UPLC-ESI-QTOF-MS assisted targeted metabolomics to study the enrichment of vinca alkaloids and related metabolites in Catharanthus roseus plants grown under controlled LED environment.

Enrichment of pharmaceutically important vinca alkaloids, vinblastine and vincristine, in the leaves of Madagascar periwinkle (Catharanthus roseus) plants through different pre- or postharvest treatments or cultivation conditions, e.g., exposing the plants to UV-irradiation, has been in focus for decades. Controlled LED environment in the visible light range offers the possibility of monitoring the changes in the concentration of metabolites in the vinca alkaloid-related pathway without involving UV-related abiotic stress. In the frame of our targeted metabolomics approach, 64 vinca alkaloids and metabolites were screened with the help of a UPLC-ESI-QTOF-MS instrumental setup from the leaf extracts of C. roseus plants grown in chambers under control (medium light), low light, and high blue / high red/ high far-red conditions. Out of the 14 metabolites that could be assigned either unambiguously with authentic standards or tentatively with high resolution mass spectrometry-based methods, all three dimer vinca alkaloids, that is, 3',4'-anhydrovinblastine, vinblastine and vincristine showed an at least nine-fold enrichment under high blue irradiation when compared with the control conditions: final concentrations of 961 mg kg-1 dry weight, 33.8 mg kg-1 dry weight, and 11.7 mg kg-1 dry weight could be achieved, respectively. As supported by multivariate statistical analysis, the key metabolites of the vinca alkaloid pathway were highly represented among the metabolites that were specifically stimulated by high blue light application.

Hypokalemia as a responsible factor related with the severity of hepatic encephalopathy: a wide multination cross-sectional study.

Several precipitating factors of hepatic encephalopathy have been recognized and studied. Hepatic encephalopathy which is a frequent and grave complication of liver failure, is associated with multiple biochemical changes like high serum ammonia, mercaptan and phenol levels, low albumin levels and derangements in electrolytes. It is characterized by a range of neuronal and psychological aberrations mainly due to the inability of liver to metabolize different neurotoxic chemicals produced in the body. Hypokalemia is one of the most important findings in hepatic encephalopathy and postulated as a precipitating factor of the condition. The authors aimed to know the frequency of hypokalemia and its relation to the severity of hepatic encephalopathy. Methods: After taking approval from the hospital ethical review committee, a total of 5000 patients with hepatic encephalopathy were recruited by consecutive sampling. They were interviewed, examined and investigated for serum potassium levels and other precipitating factors of hepatic encephalopathy. Results: Total of 5000 patients including 3070 (61.4%) males and 1930 (38.6%) females, aging 13 years and above were studied. The frequency of hypokalemia was 78% (3900 patients). Relating the serum potassium level with the severity of hepatic encephalopathy, 1200 (60%) out of 2000 patients with serum potassium below 2.5 mEq/l were in grade 4 (40%) and 800 out of 2000 were in grade 3 encephalopathy. On the other hand, only 700 patients (6.4%) out 1100 with serum potassium above 3.4 mEq/l were in grade 4 encephalopathy. Conclusion: Hypokalemia is a frequent finding in patients with hepatic encephalopathy and found to be directly related to its severity.

Ecotoxicological monitoring of potentially toxic elements contamination in Eucalyptus forest plantation subjected to long-term irrigation with recycled wastewater.

