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Cancer Science May 2024The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to...
The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.
Topics: Humans; Neuroblastoma; Male; Female; Risk Assessment; Child, Preschool; Biomarkers, Tumor; Infant; Homovanillic Acid; Vanilmandelic Acid; Child; Catecholamines; Case-Control Studies; Dopamine; Chromatography, Liquid
PubMed: 38411285
DOI: 10.1111/cas.16116 -
The Science of the Total Environment Apr 2024Hydrological droughts are expected to increase in frequency and severity in many regions due to climate change. Over the last two decades, several droughts occurred in...
Hydrological droughts are expected to increase in frequency and severity in many regions due to climate change. Over the last two decades, several droughts occurred in Europe, including the 2018-drought, which showed major adverse impacts for nature and different sectoral uses (e.g. irrigation, drinking water). While drought impacts on water quantity are well studied, little understanding exists on the impacts on water quality, particularly regarding pharmaceutical concentrations in surface waters. This study investigates the impact of the 2018-drought on concentrations of four selected pharmaceuticals (carbamazepine, sulfamethoxazole, diclofenac and metoprolol) in surface waters in Europe, with a major focus on the Elbe and Rhine rivers. Monitoring data were analysed for the period of 2010-2020 to estimate the spatiotemporal patterns of pharmaceuticals and assess the concentration responses in rivers during the 2018-drought compared to reference years. Our results indicate an overall deterioration in water quality, which can be attributed to the extremely low flow and higher water temperatures (∼ + 1.5 °C and + 2.0 °C in Elbe and Rhine, respectively) during the 2018-drought. Our results show an increase in the concentrations of carbamazepine, sulfamethoxazole, and metoprolol, but reduced concentrations of diclofenac during the 2018-drought. Significant increases in carbamazepine concentrations (+45 %) were observed at 3/6 monitoring stations in the upstream part of the Elbe, which was mainly attributed to less dilution of chemical loads from wastewater treatment plants under drought conditions. However, reduced diclofenac concentrations could be attributed to increased degradation processes under higher water temperatures (R = 0.60). Moreover, the rainfed-dominated Elbe exhibited more severe water quality deterioration than the snowmelt-dominated Rhine river, as the Elbe's reduction in dilution capacity was larger. Our findings highlight the need to account for the impacts of climate change and associated increases in droughts in water quality management plans, to improve the provision of water of good quality for ecosystems and sectoral needs.
Topics: Droughts; Ecosystem; Diclofenac; Metoprolol; Rivers; Europe; Carbamazepine; Sulfamethoxazole; Pharmaceutical Preparations
PubMed: 38408670
DOI: 10.1016/j.scitotenv.2024.171186 -
Journal of Attention Disorders Apr 2024To compare PRC-063 (multilayer-release methylphenidate) and lisdexamfetamine dimesylate (LDX) on the driving performance of young adults with attention deficit... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Phase 3, Double-Blind, Crossover Comparison of Multilayer, Extended-Release Methylphenidate (PRC-063), and Lisdexamfetamine in the Driving Performance of Young Adults With ADHD.
OBJECTIVE
To compare PRC-063 (multilayer-release methylphenidate) and lisdexamfetamine dimesylate (LDX) on the driving performance of young adults with attention deficit hyperactivity disorder (ADHD) in a randomized, double-blind, crossover study.
METHOD
Following up to 21 days of each treatment in each treatment course (PRC-063/LDX or LDX/PRC-063), subjects completed a 15-hour driving simulator laboratory assessment. The primary outcome measure was the Tactical Driving Quotient (TDQ) and the Clinical Global Impressions-Improvement (CGI-I) scale was a secondary outcome measure.
RESULTS
Forty-four subjects completed the study. PRC-063 and LDX had equivalent effects on driving performance through a 15-hour time period (least square mean difference -0.3 [standard error 1.08], 95% confidence interval [-2.4, 1.8], = .793). Consistent improvement in CGI-I was observed. The incidence of treatment-emergent adverse events was similar for each treatment sequence.
CONCLUSIONS
PRC-063 and LDX had comparable effects on driving performance, from 1 through 15 hours, the last time point measured.
Topics: Humans; Young Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Lisdexamfetamine Dimesylate; Methylphenidate; Treatment Outcome
PubMed: 38404033
DOI: 10.1177/10870547241226634 -
Microorganisms Feb 2024Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and...
