Teaguerollins5058
Neonatal hypoxic-ischemic (H-I) injury, which mainly causes neuronal damage and white matter injury (WMI), is among the predominant causes of infant morbidity (cerebral palsy, cognitive and persistent motor disabilities) and mortality. Disruptions to the oxygen and blood supply in the perinatal brain affect the cerebral microenvironment and may affect microglial activation, excitotoxicity, and oxidative stress. Microglia are significantly associated with axonal damage and myelinating oligodendrocytes, which are major pathological components of WMI. However, the effects of H-I injury on microglial functions and underlying transformation mechanisms remain poorly understood. The historical perception that these cells are major risk factors for ischemic stroke has been questioned due to our improved understanding of the diversity of microglial phenotypes and their alterable functions, which exacerbate or attenuate injuries in different regions in response to environmental instability. Unfortunately, although therapeutic hypothermia is an efficient treatment, death and disability remain the prognosis for a large proportion of neonates with H-I injury. Hence, novel neuroprotective therapies to treat WMI following H-I injury are urgently needed. Here, we review microglial mechanisms that might occur in the developing brain due to neonatal H-I injury and discuss whether microglia function as a double-edged sword in WMI. Then, we emphasize microglial heterogeneity, notably at the single-cell level, and sex-specific effects on the etiology of neurological diseases. Finally, we discuss current knowledge of strategies aiming to improve microglia modulation and remyelination following neonatal H-I injury. Overall, microglia-targeted therapy might provide novel and valuable insights into the treatment of neonatal H-I insult.In this work, the design, synthesis, and structure-activity relationships of a novel array of geranyloxy and farnesyloxy 3-acetylcoumarins were reported as potent soybean 15-lipoxygenase inhibitors. Among the prepared coumarins, 7-farnesyloxy-3-acetylcoumarin (12b) was found to be the most potent inhibitor by IC50 = 0.68 μM while O-geranyl substituents at positions 5 and 6 of 3-acetylcoumarin (10a and 11a) were not inhibitors. Using docking studies, the binding affinity and the preferred pose of synthetic compounds were considered. It was found that lipoxygenase inhibitory activity and prenyl length chain were directly related. The hydrophobic cavity of the enzyme was more effectively occupied by the farnesyl moiety of the potent inhibitor 12b rather than other derivatives. Also, with this pose of farnesyl chain in 7-farnesyloxy-3-acetylcoumarins, the acetyl group could be directed to the hydrophilic pocket in the active site.Opioid use disorder is a devastating disorder with a high burden in terms of overdose mortality, with an urgent need for more personalized prevention or therapeutic interventions. https://www.selleckchem.com/ For this purpose, the description and validation of biological measures of staging or treatment response is a highly active research field. We conducted a narrative review on the pathophysiology of opioid use disorder to propose staging of the disease and search for research studies proposing or demonstrating the predictive value of biomarkers. We propose a IV stage description of opioid use disorder, from (I) vulnerability stage to (II) disease progression, (III) constituted opioid dependence and were several type of treatments can be applied, to the reach a (IV) modified health state. We classified biomarkers studies according to the stage of the disorder they were intended to predict, and to the three categories of methods they used anatomical and functional aspects of the brain, genetic/transcriptomic/epigenetic studies, and lastly biomarkers of systemic modifications associated with opioid use disorder, especially regarding the immune system. Most studies predicting Stage III that we reviewed collected data from small samples sizes and were cross-sectional association studies comparing opioid dependent patients and control groups. Pharmacogenetic biomarkers are proposed to predict treatment response. Future research should now emphasize prospective studies, replication in independent samples, and predictive value calculation of each biomarker. The most promising results are multimodal evaluations to be able to measure the state of the brain reward system in living individuals.This study examined the theory of change of the ACT Raising Safe Kids parenting program, including whether intervention effects on children's behavior problems were explained by improvements in mothers' reported parenting practices, as well as whether baseline child behavior problems moderated these relations. Adult mothers of 3-to 8-year-old Brazilian children were assigned to the intervention (n = 97) or control (n = 46) groups. Results showed that the intervention improved mothers' perceptions of their parenting practices (positive discipline, emotional and behavioral regulation, and communication). Intervention-induced reductions in children's internalizing and externalizing behavior problems were mediated by improvements in mothers' emotional and behavioral regulation. Program effects were strongest for children with high levels of baseline behavior problems.Neoliberalism has become the dominant ideology in many parts of the world. Yet there is little empirical research on its psychological impact. On the basis of a social identity approach to health, we hypothesize that, by increasing competition and by reducing people's sense of connection to others, neoliberalism can increase loneliness and compromise our well-being. Study 1 (N = 246) shows that the more neoliberal people perceive society to be, the worse their well-being, and that this relationship is mediated via loneliness. In two experiments, we showed that exposure to neoliberal ideology increases loneliness (Study 2, N = 204) and, through this, decreases well-being (Study 3, N = 173). In Study 4 (N = 303), we found that exposure to neoliberal ideology increased loneliness and decreased well-being by reducing people's sense of connection to others and by increasing perceptions of being in competition with others. In Study 4, the effect of neoliberalism on well-being was evident for liberals only. We discuss the potential impact of neoliberalism on different social groups in society.
