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Mays Carter opublikował 5 miesięcy, 2 tygodnie temu
Glutamic acid decarboxylase 65kD autoantibody (GAD65Ab) is frequently detected in patients with refractory epilepsy and stiff person syndrome. In contrast to T1D, the pathological role of GAD65Ab in neurological disorders is still debatable. As a result, the implementation of possible immunotherapy is usually delayed. This report presents 2 cases of GAD65Ab-associated brain autoimmunity and their different management. We present clinical data and discuss management based on available evidence in the reviewed literature. Both cases presented with acute on chronic neurological symptoms and were GAD65Ab positive. Case 1, a 30-year-old man with a history of early-onset type 1 diabetes mellitus at 14 months, followed by cryptogenic temporal epilepsy at 11 years of age, presented with intractable seizures. Case 2, a 48-year-old woman, presented with a history of recurrent severe headaches, cognitive impairment, decreased memory, and behavioral symptoms. GAD65Ab was detected in both patients’ sera. Cerebrospinal fluid GAD65Ab was only checked and positive in case 1. Case 2 was diagnosed with limbic encephalitis, treated with immunotherapy, and showed a remarkable clinical improvement. Case 1 with refractory epilepsy failed multiple antiepileptic drugs and responsive-stimulator system treatments. He was finally diagnosed with autoimmune epilepsy. The delay in diagnosis resulted in a lost opportunity for early immunotherapy. In conclusion, autoantibody screening and early initiation of immunotherapy should be considered to manage GAD65Ab-associated neurological disorders.
Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises.
We tested the hypothesis that the interaction between anxiety, chronic pain, and opioid use results from altered endogenous opioid function.
A genetic model of negative affect, the Wistar-Kyoto (WKY) rat, was combined with intra-articular injection of monosodium iodoacetate (MIA; 1 mg) to mimic clinical presentation. Effects of systemic morphine (0.5-3.5 mg·kg
) on pain behaviour and spinal nociceptive neuronal activity were compared in WKY and normo-anxiety Wistar rats 3 weeks after MIA injection. Endogenous opioid function was probed by the blockade of opioid receptors (0.1-1 mg·kg
systemic naloxone), quantification of plasma β-endorphin, and expression and phosphorylation of spinal mu-opioid receptor (MOR).
Monosodium iodoacetate-treated WKY rats had enhanced OA-like p exposure. These findings shed new light on the mechanisms underlying the increased opioid analgesic use in high anxiety patients with chronic pain.Acute exacerbation of chronic obstruction pulmonary disease (AECOPD) as a respiratory disease, is considered to be related to air pollution by more and more studies. However, the evidence on how air pollution affect the incidence of AECOPD and whether there are population differences is still insufficient. Therefore, we select PM10, PM2.5, SO2, NO2, CO, and O3 as representatives combined with daily AECOPD admission data from 1 January 2015 to 26 June 2016 in the rural areas of Qingyang, northwestern China to explore the associations of air pollution with AECOPD. Based on a time-stratified case-crossover design, we constructed a distributed lag nonlinear model to qualify the single and cumulative lagged effects of air pollution on AECOPD. Stratified related risks by sex and age were also reported. The cumulative exposure-response curves were approximately linear for PM2.5, „V”-shaped for PM10, „U”-shaped for NO2 and inverted-„V” for SO2, CO and O3. Exposure to high-PM2.5 (42 μg/m3), high-PM10 (91 μg/m3), high-SO2 (58 μg/m3), low-NO2 (12 μg/m3), and high-CO (1.55 mg/m3) increased the risk of AECOPD. Females aged 15-64 were more susceptible under extreme concentrations of PM2.5, SO2, CO, and low-PM10 than other subgroups. In addition, adults aged 15-64 were more sensitive to extreme concentrations of NO2 compared with the elderly ≥65 years old, while the latter were more sensitive to high-PM10. High-SO2, high-NO2, and extreme concentrations of PM2.5 had the greatest effects on the day of exposure, while low-SO2 and low-CO had lagged effects on AECOPD. Precautionary measures should be taken with a focus on vulnerable subgroups, to control hospitalization for AECOPD associated with air pollutants.
Personality traits are important factors with regard to the tendency to experience and response to stress. This study introduces and tests a new stress-related personality scale called the Virtual Inventory of Behavior and Emotions (VIBE).
Two samples totaling 5512 individuals (with 66% between the ages of 18 and 34) completed the VIBE along with other measures of personality, stress, mood, and well-being.
Exploratory factor analyses revealed a four-factor structure for the instrument with dimensions labeled 1) stressed; 2) energetic; 3) social; and 4) disciplined. Confirmatory factor analytic procedures on the final 23-item version showed good psychometric properties and data fit while machine learning analyses demonstrated the VIBE’s ability to distinguish between groups with similar patterns of response. Strong convergent validity was suggested through robust correlations between the dimensions of the VIBE and other established rating scales.
Overall, the data suggest that the VIBE is a promising tool to help advance understanding of the relations between stress, personality, and related constructs.