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it is still unclear how these compositional changes contribute to disease etiology and progression. Furthermore, most of the available studies have focused on European, Asian, and North American cohorts, but the microbiomes of PD patients in Latin America have not been characterized. To address this problem, we obtained fecal samples from Colombian participants ( = 25 controls, = 25 PD idiopathic cases) to characterize the taxonomical community changes during disease via 16S rRNA gene sequencing. An analysis of differential composition, diversity, and personalized computational modeling was carried out, given the fecal bacterial composition and diet of each participant. We found three metabolites that differed in dietary habits between PD patients and controls: carbohydrates, trans fatty acids, and potassium. We identified six genera that changed significantly in their relative abundance between PD patients and controls, belonging to the families , , , , and . Furthermore, personalized metabolic modeling of the gut microbiome revealed changes in the predicted production of seven metabolites (Indole, tryptophan, fructose, phenylacetic acid, myristic acid, 3-Methyl-2-oxovaleric acid, and N-Acetylneuraminic acid). These metabolites are associated with the metabolism of aromatic amino acids and their consumption in the diet. Therefore, this research suggests that each individual's diet and intestinal composition could affect host metabolism. Furthermore, these findings open the door to the study of microbiome-host interactions and allow us to contribute to personalized medicine.
PubMed: 38399728
DOI: 10.3390/microorganisms12020325 -
Scientific Reports Feb 2024Dry eye syndrome (DES) is a complex ocular condition characterized by an unstable tear film and inadequate tear production, leading to tissue damage. Despite its common...
Dry eye syndrome (DES) is a complex ocular condition characterized by an unstable tear film and inadequate tear production, leading to tissue damage. Despite its common occurrence, there is currently no comprehensive in vitro model that accurately reproduce the cellular characteristics of DES. Here we modified a corneal epithelium-on-a-chip (CEpOC) model to recapitulate DES by subjecting HCE-T human corneal epithelial cells to an air-liquid (AL) interface stimulus. We then assessed the effects of AL stimulation both in the presence and absence of diclofenac (DCF), non-steroidal anti-inflammatory drug. Transcriptomic analysis revealed distinct gene expression changes in response to AL and AL_DCF, affecting pathways related to development, epithelial structure, inflammation, and extracellular matrix remodeling. Both treatments upregulated PIEZO2, linked to corneal damage signaling, while downregulating OCLN, involved in cell-cell junctions. They increased the expression of inflammatory genes (e.g., IL-6) and reduced mucin production genes (e.g., MUC16), reflecting dry eye characteristics. Metabolomic analysis showed increased secretion of metabolites associated with cell damage and inflammation (e.g., methyl-2-oxovaleric acid, 3-methyl-2-oxobutanoic acid, lauroyl-carnitine) in response to AL and even more with AL_DCF, indicating a shift in cellular metabolism. This study showcases the potential use of AL stimulus within the CEpOC to induce cellular characteristics relevant to DES.
Topics: Humans; Epithelium, Corneal; Dry Eye Syndromes; Tears; Inflammation; Diclofenac; Lab-On-A-Chip Devices
PubMed: 38379013
DOI: 10.1038/s41598-024-54736-z -
African Health Sciences Sep 2023To compare the effectiveness of paracervical block with intramuscular Diclofenac for pain relief during manual vacuum aspiration (MVA) for early pregnancy losses. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the effectiveness of paracervical block with intramuscular Diclofenac for pain relief during manual vacuum aspiration (MVA) for early pregnancy losses.
METHODOLOGY
This was an open label randomized controlled trial. Participants were randomized into two therapeutic groups (A and B) using computer generated numbers. Group A received intramuscular Diclofenac 75 mg. Group B received paracervical block using 1% Lidocaine. Participants were asked to rate their pain level on a continuous 10 cm visual analogue scale (VAS) from 0 (no pain) to 10 (the worst pain ever) within 5 minutes of completing the procedure. Participants' level of satisfaction was assessed within 30 minutes of completing the MVA using Likert scale. Data was analysed using the Statistical Package for Social Sciences (SPSS), Version 20. Test of statistical significance was set at 95% confidence level (P < 0.05). The primary outcome was the level of pain felt by the patient during the procedure (10 cm VAS). Secondary outcomes included patient's satisfaction and adverse events.
