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Three-dimensional (3D) bioprinting is one of the most promising methodologies that are currently in development for the replacement of animal experiments. Bioprinting and most alternative technologies rely on animal-derived materials, which compromises the intent of animal welfare and results in the generation of chimeric systems of limited value. The current study therefore presents the first bioprinted liver model that is entirely void of animal-derived constituents. Initially, HuH-7 cells underwent adaptation to a chemically defined medium (CDM). The adapted cells exhibited high survival rates (85-92%) after cryopreservation in chemically defined freezing media, comparable to those preserved in standard medium (86-92%). Xeno-free bioink for 3D bioprinting yielded liver models with high relative cell viability (97-101%), akin to a Matrigel-based liver model (83-102%) after 15 days of culture. The established xeno-free model was used for toxicity testing of a marine biotoxin, okadaic acid (OA). In 2D culture, OA toxicity was virtually identical for cells cultured under standard conditions and in CDM. In the xeno-free bioprinted liver model, 3-fold higher concentrations of OA than in the respective monolayer culture were needed to induce cytotoxicity. In conclusion, this study describes for the first time the development of a xeno-free 3D bioprinted liver model and its applicability for research purposes.
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Bioimpressão , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Animais , Impressão Tridimensional , Engenharia Tecidual , Alicerces TeciduaisRESUMO
PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.
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Neoplasias da Mama , Oncologistas , Tumor Filoide , Cirurgiões , Humanos , Feminino , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Estudos Transversais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
The safety of personal protective equipment (PPE) is very important, and so is the choice of materials used. The ability of electrostatic charges (ESCs) generated from the friction of engineered materials to attract or repel viruses has a significant impact on their applications. This study examined the ESCs generated on the surface of PPE used by healthcare workers to enhance their potential effectiveness in protecting the wearer from viruses. This is a crucial consideration for the newly emerged severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which has a negative charge. The magnitudes and signs of generated ESCs on the surfaces of the PPE were determined experimentally using an Ultra Stable Surface DC Voltmeter. The high negative ESCs acquired by the polyethylene disposable cap and facemask are expected to repel negatively charged viruses and prevent them from adhering to the outer layer of the material. Also, the choice of polypropylene for facemasks and gowns is excellent because it is an aggressively negatively charged material in the triboelectric series. This property guarantees that facemasks and gowns can repel viruses from the wearer. However, the positive ESCs generated on latex glove surfaces are of great concern because they can attract negatively charged viruses and create a source of infection. In conclusion, it is necessary to ensure that PPE be made of materials whose surfaces develop a negative ESC to repel viruses, as well as to select polyethylene gloves.
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COVID-19/prevenção & controle , Pessoal de Saúde/educação , Equipamento de Proteção Individual/virologia , SARS-CoV-2/química , COVID-19/transmissão , Cabelo/química , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Látex/química , Teste de Materiais , Polietileno/química , Polipropilenos/química , Pele/química , Eletricidade EstáticaRESUMO
To treat the stochastic wind nature, it is required to attain all available power from the wind energy conversion system (WECS). Therefore, several maximum power point tracking (MPPT) techniques are utilized. Among them, hill-climbing search (HCS) techniques are widely implemented owing to their various features. Regarding current HCS techniques, the rotor speed is mainly perturbed using predefined constants or objective functions, which makes the selection of step sizes a multifaceted task. These limitations are directly reflected in the overall dynamic WECS performance such as tracking speed, power fluctuations, and system efficiency. To deal with the challenges of the existing HCS techniques, this paper proposes a new adaptive HCS (AD-HCS) technique with self-adjustable step size using model reference adaptive control (MRAC) based on the PID controller. Firstly, the mechanical power fluctuations are detected, then the MRAC continuously optimizes the PID gains so as to generate an appropriate dynamic step size until harvesting the maximum power point (MPP) under the optimal tracking conditions. Looking specifically at the simulation results, the proposed AD-HCS technique exhibits low oscillations around the MPP and a small settling time. Moreover, WECS efficiency is increased by 5% and 2% compared to the conventional and recent HCS techniques, respectively. Finally, the studied system is confirmed over a 1.5 MW, gird-tied, double-fed induction generator (DFIG) WECS using MATLAB/Simulink.