Afforestation is an evergreen technology for restraining greenhouse gases (GHGs) emission and improving soil carbon sink in arid and semi-arid regions. Nonetheless, the long-term impact of woody forests irrigation using recycled wastewater resources remains inconclusive so far. For this purpose, the ecological risk benchmarks of potentially toxic elements (PTEs) were investigated on Eucalyptus forest plantation in order to gauge their bioavailability in the rhizospheric layer of Typic Torripsammentsoil and their accretion capacity in the biosphere. Water quality guidelines pointed to a moderate degree of restriction on use with elevated levels of PTEs. Notably, concentrations of As, B, Cd, Cr, Cu, Mn, Ni, V and Zn were above the permissible limits for irrigation. The geospatial mapping of PTEs concentration in soil pointed to elevated levels of most PTEs, particularly in the deforestated areas. Some of PTEs (Cd, Cu, Hg and Zn) showed values above the permissible limits. A spectrum of ecological risk indices showed considerable to high degree of contamination. Among PTEs, the water-soluble and exchangeable fractions showed high values of As, Cd and Hg (20.7, 17.2 and 11.0%, respectively). Sequential extraction showed variations among PTEs in their tendency to bind with different soil geochemical fractions: (i) carbonate (Cd, Zn and Cu), (ii) Fe-Mn oxides (Pb, Zn and Mn) and (iii) organic matter (B, Pb and Hg). Eight fungal species including Aspergillus flavus, Fusarium solani, Cephalosporimsp., Penicilliumsp., Rhizoctonia solani, Aspergillus niger, Botrytissp. and Verticilliumsp. were dominated in soil. Meanwhile, Agrobacteriumsp., phosphate solubilizing bacteria, nitrogen fixing bacteria and Escherichia coli were the dominant bacterial strains. Values of bioaccumulation index varied among PTEs, wherein B (5.15), Ni (1.98), Mn (1.62) and Cd (1.02) exhibited higher phytoextraction potentials. Other PTEs, however, exhibited values below 1.0 confirming their low phytoextraction potentials. Findings of this investigation, therefore, provide insights into biochemical signals of PTEs contamination in woody forest plantations and the urgent need to contextualize the large-scale utilization of recycled wastewater resources in such vulnerable areas.

Gum Acacia attenuates cisplatin toxic effect spermatogenesis dysfunction and infertility in rats.

This study aimed to investigate the potential benefits Gum Arabic/Acacia senegal (GA) in mitigating the harmful effects of cisplatin (CP) on spermatogenesis and testicular health in male adult rats. A total of forty albino rats were used in the study and divided into four groups; control, GA, CP, and Co-treated group, which received both CP and GA concurrently. The results revealed that CP caused a significant increase in oxidative stress and a decrease in antioxidant activities (CAT, SOD, and GSH), which disturbed the testicular machinery. This caused significant histological and ultrastructural damage to the testicular structure, including atrophied seminiferous tubules with severely reduced germinal epithelium. Additionally, CP caused a decrease in reproductive hormones (testosterone and LH), a decline in nucleic proliferation PCNA immunoexpression, and an increase in cytoplasmic apoptotic Caspase-3 protein expression in testicular tissue, when compared to the control and GA groups. Moreover, the CP treatment impaired spermatogenesis and decreased sperm number and motility with abnormal morphology. However, co-administration of GA with CP mitigated the dysfunction in spermatogenesis and reversed testicular damage caused by CP through significantly (P < 0.01) reducing oxidative stress (MDA) and increasing the activities of CAT, SOD, and GSH. Additionally, co-administration of GA elevated the levels of testosterone and luteinizing hormone in blood sera, significantly (P < 0.01) improved the histometric measurements of seminiferous tubules diameter, their epithelial height, Johnsen's score of spermatogenesis, 4-level histological grading scale Cosentino's score, immunohistochemical expression of nucleic PCNA, and cytoplasmic Caspase-3 proteins. Furthermore, TEM examination confirmed the synergistic effect of GA in restoring the germinal epithelial cells ultrastructure, the elongated and transverse sections of spermatozoa in the lumen, and the interstitial tissue. All of these effects resulted in a significant improvement in sperm quality in the Co-treated animals compared with the CP group, as well as, a significant decline in the morphological abnormalities of sperm in Co-treated rats compared to those in the CP group. GA is a valuable agent for ameliorating chemotherapy-related infertility.

Prognostic factors affecting infantile medulloblastoma outcomes in the molecular era: a 12-year single-center experience from Egypt.

