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PURPOSE: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment. METHODS: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature. RESULTS: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection. CONCLUSION: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
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Neoplasias Encefálicas , Glioblastoma , Inhibidores de Proteínas Quinasas , Receptores de Factores de Crecimiento Endotelial Vascular , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
INTRODUCTION: Intensive care unit (ICU) admissions constitute a substantial financial challenge for health care systems and patients and are linked to various potentially life-altering complications. A wide range of patient-related, surgical, and medical factors are associated with an increased risk of ICU admission following spine surgery. DISCUSSION: The most notable examples include lung, heart, and kidney disease, as well as estimated blood loss and length of surgery. Various scores that include the most significant patient- and procedure-related factors have been described to assess the risk associated with surgery for individual patients. To date, the fusion risk score and the American Society of Anesthesiologists score have been the most useful in predicting postoperative complications and admission to the ICU. However, other risk factors have also been implicated in ICU admission and length of stay. The current scores must further adapt by using the available evidence to fulfill their intended purpose. Moreover, a handful of measures have shown efficacy in decreasing ICU admission and length of stay, with their benefits still to be demonstrated by future research. CONCLUSION: This review underscores the risk factors predictive of ICU admission following spine surgery and will help surgeons and clinicians in patient stratification. However, future studies are needed to validate the role of protective measures in preventing ICU admissions and the significance of certain risk factors.
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INTRODUCTION: Research from around the world shows important differences in the impact of the COVID-19 pandemic and lockdowns on mental health. This study examined the extent of mental health challenges (depressive and anxiety symptoms and daily life difficulties) and their associations with pandemic- and response-related factors during the first lockdown in Lebanon, which happened amid a severe economic crisis and socio-political turmoil. METHODS: Data come from a cross-sectional internet-based survey (May-June 2020). Association of depressive (Patient Health Questionnaire (PHQ-9)) and anxiety symptoms (Generalized Anxiety Disorder (GAD-7)) with outbreak-related worries and knowledge, information sources, and confidence and satisfaction in response measures were estimated using logistic regression adjusted for sociodemographic and socioeconomic indicators. RESULTS: Among 510 participants (mean age 36.1±11.3; 69.4% women), 32.3% had elevated depressive and 27.3% had elevated anxiety symptoms; younger age, unemployment, loss of employment, and lower income were related to more mental health symptoms. Most prevalent daily life challenges were feelings of uncertainty (74.5%) and financial (52.2%) and emotional (42.2%) difficulties; these and all other daily life difficulties (work-related, caregiving, and online learning) were significantly higher among participants with higher depressive and anxiety symptoms. Higher outbreak-related worries were associated with higher depressive (OR = 1.36, 95% CI = 1.20,1.53) and anxiety symptoms (OR = 1.47, 95% CI = 1.30,1.67). Higher pandemic-related knowledge, reliance on and trust in local health agencies and professionals' information, and satisfaction and confidence regarding governmental and health institutions' response were all related to lower mental health symptoms. CONCLUSION: Results show that mental health burden in Lebanon during the first lockdown (when the COVID-19 outbreak was still minimal) is among the highest reported worldwide and highlight elevated emotional and financial tolls and widespread impact on daily life. In this high-burden and multiple-challenges context, results suggest an important role for the healthcare body, knowledge, and trust in the institutions managing the response.
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COVID-19 , Salud Mental , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , COVID-19/epidemiología , Líbano/epidemiología , Pandemias , Estudios Transversales , Control de Enfermedades Transmisibles , Factores de Riesgo , Depresión/epidemiología , Ansiedad/epidemiologíaRESUMEN
Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a prevalent autoimmune condition marked by diverse neuropsychiatric symptoms, primarily impacting young females. The exact mechanisms underlying the development of NMDAr encephalitis have not been fully elucidated. Nonetheless, studies have demonstrated that auto-antibodies targeting the NR1-NR2 subunits of the NMDAr can trigger receptor dysfunction within the central nervous system, thus giving rise to the associated symptoms. Notably, an association exists between NMDAr encephalitis and an underlying neoplastic condition, with approximately 38% of cases exhibiting this paraneoplastic relationship with ovarian teratomas being the most commonly associated malignancy. While the association between NMDAr encephalitis and renal cell carcinoma (RCC) is exceedingly rare. This case report presents the clinical scenario of a 20-year-old female patient diagnosed with NMDAr encephalitis in conjunction with RCC discovered incidentally on a CT abdomen and pelvis performed to rule out an ovarian teratoma. The presented case underscores the importance of adopting a multidisciplinary approach in the diagnosis and treatment of NMDAr encephalitis, particularly when it is linked to an underlying malignancy. Furthermore, it emphasizes the significance of expanding our understanding of the molecular pathogenesis of NMDAr encephalitis to enhance patient care and optimize clinical outcomes. Additionally, a comprehensive review of the existing literature is included, summarizing all reported malignancies associated with NMDAr encephalitis.
