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The pharmacodynamics of opioids for chronic peripheral neuropathic pain are complex and likely extend beyond classical opioid receptor theory. Preclinical evidence of opioid modulation of central immune signalling has not been identified in vivo in humans. Examining the cerebrospinal fluid (CSF) of patients medicated with opioids is required to identify potential pharmacodynamic mechanisms. We compared CSF samples of chronic peripheral neuropathic pain patients receiving opioids (n = 7) versus chronic peripheral neuropathic pain patients not taking opioids (control group, n = 13). Baseline pain scores with demographics were recorded. Proteome analysis was performed using mass spectrometry and secreted neuropeptides were measured by enzyme-linked immunosorbent assay. Based on Gene Ontology analysis, proteins involved in the positive regulation of nervous system development and myeloid leukocyte activation were increased in patients taking opioids versus the control group. The largest decrease in protein expression in patients taking opioids were related to neutrophil mediated immunity. In addition, notably higher expression levels of neural proteins (85%) and receptors (80%) were detected in the opioid group compared to the control group. This study suggests modulation of CNS homeostasis, possibly attributable to opioids, thus highlighting potential mechanisms for the pharmacodynamics of opioids. We also provide new insights into the immunomodulatory functions of opioids in vivo.The aim of this study is to compare the curative effect of empirical with diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients (SAAs) with invasive fungal disease (IFD) after intensive immunosuppressive therapy (IST). Patients undergoing voriconazole antifungal therapy were randomized to empirical therapy group and diagnostic-driven therapy group. Empirical therapy group accounted for 48.5% of all cases, and diagnostic-driven therapy group accounted for 51.5%. The morbidity of IFD (probable and proven cases) was slightly increased in diagnostic-driven therapy group compared with empirical therapy group (P > 0.05). The total effective rate was 62.1%. The effective rate in empirical therapy group was 78.1%, which was significantly increased compared with diagnostic-driven therapy group (47.1%) (P  less then  0.05). This value was especially significant in possible IFD cases (P  less then  0.05). The efficacy of possible IFD cases in empirical therapy group was the best (84%) followed by the probable and proven cases in empirical therapy group (57.1%). In diagnostic-driven therapy group, the efficacy of possible IFD cases was 50%, and the efficacy of probable and proven cases was only 37.5%. The difference was statistically significant (P  less then  0.05). Absolute neutrophil count (ANC) is the key anti-infection factor. The efficacy of patients whose ANC ˂ 0.1 × 109/L was 39.28%, which was significantly reduced compared with that of patients whose ANC ≥ 0.1 × 109/L (78.95%) (P  less then  0.05). This finding was especially obvious in diagnostic-driven therapy group. As empirical therapy is superior to diagnostic-driven therapy, we recommend that empirical therapy should be started for high-risk patients, and efforts should be made to definitively diagnose the disease.4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new drug-like compounds. To date it is known that thiazolidinones are able to induce CYP1A1 activity in 3T3-L1 cells. Therefore, to extend the knowledge of the mechanism of thiazolidinones in the cell, four chemically synthesized heterocycles were tested on 3T3-L1 cells. The 3T3-L1 cells were exposed to Les-2194, Les-3640, Les-5935, and Les-6166. Our study showed that 1 μM βNF, Les-2194, and Les-6166 decreased the expression of Ahr mRNA. In turn, βNF, Les-2194, and Les-3640 increased the Cyp1a1 mRNA expression at the same time interval. On the other hand, Les-5935 was found to decrease the Cyp1a1 mRNA expression. Interestingly, the expression of Cyp1a2 mRNA was activated only by βNF and Les-2194. The expression of Cyp1b1 mRNA in the 3T3 cell line increased after the βNF and Les-2194 treatment but declined after the exposure to Les-5935 and Les-6166. Moreover, the Les-2194 and Les-5935 compounds were shown to increase the activity of EROD, MROD, and PROD. Les-3640 increased the activity of EROD and decreased the activity of PROD. In turn, the treatment with Les-6166 resulted in an increase in the activity of EROD and a decrease in the activity of MROD and PROD in the 3T3-L1 cells.Currently, insulin is commonly used in the clinical management of canine diabetes. However, it must be injected preprandially causing much inconvenience to the owners. Therefore, the development of long-acting hypoglycemic agents has attracted much attention in the scientific community. This study aimed to investigate the long-acting hypoglycemic effect of canine fibroblast growth factor 21 (cFGF-21) in diabetic dogs. Diabetic dogs were administered with cFGF-21, polyethylene glycol-modified cFGF-21 (PEG-cFGF-21), or insulin once a day, once every 2, 3, or 4 days subcutaneously. The results showed that cFGF-21 and PEG-cFGF-21 maintained blood glucose comparable to normal levels for 2 and 3 days respectively while insulin maintained the blood glucose for only 2 h after a single injection. After treatment with cFGF-21, oral glucose tolerance test (OGTT) was significantly improved with glycosylated hemoglobin (HbA1c) close to the normal levels. In addition, cFGF-21 significantly repaired islet β cells, increased insulin content, and protected the pancreas from streptozotocin-induced injury. Furthermore, cFGF-21 exhibited both antioxidant and anti-inflammatory properties in the pancreas. We conclude, therefore, that cFGF-21 and PEG-cFGF-21 can maintain blood glucose comparable to normal levels for 2 and 3 days respectively after a single dose. The long-acting efficacy of cFGF-21 can be attributed to improvement in oxidative stress and the reduction of inflammation in the pancreas.Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. learn more Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium-treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition.This study investigated toxic metal distribution in roadside soil and dust in the metropolitan city of Ulsan, South Korea, and the factors affecting distribution, using Korean waste-leaching tests, determination of total concentrations, sequential extraction, and statistical analysis. Composite grab samples were collected from high-traffic roads (7 sites), low-traffic roads (2 sites), and an uncontaminated control area (2 sites) in Ulsan. The pH of roadside soil and dust was slightly alkaline. The concentrations of copper, lead, and zinc in soil as determined by Korean waste-leaching tests decreased as soil depth increased, while those of arsenic, nickel, and chromium increased. Leaching concentrations in dust were lower than in soil, with the exception of copper. Total concentrations decreased as soil depth increased, and total concentrations of metals in dust were higher than in soil. The sampling sites that exceeded the regulation levels of soil contamination in South Korea were 7 points in topsoil, 3 points in middle soil, and 9 points in dust. TCLP tests showed that the concentrations of arsenic, cadmium, and lead in topsoil and dust at Duwang and Myeongchon intersections were higher than regulatory levels. The maximum correlation coefficient among two metals in soil and dust was 0.987 (p less then 0.01), for cadmium and lead. Concentrations of cadmium, copper, arsenic, lead, nickel, and mercury, mostly from tire and brake-pad abrasion, were highly correlated. The strong positive correlation between traffic volume and metals in dust suggests that vehicle emissions may be responsible for metal contamination of soil and dust. Pollution indices of topsoil at 4 sites and all dust at 7 high-traffic sites were higher than 1.0, which is consistent with an effect of vehicle traffic on metal contamination in soil and dust.

