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BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic is a serious health problem worldwide. Early virus detection is essential for disease control and management. Viral antigen detection by ELISA is a cost-effective, rapid, and accurate antigen diagnostic assay which could facilitate early viral detection. METHOD: An antigen-capture sandwich ELISA was developed using novel nucleocapsid (NP)-specific mouse monoclonal antibodies (MAbs). The clinical performance of the assay was assessed using 403 positive and 150 negative respiratory samples collected during different SARS-CoV-2 variants outbreaks in Iran. RESULTS: The limit of detection of our ELISA assay was found to be 43.3 pg/ml for recombinant NP. The overall sensitivity and specificity of this assay were 70.72% (95% CI: 66.01-75.12) and 100% (95% CI: 97.57-100), respectively, regardless of Ct values and SARS-CoV-2 variants. There was no significant difference in our assay sensitivity for the detection of Omicron subvariants compared to Delta variant. Assay sensitivity for the BA.5 Omicron subvariant was calculated as 91.89% (95% CI: 85.17-96.23) for samples with Ct values < 25 and 82.70% (95% CI: 75.19-88.71) for samples with Ct values < 30. CONCLUSION: Our newly developed ELISA method is reasonably sensitive and highly specific for detection of SARS-CoV-2 regardless of the variants and subvariants of the virus.
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COVID-19 , SARS-CoV-2 , Animais , Camundongos , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática/métodos , Sensibilidade e Especificidade , Anticorpos Antivirais , Teste para COVID-19RESUMO
Highly functionalized pyrrolidine-2,3-diones can be synthesized efficiently and stereoselectively under mild conditions using a biocatalytic approach. The reaction led to the formation of new all-carbon quaternary stereocenters from Myceliophthora thermophila laccase (Novozym 51003) catalyzed oxidation of catechols to ortho-quinones and subsequent 1,4-addition with 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones. The reaction was conducted with various substituents on both reactants, resulting in 13 products in moderate to good yields (42-91%). The same 15 reactions were also tested with K3Fe(CN)6 as a catalyst, but here only one reaction resulted in a product (60% yield).
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A multicomponent enzyme-catalyzed process is suggested for the synthesis of a novel series of 1,3,4-oxadiazole thioether derivatives with yields ranging from 65 to 94%. Novozym 435, the immobilized form of Candida antarctica lipase B (CALB), was found to efficiently catalyze the reaction. The products were evaluated for antitumor activities against two cancer cell lines, HT-29 (human colorectal cancer cell) and HepG2 (human liver cancer cell), by MTT assays. Among them, two compounds exhibited higher antitumor activities, for both cell lines, compared to doxorubicin. In silico molecular docking and computational ADME analysis were performed to propose a mode of action for the anti-cancer activities and to predict drug-likeness, respectively.
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Antineoplásicos , Oxidiazóis , Humanos , Simulação de Acoplamento Molecular , Oxidiazóis/farmacologia , Biocatálise , Catálise , Esterificação , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Relação Estrutura-AtividadeRESUMO
This paper constructs and discusses a 1×2 decoder based on two-dimensional photonic crystals. The designed decoder is a priority decoder with one main input and one enabled input. This logic circuit's structure is very simple and compact, and it employs a photonic crystal structure with dimensions of 11×11 rods built of GaAs. The calculation results reveal that the output power values for logical mode 1 are extremely close to the power of the light source, whereas the power is very low and close to zero in logical mode 0. As a result, the difference between logical values 0 and 1 in the output will be adequate, and the circuit's accuracy will be good. The finite difference-time domain (FDTD) approach is used for time computations and light propagation in waveguides.
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INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. METHODS: This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. RESULTS: Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. CONCLUSION: Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.
