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Tumor-agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero in on specific genetic anomalies responsible for fueling malignant growth. The watershed moment for tumor-agnostic therapies arrived in 2017, with the US Food and Drug Administration's historic approval of pembrolizumab, an immune checkpoint inhibitor. This milestone marked the marriage of genomics and immunology fields, as an immunotherapeutic agent gained approval based on genomic biomarkers, specifically, microsatellite instability-high or mismatch repair deficiency (dMMR). Subsequently, the approval of NTRK inhibitors, designed to combat NTRK gene fusions prevalent in various tumor types, including pediatric cancers and adult solid tumors, further underscored the potential of tumor-agnostic therapies. The US Food and Drug Administration approvals of targeted therapies (BRAF V600E, RET fusion), immunotherapies (tumor mutational burden ≥10 mutations per megabase, dMMR) and an antibody-drug conjugate (Her2-positive-immunohistochemistry 3+ expression) with pan-cancer efficacy have continued, offering newfound hope to patients grappling with advanced solid tumors that harbor particular biomarkers. In this comprehensive review, the authors delve into the expansive landscape of tissue-agnostic targets and drugs, shedding light on the rationale underpinning this approach, the hurdles it faces, presently approved therapies, voices from the patient advocacy perspective, and the tantalizing prospects on the horizon. This is a welcome advance in oncology that transcends the boundaries of histology and location to provide personalized options.
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BACKGROUND: Current guidelines advocate for colorectal cancer (CRC) screening in adults who are at risk by using direct visualization methods such as colonoscopy. However, in Egypt, there is a paucity of data regarding the current practice of colonoscopy screening. Moreover, more information is needed about the knowledge and attitudes of potential participants regarding the procedure and possible barriers that can limit their participation. METHODS: We conducted a nationwide cross-sectional study using an interview-based survey of patients aged 45 years or above who presented to outpatient clinics of nine university hospitals throughout Egypt. Participants were surveyed to assess their compliance with CRC colonoscopy screening guidelines, their knowledge of and attitude towards colonoscopy screening, and their perspective on potential barriers to colonoscopy screening. RESULTS: A total of 1,453 participants responded to our survey in the nine study centers. Only a minority of participants (2.3%) were referred for CRC screening. Referral rates were higher among those who knew someone with a history of CRC (5.3% vs 1.5%, p < 0.001) or had a discussion with their physician about CRC (25.8% vs 0.7%, p < 0.001). Few responders (3.2%) had good knowledge regarding CRC screening. After introducing the concept of CRC screening to all participants, most patients (66.7%) showed a positive attitude towards having the procedure. Financial burden and fear of results were the two most frequently cited barriers to undergoing CRC screening (81.1%; and 60.1%, respecteively). CONCLUSIONS: Despite the positive attitude, there is insufficient knowledge about CRC screening among eligible participants in Egypt. This has probably contributed to low compliance with current CRC screening guidelines and needs to be addressed at the national level.
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Neoplasias Colorretais , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Humanos , Estudos Transversais , Egito/epidemiologia , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , ColonoscopiaRESUMO
A simple and environmentally friendly method was developed for smart and efficient waterborne polyurethane (PUR) paint. Sugarcane bagasse was recycled into reduced graphene oxide nanosheets (rGONSs). Both lanthanide-doped aluminate nanoparticles (LAN; photoluminescent agent, 7-9 nm) and rGONSs (reinforcement agent) were integrated into a waterborne polyurethane to produce a novel photoluminescent, hydrophobic, and anticorrosive nanocomposite coating. Using ferrocene-based oxidation under masked circumstances, graphene oxide nanosheets were produced from sugarcane bagasse. The oxidized semicarbazide (SCB) nanostructures were integrated into polyurethane coatings as a drying, anticorrosion, and crosslinking agent. Polyurethane coatings with varying amounts of phosphor pigment were prepared and subsequently applied to mild steel. The produced paints (LAN/rGONSs@PUR) were tested for their hydrophobicity, hardness, and scratch resistance. Commission Internationale de l'éclairage (CIE) Laboratory parameters and photoluminescence analysis established the opacity and colourimetric properties of the nanocomposite coatings. When excited at 365 nm, the luminescent transparent paints emitted a strong greenish light at 517 nm. The anticorrosion characteristics of the coated steel were investigated. The phosphor-containing (11% w/w) polyurethane coatings displayed the most pronounced anticorrosion capability and long-persistent luminosity. The prepared waterborne polyurethane paints were very photostable and durable.
