Umgang mit hochbegabten Schülern – mit Förderungsmöglichkeiten problematischen Entwicklungen entgegentreten

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Investigating the association between the autophagy markers LC3B, SQSTM1/p62, and dram and autophagy-related genes in glioma

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers\u27 expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions

AB059. Molecular signatures for survival prediction in glioma: A prospective, real-world data analysis

Background: Glioma characterization and follow-up are underreported from low-and-middle-income country centers within the literature. With the recent emphasis on molecular markers for survival prediction, there is a need for robust data exploring molecular epidemiology in these countries. In Pakistan particularly, there is a significant gap in glioma outcomes reporting and survival analysis.Methods: One hundred and sixty-five consecutive glioma patients were enrolled from 2019 onwards; histopathological and molecular analysis was performed on archived formalin-fixed paraffin-embedded (FFPE) blocks for isocitrate dehydrogenase (IDH), P53, α-thalassemia retardation X-linked (ATRX) and Ki-67 immunohistochemical (IHC) markers. Survival analysis was calculated using the Kaplan-Meier method; hazard ratios are reported through a multivariate Cox regression model.Results: Fifty-seven (35%) histopathological diagnoses were revised according to the updated criteria; 30% (n=16) glioblastoma were converted to a new category on re-analysis. IDH wild type (IDH-WT) gliomas had a significantly worse overall survival (log-rank =0.002), with a 2-year survival rate of 60% for IDH-mutant (IDH-M) and 38% for IDH-WT. Significant survival differences were seen for the Ki-67 index (log-rank =0.001) and methylguanine methyltransferase (MGMT) promotor methylation [log-rank =0.027, 2-year survival rate: 100% (methylation detected), 33% (methylation not detected)]. On Cox proportional hazards regression, gross total resection (P\u3c0.001), IDH mutation (P\u3c0.001), and updated histopathological diagnosis (P\u3c0.001) were significant predictors of survival, with good sensitivity and specificity as seen on receiver operating characteristic (ROC) analysis [area under the curve (AUC) =0.86].Conclusions: In our cohort, the revised World Health Organization (WHO) classification shows significant implications on prognosis and implications for treatment. Although these markers are not commonly used in low-and-middle-income country centers, our results strongly support their greater implementation for improved prognostication and reclassification

Autophagy-associated biomarkers ULK2, UVRAG, and miRNAs miR-21, miR-126, and miR-374: Prognostic significance in glioma patients

As the pioneering study from Pakistan, our research distinctly focuses on validating the roles of autophagy-associated genes and MicroRNAs (miRs) in the unique context of our population for glioma prognosis. The study delves into the nuanced interplay of autophagy within a miR-modulated environment, prompting an exploration of its potential impact on glioma development and survival. Employing real-time PCR (qPCR), we meticulously assessed the expression profiles of autophagy genes and miRs in glioma tissues, complemented by immunohistochemistry on Formalin-fixed paraffin-embedded tissues from the same patients. Our comprehensive statistical analyses, including the data normality hypothesis Shapiro-Wilk test, the Mann-Whitney U-test, Spearman correlation test, and Kaplan-Meier survival analysis, were tailored to unravel the intricate associations specific to low- and high-grade glioma within our population. Clinicopathological analysis revealed a predominance of male patients (66%) with a median age of 35 years. Glioblastoma (32%) and Astrocytoma (36%) were the most prevalent histopathological subtypes. Molecular analysis showed significant correlations between prognostic markers (Ki-67, IDH-1, p53) and clinicopathological factors, including age, histological type, radiotherapy, and chemotherapy. In high-grade glioma, increased expression of AKT and miR-21, coupled with reduced ULK2 and LC3 expression was distinctly observed. While correlation analysis identified a strong positive correlation between ULK2 and UVRAG, PTEN, miR-7, and miR-100 in low-grade glioma, unveiling distinctive molecular signatures unique to our study. Furthermore, a moderate positive correlation emerged between ULK2 and mTOR, miR-7, miR-30, miR-100, miR-204, and miR-374, also between miR-21 and miR-126. Similarly, a positive correlation appeared between ULK2 and AKT, LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7 and miR-374. AKT positively correlated with LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7, miR-30, miR-204, miR-374, miR-126 and miR-21 weakly correlated with AKT and miR-30 in high-grade glioma, providing further insights into the autophagy pathway within our population. The enrichment analysis for miR-21, miR-126, and miR-374 showed MAPK pathway as a common pathway along with Ras, PI3K, and mTOR pathway. The low ULK2, UVRAG, and miR-374 expression group exhibited significantly poor overall survival in glioma, while miR-21 over-expression indicated a poor prognosis in glioma patients, validating it in our population. This study provides comprehensive insights into the molecular landscape of gliomas, highlighting the dysregulation of autophagy genes ULK2, and UVRAG and the associated miR-21, miR-126 and miR-374 as potential prognostic biomarkers and emphasizing their unique significance in shaping survival outcomes in gliomas within the specific context of the Pakistani population