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Neutropenia Febril , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Vancomicina/uso terapêutico , Irã (Geográfico) , Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia Febril/tratamento farmacológico , Encaminhamento e Consulta , Neoplasias/tratamento farmacológico , Fidelidade a DiretrizesRESUMO
The oral antimicrobial and cytotoxic properties of green synthesized novel titanium dioxide nanoparticles (TiO2 NPs) using Iranian propolis extracts were investigated on oral bacteria and fibroblast cells. In this study, propolis was sampled, and alcoholic extracts were prepared. The TiO2 NPs were biosynthesized using propolis extracts. The synthesized TiO2 NPs were characterized by scanning electron microscope (SEM), X-ray diffraction analysis, energy-dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering, ultraviolet-visible (UV-Vis), transmission electron microscope, Brunauer-Emmett-Teller, and zeta potential. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), minimal inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, biofilm formation, and degradation tests were studied to clarify the oral antimicrobial properties of green synthesized TiO2 NPs. According to the FTIR analysis, the propolis extract contained flavonoids and phenolic compounds in addition to TiO2 NPs. Additionally, UV-Vis revealed that intense bands had formed NPs. EDX spectra and SEM images revealed that the stabilizing agent was in perfect quasi-spherical shapes around 21 nm. An EDX spectrum was used to verify the presence of titanium and oxygen. There were no significant cytotoxicity effects. The antibacterial results showed that Pro1TiO2 (Khalkhal sample) had better effects than Pro2TiO2 (Gilan sample) and TiO2 NPs. The present study presents a new process for synthesizing TiO2 NPs from propolis extracts with less toxic effects and user-friendly, eco-friendly, and economical materials. Pro1TiO2 NPs may be considered the best candidate for clinical application.
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Anti-Infecciosos , Ascomicetos , Nanopartículas Metálicas , Nanopartículas , Própole , Própole/farmacologia , Irã (Geográfico) , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas Metálicas/química , Difração de Raios XRESUMO
In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.
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COVID-19/virologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Adulto , COVID-19/complicações , COVID-19/mortalidade , COVID-19/transmissão , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/virologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Masculino , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/fisiopatologia , Gestantes , Nascimento Prematuro , SARS-CoV-2/genética , SARS-CoV-2/fisiologiaRESUMO
OBJECTIVE: The current study aimed to investigate the temporal trend of in-hospital and intensive care unit (ICU) mortality of coronavirus disease 2019 (COVID-19) patients over 6 months in the spring and summer of 2021 in Iran. DESIGN: We performed an observational retrospective cohort study. SETTING: Qazvin Province- Iran during 6 month from April to September 2021. PARTICIPANTS: All 14355 patients who were hospitalized with confirmed COVID-19 in hospitals of Qazvin Province. INTERVENTION: No intervention. MAIN OUTCOME MEASURES: The trends of overall in-hospital mortality and ICU mortality were the main outcome of interest. We obtained crude and adjusted in-hospital and ICU mortality rates for each month of admission and over surge and lull periods of the disease. RESULTS: The overall in-hospital mortality, early mortality and ICU mortality were 8.8%, 3.2% and 67.6%, respectively. The trend for overall mortality was almost plateau ranging from 6.5% in July to 10.7% in April. The lowest ICU mortality was 60.0% observed in April, whereas it reached a peak in August (ICU mortality = 75.7%). Admission on surge days of COVID-19 was associated with an increased risk of overall mortality (Odds ratio = 1.3, 95% confidence interval = 1.1, 1.5). The comparison of surge and lull status showed that the odds of ICU mortality in the surge of COVID-19 was 1.7 higher than in the lull period (P-value < 0.001). CONCLUSIONS: We found that the risk of both overall in-hospital and ICU mortality increased over the surge period and fourth and fifth waves of severe acute respiratory syndrome coronavirus 2 infection in Iran. The lack of hospital resources and particularly ICU capacities to respond to the crisis during the surge period is assumed to be the main culprit.
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COVID-19 , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Hospitais , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Irã (Geográfico)/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
The capability of multi-component reactions in rapid immobilization of enzymes was considered for co-immobilization of Thermomyces lanuginous lipase (TLL) and Candida antarctica lipase B (CALB) [TLL: CALB]; Rhizomucor miehei lipase (RML) and CALB [RML: CALB] on amine-functionalized silica-coated magnetic nanoparticles (Fe3O4@SiO2-NH2). Immobilization of different ratios of lipases was performed within 3 h under mild conditions; producing specific activity ranging from 29 to 35 U/mg for TLL:CALB and 21-34 U/mg for RML:CALB. The co-immobilized derivatives showed improved co-solvent and thermal stability compared to the corresponding free enzymes. All the derivatives were also used to catalyze the transesterification of waste cooking oil with methanol to produce biodiesel (fatty acid methyl esters). Response surface method (RSM) and a central composite rotatable design (CCRD) were used to study the effects of different factors on the FAME yield. Fe3O4@SiO2-NH2-RML-CALB and Fe3O4@SiO2-NH2-TLL-CALB had maximum FAME yields of 99-80%, respectively.