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Osteosarcoma (OS) is an aggressive primary bone malignancy that metastasizes rapidly. The standard of care has changed little over the previous four decades, and survival rates have plateaued. In this context, tyrosine kinase inhibitors (TKIs) emerge as potential treatments. A literature search was conducted to collect data related to receptor tyrosine kinase genetic alterations and expression in OS specimens. Gene amplification and protein expression of these receptors were linked to prognosis and tumor behavior. Relevant TKIs were evaluated as monotherapies and as parts of combination therapies. Certain TKIs, such as apatinib, regorafenib, and cabozantinib, present a potential therapeutic avenue for OS patients, especially when combined with chemotherapy. Producing long-lasting responses and enhancing quality of life remain key goals in OS treatment. To this effect, optimizing the use of TKIs by identifying biomarkers predictive of response and assessing promising TKIs in larger-scale trials to validate the efficacy and safety outcomes relative to these drugs reported in phase II clinical trials. To this effect, it is necessary to identify biomarkers predictive of response to TKIs in larger-scale trials and to validate the efficacy and safety of these drugs reported in phase II clinical trials.
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INTRODUCTION: Warfarin has been in use for more than 60 years; however, it has serious side effects including major bleeding. The high interpatient variability in the required dose impacts the sensitivity and responsiveness to warfarin in different patients. This study aims to assess the influence of CDHR3, CACNAC1, and LTA gene polymorphisms on the variability of warfarin dose requirements and susceptibility to coronary heart disease in the Jordanian population. METHODS: This study was conducted in the anti-coagulation clinic in Queen Alia Heart Institute in Amman, with 212 patients in total. Three SNPs were genotyped within CDHR3 (rs10270308), CACNAC1 (rs216013), and LTA (rs1041981) genes. RESULTS: Our findings revealed that patients with LTA polymorphism are more prone to warfarin sensitivity than others. Furthermore, carriers of the LTA polymorphism needed a lower initial dose of warfarin and are associated with less variation in doses required to achieve target INR. CONCLUSION: The current study could help in understanding the role of genetic variability in warfarin dosing and matching patients to different treatment options. Clinical applications of these findings for warfarin treatment may also contribute to improving the efficacy and safety of warfarin treatment in Jordanian patients with cardiovascular disease.
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The livestock sector is one of the most important sectors of the agricultural economy due to an increase in the demand for animal protein. This increase generates serious waste disposal concerns and has negative environmental consequences. Furthermore, the food production chain needs phosphorus (P), which is listed as a critical raw material due to its high demand and limited availability in Europe. Manure contains large amounts of P and other elements that may be recycled, in the frame of circular economy and "zero waste" principles, and reused as a by-product for fertilizer production and other applications. This paper focuses on the extraction and recovery of amorphous silica from rice husk poultry litter ash. Two different extraction procedures are proposed and compared, and the obtained silica is characterized. This work shows that amorphous silica can be recovered as an almost pure material rendering the residual ash free of P. It also addresses the possibility of more specific phosphorous extraction procedures via acid leaching.
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This work proposes new eco-materials for the adsorption of diclofenac (DCF). The large consumption of this nonsteroidal anti-inflammatory drug combined with the inefficiency of wastewater treatment plants (WWTPs) leads to its presence in aquatic environments as an emerging pollutant. The adsorption technique is widely used for pharmaceutical removal. Moreover, due to the large effect of commercial adsorbents, in the frame of the Azure Chemistry approach, new sustainable materials are mandatory for removal as emerging pollutants. The work proposes three adsorbents that were obtained from different stabilization methods of fly ash derived from an incinerator plant; the stabilization techniques involved the use of various industrial by-products such as bottom ash, flue gas desulphurization residues, coal fly ash, and silica fume. The best performance, although less than activated carbon, was obtained by COSMOS (COlloidal Silica Medium to Obtain Safe inert: the case of incinerator fly ash), with a removal efficacy of approximately 76% with 15 g/L of material. Several advantages are expected not only from the DCF removal but also from an economic perspective (the newly obtained adsorbents are eco-materials, so they are cheaper in comparison to conventional adsorbents) and in terms of sustainability (no toxic reagents and no heating treatment are involved). This work highlights the adsorption performance of the new eco-materials and their potential use in WWTPs.
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This paper reports a complete characterization of the lowest fractions of bottom ash derived from co-combustion of municipal solid waste with sewage sludge (COBA), with the aim to suggest suitable reuse strategies of this by-product. X-Ray Microanalysis is coupled with mineralogical characterization, based on X-Ray Diffraction and Rietveld refinement, to extract information about COBA crystalline and amorphous phases. The composition of different particle size fractions shows that amount of amorphous increases with the increase of fractions sizes. In particular, the finest COBA size fraction (<300 µm) shows more leachable heavy metals (i.e. Pb, and Zn) compared to the investigated fraction with the highest sizes (1400 µm). On the basis of their composition, lowest particle size fractions show a better hydraulic behavior compared to bottom ash obtained from incineration of only municipal solid waste, suggesting possible attractive COBA applications, as for example, Portland cement substitution. In addition, COBA with size fractions in the range of 1000-1400 µm are proposed to be used to produce glass and ceramic. Finally, due to its high amount of reactive amorphous phase (about 73% for fraction size of 1400 µm) COBA is used, in combination with other by-products (coal fly ash and flue gas desulphurization residues), to stabilize municipal solid waste incinerator fly ash produced at the same incinerator plant, following the azure chemistry principle of use a waste to stabilize another waste.
