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INTRODUCTION: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. OBJECTIVE: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. METHODS: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. RESULTS: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). CONCLUSION: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.
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Fatores Imunológicos , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla Recidivante-Remitente , Natalizumab , Humanos , Natalizumab/uso terapêutico , Natalizumab/efeitos adversos , Feminino , Adulto , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Vírus JC/imunologia , Pessoa de Meia-Idade , Substituição de Medicamentos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Cloridrato de Fingolimode/uso terapêutico , Alemtuzumab/efeitos adversos , Alemtuzumab/uso terapêuticoRESUMO
BACKGROUND: Evaluation of the influence of the age of the patients upon the outcomes of liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent LR between 2010 and 2020 were analyzed. They were divided into 3 groups depending on the patient's age. Group I (patients less than 60 years), Group II (patients between 60 and 69 years), and Group III (patients equal to or more than 70 years). RESULTS: 364 patients were included. A significantly higher serum bilirubin and alpha feto-protein were noted in Group I and serum creatinine was noted in Group III. The study groups did not show any significant differences regarding HCC site, number, macrovascular invasion, the extent of LR, Pringle maneuver, and perioperative blood transfusions. Longer operation time was found in Groups II and III, while more blood loss was noted in Group (I) Group I patients had longer hospital stays. Higher postoperative morbidities were noted in both Group I and Group (II) Higher incidence of post-hepatectomy liver dysfunction was noted in Group I. More early mortalities were found in Group I, related to liver failure. We did not experience early mortality in Group (III) Late Mortalities occurred in 117 patients (32.1%). HCC recurrence occurred in 165 patients (45.3%). Regarding the overall- and tumor-free survival, we did not experience any significant differences among the 3 groups (Log Rank: p = 0.371 and 0.464 respectively). CONCLUSIONS: Curative LR can be safely performed in selected elderly patients with HCC. An advanced patient's age should not be considered as a contraindication for curative LR.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Hepatectomia/métodos , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Fatores Etários , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Adulto , Duração da Cirurgia , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: To evaluate the impact of tumor size on the perioperative and long-term outcomes of liver resection for hepatocellular carcinoma (HCC). METHODS: We reviewed the patients' data who underwent liver resection for HCC between November 2009 and 2019. Patients were divided into 3 groups according to the tumor size. Group I: HCC < 5 cm, Group II: HCC between 5 to 10 cm, and Group III: HCC ≥ 10 cm in size. RESULTS: Three hundred fifteen patients were included in the current study. Lower platelets count was noted Groups I and II. Higher serum alpha-feto protein was noted in Group III. Higher incidence of multiple tumors, macroscopic portal vein invasion, nearby organ invasion and presence of porta-hepatis lymph nodes were found in Group III. More major liver resections were performed in Group III. Longer operation time, more blood loss and more transfusion requirements were found in Group III. Longer hospital stay and more postoperative morbidities were noted in Group III, especially posthepatectomy liver failure, and respiratory complications. The median follow-up duration was 17 months (7-110 months). Mortality occurred in 100 patients (31.7%) and recurrence occurred in 147 patients (46.7%). There were no significant differences between the groups regarding recurrence free survival (Log Rank, p = 0.089) but not for overall survival (Log Rank, p = 0.001). CONCLUSION: HCC size is not a contraindication for liver resection. With proper selection, safe techniques and standardized care, adequate outcomes could be achieved.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgiaRESUMO
Smart Sensing has shown notable contributions in the healthcare industry and revamps immense advancement. With this, the present smart sensing applications such as the Internet of Medical Things (IoMT) applications are elongated in the COVID-19 outbreak to facilitate the victims and alleviate the extensive contamination frequency of this pathogenic virus. Although, the existing IoMT applications are utilized productively in this pandemic, but somehow, the Quality of Service (QoS) metrics are overlooked, which is the basic need of these applications followed by patients, physicians, nursing staff, etc. In this review article, we will give a comprehensive assessment of the QoS of IoMT applications used in this pandemic from 2019 to 2021 to identify their requirements and current challenges by taking into account various network components and communication metrics. To claim the contribution of this work, we explored layer-wise QoS challenges in the existing literature to identify particular requirements, and set the footprint for future research. Finally, we compared each section with the existing review articles to acknowledge the uniqueness of this work followed by the answer of a question why this survey paper is needed in the presence of current state-of-the-art review papers.
