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Amyotrophic lateral sclerosis (ALS) is the most common and devastating motor neuron (MN) disease. Its pathophysiological cascade is still enigmatic. More than 90% of ALS patients suffer from sporadic ALS, which makes it specifically demanding to generate appropriate model systems. One interesting aspect considering the seeding, spreading and further disease development of ALS is the cerebrospinal fluid (CSF). We therefore asked whether CSF from sporadic ALS patients is capable of causing disease typical changes in human patient-derived spinal MN cultures and thus could represent a novel model system for sporadic ALS. By using induced pluripotent stem cell (iPSC)-derived MNs from healthy controls and monogenetic forms of ALS we could demonstrate a harmful effect of ALS-CSF on healthy donor-derived human MNs. Golgi fragmentation-a typical finding in lower organism models and human postmortem tissue-was induced solely by addition of ALS-CSF, but not control-CSF. No other neurodegenerative hallmarks-including pathological protein aggregation-were found, underpinning Golgi fragmentation as early event in the neurodegenerative cascade. Of note, these changes occurred predominantly in MNs, the cell type primarily affected in ALS. We thus present a novel way to model early features of sporadic ALS.Bacterial infections constitute a severe problem in various areas of everyday life, causing pain and death, and adding enormous costs to healthcare worldwide. Besides, they cause important concerns in other industries, such as cloth, food packaging, and biomedicine, among others. Despite the intensive efforts of academics and researchers, there is lack of a general solutions to restrict bacterial growth. Among the various approaches, the use of antibacterial nanomaterials is a very promising way to fight the microorganisms due to their high specific surface area and intrinsic or chemically incorporated antibacterial action. Graphene, a 2D carbon-based ultra-thin biocompatible nanomaterial with excellent mechanical, thermal, and electrical properties, and its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), are highly suitable candidates for restricting microbial infections. However, the mechanisms of antimicrobial action, their cytotoxicity, and other issues remain unclear. This mini-review provides select examples on the leading advances in the development of antimicrobial nanocomposites incorporating inorganic nanoparticles and graphene or its derivatives, with the aim of providing a better understanding of the antibacterial properties of graphene-based nanomaterials.Results from several studies show that only obese, unfit subjects, but not obese, fit subjects, are at higher mortality risk than are normal-weight fit subjects. The aim of the study was two-fold (1) to examine the differences in C-reactive protein levels across different metabolic phenotypes (healthy and unhealthy) of weight status and (2) ascertain whether high levels of cardiorespiratory fitness (CRF) attenuate the association of C-reactive protein and metabolic phenotypes of weight status. This was a pooled study, which included data from three cross-sectional projects (1706 youth (921 girls) aged 12-18 years). We used a Shuttle run test to assess CRF. Adolescents were classified into six metabolic phenotypes (healthy and unhealthy) of weight status (non-overweight, overweight and obese), based on age- and sex-specific cutoff points for triglycerides, systolic blood pressure, HDL-cholesterol, glucose and body mass index. High-sensitivity assays were used to obtain the C-reactive protein as inflammatory biomarker. After adjustment for potential confounders (age, sex, pubertal stage and country), the analysis of covariance (ANCOVA) shows that C-reactive protein is directly associated with metabolic phenotypes of weight status. Subjects with obesity, regardless of their metabolic profile, had higher levels of C-reactive protein Z-score. In addition, (after adjustments for potential confounders) a two-way ANCOVA showed that high levels of CRF attenuated the associations of C-reactive protein levels in metabolic healthy non-overweight and in adolescents with obesity. In conclusion, higher CRF levels may attenuate the detrimental association between obesity and C-reactive protein independently of metabolic phenotype. Findings from this study are important for prevention, clinical practice on issues associated with adiposity and metabolic disorders.We aimed to investigate the effect of bromelain, the extract from stems of pineapples on the high-fat diet (HFD)-induced deregulation of hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD), and its underlying mechanism in mice. Mice were daily administrated with HFD with or without bromelain (20 mg/kg) for 12 weeks, and we found that bromelain decreased the HFD-induced increase in body weight by ~30%, organ weight by ~20% in liver weight and ~40% in white adipose tissue weight. Additionally, bromelain attenuated HFD-induced hyperlipidemia by decreasing the serum level of total cholesterol by ~15% and triglycerides level by ~25% in mice. Moreover, hepatic lipid accumulation, particularly that of total cholesterol, free cholesterol, triglycerides, fatty acids, and glycerol, was decreased by 15-30% with bromelain treatment. Mechanistically, these beneficial effects of bromelain on HFD-induced hyperlipidemia and hepatic lipid accumulation may be attributed to the decreased fatty acid uptake and cholesteryl ester synthesis and the increased lipoprotein internalization, bile acid metabolism, cholesterol clearance, the assembly and secretion of very low-density lipoprotein, and the β-oxidation of fatty acids by regulating the protein expression involved in the