Aims: To assess the clinical, pathological and molecular characteristics (Sonic hedgehog and group 3/4 molecular subtypes expression) and treatment modalities for infantile medulloblastoma in correlation with outcomes. Materials & methods: A retrospective study of 86 medulloblastoma patients (≤3 years) was conducted. M0 patients <2.5 years received four cycles of chemotherapy followed by focal radiotherapy (FRT) and chemotherapy. Between 2007 and 2015, Metastatic patients <2.5 years received craniospinal irradiation (CSI) after the end of chemotherapy. After 2015, metastatic patients <2.5 years received CSI postinduction. Results: The hazard ratio for death was significantly higher in the FRT (HR = 2.8) group compared with the CSI group (hazard ratio = 1). Metastatic disease significantly affected the overall survival of the Sonic hedgehog group and the overall survival and event-free survival of group 3/4. Conclusion: Metastatic disease had a significant impact on outcomes. FRT is not effective in treating infantile medulloblastoma.

This study aimed to analyze the management of and prognostic factors affecting the outcomes of 86 young children (<3 years of age at presentation) diagnosed with medulloblastoma, an aggressive brain tumor that is commonly seen in this age group. All children had surgical operations aiming at resecting their tumors, followed by chemotherapy and irradiation. Study results showed that disease disseminated into the nervous system was associated with poorer outcomes compared with localized disease. Administration of local irradiation to the primary tumor site in the brain only, without exposing the spinal cord to radiotherapy, was associated with a higher risk of death.

Fault Detection and Classification of CIGS Thin-Film PV Modules Using an Adaptive Neuro-Fuzzy Inference Scheme.

The use of artificial intelligence to automate PV module fault detection, diagnosis, and classification processes has gained interest for PV solar plants maintenance planning and reduction in expensive inspection and shutdown periods. The present article reports on the development of an adaptive neuro-fuzzy inference system (ANFIS) for PV fault classification based on statistical and mathematical features extracted from outdoor infrared thermography (IRT) and I-V measurements of thin-film PV modules. The selection of the membership function is shown to be essential to obtain a high classifier performance. Principal components analysis (PCA) is used to reduce the dimensions to speed up the classification process. For each type of fault, effective features that are highly correlated to the PV module's operating power ratio are identified. Evaluation of the proposed methodology, based on datasets gathered from a typical PV plant, reveals that features extraction methods based on mathematical parameters and I-V measurements provide a 100% classification accuracy. On the other hand, features extraction based on statistical factors provides 83.33% accuracy. A novel technique is proposed for developing a correlation matrix between the PV operating power ratio and the effective features extracted online from infrared thermal images. This eliminates the need for offline I-V measurements to estimate the operating power ratio of PV modules.

Role of endoscopic ultrasound in evaluation of patients with missed common bile duct stones.

BACKGROUND: Choledocholithiasis develops in up to 20% of patients with gall bladder stones. The challenge in diagnosis usually occurs with small stones that may be missed by magnetic resonance cholangiopancreatography (MRCP). Endoscopic ultrasound (EUS) is accurate in detecting common bile duct (CBD) stones missed by MRCP, especially the small ones or those impacted at the distal CBD or the papillary region. AIM: To evaluate the accuracy of EUS in detecting CBD stones missed by MRCP. METHODS: Patients with an intermediate likelihood of choledocholithiasis according to ESGE guidelines and those with acute pancreatitis of undetermined cause were included. The presence of choledocholithiasis was evaluated by MRCP and EUS, and then results were confirmed by endoscopic retrograde cholangiopancreatography (ERCP). The sensitivity and specificity of EUS and MRCP were compared regarding the presence of stones, the size, and the number of detected stones. RESULTS: Ninety out of 100 involved patients had choledocholithiasis, while ten patients were excluded as they had pancreatic or gall bladder masses during EUS examination. In choledocholithiasis patients, the mean age was 52.37 ± 14.64 years, and 52.2% were males. Most patients had biliary obstruction (74.4%), while only 23 (25.6%) patients had unexplained pancreatitis. The overall prevalence of choledocholithiasis was 83.3% by EUS, 41.1% by MRCP, and 74.4% by ERCP. Also, the number and size of CBD stones could be detected accurately in 78.2% and 75.6% by EUS and 41.1% and 70.3% by MRCP, respectively. The sensitivity of EUS was higher than that of MRCP (98.51% vs 55.22%), and their predictive value was statistically different (P < 0.001). Combination of both tools raised the sensitivity to 97.22% and specificity to 100%. CONCLUSION: EUS could be a useful tool in assessing patients with suspected choledocholithiasis especially if combined with MRCP. However, its usefulness depends on its availability and the experience of the local centers.