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Grafite , Interações Hidrofóbicas e Hidrofílicas , Nanocompostos , Pintura , Poliuretanos , Poliuretanos/química , Grafite/química , Nanocompostos/química , Luminescência , Corrosão , Química VerdeRESUMO
In order to make commercial products less vulnerable to counterfeiting, thermochromic inks have proven to be a viable authentication strategy. Herein, we developed a thermochromic ink for authentication by combining an anthocyanidin (ACYD) extract with alginate (ALG). To increase the anthocyanidin/alginate ink stability, a mordant (ferrous sulfate) was employed to tie up the anthocyanidin biomolecules with alginate. ACYD was extracted from red-cabbage and then immobilized into alginate to serve as an environmentally friendly spectroscopic probe. Thermochromic composite inks (ACYD@ALG) were made by adjusting the content of anthocyanidin. A homogenous blue film (608 nm) was printed on a paper surface and investigated by the CIE Lab coordinate system. The blue color transformed into reddish (477 nm) when heated from 35°C to 65°C. Nanoparticles (NPs) of anthocyanidin/mordant (ACYD/M) were examined for their size and morphology to indicate diameters of 80-90 nm, whereas the ACYD/M-encapsulated alginate nanoparticles showed diameters of 120-150 nm. Multiple analytical techniques were utilized to examine the printed papers. The mechanical and rheological performance of both stamped sheets and ink fluid were explored. The cytotoxicity and antimicrobial efficacy of ink (ACYD@ALG) were investigated.
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Alginatos , Antocianinas , Tinta , Nanopartículas , Alginatos/química , Antocianinas/química , Antocianinas/farmacologia , Nanopartículas/química , Temperatura , Tamanho da Partícula , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Testes de Sensibilidade Microbiana , Humanos , Propriedades de SuperfícieRESUMO
In this work, a novel series of N-(arylcarbamothioyl)arylmide) 2-11 were synthesized by treating One-Pot three-multicomponent of Aroyl chloride ammonium isothiocyanate and amine compounds under refluxing conditions. Using spectroscopic methods, the chemical structure of the novelty developed compounds were investigated. After five days, the proposed derivatives' insecticidal bioassay was assessed using the median lethal concentration (LC50) against the second & fourth larvae of Spodoptera frugiperda as toxicity agents. The findings showed that, to varying degrees, every tested substance exerted insecticidal effects on S. frugiperda larvae in both of their instars. Compound 9 was the most poisonous of them all, having an LC50 against larvae in their second and fourth instars of 60.45 and 123.21 mg/L, respectively. Additionally, a few biological and biochemical characteristics of the substances that were generated in a lab setting were also looked at. Furthermore, this work discusses how to discover novel compounds that may one day be employed as insecticidal agents. Finally, all the designed components were monitored for their antibacterial effectiveness toward both Gram-positive & Gram-negative bacteria.
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Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03â mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.
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Álcoois , Afídeos , Inseticidas , Animais , Inseticidas/química , Micro-Ondas , Neonicotinoides/farmacologia , Sódio/farmacologiaRESUMO
BACKGROUND: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt. METHODS: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns. We invited 1332 participants to our survey using a systematic random sampling that included participants across nine medical schools in Egypt during the 2021-2022 academic year. RESULTS: Out of 1332 participants, 1141 completed our questionnaire with a response rate of 85.7%. Overall, 43% of the participants had intermediate knowledge (knew 2-3 HCWs' recommended vaccines). Furthermore, 36.7% had received a booster dose of at least one of the HCWs' recommended vaccines over the last 10 years, with only 6.1% having received all recommended vaccines. Hepatitis B vaccine was the most widely known (71%) and received (66.7%). Interns were more likely to know, receive, and recommend HCWs' recommended vaccines. The majority (> 90%) agreed that vaccination is beneficial and safe, with a median score of eight (interquartile range [IQR: Q25-Q75]: 7-9) out of ten for vaccine efficacy and eight (IQR: 7-8) for safety. However, the median score for hesitancy was five (IQR: 2-7). The most common influential and limiting factors for vaccination were scientific facts (60.1%) and fear of vaccine side effects (44.9%). CONCLUSION: Although medical students in Egypt have good knowledge of and attitudes towards vaccination, there is a gap in their practices. Interventions are needed to improve vaccination uptake among medical students in Egypt.