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Biocombustíveis , Nanopartículas de Magnetita , Dióxido de Silício , Enzimas Imobilizadas , Lipase , Proteínas Fúngicas , CulináriaRESUMO
Background and objective: Among the broad variety of chemokines, monocyte chemoattractant protein-1 (MCP-1) is considered to be one of the most important chemokines. Among others, MCP-1 activates monocytes and other immune cells highly involved in inflammation. In the present systematic review and meta-analysis, we evaluated the relationship between serum/plasma MCP-1 levels and the risk of obstructive sleep apnea (OSA) in adults as a disease related to inflammation. Materials and methods: Four databases were systematically investigated until 12 July 2022. We used the Review Manager 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) to extract and calculate the standardized mean difference (SMD) and its 95% confidence interval (CI) of plasma/serum levels of MCP-1 between adults with and without OSA. Results: Eight articles including eleven studies in adults were entered into the meta-analysis. The serum/plasma MCP-1 levels in adults with OSA were higher than that in the controls (SMD = 0.81; p = 0.0007) and as well as for adults with severe OSA compared to those with mild and moderate OSA (SMD = 0.42; p < 0.0001). The subgroup analysis showed that ethnicity was an effective factor in the pooled analysis of blood MCP-1 levels in adults with OSA compared to the controls (Asians: (p < 0.0001), mixed ethnicity: (p = 0.04), and Caucasians: (p = 0.89)). The meta-regression showed increasing serum/plasma MCP-1 levels in adults with OSA versus the controls, publication year, age of controls, body mass index (BMI) of controls, and sample size reduced, and also BMI and the apnea−hypopnea index of adults with OSA increased. Conclusions: The meta-analysis showed that compared to the controls, serum/plasma levels of MCP-1 in adults with OSA were significantly more, as well as adults with severe OSA having more serum/plasma MCP-1 levels compared to the adults with mild to moderate OSA. Therefore, MCP-1 can be used as a diagnostic and therapeutic factor in adults with OSA.
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Quimiocina CCL2 , Apneia Obstrutiva do Sono , Adulto , Humanos , Inflamação , MonócitosRESUMO
Immunotherapy of HER2-overexpressing cancers by FDA approved monoclonal antibodies (mAbs) such as trastuzumab and pertuzumab has shown promising results. We have recently produced a novel humanized anti-HER2 mAb, hersintuzumab, which did not sterically inhibit binding of trastuzumab and pertuzumab to HER2, thus recognizing a distinct epitope on subdomain I + II of HER2. In this study, we assessed the in vitro and in vivo anti-tumor activity of this mAb individually and in combination with trastuzumab. Different HER2-overexpressing human cancer cell lines, including SKOV3, NCI-N87 HCC1954 and BT-474 were cultured and binding reactivity of Hersintuzumab to these cell lines was analyzed by flow cytometry. In addition, the inhibitory effect of different concentrations of hersintuzumab, trastuzumab and their combination on tumor cells growth was assessed by XTT assay. For Assessment of tumor growth inhibition in xenograft model, Balb/c athymic nude mice were subcutaneously injected with NCI-N87 and SKOV3 tumor cells and then treated intravenously with these mAbs. Our results showed that hersintuzumab could bind to all HER2-overexpressing cell lines similar to trastuzumab. In vitro experiments showed that both hersintuzumab and trastuzumab individually and in combination inhibited growth of all cell lines with the exception of HCC-1954.Inhibitory effect of the combination of mAbs was significantly higher than that of each mAb alone. Similar results were obtained in the gastric (NCI-N87) and ovarian (SKOV-3) tumor xenograft models. Hersintuzumab in combination with trastuzumab induces synergic anti-tumor effects on HER2-overexpressing cells in vitro and in vivo and is potentially a therapeutic tool for treatment of HER2-overexpressing cancers.