To compare the long-term efficacy of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors as second-line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD).
In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks.
Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m
, 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11).
The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.
The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.
The pathophysiology of cervical dystonia is still unclear. Recent evidence points toward a network disorder affecting several brain areas. The objective of this study was to assess the saccadic inhibition as a marker of corticostriatal function in cervical dystonia.
We recruited 31 cervical dystonia patients and 17 matched healthy controls. Subjects performed an overlap prosaccade, an antisaccade, and a countermanding task on an eye tracker to assess automatic visual response and response inhibition.
Cervical dystonia patients made more premature saccades (P= 0.041) in the overlap prosaccade task and more directional errors in the antisaccade task (P= 0.011) and had a higher rate of failed inhibition in the countermanding task (P= 0.001).
The results suggest altered saccadic inhibition in cervical dystonia, possibly as a consequence of dysfunctional corticostriatal networks. Further studies are warranted to confirm whether these abnormalities are affected by the available therapies and whether this type of impairment is found in other focal dystonias. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
The results suggest altered saccadic inhibition in cervical dystonia, possibly as a consequence of dysfunctional corticostriatal networks. Further studies are warranted to confirm whether these abnormalities are affected by the available therapies and whether this type of impairment is found in other focal dystonias. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.The present study was conducted to evaluate the intake, digestibility and nitrogen balance of diets for finishing sheep, containing leucaena hay as a source of effective fibre and forage palm. Twenty-one male sheep were used in a randomized block design with three treatments, represented by total diets, where the forage was leucaena hay and forage palm in natura in proportions 350650, 450550 and 550450 g/kg respectively. For the pH and NH3 -N in the ruminal fluid, and urea in the blood serum, plots split in time were adopted. Dry matter and nutrient digestibility, and the nitrogen balance were not influenced (p > .05) by the diets. The neutral detergent fibre digestibility decreased (p less then .05) as the proportions of leucaena hay in the diets increased. The pH and NH3 -N were suitable for ruminal fermentation, and blood urea was maintained under normal physiological conditions for sheep. Combining 350 to 550 g/kg of leucaena hay with 450 to 650 g/kg of forage palm in total diets with a forageconcentrate ratio of 6040 in late-maturing sheep meets the nutritional requirements for daily gain 200 g, characterizing leucaena hay as important source of effective fibre and nutrients in diets.Here we show that by adjusting the concentration of tetrabutyl ammonium and phosphonium salts in water (≈1.5-2.0 m), hydrophobic solvation triggers the formation of a unique, highly incompressible supramolecular liquid, with a dynamic structure similar to clathrates, involving essentially all H2 O molecules of the solvent. Despite the increasing local order, the thermal diffusivity, and compressibility of these supramolecular liquids is strongly decreased with respect to bulk water due to slower relaxation dynamics. The results presented in this paper open an avenue to design a new family of supramolecular fluids, stable under atmospheric conditions, which can find important technological applications in energy storage and conversion.