RESULTS
There was significant difference in the mean pain level between the intramuscular diclofenac group; 6.5±1.5 (moderate) and those that received paracervical block; 2.3±1.5 (mild), (p-value=0.005). Patients' satisfaction was also better in paracervical block group compared to intramuscular diclofenac group, (p-value=0.005). Both groups were comparable in terms of complications and drug side effects.
CONCLUSION
Findings from the study suggest that the use of paracervical block compared to intramuscular Diclofenac for pain relief during MVA for incomplete miscarriage significantly reduced pain, improved patients' satisfaction and was comparably safe.
Topics: Pregnancy; Female; Humans; Diclofenac; Vacuum Curettage; Anesthesia, Obstetrical; Pain; Lidocaine; Anesthetics, Local
PubMed: 38357159
DOI: 10.4314/ahs.v23i3.4 -
Journal of Agricultural and Food... Feb 2024Cranberries contain proanthocyanidins with different interflavan bond types and degrees of polymerization. These chemical differences may impact the metabolism of...
Cranberries contain proanthocyanidins with different interflavan bond types and degrees of polymerization. These chemical differences may impact the metabolism of proanthocyanidins by the intestinal microbiome. In our previous study, we found that healthy microbiomes produced higher concentrations of the phenolic acid metabolites 5-(3',4'-dihydroxyphenyl)--valerolactone and 3-hydroxyphenylacetic acid from the cranberry extract in comparison to ulcerative colitis (UC) microbiomes . To understand this difference, LC-ESI-MS/MS was utilized to characterize the metabolism of the precursor proanthocyanidins. Healthy microbiomes metabolized procyanidin A2, procyanidin B2, and procyanidin dimeric intermediates but not A-type trimers, to a greater extent than UC microbiomes. The metabolism of procyanidin A2 and procyanidin B2 by fecal microorganisms was then compared to identify their derived phenolic acid metabolites. 5-(3',4'-Dihydroxyphenyl)--valerolactone and 3-hydroxyphenylacetic acid were identified as unique metabolites of procyanidin B2. Based on these results, the metabolism of procyanidin B2 contributed to the differential metabolism observed between healthy and UC microbiomes.
Topics: Proanthocyanidins; Vaccinium macrocarpon; Tandem Mass Spectrometry; Gastrointestinal Microbiome; Dysbiosis; Colitis, Ulcerative; Fruit; Plant Extracts; Microbiota; Phenylacetates; Hydroxybenzoates
PubMed: 38350030
DOI: 10.1021/acs.jafc.4c00042 -
Acta Oncologica (Stockholm, Sweden) Feb 2024Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this...
BACKGROUND
Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this study was to use 'real-world' data to evaluate the effect and side effects of using methylphenidate in palliative cancer care with a focus on the late palliative phase and dose-response.
METHOD
A retrospective review of medical records from a palliative care unit in Sweden was performed to evaluate the effect and adverse events (AEs) of using methylphenidate to treat CRF. Univariable and multivariable regression was performed and odds ratio (OR) calculated. Adjustments were made for sex, age, cancer type, dose and starting treatment <4 weeks before death.
RESULTS
Of the 2,419 screened patients, 112 had been treated with methylphenidate for CRF. The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, including anxiety, palpitations, and insomnia. Patients starting the treatment <4 weeks before death (n = 54) were less likely to have an effect from treatment compared to those starting earlier; adjusted OR 0.24 (95% CI 0.10-0.55). Doses of 20 mg and above were well-tolerated and had a higher frequency of effect in the crude data but not after adjustment for confounding factors.
CONCLUSION
Methylphenidate is generally effective and well-tolerated for the treatment of CRF in palliative care. However, patients with a short life expectancy (<4 weeks) seem to benefit less from the treatment regardless of age, cancer type and dose.
Topics: Humans; Infant, Newborn; Methylphenidate; Palliative Care; Fatigue; Anxiety Disorders; Neoplasms
PubMed: 38348853
DOI: 10.2340/1651-226X.2024.24156 -
Chemosphere Mar 2024Unconventional substrata like activated carbon or clay beads can enhance micropollutant removal in constructed wetlands. However, hydroponic materials widely used in...