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Anticorpos Monoclonais Humanizados , Antineoplásicos , Neoplasias Ovarianas , Receptor ErbB-2 , Neoplasias Gástricas , Animais , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Epitopos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Trastuzumab , Carga Tumoral , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The polysaccharide-fucoidan plays a fundamental role in shrimp aquaculture by being used as a natural immunostimulant and dietary supplementation. In this study, Cystoseira trinodis fucoidan (FCT) was extracted, its structure was determined using FT-IR analysis, and its effect of fucoidan on growth performance and WSSV resistance in Litopenaeus vannamei was evaluated. Four experimental diets, including the control (without FCT), 0.1, 0.2, and 0.4% FCT, were formulated and fed to shrimps for 60 days. Next, they were exposed to WSSV, and their mortality rate was noted daily up to 20 days. The results of the growth experiment demonstrated a significant increase in the final weight, WG, and SGR, and a lower FCR in treatments than in control. During the challenge trial, 100% mortality was recorded in control within ten days. However, FCT-treated shrimps indicated a mortality increase from 43.33 to 75.00% during 20 days of infection. The immunological and biochemical parameters and the expression of immune-related genes in individuals fed the FCT-incorporated diet considerably (p < 0.01) improved over control before the challenge (0 days) and after the challenge on days 5, 10, 15, and 20. It was concluded that L. vannamei fed on diets supplemented with all concentrations of FCT (especially 0.4%) had improved the growth, immunological and biochemical parameters, and the expression of immune-related genes, as well as enhancing the resistance against WSSV.
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Penaeidae , Phaeophyceae , Alga Marinha , Ração Animal/análise , Animais , Dieta/veterinária , Resistência à Doença , Imunidade Inata , Penaeidae/genética , Polissacarídeos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this study, we designed and developed novel poly(ε-caprolactone) (PCL)-based biomaterials, for use as bone scaffolds, through modification with both biphasic calcium phosphate (BCP), to impart bioactive/bioresorbable properties, and with silver nitrate, to provide antibacterial protection against Staphylococcus aureus, a microorganism involved in prosthetic joint infections (PJIs). Field emission scanning electron microscopy (FESEM) showed that the samples were characterized by square-shaped macropores, and energy dispersive X-ray spectroscopy analysis confirmed the presence of PCL and BCP phases, while inductively coupled plasma-mass spectrometry (ICP-MS) established the release of Ag+ in the medium (~0.15-0.8 wt% of initial Ag content). Adhesion assays revealed a significant (p < 0.0001) reduction in both adherent and planktonic staphylococci on the Ag-functionalized biomaterials, and the presence of an inhibition halo confirmed Ag release from enriched samples. To assess the potential outcome in promoting bone integration, preliminary tests on sarcoma osteogenic-2 (Saos-2) cells indicated PCL and BCP/PCL biocompatibility, but a reduction in viability was observed for Ag-added biomaterials. Due to their combined biodegrading and antimicrobial properties, the silver-enriched BCP/PCL-based scaffolds showed good potential for engineering of bone tissue and for reducing PJIs as a microbial anti-adhesive tool used in the delivery of targeted antimicrobial molecules, even if the amount of silver needs to be tuned to improve osteointegration.
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Materiais Biocompatíveis/química , Poliésteres/química , Prata/química , Regeneração Óssea/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
Background: Treatment of patients with anosmia is a major therapeutic challenge. The present study evaluated the efficacy of platelet-rich plasma (PRP) in the treatment of anosmia in patients with sinonasal polyposis. Methods:In the present clinical trial, atotal of 48 patients with sinonasal polyposis with theIran Smell Identification Test (I-SIT) score of <6 who completed the medical treatment and were observed 3 months after the sinus surgery were included and randomly divided in to 2groups. After endoscopic sinus surgery, the intranasal injection of 1 mL PRP and normal saline was performed in the olfactory region in the intervention and control groups, respectively. Odor function was assessed using the I-SIT at the baseline and at the end of the studyby an independent samples ttest. Results: Based on the findings of the present study, the I-SIT improved in both groups during the follow-up, as it reached from 2.63 ± 2.63 to 5.85 ± 2.46 after oral steroid administration and 18.93 ± 1.14 after surgery in the intervention group and from the baseline of 2.10 ± 2.83 to 5.62 ± 2.99 after receiving standard medical treatment and 18.43 ± 1.36in the control groupafter surgery. Although this improvement was significant in both groups in either time interval (all with p<0.001), there was no significant difference between the 2groups in terms of changes in the I-SIT score (p=0.802). Conclusion: According to the current study, PRP injection showed no short-term effect on the recovery of olfactory function in patients with sinonasal polyposis.