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OBJECTIVE: The current clinical trial was conducted to evaluate the effect of proximal indirect restorations in endodontically treated posterior teeth with deeply located margins following deep margin elevation compared to surgical crown lengthening. MATERIAL AND METHODS: Deep proximal cavities in endodontically treated posterior teeth were randomly assigned into two groups; deep margin elevation (DME) or crown lengthening (CL). The clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), crestal bone level (CBL), and secondary caries were evaluated at the baseline, 1, 3, 6, 9, and 12 months. RESULTS: A total of 20 proximal cavities were included in the study; there was no significant difference between the two groups regarding mean CAL values at the baseline and 1 month, while there was a significant difference between the two groups in all other periods. Regarding the PD, there was no statistical significance between the two groups except at 9 and 12 months, where CL showed higher mean PD values than DME. There was no statistically significant difference in BOP or CBL between the two groups. CONCLUSIONS: DME and CL are considered clinically successful with favorable biologic responses. CLINICAL RELEVANCE: The deep margin elevation approach could provide a more conservative solution when relocating deeply seated cervical margins in a more coronal position. DME reduced the number of visits and time needed for the restoration of endodontically treated teeth. Surgical crown lengthening remains a gold standard procedure in the re-establishment of the supracrestal tissue attachment, especially in cases where cervical margins are beyond the elevation capacity.
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Cárie Dentária , Dente não Vital , Humanos , Aumento da Coroa Clínica , PescoçoRESUMO
The present study involves design and synthesis of five series of 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines 9a-l, 11a-e, 13a-c, 14a-f and 15a-e. Candidates 9a-l and 11a-e were evaluated for their EGFR and HER2 inhibitory activity compared to Lapatinib. Compounds 9b, 9d, 9f, 11b and 11c were further screened for their in vitro cytotoxicity against two human breast cancer cell lines: AU-565 and MDA-MB-231 in addition to normal breast cell line MCF10A. Compound 9d revealed a remarkable cytotoxic efficacy against AU-565 cell line (IC50 = 1.54 µM) relative to Lapatinib (IC50 = 0.48 µM), whereas compounds 9d and 11c showed a superior cytotoxicity towards MDA-MB-231 (IC50 = 2.67 and 1.75 µM, respectively) in comparison to Lapatinib (IC50 = 9.29 µM). Moreover, compounds 13a-c, 13a-c, 14a-f and 15a-e were tested for their VEGFR-2 inhibitory activity compared to Sorafenib. Compounds 13a, 14c and 14e exhibited remarkable inhibition (IC50 = 79.80, 50.22 and 78.02 nM, respectively) relative to Sorafenib (IC50 = 51.87 nM). In vitro cytotoxicity of these compounds against HepG2, HCT-116 and normal cell (WISH) revealed a superior cytotoxicity against HepG2, HCT-116 especially 13a (IC50 = 17.51 and 5.56 µM, respectively) and 14c (IC50 = 10.40 and 3.37 µM, respectively) compared to Sorafenib (IC50 = 19.33 and 6.82 µM, respectively). Compounds 9d, 11c and 14c were subjected to cell cycle analysis and apoptotic assay. Molecular docking and ADME prediction studies were fulfilled to illustrate the interaction of the potent derivatives with the hot spots of the active site of EGFR, HER2 and VEGFR-2 along with prediction of their pharmacokinetic and physicochemical properties.
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Antineoplásicos , Quinazolinas , Antineoplásicos/química , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Humanos , Lapatinib/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases , Quinazolinas/química , Quinazolinas/farmacologia , Sorafenibe/farmacologia , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio VascularRESUMO
BACKGROUND: To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS: Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS: Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION: Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.