Unconventional substrata like activated carbon or clay beads can enhance micropollutant removal in constructed wetlands. However, hydroponic materials widely used in horticulture have not yet been investigated for their potential to remove micropollutants. In addition, potential effect of plant species other than reeds on micropollutant removal has not been sufficiently investigated. Therefore, a nature-based, post-treatment technology called improved vertical flow constructed wetlands (CW) with hydroponic (H) materials (CWH) was designed by employing cocopeat and mineral with ornamental plant species syngonium and periwinkle. A mesocosm CWH system was tested in a climate-controlled greenhouse for 550 days for its potential to remove frequently found micropollutants in wastewater, namely sulfamethoxazole, trimethoprim, diclofenac, erythromycin, carbamazepine, pyrimethanil, tebuconazole, pymetrozine, atrazine and DEET from wastewater effluent. The main focus was to understand the contribution of sorption, microbial degradation and phytoremediation on the removal of those micropollutants. It was found that cocopeat showed a capacity for sorbing micropollutants, ranging between 80 and 99% of the compounds added while less than 10% sorption was observed for mineral wool. Additionally moderate to high biological removal (25-60 μg of compound/kg dry weight of substratum/day) for most of the studied compounds was observed in all the cocopeat biotic groups. Furthermore, it could be stated that plants appear not to be an important factor for micropollutant removal. The observed differences in removal between the cocopeat and mineral wool systems could be explained by the difference in physico-chemical properties of the substrata, where cocopeat has a higher water holding capacity, moisture content, nutrient and organic matter content, and a higher intraparticle porosity and surface area. This study revealed notable removal of persistent and mobile micropollutants in cocopeat CWH, namely carbamazepine (80-86%) and diclofenac (97-100%). These results demonstrate the potential beneficial use of hydroponic materials as substratum in more advanced constructed wetlands designed to remove micropollutants.
Topics: Wastewater; Waste Disposal, Fluid; Wetlands; Hydroponics; Diclofenac; Water Pollutants, Chemical; Plants; Carbamazepine; Calcium Compounds; Silicates
PubMed: 38346507
DOI: 10.1016/j.chemosphere.2024.141388 -
Journal of Physiology and Pharmacology... Dec 2023We explored the involvement of orphan nuclear receptor 4 A1 (NR4A1) in myocardial fibrosis mediated by transforming growth factor-beta1 (TGF-β1) and its response to...
We explored the involvement of orphan nuclear receptor 4 A1 (NR4A1) in myocardial fibrosis mediated by transforming growth factor-beta1 (TGF-β1) and its response to cytosporone B (Csn-B). We developed a diabetic cardiomyopathy mouse model by administering a high-fat diet in conjunction with a low-dose streptozotocin injection. Our analysis involved monitoring alterations in blood glucose and lipid levels, cardiac function and structure, as well as profibrotic factors such as α smooth muscle actin (α-SMA), collagen I, collagen III, TGF-β1, connective tissue growth factor, and fibronectin. These assessments were conducted using biochemical techniques, Doppler ultrasound, histopathology, and real-time quantitative polymerase chain reaction. Cardiac fibroblasts (CFs) were extracted from suckling mice and cultivated in a high-glucose medium to simulate diabetes-induced myocardial fibrosis in vitro. These CFs were then subjected to coculture experiments with TGF-β1 or Csn-B. The proliferation and migration of CFs were assessed using cell counting kit 8 (CCK-8) assays and Transwell assays, respectively. Western blotting and immunofluorescence assays were employed to evaluate the expression levels of NR4A1, p-NR4A1, and α-SMA in CFs treated with TGF-β1 after NR4A1 knockdown or Csn-B administration, respectively. In diabetic heart tissue, the expression of p-NR4A1 was notably elevated. Furthermore, CFs exhibited enhanced proliferative capabilities and increased p-NR4A1 expression following high glucose exposure. Interestingly, NR4A1 knockdown resulted in a significant increase in the expression of fibrosis-related proteins in CFs following treatment with TGF-β1. Moreover, our observations revealed a marked decrease in p-NR4A1 levels and a reduction in the expression of fibrosis-related proteins after Csn-B treatment. In diabetic mice treated with Csn-B, we noted diminished NR4A1 phosphorylation and a mitigation of myocardial fibrosis. We concluded that in the mouse model, Csn-B played a pivotal role in inhibiting diabetes-induced myocardial fibrosis by activating NR4A1.
Topics: Animals; Mice; Collagen; Diabetes Mellitus, Experimental; Disease Models, Animal; Fibroblasts; Fibrosis; Glucose; Orphan Nuclear Receptors; Phenylacetates; Transforming Growth Factor beta1
PubMed: 38345443
DOI: 10.26402/jpp.2023.6.04