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Developing a biopsychosocial type of cancer-related fatigue: the BIOCARE Manufacturer cohort review process.
Engagement in sexual behavior can impact neurosteroidogenesis, in particular production of the prohormone testosterone (T) and likely its subsequent metabolism to 5α-androstane-3α-17β-Diol (3α-Diol) or aromatization to estradiol (E2). Androgens and their metabolites vary across the lifespan and impact many behaviors, including cognition, anxiety, and sexual behavior. Thus, we hypothesized that mating may alter cognitive performance via androstane neurosteroids in an age- and experience-dependent manner. We first investigated if exposure to mating during memory consolidation could enhance performance in the novel object recognition task (NOR). Male rats were trained in NOR and then immediately exposed to mating-relevant or control stimuli. Following a 4 h inter-trial interval (ITI), male rats were tested for object memory. Male rats that were exposed to a receptive female during the ITI had better performance in NOR. We then investigated if these effects were due to novelty associated with mating. Male rats wees that were mated during the ITI had better cognitive performance, T metabolites were decreased compared to controls. These findings suggest that T metabolites, but not the prohormone, may influence learning dependent on sexual proclivity, experience, and proximate opportunity to mate. Copyright © 2020 Kohtz and Frye.Background The mechanism of post-stroke cognitive impairment (PSCI) has not been explained. We aimed to investigate whether miR-let-7i participates in the PSCI and illuminates its underlying role in oxygen-glucose deprivation (OGD)-induced cell apoptosis. Methods Blood samples from 36 subjects with PSCI and 38 with post-stroke cognitive normality (Non-PSCI) were collected to evaluate the differential expression of miR-let-7 family members, using qRT-PCT analysis. Spearman correlation was performed to estimate the correlation between the miR-1et-7i level and Montreal Cognitive Assessment (MoCA) score. Treatment of SH-SY5Y cells with OGD was used to induce cell apoptosis in vitro. Effects of miR-let-7i on OGD-induced cell apoptosis was estimated after transfection. The target gene of miR-let-7i was analyzed by dual luciferase reporter gene assay. Results The expression of miR-let-7i was up-regulated in PSCI patients compared with Non-PSCI (p less then 0.001) and negatively correlated with MoCA score (r = -0.643, p less then 0.001). When exposed to OGD, SH-SY5Y cells showed significant apoptosis accompanied by miR-let-7i up-regulation. In OGD-treated cells, miR-let-7i up-regulation was accompanied by cell apoptosis, while down-regulation showed the opposite effect. Luciferase reporter assay showed that Bcl-2 was a target gene of miR-let-7i. Western blot showed that miR-let-7i up-regulation promoted Bcl-2 expression, while qRT-PCR showed that miR-let-7i had no effect on Bcl-2 expression. Conclusion miR-let-7i was overexpressed in PSCI patients and it could be used as a diagnostic biomarker for PSCI. We illuminated the potential mechanism that miR-let-7i alleviated OGD-induced cell damage by targeting Bcl-2 at the post-transcriptional level. Copyright © 2020 Wang, Li, Huang, Huo and Lv.Objective The relationship between sleep (caregiver-reported and actigraphy-measured) and other caregiver-reported behaviors in children and adults with autism spectrum disorder (ASD) was examined, including the use of machine learning to identify sleep variables important in predicting anxiety in ASD. Methods Caregivers of ASD (n = 144) and typically developing (TD) (n = 41) participants reported on sleep and other behaviors. ASD participants wore an actigraphy device at nighttime during an 8 or 10-week non-interventional study. Mean and variability of actigraphy measures for ASD participants in the week preceding midpoint and endpoint were calculated and compared with caregiver-reported and clinician-reported symptoms using a mixed effects model. An elastic-net model was developed to examine which sleep measures may drive prediction of anxiety. Results Prevalence of caregiver-reported sleep difficulties in ASD was approximately 70% and correlated significantly (p less then 0.05) with sleep efficiency measured by actigraphy. Mean and variability of actigraphy measures like sleep efficiency and number of awakenings were related significantly (p less then 0.05) to ASD symptom severity, hyperactivity and anxiety. In the elastic net model, caregiver-reported sleep, and variability of sleep efficiency and awakenings were amongst the important predictors of anxiety. Conclusion Caregivers report problems with sleep in the majority of children and adults with ASD. Reported problems and actigraphy measures of sleep, particularly variability, are related to parent reported behaviors. Measuring variability in sleep may prove useful in understanding the relationship between sleep problems and behavior in individuals with ASD. These findings may have implications for both intervention and monitoring outcomes in ASD. Copyright © 2020 Bangerter, Chatterjee, Manyakov, Ness, Lewin, Skalkin, Boice, Goodwin, Dawson, Hendren, Leventhal, Shic, Esbensen and Pandina.In the event of visual impairment or blindness, information from other intact senses can be used as substitutes to retrain (and in extremis replace) visual functions. Abilities including reading, mental representation of objects and spatial