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Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina , Humanos , Estudos Transversais , Egito , Estudantes de Medicina/psicologia , Masculino , Feminino , Adulto , Vacinação/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem , Pessoal de Saúde/educação , Atitude do Pessoal de SaúdeRESUMO
INTRODUCTION: The assessment of hemodynamic status in polytrauma patients is an important principle of the primary survey of trauma patients, and screening for ongoing hemorrhage and assessing the efficacy of resuscitation is vital in avoiding preventable death and significant morbidity in these patients. Invasive procedures may lead to various complications and the IVC ultrasound measurements are increasingly recognized as a potential noninvasive replacement or a source of adjunct information. AIMOF THIS STUDY: The study aimed to determine if repeated ultrasound assessment of the inferior vena cava (diameter, collapsibility (IVC- CI) in major trauma patients presenting with collapsible IVC before resuscitation and after the first hour of resuscitation will predict total intravenous fluid requirements at first 24 h. PATIENTS & METHODS: The current study was conducted on 120 patients presented to the emergency department with Major blunt trauma (having significant injury to two or more ISS body regions or an ISS greater than 15). The patients(cases) group (shocked group) (60) patients with signs of shock such as decreased blood pressure < 90/60 mmHg or a more than 30% decrease from the baseline systolic pressure, heart rate > 100 b/m, cold, clammy skin, capillary refill > 2 s and their shock index above0.9. The control group (non-shocked group) (60) patients with normal blood pressure and heart rate, no other signs of shock (normal capillary refill, warm skin), and (shock index ≤ 0.9). Patients were evaluated at time 0 (baseline), 1 h after resucitation, and 24 h after 1st hour for:(blood pressure, pulse, RR, SO2, capillary refill time, MABP, IVCci, IVCmax, IVCmin). RESULTS: Among 120 Major blunt trauma patients, 98 males (81.7%) and 22 females (18.3%) were included in this analysis; hypovolemic shocked patients (60 patients) were divided into two main groups according to IVC diameter after the first hour of resuscitation; IVC repleted were 32 patients (53.3%) while 28 patients (46.7%) were IVC non-repleted. In our study population, there were statistically significant differences between repleted and non-repleted IVC cases regarding IVCD, DIVC min, IVCCI (on arrival) (after 1 h) (after 24 h of 1st hour of resuscitation) ( p-value < 0.05) and DIVC Max (on arrival) (after 1 h) (p-value < 0.001). There is no statistically significant difference (p-value = 0.075) between repleted and non-repleted cases regarding DIVC Max (after 24 h).In our study, we found that IVCci0 at a cut-off point > 38.5 has a sensitivity of 80.0% and Specificity of 85.71% with AUC 0.971 and a good 95% CI (0.938 - 1.0), which means that IVCci of 38.6% or more can indicate fluid responsiveness. We also found that IVCci 1 h (after fluid resuscitation) at cut-off point > 28.6 has a sensitivity of 80.0% and Specificity of 75% with AUC 0.886 and good 95% CI (0.803 - 0.968), which means that IVCci of 28.5% or less can indicate fluid unresponsiveness after 1st hour of resuscitation. We found no statistically significant difference between repleted and non-repleted cases regarding fluid requirement and amount of blood transfusion at 1st hour of resuscitation (p-value = 0.104). CONCLUSION: Repeated bedside ultrasonography of IVCD, and IVCci before and after the first hour of resuscitation could be an excellent reliable invasive tool that can be used in estimating the First 24 h of fluid requirement in Major blunt trauma patients and assessment of fluid status.