Impact on plant productivity under low-fertility sandy soil in arid environment by revitalization of lentil roots.

Lentil is one of the essential legume crops, which provides protein for humans and animals. This legume can improve soil fertility through nitrogen fixation, which is imperative in low-fertility soils. The growth and productivity of lentil could be enhanced through improving nutrition and root revitalization. Therefore, the objective of this study was to assess the impact of root activator (RA) and phosphorus (P) application on morphological, physiological, agronomic, and quality traits of lentil under newly reclaimed low-fertility sandy soil in an arid environment. The RA was applied at four levels of 0 (RA0-untreated control), 1.25 (RA1), 2.5 (RA2), and 3.75 (RA3) l ha-1. RA contained 9% potassium humate, 1,600 ppm indole butyric acid, 200 ppm gibberellic acid, and 200 ppm naphthalene acetic acid. The recommended rate of phosphorus (P) fertilization in the newly reclaimed low-fertility sandy soil (75 kg P2O5 ha-1) was applied, and its amount was increased and decreased by 25 kg P2O5 ha-1 vs. non-added control. Thus, P rates were applied at four rates 0 (P0; control), 50 (P1), 75 (P2), and 100 (P3) kg phosphorus pentoxide (P2O5) ha-1. Our results revealed that treated lentil plants with the high levels of both treatments (RA3 and P3) exhibited superiority in root measurements (root length, total number of nodules plant-1, number of active nodules plant-1, dry weights of active nodules, and total root), nitrogenase activity, chlorophyll a and b, carotenoids, yield traits, and seed proteins and carbohydrates. However, the recommended P level (75 kg P2O5 ha-1, P2) under the high level of RA (3.75 l ha-1, RA3) displayed non-significant differences in yield traits (plant height, 1,000-seed weight, seed yield ha-1) and quality traits (protein and carbohydrate) with the high P level (100 kg P2O5 ha-1, P3). Accordingly, its recommended economically and environmentally to use this coapplication of RA3 and P3 in low-fertility soil for better lentil growth, and seed yield and quality.

Consecutive seasonal effect on yield and water productivity of drip deficit irrigated sorghum in saline soils.

Drought stress destructively affects the growth and productivity of sorghum crop, especially under saline soils. Therefore, Field trials were performed to determine the influence of water stress on water productivity (water productivity for grain, (G-WP) and water productivity for forage, (F-WP), yield of sorghum and soil properties in salt-affected soil (8.20 dS m-1) under different sowing dates and irrigation regimes. The summer sowing (SS) was performed on 1 April while fall sowing (FS) was established on 2 August. The irrigation regimes were; 100, 90, 80, and 70% of crop evapotranspiration (ETc). The findings displayed that the fodder and grain yields were increased by 23% and 26% under SS compared to FS over the two seasons 2017 and 2018, respectively. Among irrigation levels, the maximum values of grain and fodder yield were given by 100% of ETc, while a non-significant difference was observed between 100% and 90% of ETc. Moreover, the maximum values of G-WP (1.31%) and F-WP (9.00%) were recorded for 90% of ETc. Interestingly, the soil salinity was decreased in 0-0.6 m depth, and more decline was noted in 0-0.2 m depth using 90% of ETc. The highest salt accumulation withinside the soil profile was recorded under 70% of ETc in comparison to 100% of ETc. Thereupon, under water scarcity, application of 90% of ETc is recommended with SS to save 10% of the applied irrigation water without a significant decrease in grain yield (GY).