Clarke, Gold and Pedersen are validated methods to assess awareness of hypoglycaemia. Identifying impaired awareness of hypoglycaemia (IAH) is critical for supporting people with structured education and diabetes technologies, to reduce harm of hypoglycaemia. This study compares the Clarke score, Gold score and Pedersen methods and their correlations with features of hypoglycaemia unawareness and patient characteristics, to evaluate the accuracy of the methods in identifying IAH.

This retrospective, observational questionnaire-based study collected routine clinical data from 100 people with type1 diabetes. The questionnaire included the three validated scoring methods, frequency of severe and nocturnal hypoglycaemia, knowledge and worry of hypoglycaemia and hypoglycaemia symptom scores using the Edinburgh Hypoglycaemia Scale. Data were analysed for IAH prevalence and the associations with features of IAH. The concordance of Clarke, Gold and Pedersen methods was evaluated using Spearman's correlation coefft performing more than one score is important for a reliable risk assessment of IAH.

Whilst Clarke and Gold methods determined a similar prevalence of IAH, people identified with IAH assessed by the Clarke method had a significant association with the features and characteristics of IAH, including reduced autonomic symptoms. This study suggests that performing more than one score is important for a reliable risk assessment of IAH.

Epidemics and pandemics and the measures taken to contain their spread are accompanied by numerous stressors, which can lead in particular to severe anxiety.

This article describes the components and determinants of these anxiety symptoms, potential resilience and risk factors and appropriate recommendations for action.

The article presents an overview of research results regarding COVID-19 and previous epidemics and pandemics (e.g., HIV, SARS, MERS, Ebola and swine flu). Furthermore, official recommendations for action are presented.

Anxiety symptoms frequently occur in epidemics and pandemics, especially in the early phase and usually decrease in the further course. Although other aspects of different infectious diseases vary, the associated fears are similar and include e.g. the fear of health-related, social and economic consequences. Resilience and risk factors in various epidemics and pandemics are comparable. Self-efficacy expectation, tolerance of uncertainty, normalization, routines, safety and social support usually have aprotective effect.