Environmental, Energy, and Water Footprints of Marble Tile Production Chain in a Life Cycle Perspective

The marble industry is growing in Pakistan, and Khyber Pakhtunkhwa province is the largest producer of marble tiles in Pakistan. Marble production consumes a considerable amount of water during its life cycle stages and impacts various environmental compartments, such as air, water, and soil; therefore, this study aimed to quantify the environmental impacts, water footprint, and cumulative energy demand of one-tonne marble tile manufactured in a small industrial estate Mardan (SIEM), Pakistan, and provide recommendations to improve its environmental impact profile. The study covers water consumption, energy use, and associated environmental impacts of raw materials and processes through different stages of the marble life-cycle during 2017–2018. The cradle-to-gate (extraction to factory gate or store house) life cycle assessment approach was followed in this study. The functional unit for the current study was one tonne of finished marble tile produced. Primary data from the field surveys and secondary data were modeled using the water scarcity index (WSI), CML 2000 v.2.05 methodology, and the cumulative energy demand indicator present by default in SimaPro v.8.3 software. The total water footprint required for one tonne of finished marble tile was 3.62 cubic meters per tonne (m3/t), with electricity consumed at processing units contributing to environmental burdens the most. Similarly, electricity consumed (at processing units and during polishing) and transportation of finished marble tile to the local market were responsible for global warming potential (388 kg CO2 eq/tonne tile), human toxicity (84.34 kg 1,4-DB-eq/tonne), freshwater aquatic ecotoxicity (94.97kg 1,4-DB eq/tonne) and abiotic depletion (7.1 × 10−5 kg Sb eq/tonne). The results of our study follow other marble tile LCA studies conducted globally (such as in Turkey and Italy), which also reported a high contribution to GWP, AP, EP, and HT due to electricity and fossil fuels consumption. The total cumulative energy demand (CED) was calculated as 5863.40 MJ (Mega Joule), with most energy usage associated with non-renewable fossil fuel sources. The results indicated that reducing electricity (using standard automatic machinery) and waste materials, especially paper and plastic wastes, can reduce environmental impacts. Most of the surveyed industrial units did not have wastewater treatment and recycling plants, and wastewater directly flows to nearby freshwater bodies and terrestrial ecosystems. These wastewaters should be adequately treated before being discharged into freshwater aquatic bodies. Environmental impacts must be improved by using the latest automatic machinery, reducing waste materials generation, reducing the distance between processing units and the market, and installing wastewater recycling plants

Anticancer activity of broccoli, its organosulfur and polyphenolic compounds

The use of natural bioactive constituents from various food sources for anticancer purposes has become increasingly popular worldwide. Broccoli (Brassica oleracea var. italica) is on the top of the consumed vegetables by the masses. Its raw matrix contains a plethora of phytochemicals, such as glucosinolates and phenolic compounds, along with rich amounts of vitamins, and minerals. Consumption of broccoli-derived phytochemicals provides strong antioxidant effects, particularly due to its sulforaphane content, while modulating numerous molecules involved in cell cycle regulation, control of apoptosis, and tuning enzyme activity. Thus, the inclusion of broccoli in the daily diet lowers the susceptibility to developing cancers. Numerous studies have underlined the undisputable role of broccoli in the diet as a chemopreventive raw food, owing to the content in sulforaphane, an isothiocyanate produced as a result of hydrolysis of precursor glucosinolates called glucoraphanin. This review will provide evidence supporting the specific role of fresh florets and sprouts of broccoli and its key bioactive constituents in the prevention and treatment of different cancers; a number of studies carried out in the in vitro and in vivo conditions as well as clinical trials were analyzed

Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes

Aims/introductionLimited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years.Materials and methodsParticipants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up.ResultsParticipants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P ConclusionsIn participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss

Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes

Aims/introduction: Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years. Materials and methods: Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up. Results: Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P Conclusions: In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.</p