Management and outcome of pediatric brainstem and cerebellar peduncular low-grade gliomas: a retrospective analysis of 62 cases.

PURPOSE: This study was designed to present our experience and recommendations regarding the management of pediatric brainstem and peduncular low-grade gliomas (LGGs). METHODS: Retrospective analysis was performed for pathologically proven brainstem or cerebellar peduncular LGGs in patients admitted between 2014 and 2019. These lesions were classified into the dorsal exophytic, focal brainstem, cervicomedullary, lower peduncular, and upper peduncular groups, and this classification was the basis for the surgical approach for the lesions. RESULTS: Sixty-two pediatric patients were included, and their distribution among the aforementioned groups were as follows: 12, 12, 3, 16, and 19 cases in the dorsal exophytic, focal brainstem, cervicomedullary, upper peduncular, and lower peduncular groups, respectively. Stereotactic biopsy was performed for all cases in the focal brainstem group, whereas other groups underwent open excision. Gross total resection (GTR) was achieved in 20 cases (40%), near-total resection (NTR) was achieved in 17 cases (34%), and subtotal resection (STR) was achieved in 13 cases (26%). The extent of GTR and NTR for the upper peduncular, lower peduncular, dorsal exophytic, and cervicomedullary groups were 81.2%, 68.4%,75%, and 66.6%, respectively. Then, 32 cases received chemotherapy. The 3- and 5-year progression-free survival rates were 95% (95% confidence interval (CI) 89.5-100%) and 90.3% (95% CI 79.9-100%), respectively. A significant difference in the 3-year progression-free survival rate was observed between the GTR and NTR groups (p = 0.06; 100% vs. 88.2% (95% CI 72.9-100%)). CONCLUSION: Surgery plays a definitive curative role in grossly resected cases. Additionally, the role of surgical debulking should be considered, even if GTR is impossible. Meanwhile, chemotherapy showed a beneficial role in patients with focal brainstem lesions and progressive lesions, those with STR, and some patients with NTR.

Molecular characterization of Toll-like receptor type-3 in mallard duck and its response to Newcastle disease virus infection.

Toll-like receptors (TLRs), type I transmembrane pattern recognition receptors (PRRs), are composed of the extracellular domain that is implicated in the recognition of microbial products and initiates the innate and adaptive immune response. Previous reports on TLRs in birds showed significant levels of inter- and intraspecific genetic variation. Little is known about the structure and function of the avian immune system, especially waterfowl species. This work aimed to identify and clone Anas platyrhynchos (mallard duck) TLR-3 (dTLR-3) and its expression level following challenge with velogenic Newcastle disease virus (NDV) as a model for waterfowl species. The mallard duck TLR-3 full-length cDNA sequence had been cloned, which consisted of 2457 nucleotides. The translated amino acid sequence showed identity degree as 97% with Muscovy duck, 95% with geese, 89% with helmeted guineafowls, 88% with the chickens TLR-3 gene, 82% with turkey TLR-3, and 79% with zebra finch, while it showed 54% with human one; the analysis data suggested that the new sequence is probably homologous to vertebrates' TLR-3. The predicted protein encoded by the duck dTLR-3 mRNA sequence is composed of 819 amino acids. Analysis of the deduced amino acid sequence indicated that dTLR-3 has typical structural features and contains the main components of proteins in the TLR family. The dTLR-3 expressed in almost all examined tissues of mallard duck following quantitative real-time polymerase chain reaction (qPCR) analysis and using B-actin as a housekeeping gene. To check the functionality of the receptor and its role in viral infection, we evaluate the expression level in different tissues and its changes following NDV infection. The results showed significant (P < 0.05) upregulated in the brain at 24 h (1.84-fold), reached a peak at 48 h (4.82-fold), and recovered to normal levels at 72 h post-infection. These results indicate a complete and functional dTLR-3 that is orthologous to other vertebrate receptors with its potential role in early response against viral infection in mallard duck species.