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Serviço Hospitalar de Emergência , Hidratação , Ressuscitação , Ultrassonografia , Veia Cava Inferior , Ferimentos não Penetrantes , Humanos , Veia Cava Inferior/diagnóstico por imagem , Feminino , Masculino , Adulto , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia , Hidratação/métodos , Ressuscitação/métodos , Pessoa de Meia-Idade , Hospitais Universitários , Adulto Jovem , Estudos Prospectivos , Irã (Geográfico)RESUMO
Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (nâ =â 20) and non-colorectal cancers (nâ =â 8); and healthy volunteers (nâ =â 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (Pâ =â .001) and normal donors (Pâ =â .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; Pâ =â .027).
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DNA Tumoral Circulante , Neoplasias Colorretais , Neoplasias , Humanos , Metilação , DNA Tumoral Circulante/genética , Biópsia Líquida , Mutação , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genéticaRESUMO
Bacterial infections that cause chronic wounds provide a challenge to healthcare worldwide because they frequently impede healing and cause a variety of problems. In this study, loaded with tungsten oxide (WO3 ), Magnesium oxide (MgO), and graphene oxide (GO) on chitosan (CS) membrane, an inexpensive polymer casting method was successfully prepared for wound healing applications. All fabricated composites were characterized by X-ray powder diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). A scanning electron microscope (SEM) was used to study the synthesized film samples' morphology as well as their microstructure. The formed WO3/MgO@CS shows a great enhancement in the UV/VIS analysis with a highly intense peak at 401â nm and a narrow band gap (3.69â eV) compared to pure CS. The enhanced electron-hole pair separation rate is responsible for the WO3/MgO/GO@CS scaffold's antibacterial activity. Additionally, human lung cells were used to determine the average cell viability of nanocomposite scaffolds and reached 121 % of WO3 /MgO/GO@CS nanocomposite, and the IC50 value was found to be 1654â µg/mL. The ability of the scaffold to inhibit the bacteria has been tested against both E. coli and S. aureus. The 4th sample showed an inhibition zone of 11.5±0.5â mm and 13.5±0.5â mm, respectively. These findings demonstrate the enormous potential for WO3 /MgO/GO@CS membrane as wound dressings in the clinical management of bacterially infected wounds.
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Quitosana , Grafite , Humanos , Quitosana/química , Tungstênio/química , Grafite/química , Óxido de Magnésio , Magnésio , Staphylococcus aureus , Espectroscopia de Infravermelho com Transformada de Fourier , Escherichia coli , Óxidos/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
A new series of Schiff-benzimidazole hybrids 3a-o has been designed and synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analysis tools. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI single- and five-dose protocols. Consequently, four compounds were further examined against the most sensitive lung cancer A549 and NCI-H460 cell lines. Compounds 3e and 3g were the most active, achieving 3.58 ± 0.53, 1.71 ± 0.17 and 1.88 ± 0.35, 0.85 ± 0.24 against A549 and NCI-H460 cell lines, respectively. Moreover, they showed remarkable inhibitory activity on the VEGFR-2 TK with 86.23 and 89.89%, respectively, as compared with Sorafenib (88.17%). Moreover, cell cycle analysis of NCI-H460 cells treated with 3e and 3g showed cellular cycle arrest at both G1 and S phases (supported by caspases-9 study) with significant pro-apoptotic activity, as indicated by annexin V-FITC staining. The binding interactions of these compounds were confirmed through molecular docking studies; the most active compounds displayed complete overlay with, and a similar binding mode and pose to, Sorafenib, a reference VEGFR-2 inhibitor.
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Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Antineoplásicos/química , Apoptose , Benzimidazóis/química , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estrutura Molecular , Bases de Schiff/farmacologia , Sorafenibe/farmacologia , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC. METHODS: Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry. RESULTS: Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency. CONCLUSION: Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies. (ClinicalTrials.gov Identifier: NCT03740100).