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Carcinoma Hepatocelular/cirurgia , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Egito/epidemiologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: Post-hepatectomy liver failure (PHLF) is one of the most feared morbidities after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to investigate the incidence and predictors of PHLF after LR for HCC and its impact on survival outcomes. METHODS: We reviewed the patients who underwent LR for HCC during the period between January 2010 and 2019. RESULTS: Two hundred sixty-eight patients were included. Patients were divided into two groups according to the occurrence of PHLF, defined according to ISGLS. The non-PHLF group included 138 patients (51.5%), while the PHLF group included 130 patients (48.5%). Two hundred forty-six patients (91.8%) had hepatitis C virus. Major liver resections were more performed in the PHLF group (40 patients (30.8%) vs. 18 patients (13%), p = 0.001). Longer operation time (3 vs. 2.5 h, p = 0.001), more blood loss (1000 vs. 500 cc, p = 0.001), and transfusions (81 patients (62.3%) vs. 52 patients (37.7%), p = 0.001) occurred in PHLF group. The 1-, 3-, and 5-year Kaplan-Meier overall survival rates for the non-PHLF group were 93.9%, 79.5%, and 53.9% and 73.2%, 58.7%, and 52.4% for the PHLF group, respectively (log rank, p = 0.003). The 1-, 3-, and 5-year Kaplan-Meier disease-free survival rates for the non-PHLF group were 77.7%, 42.5%, and 29.4%, and 73.3%, 42.9%, and 25.3% for the PHLF group, respectively (log rank, p = 0.925). Preoperative albumin, bilirubin, INR, and liver cirrhosis were significant predictors of PHLF in the logistic regression analysis. CONCLUSION: Egyptian patients with HCC experienced higher PHLF incidence after LR for HCC. PHLF significantly affected the long-term survival of those patients.
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Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Estudos RetrospectivosRESUMO
The present study describes the synthesis of 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines starting from 4-chloro derivative VI via the reaction with either phenolic compounds to obtain VIIa-f, IXa-d, 2-amino-6-(un)substituted benzothiazole to produce VIIIa-c or hydrazine hydrate to give X. Reaction of the hydrazino functionality of X with appropriate acid anhydride, acid chloride or aldehyde affords XIa-c, XIIa-c and XIVa-i, respectively. The target compounds were screened for their efficacy as EGFR inhibitors compared to gefitinib. Compounds eliciting superior EGFR inhibitory activity were further screened for their in vitro cytotoxicity against two human cancer cell lines namely: MCF7 (breast) and A549 (lung), in addition to normal fibroblast cell WI38 relative to gefitinib as a reference. Furthermore, compounds that showed potent inhibitory activity on wild-type EGFR were screened against mutant EGFR and assayed for their cytotoxicity against mutant EGFR-expressing cell lines PC9 and HCC827. The unsubstituted benzothiazol-2-amine VIIa showing superior EGFR inhibition (IC50 = 0.096 µM) and anticancer activity against MCF-7 cell line (IC50 = 2.49 µM) was subjected to cell cycle analysis and apoptotic assay. Moreover, a molecular docking study was performed to investigate the interaction of some representive compounds with the active site of EGFR- TK.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
PURPOSE: The extracorporeal shockwave lithotripsy (ESWL) remains the most common first line of treatment for renal stones in the pediatric population. The purpose of this study is to evaluate and compare the outcomes of the ESWL and mini-percutaneous nephrolithotomy (mini-PCNL). PATIENTS AND METHODS: A total of 108 patients younger than 12 years of age with 1-2 cm single renal stone (pelvic or calyceal) were randomized into two groups, each containing 54 patients. Patients in group A were subjected to mini-PCNL using 16.5 Fr percutaneous sheath while those in group B underwent ESWL using Dornier Compact Sigma. RESULTS: The stone-free rate (SFR) after first session was 88.9% (48 cases) and 55.6% (30 cases) for groups A and B, respectively. The difference is highly statistically significant P = 0.006. Two patients (3.7%) in group A needed 2nd session of PCNL, while 18 patients (33.3%)in group B needed a 2nd session, of theses 18 patients six patients needed a 3rd session of ESWL. After the third session of ESWL and second look PCNL the stone-free rates were 92.59% (50 cases) and 88.89% (48 cases) for groups A and B, respectively, (P = 0.639), which is statistically insignificant. The mean hospital stay and fluoroscopy exposure were significantly longer in the mini-PCNL group. The complication rate in groups A and group B were (22.2%) and (14.8%), respectively, which is statistically insignificant (P = 0.484). CONCLUSIONS: According to Clavien grade of complications mini-PCNL is a safe procedure, and after three session of ESWL, mini-PCNL has a similar stone-free rate with a lower retreatment rate. However, the mini-PCNL has more radiation exposure, and requires a longer hospital stay.