above mentioned hepatic metabolic pathways. Collectively, these findings suggest that bromelain has therapeutic value for treating NAFLD and metabolic diseases.Sesamol found in sesame oil has been shown to ameliorate obesity by regulating lipid metabolism. However, its effects on energy expenditure and the underlying molecular mechanism have not been clearly elucidated. In this study, we show that sesamol increased the uncoupling protein 1 (Ucp1) expression in adipocytes. The administration of sesamol in high-fat diet (HFD)-fed mice prevented weight gain and improved metabolic derangements. The three-week sesamol treatment of HFD-fed mice, when the body weights were not different between the sesamol and control groups, increased energy expenditure, suggesting that an induced energy expenditure is a primary contributing factor for sesamol's anti-obese effects. Consistently, sesamol induced the expression of energy-dissipating thermogenic genes, including Ucp1, in white adipose tissues. The microarray analysis showed that sesamol dramatically increased the Nrf2 target genes such as Hmox1 and Atf3 in adipocytes. Moreover, 76% (60/79 genes) of the sesamol-induced genes were also regulated by tert-butylhydroquinone (tBHQ), a known Nrf2 activator. We further verified that sesamol directly activated the Nrf2-mediated transcription. In addition, the Hmox1 and Ucp1 induction by sesamol was compromised in Nrf2-deleted cells, indicating the necessity of Nrf2 in the sesamol-mediated Ucp1 induction. Together, these findings demonstrate the effects of sesamol in inducing Ucp1 and in increasing energy expenditure, further highlighting the use of the Nrf2 activation in stimulating thermogenic adipocytes and in increasing energy expenditure in obesity and its related metabolic diseases.Background Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). Ceftaroline The literature on GDM rates in triplet pregnancies is scarce. Methods A retrospective cohort study was performed to assess the prevalence of GDM in women with a triplet pregnancy. GDM was defined through an abnormal oral glucose tolerance test (OGTT). A meta-analysis of GDM prevalence was also carried out. Results A cohort of 60 women was included in the analysis. Of these, 19 (31.7%) were diagnosed with GDM. There were no differences in pregnancy outcomes between women with and without GDM. In the meta-analysis of 12 studies, which used a sound GDM definition, an estimated pooled prevalence of 12.4% (95% confidence interval 6.9%-19.1%) was found. In a leave-one-out sensitivity analysis, the estimated GDM prevalence ranged from 10.7% to 14.1%. Conclusion The rate of GDM seems increased in women with triplets compared to singleton pregnancies. However, GDM did not impact short-term pregnancy outcomes.This research seeks to determine and analyze the reaction to an increase in the water invoice with the aim of introducing improvements in wastewater treatments. To this end, the purification situation is analyzed and the price elasticities of demand are obtained through Ordinary Minimum Squares. The results show that there are several small noncompliant treatment plants, as well as a complex interaction among consumption, price, and income. In many cases, the results offer small or significant differences without a clear pattern. However, it highlights the number of household members as it is strongly related to consumption and price and not considering it in the elaboration or modification of the water tariff would lead to inefficiencies. A reduction in revenue has also been found due to the strong consumer reaction, so it is necessary to assess in more depth what kind of price change would be most appropriate, as well as whether such measures would be best suited to address the problem.Alzheimer's disease (AD) is the most common form of dementia among older people. Amyloid β (Aβ) aggregation has been the focus for a therapeutic target for the treatment of AD. Naturally occurring polyphenols have an inhibitory effect on Aβ aggregation and have attracted a lot of attention for the development of treatment strategies which could mitigate the symptoms of AD. However, considerable evidence has shown that the pro-oxidant mechanisms of polyphenols could have a deleterious effect. Our group has established an assay system to evaluate the pro-oxidant characteristics of chemical compounds, based on their reactivity with DNA. In this review, we have summarized the anti-Aβ aggregation and pro-oxidant properties of polyphenols. These findings could contribute to understanding the mechanism underlying the potential risk of polyphenols. We would like to emphasize the importance of assessing the pro-oxidant properties of polyphenols from a safety point of view.We address the problem of machine learning of constitutive laws when large experimental deviations are present. This is particularly important in soft living tissue modeling, for instance, where large patient-dependent data is found. We focus on two aspects that complicate the problem, namely, the presence of an important dispersion in the experimental results and the need for a rigorous compliance to thermodynamic settings. To address these difficulties, we propose to use, respectively, Topological Data Analysis techniques and a regression over the so-called General Equation for the Nonequilibrium Reversible-Irreversible Coupling (GENERIC) formalism (M. Grmela and H. Ch. Oettinger, Dynamics and thermodynamics of complex fluids. I. Development of a general formalism. Phys. Rev. E 56, 6620, 1997). This allows us, on one hand, to unveil the true "shape" of the data and, on the other, to guarantee the fulfillment of basic principles such as the conservation of energy and the production of entropy as a consequence of viscous dissipation.