navigation can be performed using tactile information. Current technologies can convey a restricted library of stimuli, either because they depend on real objects or renderings with low resolution layouts. Digital haptic technologies can overcome such limitations. The applicability of this technology was previously demonstrated in sighted participants. Here, we reasoned that visually-impaired and blind participants can create mental representations of letters presented haptically in normal and mirror-reversed form without the use of any visual information, and mentally manipulate such representations. Visually-impaired and blind volunteers were blindfolded and trained on the haptic tablet with two letters (either L and P or F and G). During testing, they haptically exploremanipulation. Copyright © 2020 Tivadar, Chappaz, Anaflous, Roche and Murray.Background Preclinical studies suggest that stem cells may be a valuable therapeutic tool in amyotrophic lateral sclerosis (ALS). As it has been demonstrated that there are molecular changes at the end-plate during the early stages of motorneuron degeneration in animal models, we hypothesize that the local effect of this stem cell delivery method could slow the progressive loss of motor units (MUs) in ALS patients. Methods We designed a Phase I/II clinical trial to study the safety of intramuscularly implanting autologous bone marrow mononuclear cells (BMMCs), including stem cells, in ALS patients and their possible effects on the MU of the tibialis anterior (TA) muscle. Twenty-two patients participated in a randomized, double-blind, placebo-controlled trial that consisted of a baseline visit followed by one intramuscular injection of BMNCs, follow-up visits at 30, 90, 180, and 360 days, and an additional year of clinical follow-up. learn more In each patient, one TA muscle was injected with a single dose of BMMCs while parameters when studying treatment effects. Given the low number of patients and their heterogeneity, these results justify exploring the efficacy of this procedure in further patients and other muscles, through Phase II trials. Clinical Trial Registration www.clinicaltrials.gov (identifier NCT02286011); EudraCT number 2011-004801-25. Copyright © 2020 Geijo-Barrientos, Pastore-Olmedo, De Mingo, Blanquer, Espuch, Iniesta, Iniesta, García-Hernández, Martín-Estefanía, Barrios, Moraleda and Martínez.The goal of neurocritical care in patients with traumatic brain injury (TBI) is to prevent secondary brain damage. Pathophysiological mechanisms lead to loss of body mass, negative nitrogen balance, dysglycemia, and cerebral metabolic dysfunction. All of these complications have been shown to impact outcomes. Therapeutic options are available that prevent or mitigate their negative impact. Nutrition therapy, glucose control, and multimodality monitoring with cerebral microdialysis (CMD) can be applied as an integrated approach to optimize systemic immune and organ function as well as adequate substrate delivery to the brain. CMD allows real-time bedside monitoring of aspects of brain energy metabolism, by measuring specific metabolites in the extracellular fluid of brain tissue. Sequential monitoring of brain glucose and lactate/pyruvate ratio may reveal pathologic processes that lead to imbalances in supply and demand. Early recognition of these patterns may help individualize cerebral perfusion targets and systemic glucose control following TBI. In this direction, recent consensus statements have provided guidelines and recommendations for CMD applications in neurocritical care. In this review, we summarize data from clinical research on patients with severe TBI focused on a multimodal approach to evaluate aspects of nutrition therapy, such as timing and route; aspects of systemic glucose management, such as intensive vs. moderate control; and finally, aspects of cerebral metabolism. Research and clinical applications of CMD to better understand the interplay between substrate supply, glycemic variations, insulin therapy, and their effects on the brain metabolic profile were also reviewed. Novel mechanistic hypotheses in the interpretation of brain biomarkers were also discussed. Finally, we offer an integrated approach that includes nutritional and brain metabolic monitoring to manage severe TBI patients. Copyright © 2020 Kurtz and Rocha.Cerebellar ataxias (CAs) consist of a heterogeneous group of neurodegenerative diseases hallmarked by motor deficits and deterioration of the cerebellum and its associated circuitries. Neuroinflammatory responses are present in CA brain, but how neuroinflammation may contribute to CA pathogenesis remain unresolved. Here, we investigate whether transforming growth factor (TGF)-β1, which possesses anti-inflammatory and neuroprotective properties, can ameliorate the microglia-mediated neuroinflammation and thereby alleviate neurodegeneration in CA. In the current study, we administered TGF-β1 via the intracerebroventricle (ICV) in CA model rats, by intraperitoneal injection of 3-acetylpyridine (3-AP), to reveal the neuroprotective role of TGF-β1. The TGF-β1 administration after 3-AP injection ameliorated motor impairments and reduced the calbindin-positive neuron loss and apoptosis in the brain stem and cerebellum. Meanwhile, 3-AP induced microglial activation and inflammatory responses in vivo, which were deter 2020 Cao, Zhang, Du, Liu, Qiu and Peng.Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively.
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