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Tratamento por Ondas de Choque Extracorpóreas/métodos , Cálculos Renais/terapia , Nefrolitotomia Percutânea/métodos , Criança , Pré-Escolar , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Feminino , Humanos , Masculino , Nefrolitotomia Percutânea/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To assess semiquantitative parameters of dynamic contrast-enhanced perfusion MR imaging (DCE) in differentiation of subtypes of renal cell carcinoma (RCC). MATERIAL/METHODS: Prospective study conducted upon 34 patients (27 M, 7 F, aged 25-72 ys: mean 45 ys) with RCC. Abdominal dynamic contrast-enhanced gradient-recalled echo MR sequence after administration of gadopentetate dimeglumine was obtained. The time signal intensity curve (TIC) of the lesion was created with calculation of enhancement ratio (ER), and washout ratio (WR). RESULTS: The subtypes of RCC were as follows: clear cell carcinomas (n=23), papillary carcinomas (n=6), and chromophobe carcinomas (n=5). The mean ER of clear cell, papillary and chromophobe RCC were 188±49.7, 35±8.9, and 120±41.6 respectively. The mean WR of clear cell, papillary and chromophobe RCCs were 28.6±6.8, 47.6±5.7 and 42.7±10, respectively. There was a significant difference in ER (P=0.001) and WR (P=0.001) between clear cell RCC and other subtypes of RCC. The threshold values of ER and WR used for differentiating clear cell RCC from other subtypes of RCC were 142 and 38 with areas under the curve of 0.937 and 0.895, respectively. CONCLUSIONS: We concluded that ER and WR are semiquantitative perfusion parameters useful in differentiation of clear cell RCC from chromophobe and papillary RCCs.
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OBJECTIVE: The purpose of the current in-vivo study was to assess the effect of using 0.12% chlorhexidine (CHX) mouth rinse, before bonding, on shear bond strength of polycarbonate brackets bonded with composite adhesive. SUBJECTS AND METHODS: Eighteen orthodontic patients with a mean age 21.41 ± 1.2 years, who were scheduled to have 2 or more first premolars extracted, were included in this study. Patients were referred for an oral prophylaxis program which included, in part, the use of a mouth rinse. Patients were divided into 2 groups, a test group of 9 patients who used 0.12% CHX gluconate mouth rinse twice daily and a control group of 9 patients who used a mouth rinse without CHX, but with same color. After 1 week, polycarbonate brackets were bonded to first premolars with Transbond XT composite adhesive. Premolars were extracted after 28 days and tested for shear bond strength on a universal testing machine. Student's t-test was used to compare shear bond strengths of both groups. RESULTS: No statistically significant difference was found in bond strengths' values between both groups. The test group (with CHX) has mean shear bond strength of 14.21 ± 2.42 MPa whereas the control group (without CHX) revealed a mean strength of 14.52 ± 2.31 MPa. CONCLUSION: The use of 0.12% CHX mouth rinse, for one week before bonding, did not affect the shear bond strength of polycarbonate brackets bonded with Transbond composite. Furthermore, these brackets showed clinically acceptable bond strength.