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Neoplasias de Cabeça e Pescoço , Fosfatidilinositol 3-Quinase , Humanos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Fosfatidilinositóis , Receptor Notch1/genéticaRESUMO
Soluble fibrin (SF) in blood consists of monomers lacking both fibrinopeptides A with a minor population in multimeric clusters. It is a substantial component of isolated fibrinogen (fg), which spontaneously self-assembles into protofibrils progressing to fibers at sub-physiologic temperatures, a process enhanced by adsorption to hydrophobic and some metal surfaces. Comparisons of SF-rich (FR) and SF-depleted (FD) fg isolates disclosed distinct molecular imprints of each via an adsorption/desorption procedure using gold surfaced silica microplates. Accelerated plasminogen activator-induced lysis and decreased stiffness (G') of thrombin-induced FR fg clots were revealed by thomboelastography. Erythrocyte sedimentation (ESR) in afibrinogenemic plasma (Hematocrit 25-33%) was accelerated by FR fg nearly threefold that of FD fg. Stained smears disclosed frequent rouleaux formations and fibers linking stacked erythrocytes in contrast to no rouleaux by FD fg. Rouleaux formations were more pronounced at 4 °C than at ambient temperatures and at fiber-membrane contacts displayed irregular, knobby membrane contours. One of several FR fg isolates also displayed incomplete fiber networks in cell-free areas. What is more, pre-mixing FR fg with each of three monoclonal IgG anti-fg antibodies at 1.5 mol/mol fg, that inhibited fibrin polymerization, prevented rouleaux formation save occasional 2-4 erythrocyte aggregates. We conclude that spontaneously generated SF fibers bound to erythrocytes forming intercellular links culminating in rouleaux formation and ensuing ESR acceleration which in clinical settings reflects hypercoagulability. Also, the results can explain the reported fg binding to erythrocytes via ligands such as CD47, stable in vivo RBC aggregates in capillaries, and red areas of pathologic thrombi.
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Fibrina , Trombofilia , Aceleração , Sedimentação Sanguínea , Eritrócitos , HumanosRESUMO
BACKGROUND: Accurate rectal tumor staging guides the choice of treatment options. EUS and MRI are the main modalities for staging. AIM OF THE WORK: To compare the performance of EUS and MRI for loco-regional staging of anorectal cancer after neo-adjuvant therapy. METHODS: Seventy-three (37 male, 36 female) patients with rectal cancer after neo-adjuvant chemoradiotherapy were enrolled. Histopathological staging after surgery were used as reference for comparing the yield of loco-regional staging for EUS and MRI. EUS and MRI were done 1 month after completion of neo-adjuvant therapy. RESULTS: Regarding post-surgical T staging, eight patients had early tumor (T2 = 16 and T1 = 9) and thirty six were locally advanced (T3 = 36), while N staging, forty patients with negative nodes and 33 were positive (N1 = 22 and N2 = 11). Comparing EUS to MRI, it showed a higher sensitivity (95.7% vs. 78.7%), specificity (84.6% vs. 68.0%) and accuracy (91.8% vs. 75.3%) for staging early and locally advanced tumor. Also, it had a higher sensitivity (78.8% vs. 69.7%), specificity (75.0% vs. 65.0%) and accuracy (76.7% vs. 67.1%) for detection of lymph nodes. CONCLUSION: EUS appears to be more accurate than MRI in loco-regional staging of rectal carcinoma after neo-adjuvant therapy.
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Neoplasias do Ânus , Neoplasias Retais , Humanos , Masculino , Feminino , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante , Endossonografia/métodos , Neoplasias do Ânus/patologia , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética/métodos , Sensibilidade e EspecificidadeRESUMO
Unstable hemodynamics and prematurity are the main players in intraventricular hemorrhage (IVH) development. Our objective was to study 8 the use of superior vena cava flow (SVCF), left ventricular output (LVO), and right ventricular output (RVO), and anterior cerebral artery (ACA) Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks and birth weight ≤ 1500 g. This prospective cohort study was conducted in 55NICU of Alexandria University maternity hospital. Of 147 enrolled patients, 132 infants born ≤ 32 weeks GA and birth weight ≤ 1500 g were eligible for- the study. One hundred twenty-seven infants completed the study. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVCF, LVO, and RVO using functional echocardiography in the first 24 h after birth. Patients had another two scans on DOL3 and 7 to detect IVH development. Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with OR, 3.16; 95%CI, 1.19-8.39; P = 0.02 and OR, 1.64; 95%Cl, 1.10-2.44; P = 0.02, respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P = 0.025 and 0.023, respectively. Combined use of low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity. CONCLUSIONS: There are strong relations between both low SVCF and high ACA-RI, and IVH development in premature neonates ≤ 32 weeks and birth weight ≤ 1500 g, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVCF. Maternal anemia, patent ductus arteriosus size (mm/kg), and capillary refill time were significantly associated with high ACA-RI. These findings help in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome. TRIAL REGISTRATION: This work was registered in clinical trial.gv no NCT05050032. WHAT IS KNOWN: â¢Whether SVCF and RI-ACA can predict IVH in preterm neonates is still debatable. WHAT IS NEW: â¢Low SVC flow and high ACA-RI significantly increased risk of IVH, confirming the role of hypoperfusion-reperfusion cycle in IVH development. The most striking result that combined metrics using the cut-off value of < 41 ml/kg/min for SVCF and > 0.85 for ACA-RI "in the first day of life" can correctly reject the presence of IVH in 98% of patients "during the first week of life."
