addition, we emphasise adolescence as a sensitive period for the confluence of alcohol harmful effects and emotional dysregulation in the developing gut-brain axis. CC has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754535. SL has received support from the Belgian American Educational Foundation. PM (Senior Research Associate) is funded by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Brussels, Belgium). EL-C was supported by the Portuguese Foundation for Science and Technology (FCT), within the scope of the Individual Call to Scientific Employment Stimulus (CEECIND/02979/2018).

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (> 1.5 kcal/g) and Low (

In medial tibial stress syndrome (MTSS) bone marrow and periosteal edema of the tibia on the magnetic resonance imaging (MRI) is frequently reported. The relationship between these MRI findings and recovery has not been previously studied. This prospective study describes MRI findings of 52 athletes with MTSS. Baseline characteristics were recorded and recovery was related to these parameters and MRI findings to examine for prognostic factors. Results showed that 43.5% of the symptomatic legs showed bone marrow or periosteal edema. Absence of periosteal and bone marrow edema on MRI was associated with longer recovery (P = 0.033 and P = 0.013). A clinical scoring system for sports activity (SARS score) was significantly higher in the presence of bone marrow edema (P = 0.027). When clinical scoring systems (SARS score and the Lower Extremity Functional Scale) were combined in a model, time to recovery could be predicted substantially (explaining 54% of variance, P = 0.006). In conclusion, in athletes with MTSS, bone marrow or periosteal edema is seen on MRI in 43,5% of the symptomatic legs. Furthermore, periosteal and bone marrow edema on MRI and clinical scoring systems are prognostic factors. Future studies should focus on MRI findings in symptomatic MTSS and compare these with a matched control group.

An assay for vesicle--vesicle fusion involving resonance energy transfer between N-(7-nitro-2,1,3-benzoxadiazol-4-yl), the energy donor, and rhodamine, the energy acceptor, has been developed. The two fluorophores are coupled to the free amino group of phosphatidylethanolamine to provide analogues which can be incorporated into a lipid vesicle bilayer. When both fluorescent lipids are in phosphatidylserine vesicles at appropriate surface densities (ratio of fluorescent lipid to total lipid), efficient energy transfer is observed. When such vesicles are fused with a population of pure phosphatidylserine vesicles by the addition of calcium, the two probes mix with the other lipids present to form a new membrane. This mixing reduces the surface density of the energy acceptor resulting in a decreased efficiency of resonance energy transfer which is measured experimentally. These changes in transfer efficiency allow kinetic and quantitative measurements of the fusion process. Using this system, we have studied the ability of phosphatidylcholine, phosphatidylserine, and phosphatidylcholine--phosphatidylserine (1:1) vesicles to fuse with cultured fibroblasts. Under the conditions employed, the majority of the cellular uptake of vesicle lipid could be attributed to the adsorption of intact vesicles to the cell surface regardless of the composition of the vesicle bilayer.

Previous studies have shown that both 3-amino-1,2,4-triazole (AT), which inhibits metabolism of ethanol (EtOH) to acetaldehyde by inhibiting catalase, and D-penicillamine (D-P), an acetaldehyde-sequestering agent, modulate EtOH-conditioned place preference (CPP) in male albino Swiss (IOPS Orl) mice. These studies followed a reference-dose-like procedure, which involves comparing cues that have both been paired with EtOH. However, the role of EtOH-derived acetaldehyde has not been examined using a standard CPP method, and efficacy of these treatments could be different under the two circumstances. In the present investigation, we manipulated the strength of CPP across five separate studies and evaluated the effect of D-P and AT on EtOH-induced CPP following a standard unbiased CPP procedure. Mice received pairings with vehicle-saline injections with one cue and, alternatively, with AT- and D-P-EtOH with another cue. Our studies indicate that AT and D-P only disrupt CPP induced by EtOH in mice when the number of conditioning sessions and the dose of EtOH are low. These findings suggest that acquisition of EtOH-induced CPP may depend on the levels of acetaldehyde available during memory acquisition and the strength of the memory. Therefore, we propose that, at least when the memory processes are labile, brain acetaldehyde could participate in the formation of Pavlovian learning elicited by EtOH.