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Manipulation of micro- and nanoparticles in complex biofluids is highly demanded in most biological and biomedical applications. A significant number of microfluidic platforms have been developed for inexpensive, rapid, accurate, and efficient particle manipulation. Due to the enormous potential of viscoelastic fluids (VEFs) for particle manipulation, various emerging microfluidic-based VEFs techniques have been presented over the last decade. This review provides an intuitive understanding of VEF physics for particle separation in different microchannel geometries. Besides, active and passive VEF methods are critically reviewed, highlighting the potential and practical challenges of each technique for particle/cell focusing, sorting, and separation. The outcome of this study could enable recognizing deliverable VEF technology with the promising prospect in the manipulation of submicron biological samples (e.g., exosomes, DNA, and proteins).
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Técnicas Analíticas Microfluídicas , Nanopartículas/química , Nanotecnologia , Animais , Separação Celular/instrumentação , Células Cultivadas , Elasticidade , Desenho de Equipamento , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Tamanho da Partícula , ViscosidadeRESUMO
INTRODUCTION: Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. METHOD: This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. RESULT: Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). CONCLUSION: Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.
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Neutropenia Febril/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Prescrição Inadequada/prevenção & controle , Neoplasias/tratamento farmacológico , Profilaxia Pré-Exposição/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neutropenia Febril/diagnóstico , Neutropenia Febril/epidemiologia , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Prescrição Inadequada/tendências , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Profilaxia Pré-Exposição/tendências , Estudos Prospectivos , Adulto JovemRESUMO
Functional properties of each enzyme strictly depend on immobilization protocol used for linking enzyme and carrier. Different strategies were applied to prepare the immobilized derivatives of Rhizomucor miehei lipase (RML) and chemically aminated RML (NH2-RML). Both RML and NH2-RML forms were covalently immobilized on glyoxyl sepharose (Gx-RML and Gx-NH2-RML), glyoxyl sepharose dithiothreitol (Gx-DTT-RML and Gx-DTT-NH2-RML), activated sepharose with cyanogen bromide (CNBr-RML and CNBr-NH2-RML) and heterofunctional epoxy support partially modified with iminodiacetic acid (epoxy-IDA-RML and epoxy-IDA-NH2-RML). Immobilization varied from 11% up to 88% yields producing specific activities ranging from 0.5 up to 1.9 UI/mg. Great improvement in thermal stability for Gx-DTT-NH2-RML and epoxy-IDA-NH2-RML derivatives was obtained by retaining 49% and 37% of their initial activities at 70 °C, respectively. The regioselectivity of each derivative was also examined in hydrolysis of fish oil at three different conditions. All the derivatives were selective between cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) in favor of EPA. The highest selectivity (32.9 folds) was observed for epoxy-IDA-NH2-RML derivative in the hydrolysis reaction performed at pH 5 and 4 °C. Recyclability study showed good capability of the immobilized biocatalysts to be used repeatedly, retaining 50-91% of their initial activities after five cycles of the reaction.
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Enzimas Imobilizadas/química , Óleos de Peixe/química , Lipase/química , Rhizomucor/enzimologia , Catálise , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Hidrólise , Solventes/química , TemperaturaRESUMO
Isolation of circulating tumor cells (CTCs) from blood has long been a challenge due to the rarity and heterogeneity of these cells. Detection technologies have predominantly focused on different molecular or physical properties of CTCs. Size-based isolation approach using microfilters have been widely used to capture CTCs because of the difference in size and stiffness of the cells compared to other hemocytes. Isolation of rare cells based on their size was the original CTC enrichment technique and it demonstrated a simple yet rapid method that enhanced the recovery of cells with high throughput. In this review, we highlight key technical aspects of filter-based isolation, detection, and characterization of CTCs, and compare the clinical performance of filter-based devices with the approved platforms and immunoassays used for the analysis of CTCs. We have also discussed future prospective and incorporation of advances in immunochemistry technique into the filter-based platforms for enhancing the utility in clinical settings.
Assuntos
Separação Celular/métodos , Células Neoplásicas Circulantes , Animais , HumanosRESUMO
PURPOSE: Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). MATERIALS AND METHODS: Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-ß1, FOX P3, IFN-γ, CXCL12 and ß-actin mRNA expression. RESULTS: UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-ß1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. CONCLUSION: Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.