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Ceniza del Carbón , Metales Pesados , Incineración , Aguas del Alcantarillado , Residuos Sólidos/análisisRESUMEN
This paper reports a complete characterisation of poultry litter ash and its potential use as a heavy metal stabiliser. We propose a novel approach, in which the ashes deriving from municipal solid waste incineration (MSWI) are combined with poultry litter ash, rather than with coal combustion flue gas desulfurisation (FGD) residues. Heavy metals stabilisation was demonstrated by comparing the elemental concentrations in the leaching solutions of the starting raw and stabilised materials: leachable Pb and Zn showed a reduced solubility. The characterisation was conducted by total reflection X-ray fluorescence (TXRF), X-ray diffraction (XRD), micro-Raman spectroscopy and scanning electron microscopy combined with energy-dispersive X-ray spectrometry (SEM-EDX). The results showed that the poultry litter ash was Ca-, P-, K- and S-rich (>29 g/kg). It contained amorphous materials (i.e. fly ash economiser (FAECO) 73% and fly ash cyclone (FACYC) 61%) and soluble phases (e.g. arkanite and sylvite; up to 13% FAECO and 28% FACYC), as well as resilient crystalline (up to 2% of FAECO and FACYC) and amorphous phases (e.g. hydroxyapatite). After two months, the Pb and Zn concentrations in the leachate solutions were below the limit set by the European regulations for waste disposal (<0.2 mg/L and 1.5 mg/L, respectively). We propose a mechanism for the heavy metals stabilisation based on the carbonation process and high amounts of P, Ca and reactive amorphous phases. In conclusion, it is demonstrated that poultry litter ash can be an effective secondary source of heavy metals, allowing their immobilisation through P- and Ca-based reactive amorphous phases.
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Metales Pesados , Eliminación de Residuos , Animales , Carbono , Ceniza del Carbón , Incineración , Material Particulado , Aves de Corral , Residuos SólidosRESUMEN
Municipal solid waste incineration (MSWI) provides significant benefits on waste treatment technologies. Nevertheless some by-products such as fly ash (FA) and bottom ash (Ash) are produced in the incineration plant. Indeed, FA is considered a toxic waste due to the presence of leachable heavy metals (i.e Zn, Cd, Pb, Hg) and metalloid (like As). This data article aims to investigate the reactivity of Ca(OH)2 and Mg(OH)2 as possible substitute of flue gas desulfurization (FGD) residues by mixing with FA, BA and silica fume through a low cost technology. To assess the immobilization process of heavy metals and metalloid, three different samples' compositions were prepared for Ca(OH)2 and Mg(OH)2 series, respectively. Elemental chemical analysis of leaching solutions were carried out by Total reflection X-Ray Fluorescence spectroscopy (TXRF). Data revealed that mixing municipal solid waste ashes with Mg(OH)2 decrease significantly Pb and Zn leachability after two months, and reduce their environmental impact in landfill.
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Mineral carbonation, involving reactions of alkaline earth oxides with CO2, has received great attention, as a potential carbon dioxide sequestration technology. Indeed, once converted into mineral carbonate, CO2 can be permanently stored in an inert phase. Several studies have been focalized to the utilization of industrial waste as a feedstock and the reuse of some by-products as possible materials for the carbonation reactions. In this work municipal solid waste incineration fly ash and other ashes, as bottom ash, coal fly ash, flue gas desulphurization residues, and silica fume, are stabilized by low-cost technologies. In this context, the CO2 is used as a raw material to favor the chemical stabilization of the wastes, by taking advantage of the pH reduction. Four different stabilization treatments at room temperature are performed and the carbonation reaction evaluated for three months. The crystalline calcium carbonate phase was quantified by the Rietveld analysis of X-ray diffraction (XRD) patterns. Results highlight that the proposed stabilization strategy promotes CO2 sequestration, with the formation of different calcium carbonate phases, depending on the wastes. This new sustainable and promising technology can be an alternative to more onerous mineral carbonation processes for the carbon dioxide sequestration.
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This work reports on qualitative and semi-quantitative elemental analysis of particulate matter (PM) collected on PTFE membrane filters, for a source apportionment study conducted in Brescia (Italy). Sampling was undertaken in a residential area where an increase in Mn emissions has been highlighted by previous studies. Filters are measured by means of X-ray Fluorescence (XRF) based techniques such as micro-XRF and grazing incidence XRF using synchrotron radiation, Mo or W excitation sources, after applying an automatized sample preparation method. A heterogeneous distribution in PM shape, size and composition was observed, with features typical of anthropogenic sources. XRF measurements performed at various incidence angle, on large areas and different experimental setup were reproducible. The results demonstrate a successful comparison of the various XRF instrumentation, and the decrease in Mn content with the distance away from the identified emission source. This work highlights the potentialities of the presented approach to provide a full quantitative analysis, and ascertain its suitability for providing a direct, fast, simple and sensitive elemental analysis of filters in source apportionment studies and screening purposes.