Sequential Antioxidants Foliar Application Can Alleviate Negative Consequences of Salinity Stress in Vicia faba L.

Salinity is one of the most limiting abiotic stresses in agricultural productivity. Exogenously applied antioxidants successfully enabled salt-stressed plants to cope with stress. Two-season field experiments were conducted consecutively in 2016/17 and 2017/18 to study the effects of foliar applications of singular (ascorbate, AsA; proline, Pro; and glutathione, GSH) or sequential (AsA-Pro-GSH and GSH-Pro-AsA) antioxidants on growth, yield, physio-biochemical attributes, and enzymatic and non-enzymatic antioxidative defense system of Vicia faba L. (CV. Sakha-1) plants grown under saline soil conditions (EC = 4.53 dS m-1). Under soil salinity conditions, AsA, Pro, or GSH-Pro-ASA improved growth and productivity, photosynthesis efficiency, stomatal conductance (gs), plant water status, as well as enzymatic and non-enzymatic antioxidants. However, sequential AsA-Pro-GSH foliar application followed by singular GSH significantly exceeded all other treatments (i.e., AsA, Pro, and GSH-Pro-AsA), improving growth characteristics (shoot length, shoot fresh and dry weights, and leaves area), photosynthesis efficiency, stomatal conductance, plant water status, and yield and its components (green pods weight/plant-1, green pods yield/hectare-1, and seed yield/hectare-1), as well as enzymatic (ascorbate peroxidase, catalase, superoxide dismutase, and glutathione reductase) and non-enzymatic (AsA, GSH, Pro, phenolic aglycone, phenolic glycosides) antioxidants compared to control. Overall, our results clearly demonstrate that sequential AsA-Pro-GSH foliar application has a positive effect on salt-stressed Vicia faba plants.

A Framework for Revisiting Brain Death: Evaluating Awareness and Attitudes Toward the Neuroscientific and Ethical Debate Around the American Academy of Neurology Brain Death Criteria.

BACKGROUND: There remains a lack of awareness around the American Academy of Neurology (AAN) procedural criteria for brain death and the surrounding controversies, leading to significant practice variability. This survey study assessed for existing knowledge and attitude among healthcare professionals regarding procedural criteria and potential change after an educational intervention. METHODS: Healthcare professionals with increased exposure to brain injury at Mayo Clinic hospitals in Arizona and Florida were invited to complete an online survey consisting of 2 iterations of a 14-item questionnaire, taken before and after a 30-minute video educational intervention. The questionnaire gathered participants' opinion of (1) their knowledge of the AAN procedural criteria, (2) whether these criteria determine complete, irreversible cessation of brain function, and (3) on what concept of death they base the equivalence of brain death to biological death. RESULTS: Of the 928 people contacted, a total of 118 and 62 participants completed the pre-intervention and post-intervention questionnaire, respectively. The results show broad, unchanging support for the concept of brain death (86.8%) and that current criteria constitute best practice. While 64.9% agree further that the loss of consciousness and spontaneous breathing is sufficient for death, contradictorily, 37.6% believe the loss of additional integrated bodily functions such as fighting infection is necessary for death. A plurality trusts these criteria to demonstrate loss of brain function that is irreversible (67.6%) and complete (43.6%) at baseline, but there is significantly less agreement on both at post-intervention. CONCLUSION: Although there is consistent support that AAN procedural criteria are best for clinical practice, results show a tenuous belief that these criteria determine irreversible and complete loss of all brain function. Despite support for the concept of brain death first developed by the President's Council, participants demonstrate confusion over whether the loss of consciousness and spontaneous breath are truly sufficient for death.