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BACKGROUND/AIMS: Inflammatory bowel disease is a chronic or remitting/relapsing intestinal inflammation, which comprises Crohn's disease and ulcerative colitis (UC). Severe UC is a life-threatening condition that requires corticosteroids (CS) as a first-line rescue therapy. Some patients are refractory to CS and may require alternative immunosuppressive therapy. Oral tacrolimus (FK506), an immunosuppressive agent, has been reported to be effective in the management of severe refractory UC, but it can cause serious adverse effects. This work aims to study the effect of tacrolimus delivered by a colon-targeted delivery system (CTDS) in a dextran sulfate sodium (DSS)-induced animal model of colitis. MATERIALS AND METHODS: We developed and evaluated an oral CTDS of tacrolimus (FK506) loaded pH-dependent polymeric microspheres, composed of Eudragit® S100 as a pH-sensitive polymer using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these microparticles in gastrointestinal tract (GIT) conditions were examined. A DSS-induced colitis rat model was used to evaluate the potential remedial and in vivo distribution of microspheres. RESULTS: The pH-microspheres prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the rat GIT demonstrated that pH-microspheres were successfully delivered to the inflamed colon. Moreover, it also demonstrated a significant decrease of disease activity and expression of proinflammatory cytokines, such as tumor necrosis factor α, interleukin-1ß (IL-1ß), and IL-6, and minimized the histological and morphometric changes. CONCLUSION: The results confirmed the efficacy of tacrolimus (FK506) CTDs in the management of DSS-induced colitis.
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Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Administração Oral , Animais , Colite/induzido quimicamente , Colo/patologia , Citocinas/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Concentração de Íons de Hidrogênio , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Masculino , Microesferas , Ácidos Polimetacrílicos/administração & dosagem , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/uso terapêutico , Ratos , Ratos Wistar , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinéticaRESUMO
BACKGROUND: Urgent care centers (UCCs) can offer a cheap alternative to emergency departments (EDs) for some patients with acute complaints. However, if patients who initially present to a UCC are unnecessarily transferred to an ED, those patients may suffer undue financial harm. The group of patients transferred from UCCs to EDs have never previously been studied. OBJECTIVES: The primary objective of this study was to determine the fraction of transfers from a UCC to an ED that were unnecessary. We also assessed the frequency with which these patients were discharged from the ED, and tried to determine which groups of patients were most likely to be unnecessarily transferred. METHODS: This was a retrospective chart review performed on patients transferred from UCCs to our ED. If the transferred patient had no advanced imaging tests, advanced procedures, or specialty consultations in the ED, and was not admitted, we considered the transfer to be unnecessary. Patients were stratified by age (adult vs. pediatric) and type of insurance. RESULTS: We identified 3232 patients who were transferred from UCCs to our ED over a 1-year period. Among those, 1159 (35.9%; 95% confidence interval [CI] 34.2-37.5%) met our criteria as unnecessary, and 2075 (64.2%; 95% CI 62.5-65.8%) were discharged from the ED. Notably, pediatric patients were more likely than adult patients to be unnecessarily transferred. Patients without medical insurance were not more likely to be transferred than those with private insurance. CONCLUSION: Most patients transferred to our ED from a UCC were discharged, and many transfers were unnecessary, especially those involving pediatric patients. These transfers may represent an economic burden to our society.