Overall, the data suggest that the VIBE is a promising tool to help advance understanding of the relations between stress, personality, and related constructs.[This corrects the article DOI 10.1021/acsomega.0c02090.].[This corrects the article DOI 10.1021/acsomega.1c04205.].Carboxyl (-COOH)-stabilized iron oxide nanoparticles (IONPs) synthesized through co-precipitation were used to modify an indium tin oxide (ITO) electrode, which was chemically functionalized with 3-aminopropyltriethoxysilane (APTES) for heavy metal detection. The effect of soaking time (30, 60, 90, and 120 min) of IONP-COOH self-assembled on an APTES-ITO electrode was studied. Cyclic voltammetry and scanning electron microscopy were applied to analyze the electrochemical properties and morphologies of IONP-COOH/APTES-ITO modified electrode. The modified electrodes were then employed for the simultaneous detection of Cd(II) and Pb(II) by using square wave anodic stripping voltammetry. At 90 min of soaking time, excellent electrochemical performance and larger effective surface area (A e) were obtained. The linear range for the simultaneous detection of Cd(II) and Pb(II) ions using the modified electrode was 10-100 ppb with limits of detection of 0.90 and 0.60 ppb, respectively. The interference study revealed a low interference effect from Cr(III), Hg(II), Zn(II), Cu(II), Mg(II), Na(I), and K(I) toward the simultaneous detection of Cd(II) and Pb(II). Finally, the IONP-COOH/APTES-ITO-modified electrode was applied to analyze seawater samples and was able to simultaneously detect Cd(II) and Pb(II) ions.Glucokinase (GK) and PPARγ are important targets for antidiabetic use. Silybin is one of the major active ingredients of Silybum marianum. The regioselective modification of the five hydroxyl groups in the silybin structure has always been a challenge. In this study, we found that silybin was an agonist of GK and PPARγ. A novel synthesis scheme of silybin derivatives was designed, and a series of novel silybin derivatives has been synthesized. The derivative 8d showed relatively strong activation activity for GK and PPARγ in enzyme activity and transactivation assays (GK activation fold 1.86; PPARγ transactivation activation percentage 90.32%). This research suggests that silybin and its derivatives could be used as novel GK and PPARγ dual-target agonists.A gas-solid separation fluidized bed, which belongs to dry separation and can save a lot of water resources, is an important method for coal quality improvement. The effect of regional blockage of the air distributor on the fluidization effect was investigated by varying the blockage area and fluidization gas velocity, and the influence law of blockage of an air distributor on bed stability was revealed. In this paper, the micro-differential pressure sensor is used as a testing tool to analyze the regional characteristics of the fluidized bed blockage hole. The results show that when the air distributor is plugged, the standard deviations of the pressure fluctuation are largest at a height of 100 mm, all reaching more than 2.0, and that the pressure fluctuation at the bottom is greater than that at the top. When the plugged area fraction increases from 1/8 to 1/2, the density fluctuation range at the bottom of the plugged area decreases from 0.2 to 0.04 g/cm3, while the range of influence increases from 10 to 16 cm axially. With the increase of fluidization gas velocity, the mixing effect of particles is improved to an extent, and the range of the affected zone is gradually reduced.The biomolecular motor protein kinesin and its associated filamentous protein microtubule have been finding important nanotechnological applications in the recent years. Rigidity of the microtubules, which are propelled by kinesin motors in an in vitro gliding assay, is an important metric that determines the success of utilization of microtubules and kinesins in various applications, such as transportation, sensing, sorting, molecular robotics, etc. Therefore, regulating the rigidity of kinesin-propelled microtubules has been critical. In this work, we report a simple strategy to regulate the rigidity of kinesin-propelled microtubules in an in vitro gliding assay. We demonstrate that rigidity of the microtubules, propelled by kinesins in an in vitro gliding assay, can be modulated simply by using the natural osmolyte trimethylamine N-oxide (TMAO). By varying the concentration of TMAO in the gliding assay, the rigidity of microtubules can be modulated over a wide range. Based on this strategy, we are able to reduce the persistence length of microtubules, a measure of microtubule rigidity, ∼8 fold by using TMAO at the concentration of 1.5 M. Furthermore, we found that the decreased rigidity of the kinesin-propelled microtubules can be restored upon elimination of TMAO from the in vitro gliding assay. Alteration in the rigidity of microtubules is accounted for by the non-uniformity of the force applied by kinesins along the microtubules in the presence of TMAO. This work offers a facile strategy to reversibly regulate the rigidity of kinesin-propelled microtubules in situ, which would widen the applications of the biomolecular motor kinesin and its associated protein microtubule in various fields.In the present work, a concise library of 1,3,5-triaryl-2-pyrazolines (2a-2q) was designed and synthesized by employing a multistep strategy, and the newly synthesized compounds were screened for their urease and α-glucosidase inhibitory activities. The compounds (2a-2q) were characterized using a combination of several spectroscopic techniques including FT-IR, 1H NMR, 13C NMR, and EI-MS. All the synthesized compounds, except compound 2i, were potent against urease as compared to the standard inhibitor thiourea (IC50 = 21.37 ± 0.26 μM). These analogs disclosed varying degrees of urease inhibitory activities ranging from 9.13 ± 0.25 to 18.42 ± 0.42 μM. Compounds 2b, 2g, 2m, and 2q having IC50 values of 9.36 ± 0.27, 9.13 ± 0.25, 9.18 ± 0.35, and 9.35 ± 0.35 μM, respectively, showed excellent inhibitory activity as compared to standard thiourea (IC50 = 21.37 ± 0.26 μM). A kinetic study of compound 2g revealed that compound 2g inhibited urease in a competitive mode. Among the synthesized pyrazolines, the compounds 2c, 2k, 2m, and 2o exhibited excellent α-glucosidase inhibitory activity with the lowest IC50 values of 212.