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Anti-Infecciosos Locais/química , Clorexidina/análogos & derivados , Colagem Dentária , Materiais Dentários/química , Antissépticos Bucais/química , Braquetes Ortodônticos , Cimento de Policarboxilato/química , Condicionamento Ácido do Dente/métodos , Adolescente , Clorexidina/química , Resinas Compostas/química , Lâmpadas de Polimerização Dentária/classificação , Ligas Dentárias/química , Análise do Estresse Dentário/instrumentação , Humanos , Ácidos Fosfóricos/química , Placebos , Cimentos de Resina/química , Resistência ao Cisalhamento , Aço Inoxidável/química , Estresse Mecânico , Adulto JovemRESUMO
Prevention of transfusion-transmitted viral infections and insurance of safe blood transfusion are the main goals of all blood banks worldwide. Despite the high sensitivity and specificity of currently used enzyme linked immunosorbent assay (ELISA) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) testing, viral transmission could still occur during the window period. Introducing viral individual donation nucleic acid testing (ID-NAT) can greatly decrease such risk providing an additional layer in securing blood transfusion. We aimed to assess the clinical significance of viral markers testing by ELISA and ID-NAT for blood screening in the Blood Bank of Suez Canal University Hospital. We studied all donations (2132) collected during a two-months period. Blood donor samples were screened by ELISA and ID-NAT tests for HBV, HCV, and HIV. Serological testing results for HCV by ELISA revealed 2,122 (99.5 %) negative donations compared to 2,131 (99.95 %) negative donations by ID-NAT testing. Of the positive ELISA samples, only one was NAT positive. For HBV ELISA testing, 2,115 (99.2 %) donations were negative, also by ID-NAT testing 2,115 (99.2 %) donations were HBV DNA negative. Out of the negative ELISA samples, two samples were ID-NAT reactive donors which were missed by serology assay being in the window period. HIV ELISA testing revealed negative 2,130 (99.9 %) donations while ID-NAT testing showed 2,131 (99.95 %) negative donations and one positive donation. In conclusion, this is the first study carried out in the Suez Canal and Sinai region, Egypt to assess the importance of ID-NAT implementation. The introduction of ID-NAT in blood banks is an effective method for increasing safety of the blood transfusion.
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Infecções por HIV , Hepatite C , Ácidos Nucleicos , Humanos , Bancos de Sangue , Relevância Clínica , Egito , Ensaio de Imunoadsorção Enzimática , Hepacivirus/genética , Vírus da Hepatite B/genética , Hepatite C/diagnóstico , BiomarcadoresRESUMO
Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.
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Neoplasias da Mama , Exossomos , Células-Tronco Mesenquimais , Células-Tronco Neoplásicas , Vincristina , Exossomos/metabolismo , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Vincristina/farmacologia , Portadores de Fármacos/químicaRESUMO
Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.
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Hidróxido de Cálcio , Dano ao DNA , Inflamação , Potencial da Membrana Mitocondrial , Nanopartículas , Espécies Reativas de Oxigênio , Titânio , Ítrio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Dano ao DNA/efeitos dos fármacos , Hidróxido de Cálcio/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Titânio/química , Titânio/toxicidade , Inflamação/metabolismo , Inflamação/patologia , Ítrio/química , Nanopartículas/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , DNA Mitocondrial/metabolismoRESUMO
BACKGROUND: Chronic total occlusion (CTO) lesions in coronary arteries pose a significant challenge for coronary interventionists, often leading to referrals for coronary artery bypass graft surgery (CABG). Successful percutaneous coronary intervention (PCI) for CTOs requires accurate assessment of procedural potential. This study, comprising 100 Egyptian patients aged 37-81, compares the predictive efficacy of various CTO scoring systems in PCI success determination. Patients with CTO in at least one coronary artery, planned for elective PCI based on objective evidence of ischemia, were included. Experienced operators performed PCI, recording procedural variables, and assessing complications. Logistic regression analysis revealed an inverse linear relationship between success rates and score values across all systems. RESULTS: Although, the predictive capacity of the scores was similar, with slight differences. The Euro CTO (CASTLE) score10 exhibited superior predictive efficacy, followed by the CL score9, while PROGRESS8 and J-CTO7 scores showed lower significance. ORA CTO11 score demonstrated intermediate predictive ability, and PROGRESS score8 had the least predictive value. CONCLUSION: The CASTLE score10 proved most effective in predicting PCI success for CTO cases in Egyptian patients, with operators advised to choose scoring systems based on experience and case characteristics. Proper planning remains crucial for optimizing success rates in CTO PCI procedures, irrespective of the scoring system employed.
