Tag: nevin manimala

Inflammopharmacology. 2023 Sep 4. doi: 10.1007/s10787-023-01313-x. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-β (Aβ) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1β, and CRP activity, and the western blot results demonstrate the significantly attenuated Aβ aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aβ aggregation might be a novel target for the development of AD.

PMID:37665449 | DOI:10.1007/s10787-023-01313-x

Environ Sci Pollut Res Int. 2023 Sep 4. doi: 10.1007/s11356-023-29536-z. Online ahead of print.

ABSTRACT

Global warming is currently an area of concern. Human activities are the leading cause of urban greenhouse gas intensification. Inversing the spatial distribution of carbon emissions at microscopic scales such as communities or controlling detailed planning plots can capture the critical emission areas of carbon emissions, thus providing scientific guidance for intracity low-carbon development planning. Using the Sino-Singapore Tianjin Eco-city as an example, this paper uses night-light images and statistical yearbooks to perform linear fitting within the Beijing-Tianjin-Hebei city-county region and then uses fine-scale data such as points of interest, road networks, and mobile signaling data to construct spatial characteristic indicators of carbon emissions distribution and assign weights to each indicator through the analytic hierarchy process. As a result, the spatial distribution of carbon emissions based on detailed control planning plots is calculated. The results show that among the selected indicators, the population distribution significantly influences carbon emissions, with a weight of 0.384. The spatial distribution of carbon emissions is relatively distinctive. The primary carbon emissions are from the Sino-Singapore Cooperation Zone due to its rapid urban construction and development. In contrast, carbon emissions from other areas are sparse, as there is mostly unused land under construction.

PMID:37665441 | DOI:10.1007/s11356-023-29536-z

Neurosurg Rev. 2023 Sep 4;46(1):222. doi: 10.1007/s10143-023-02111-3.

ABSTRACT

Cerebral aneurysm is one of the common cerebrovascular diseases in neurosurgery, and rupture of cerebral aneurysm is the most important cause of spontaneous subarachnoid hemorrhage. How to precisely clip the aneurysm has been a topic worth discussing, so the authors explore the value of ICGA combined with electrophysiological monitoring in the microclipping of cerebral aneurysms. Using the method of retrospective analysis of cases, 661 patients with cerebral aneurysms admitted to the Department of Neurosurgery, Zhongnan Hospital of Wuhan University, from 2021.8 to 2022.10 were studied, 390 patients with aneurysm clipping were included, and patients with Hunt-Hess classification ≥ 4 were excluded, and whether to use ICGA combined with EP in microclipping of the ruptured and unruptured aneurysm in pterional approach was investigated at the time of discharge, respectively. The MRS and total hospital days were compared to investigate the value of ICGA combined with EP in the microclipping of cerebral aneurysms. All 390 patients enrolled in the group had successful aneurysm clipping, 178 patients were screened for ruptured aneurysm pterional approach and 120 patients for unruptured aneurysm pterional approach access; the MRS at discharge was significantly lower in the ICGA combined with EP group than in the no-EP group for ruptured aneurysm pterional approach microclipping (p < 0.001), and the mean number of days in hospital was significantly lower (p < 0.01). Patients in the ICGA combined with EP group in microclipping of unruptured aneurysms with pterional approach also had significantly lower MRS at discharge compared with patients in the ICGA alone group (p < 0.001), with no statistically significant difference in the mean number of days in hospital (p = 0.09). In open cerebral aneurysm microclipping, ICGA combined with EP monitoring for both ruptured and unruptured aneurysms can effectively reduce the false-negative rate of ICGA, significantly reduce the incidence of postoperative neurological deficits, and shorten the total hospital stay to some extent. ICGA combined with EP monitoring may be an effective means to reduce the rate of false clipping of the penetrating vessels and to avoid stenosis or occlusion of the aneurysm-carrying artery and is worth promoting in microclipping of cerebral aneurysms except for Hunt-Hess ≥ 4.

PMID:37665412 | DOI:10.1007/s10143-023-02111-3

Eur Radiol. 2023 Sep 4. doi: 10.1007/s00330-023-10164-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis.

METHODS: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs).

RESULTS: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869).

CONCLUSION: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL.

CLINICAL RELEVANCE STATEMENT: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology.

KEY POINTS: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility.

PMID:37665391 | DOI:10.1007/s00330-023-10164-7

Eur Radiol. 2023 Sep 4. doi: 10.1007/s00330-023-10194-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer.

METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (K^trans), rate constant (k_ep), fractional extravascular extracellular space volume (v_e), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters.

RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. K^trans was lower in severe acute RRI group than mild acute RRI group (0.032 min^-1 vs 0.054 min^-1; p = 0.008), but difference of other parameters (k_ep, v_e and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of K^trans was 0.72 (95% confidence interval: 0.57, 0.84). With a K^trans cutoff value of 0.047 min^-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively.

CONCLUSION: K^trans demonstrated moderate diagnostic performance in predicting severe acute RRI.

CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury.

KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (K^trans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

PMID:37665390 | DOI:10.1007/s00330-023-10194-1

Knee Surg Sports Traumatol Arthrosc. 2023 Sep 4. doi: 10.1007/s00167-023-07555-0. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the safety and efficacy of intra-knee stromal vascular fraction (SVF) injection in patients with symptomatic knee osteoarthritis at the midterm (3-year) follow-up.

METHODS: SVF injection was applied to 25 knees of 20 patients. Eighteen patients (90%) were female, and the means ± standard deviations of age was 61.9 ± 7.8 (range, 50-76) years. Patients who received conservative treatment for at least 6 months and had radiographic Kellgren-Lawrence (K-L) grades 2 and 3 varus gonarthrosis were included in the study. SVF was obtained from the umbilical region by liposuction using local anaesthesia. Patients were followed-up for 36 months. Their visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Lysholm scores were evaluated before and at 6, 12, 24 and 36 months post-SVF injection.

RESULTS: A statistically significant improvement (p < 0.05) was observed in VAS, WOMAC and Lysholm scores at the first 2-year follow-up compared to baseline. However, no statistically significant difference (n.s.) was observed in VAS, WOMAC and Lysholm scores at the 3-year follow-up compared with baseline.

CONCLUSION: Intra-articular SVF injection decreased pain and significantly improved the functional outcomes in the first 2 years in knees with grade 2-3 osteoarthritis; however, these positive effects of the injection disappeared in the 3rd year. Although short-term successful results of SVF have been reported in the literature, prospective studies are needed for medium- and long-term results.

PMID:37665373 | DOI:10.1007/s00167-023-07555-0

Arch Toxicol. 2023 Sep 4. doi: 10.1007/s00204-023-03572-7. Online ahead of print.

ABSTRACT

Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC-MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones.

PMID:37665362 | DOI:10.1007/s00204-023-03572-7

Integr Environ Assess Manag. 2023 Sep 4. doi: 10.1002/ieam.4836. Online ahead of print.

ABSTRACT

Quantifying the effects of environmental stressors on natural resources is problematic due to complex interactions among environmental factors that influence endpoints of interest. This complexity, coupled with data limitations, propagates uncertainty that can make it difficult to causally associate specific environmental stressors with injury endpoints. The Natural Resource Damage Assessment and Restoration (NRDAR) regulations under the Comprehensive Environmental Response, Compensation, and Liability Act and Oil Pollution Act aims to restore natural resources injured by oil spills and hazardous substance releases into the environment; exploration of alternative statistical methods to evaluate effects could be beneficial to addressing NRDAR legal claims. Bayesian networks (BNs) are statistical tools that can be used estimate the influence and interrelatedness of abiotic and biotic environmental variables on environmental endpoints of interest. We investigated the application of a BN for injury assessment using a hypothetical case study by simulating data of acid mine drainage (AMD) affecting a fictional stream-dwelling bird species. We compared the BN-generated probability estimates for injury to a more traditional approach using toxicity thresholds for water and sediment chemistry. BNs offered several distinct advantages compared to traditional approaches, including formalizing the use of expert knowledge, probabilistic estimates of injury using intermediate direct and indirect effects, and the incorporation of a more nuanced and ecologically relevant representation of effects. Given the potential that BNs have for natural resource injury assessment, more research and field-based application is needed to determine their efficacy in NRDAR. We expect the resulting methods will be of interest to many U.S. Federal, State, and Tribal programs devoted to the evaluation, mitigation, remediation, and/or restoration of natural resources injured by releases or spills of contaminants.

PMID:37664978 | DOI:10.1002/ieam.4836

Pediatr Blood Cancer. 2023 Sep 4:e30658. doi: 10.1002/pbc.30658. Online ahead of print.

ABSTRACT

BACKGROUND: Topotecan, an antitumor drug with systemic exposure (SE)-dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure-response relationships.

PROCEDURE: Our previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies. A simulation-based Bayesian analysis was performed to determine if a single blood sample could be sufficient to estimate individual topotecan clearance. Following the Bayesian approach, single pharmacokinetic samples collected from a Children’s Oncology Group Phase III clinical trial (ANBL0532; NCT0056767) were analyzed to estimate individual topotecan SE. Associations between topotecan SE and toxicity or early response were then evaluated.

RESULTS: The updated population model included the impact of patient body surface area (BSA), age, and renal function on topotecan clearance. The Bayesian analysis with the updated model and single plasma samples showed that individual topotecan clearance values were estimated with good precision (mean absolute prediction error ≤16.2%) and low bias (mean prediction error ≤7.2%). Using the same approach, topotecan SE was derived in patients from ANBL0532. The exposure-response analysis showed an increased early response after concomitant cyclophosphamide and topotecan up to a topotecan SE of 45 h ng/mL.

CONCLUSIONS: A simple single-sample approach during topotecan therapy could guide dosing for patients, resulting in more patients reaching target attainment.

PMID:37664968 | DOI:10.1002/pbc.30658

Front Biosci (Landmark Ed). 2023 Aug 23;28(8):175. doi: 10.31083/j.fbl2808175.

ABSTRACT

BACKGROUND: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD.

METHODS: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models.

RESULTS: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control.

CONCLUSIONS: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.

PMID:37664927 | DOI:10.31083/j.fbl2808175