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Neurotoxicity is mediated by a variety of modes-of-actions leading to disturbance of neuronal function. In order to screen larger numbers of compounds for their neurotoxic potential, in vitro functional neuronal networks (NN) might be helpful tools. We established and characterized human NN (hNN) from hiPSC-derived neural progenitor cells by comparing hNN formation with two different differentiation media in presence (CINDA) and absence (neural differentiation medium (NDM)) of maturation-supporting factors. As a NN control we included differentiating rat NN (rNN) in the study. Gene/protein expression and electrical activity from in vitro developing NN were assessed at multiple time points. Transcriptomes of 5, 14 and 28 days in vitro CINDA-grown hNN were compared to gene expression profiles of in vivo human developing brains. Molecular expression analyses as well as measures of electrical activity indicate that NN mature into neurons of different subtypes and astrocytes over time. In contrast to rNN, hNN are less electrically active within the same period of differentiation time, yet hNN grown in CINDA medium develop higher firing rates than hNN without supplements. Challenge of NN with neuronal receptor stimulators and inhibitors demonstrate presence of inhibitory, GABAergic neurons, whereas glutamatergic responses are limited. hiPSC-derived GABAergic hNN grown in CINDA medium might be a useful tool as part of an in vitro battery for assessing neurotoxicity. BACKGROUND Cystic Fibrosis (CF), affecting functional exercise capacity generally measured by submaximal exercise test such as 6min walk test, is a progressive, autosomal recessive and metabolic disorder. Three-axis accelerometers, which are used during gait, are an easy way to assess gait parameters in patients and healthy individuals. Gait parameters were significantly associated with clinical outcomes of COPD. However, the association between gait parameters and clinical outcomes in children with CF is unclear. RESEARCH QUESTION Do clinical outcomes in CF have an important role in determining gait parameters?. METHODS Twenty-one CF and 21 healthy subjects participated in this case-control study. Body composition was evaluated using Tanita-BC 418. Respiratory and knee extension muscle strengths were assessed. Functional exercise capacity was evaluated using the 6-min walk test (6MWT). Spatiotemporal gait parameters were evaluated using a validated wireless inertial sensing device (G-Sensor, BTS Bioengineering S.p.A., Italy) during the 6MWT and 7-meter gait test. RESULTS MIP, the distance of 6MWT, and stride length were significantly lower in the CF group compare to healthy children (p less then 0.05). Gait speed and functional exercise capacity, cadence and functional exercise capacity, quadriceps muscle strength, FEV1, fat-free mass were found to be correlated in CF patients (p less then 0.05). SIGNIFICANCE The aerobic capacity and gait parameters were affected in CF patients with mild disease severity in our study. Clinical outcomes were associated with gait parameters in CF patients. This is the first study to use the 3-axis accelerometer to evaluate functional exercise capacity and gait parameters of CF and healthy children. A three-axis accelerometer can be used to assess functional exercise capacity and gait parameters in CF patients at the clinics. BACKGROUND Children with cerebral palsy (CP) often have altered gait patterns compared to their typically developing peers. These gait patterns are characterized based on sagittal plane kinematic deviations; however, many children with CP also walk with altered transverse plane kinematics. RESEARCH QUESTION How do both altered skeletal alignment and kinematic deviations affect muscles' capacity to accelerate the body during gait? METHODS A three-dimensional gait analysis was completed for 18 children with spastic CP (12.5 ± 2.9 years; GMFCS level II). Musculoskeletal models were developed for each participant, and tibial torsion, measured during a static standing trial and assessed using motion capture, was incorporated. An induced acceleration analysis was performed to evaluate the capacity of muscles to accelerate the body center of mass throughout stance. Differences between the root-mean-square muscle capacity for children with CP walking with internally rotated, standard, and externally rotated postures were evaluated. RESULTS Externally rotated postures resulted in a lower capacity to accelerate the body center of mass compared with internally rotated postures. Both changes in skeletal alignment and kinematics contributed to changes in muscle capacity to accelerate the body. SIGNIFICANCE Altered transverse plane skeletal alignment and compensatory kinematics should both be considered in surgical treatment of children with CP. Telratolimod OBJECTIVE The steep rise in the prevalence of obesity and its related metabolic syndrome have become a major worldwide health concerns. Melanocortin peptides from hypothalamic arcuate nucleus (Arc) POMC neurons induce satiety to limit food intake. Consequently, Arc Pomc-deficient mice (ArcPomc-/-) exhibit hyperphagia and obesity. Previous studies demonstrated that the circulating levels of adiponectin, a protein abundantly produced and secreted by fat cells, negatively correlate with obesity in both rodents and humans. However, we found that ArcPomc-/- mice have increased circulating adiponectin levels despite obesity. Therefore, we investigated the physiological function and underlying mechanisms of hypothalamic POMC in regulating systemic adiponectin levels. METHODS Circulating adiponectin was measured in obese ArcPomc-/- mice at ages 4-52 weeks. To determine whether increased adiponectin was a direct result of ArcPomc deficiency or a secondary effect of obesity, we examined plasma adiponectin levels in callating adiponectin levels, which demonstrated that increased fat mass is not necessarily correlated with hypoadiponectinemia. Our investigation also found a previously unknown physiological pathway connecting POMC neurons via the sympathetic nervous system to circulating adiponectin, thereby shedding light on the biological regulation of adiponectin.
My Website: https://www.selleckchem.com/products/telratolimod.html
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