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Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the effect of these nanoparticles on genomic DNA integrity and inflammation induction in the gastric tissues. Hence, this study estimated the effect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and inflammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to significant elevations in DNA damage induction and ROS generation, in contrast to the non-significant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and inflammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH)2 nanoparticles.
Assuntos
Gastrite , Nanopartículas , Humanos , Camundongos , Masculino , Animais , Hidróxido de Cálcio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Ciclo-Oxigenase 2/genética , Ítrio , Dano ao DNA , InflamaçãoRESUMO
Intensive uses of Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the effect of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs and Y2O3NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)2NPs or CaTiO3NPs alone together with high Ca(OH)2NPs induced reactive oxygen species (ROS) generation and a slight CaTiO3NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs up to the negative control level. Oral administration of Y2O3NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)2NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO3NPs and Y2O3NPs separately or simultaneously together with Ca(OH)2NPs. Conclusion: Ca(OH)2NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO3NPs administration. However, administration of Y2O3NPs alone was non-genotoxic and coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)2NPs and CaTiO3NPs. Thus co-administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs is recommended to counter Ca(OH)2NPs and CaTiO3NPs induced genotoxicity and oxidative stress.
Assuntos
Cálcio , Nanopartículas , Camundongos , Humanos , Animais , Cálcio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Hidróxido de Cálcio/toxicidade , Proteínas Proto-Oncogênicas p21(ras)/genética , Estresse Oxidativo , Proteína Supressora de Tumor p53/metabolismo , Nanopartículas/toxicidade , Dano ao DNA , DNA/metabolismoRESUMO
BACKGROUND: Previous studies have reported conflicting results about the association of vitamin D (VD) level with coronary artery disease (CAD). We aimed to study the association of VD with atherosclerotic CAD in Egyptian individuals. RESULTS: We prospectively enrolled 188 consecutive CAD patients with a median age of 55(50-62) years; 151(80.3%) were male. All patients were diagnosed by cardiac catheterization and were compared with 131 healthy controls. VD levels were measured in serum samples of all participants. Compared to controls, CAD patients had a significantly lower median VD level, 14.65 (9.25-21.45) versus 42.0 (32.0-53.0) ng/mL, p < 0.001. VD was correlated with the number of diseased coronary arteries and lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, p < 0.001 for each). By multivariate analyses, VD was an independent predictor of CAD [OR 1.22 (95% CI 1.07-1.4), p = 0.003, optimal cut-off value 30 ng/mL (AUC 0.92, sensitivity 81% and specificity 81.4%), p < 0.001], and the number of diseased coronary arteries, p < 0.001, especially three-vessel disease [OR 0.83 (95% CI 0.72-0.95), p = 0.008]. CONCLUSIONS: We have shown that low VD should be considered a non-traditional risk factor for CAD in Egyptian individuals. Low VD was correlated with coronary atherosclerosis, especially in patients with multivessel effects.
RESUMO
Recently, there has been considerable growth in the internet of things (IoT)-based healthcare applications; however, they suffer from a lack of intrusion detection systems (IDS). Leveraging recent technologies, such as machine learning (ML), edge computing, and blockchain, can provide suitable and strong security solutions for preserving the privacy of medical data. In this paper, FIDChain IDS is proposed using lightweight artificial neural networks (ANN) in a federated learning (FL) way to ensure healthcare data privacy preservation with the advances of blockchain technology that provides a distributed ledger for aggregating the local weights and then broadcasting the updated global weights after averaging, which prevents poisoning attacks and provides full transparency and immutability over the distributed system with negligible overhead. Applying the detection model at the edge protects the cloud if an attack happens, as it blocks the data from its gateway with smaller detection time and lesser computing and processing capacity as FL deals with smaller sets of data. The ANN and eXtreme Gradient Boosting (XGBoost) models were evaluated using the BoT-IoT dataset. The results show that ANN models have higher accuracy and better performance with the heterogeneity of data in IoT devices, such as intensive care unit (ICU) in healthcare systems. Testing the FIDChain with different datasets (CSE-CIC-IDS2018, Bot Net IoT, and KDD Cup 99) reveals that the BoT-IoT dataset has the most stable and accurate results for testing IoT applications, such as those used in healthcare systems.