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Doenças do Recém-Nascido , Doenças do Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Circulação Cerebrovascular/fisiologia , Hemodinâmica/fisiologia , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/etiologia , Estudos Prospectivos , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/fisiologiaRESUMO
N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide (5), C19H15NO3Se, was prepared in two steps from 4,4'-diselanediyldianiline (3) via reduction and subsequent nucleophilic reaction with 2-methyl-3-bromo-1,4-naphthalenedione, followed by acetylation with acetic anhydride. The cytotoxicity was estimated against 158N and 158JP oligodendrocytes and the redox profile was also evaluated using different in vitro assays. The technique of single-crystal X-ray diffraction is used to confirm the structure of compound 5. The enantiopure 5 crystallizes in space group P21 with Flack parameter 0.017 (8), exhibiting a chiral layered absolute structure. Molecular structural studies showed that the crystal structure is foremost stabilized by N-H···O and relatively weak C-H···O contacts between molecules, and additionally stabilized by weak C-H···π and Se···N interactions. Hirshfeld surface analysis is used to quantitatively investigate the noncovalent interactions that stabilize crystal packing. Framework energy diagrams were used to graphically represent the stabilizing interaction energies for crystal packing. The analysis of the energy framework shows that the interactions energies of and C-H···π and C-O···π are primarily dispersive and are the crystal's main important forces. Density functional theory (DFT) calculations were used to determine the compound's stability, chemical reactivity, and other parameters by determining the HOMO-LUMO energy differences. The determination of its optimized surface of the molecular electrostatic potential (MEP) was also carried out. This study was conducted to demonstrate both the electron-rich and electron-poor sites.
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Halogênios , Hidrogênio , Acetamidas , Cristalografia por Raios X , Teoria da Densidade Funcional , Ligação de HidrogênioRESUMO
Novelmanganese(II), iron(III), cobalt(II), nickel(II), and copper(II) chelates were synthesized and studied using elemental analysis (EA), infrared spectroscopy, mass spectrometry, ultraviolet-visible spectroscopy, and conductivity, as well as magnetic measurements and thermogravimetric analysis (TG). The azo-ligand 1-[(4-nitrophenyl)diazenyl]-2-naphthol (HL) chelates to the metal ions via the nitrogen and oxygen centers of the azo group and the hydroxyl, respectively. The amounts of H2O present and its precise position were identified by thermal analysis. Density functional theory (DFT) was employed to theoretically elucidate the molecular structures of the ligand and the metal complexes. Furthermore, the quantum chemical parameters were also evaluated. The antimicrobial properties were evaluated against a group of fungal and bacterial microbes. Interestingly, the bioactivity of the complexes is enhanced compared to free ligands. Within this context, the CuL complex manifested the lowest activity, whereas the FeL complex had the greatest. Molecular docking was used to foretell the drugs' binding affinity for the structure of Escherichia coli (PDB ID: 1hnj). Protein-substrate interactions were resolved, and binding energies were accordingly calculated.
Assuntos
Complexos de Coordenação , Cobre , Cobre/química , Níquel/química , Ferro/química , Manganês/química , Cobalto/química , Simulação de Acoplamento Molecular , Ligantes , Espectrofotometria Infravermelho , Quelantes , Complexos de Coordenação/químicaRESUMO
In this study, pumice is used as a novel natural heterogeneous catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones via the one-pot multi-component condensation of aromatic aldehydes, urea/thiourea, and ethyl acetoacetate or acetylacetone in excellent yields (up to 98%). The physical and chemical properties of the catalyst were studied. Their geochemical analysis revealed a basaltic composition. Furthermore, X-ray diffraction showed that it is composed of amorphous materials with clinoptilolite and heulandites zeolite minerals in its pores. Moreover, pumice has a porosity range from 78.2-83.9% (by volume) and is characterized by a mesoporous structure (pore size range from 21.1 to 64.5 nm). Additionally, it has a pore volume between 0.00531 and 0.00781 m2/g and a surface area between 0.053 and 1.47 m2/g. The latter facilitated the reaction to proceed in a short time frame as well as in excellent yields. It is worth noting that our strategy tolerates the use of readily available, cheap, non-toxic, and thermally stable pumice catalyst. The reactions proceeded smoothly under solvent-free conditions, and products were isolated without tedious workup procedures in good yields and high purity. Indeed, pumice can be reused for at least five reuse cycles without affecting its activity.
Assuntos
Tionas , Zeolitas , Aldeídos/química , Catálise , Silicatos , Solventes , Tionas/química , Tioureia/química , Ureia/químicaRESUMO
BACKGROUND: Type B aortic dissection (TBAD) occurs seldomly, particularly in pregnancy, but has disastrous consequences for both mother and fetus. The focus of immediate surgical repair of type A aortic dissection due to higher mortality of patients is less clear in its counterpart, TBAD, in which management is controversial and debated. This article collates knowledge so far on this rare event during pregnancy. METHODS: A comprehensive literature search was performed in PubMed, Scopus, Google Scholar, Embase, and Medline. Key search terms included "type B aortic dissection," "pregnancy," and corresponding synonyms. Non-English papers were excluded. RESULTS: Risk factors for TBAD include aortic wall stress due to hypertension, previous cardiac surgery, structural abnormalities (bicuspid aortic valve, aortic coarctation), and connective tissue disorders. In pregnancy, pre-eclampsia is a cause of increased aortic wall stress. Management of this condition is often conservative, but this is dependent on a number of factors, including gestation, cardiovascular stability of the patient, and symptomology. In most cases, a cesarean section before intervention is carried out unless certain indications are present. CONCLUSIONS: Due to a scarce number of cases across the decades, it is difficult to determine which management is optimal. The gold-standard management of TBAD has traditionally been the medical treatment for uncomplicated cases and open surgery for those needing urgent intervention, but with the advent of techniques, such as thoracic endovascular aortic repair, the management of these group of patients continues to develop.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Procedimentos Endovasculares , Complicações Cardiovasculares na Gravidez , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Cesárea , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Type A acute aortic dissection (TAAD) during pregnancy is a life-threatening event for both the mother and the unborn baby. Pregnancy has been recognized as an independent risk factor for TAAD, postulated to be due to physiological changes that cause hyperdynamic circulation. This review seeks to outline the current controversies around this unique group. METHODS: A comprehensive literature search was carried out across large databases to assimilate relevant papers regarding acute aortic dissection in pregnant women. RESULTS: The presentation can be atypical in many cases and further concern from clinicians of fetal radiation exposure can result in missed or delayed diagnoses. Investigation via the quickest form of imaging, whether computed tomography, magnetic resonance imaging, or transesophageal echocardiography, should be carried out promptly due to the high risk of mortality. Surgical management of TAAD in pregnancy revolves primarily around the decision to deliver the fetus concomitantly or to perform the aortic repair with the fetus in utero. CONCLUSIONS: Management of this group includes rapid and dynamic assessment without delay. From conception to postpartum, there are multiple stages in which to manage these women. Challenges in carrying out management in the form of operative techniques and cardiopulmonary bypass place the fetus at risk and must be approached with caution, particularly as there is little evidence-base for many of these decisions. Further research into reducing maternal and fetal mortality is necessary.