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Instituições de Assistência Ambulatorial/normas , Serviço Hospitalar de Emergência/normas , Transferência de Pacientes/normas , Adulto , Instituições de Assistência Ambulatorial/organização & administração , Serviço Hospitalar de Emergência/organização & administração , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Nevada , Alta do Paciente/tendências , Transferência de Pacientes/métodos , Estudos RetrospectivosRESUMO
IMPORTANCE: Basic essence of Pharmacovigilance is prevention of ADRs and its precise diagnosis is crucially a primary step, which still remains a challenge among clinicians. OBJECTIVE: This study is undertaken with the objective to scrutinize and offer a notion of commonly used as well as recently developed methods of causality assessment tools for the diagnosis of adverse drug reactions and discuss their pros and cons. EVIDENCE REVIEW: Overall 49 studies were recognized for all assessment methods with five major decisive factors of causality evaluation, all the information regarding reasons allocating causality, the advantages and limitations of the appraisal methods were extracted and scrutinized. FINDINGS: From epidemiological information a past prospect is designed and subsequent possibility merged this background information with a clue in the individual case to crop up with an approximation of causation. Expert judgment is typically based on the decisive factor on which algorithms are based, nevertheless in imprecise manner. The probabilistic methods use the similar principle; however connect probabilities to each measure. Such approaches are quite skeptical and liable to generate cloudy causation results. Causation is quite intricate to ascertain than correlation in Pharmacovigilance due to numerous inherent shortcomings in causality assessment tools. CONCLUSIONS AND RELEVANCE: We suggest that there is a need to develop a high quality assessment tool which can meticulously establish suitable diagnostic criteria for ADRs with universal acceptance to improvise the fundamental aspect of drug safety and evade the impending ADRs with the motive to convert Pharmacovigilance into a state of art.
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OBJECTIVE: To determine the PPVs of selected ten medication antidote signals in recognizing potential ADRs and comparison of their sensitivity with manual chart analysis, and voluntary reporting recognizing the same ADRs. METHOD: The inpatient EMR database of internal medicine department was utilized for a period of one year, adult patients prescribed at least one of the ten signals, were included in the study, recipient patients of antidote signals were assessed for the occurrence of an ADR by Naranjo's tool of ADR evaluation. PPVs of each antidote signal were verified. RESULT: PPV of Methylprednisolone and Phytonadione was 0.28, Metoclopramide and Potassium Chloride - 0.29, Dextrose 50%, Promethazine, Sodium Polystyrene and Loperamide - 0.30, Protamine and Acetylcysteine - 0.33. In comparison of confirmed ADRs of antidote signals with other methods, Dextrose 50%, Metoclopramide, Sodium Polystyrene, Potassium Chloride, Methylprednisolone and Promethazine seem to be extremely significant (P value > 0.0001), while ADRs of Phytonadione, Protamine, Acetylcysteine and Loperamide were insignificant. CONCLUSION: Antidote medication signals have definitive discerning evaluation value of ADRs over routine methods of ADR detection with a high detection rate with a minimum cost; Their integration with hospital EMR database and routine patient safety surveillance enhances transparency, time-saving and facilitates ADR detection.
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BACKGROUND AND OBJECTIVES: Dysphagia is a common complication following stroke. It corresponds to the development of pneumonia, which is always associated with bad prognosis, longer hospital stays and increased mortality. The aim of the study was to assess the impact of physical therapy intervention of dysphagia on preventing pneumonia in acute stroke patients. METHODS: A single-blind randomized controlled trial was carried out on 70 ischemic stroke patients with oropharyngeal dysphagia, age ranged from 49 to 65 years. They were randomly assigned to two groups (control and study) of equal number. Patients in the control group received oral care and nasogastric tube feeding, while patients in the study group received the same program in addition to the designed physical therapy program (exercises and neuromuscular electrical stimulation). The intervention program was applied for 40 min/session, 1 session/day, and 5 days/week for 4 weeks. Gugging swallowing screen (GUSS), and stroke associated pneumonia (SAP) control and prevention criteria were used to assess dysphagia and incidence of pneumonia at baseline, after two and 4 weeks of intervention for both groups. RESULTS: Before treatment, all patients were susceptible to pneumonia after two and 4 weeks of intervention; there were a significant increase in GUSS score in both groups with more improvement in favor of the study group (p < 0.05) and a statistically significant increase in incidence of SAP after 2 weeks of intervention only in the control group (p < 0.05). The results also showed a significant negative correlation between GUSS score and SAP (r = - 0.3662, p = 0.0018) IMPLICATIONS FOR PHYSIOTHERAPY PRACTICE: adding physical therapy (exercise therapy and neuromuscular electrical stimulation) to oral care and nasogastric tube feeding is effective in improving oropharyngeal dysphagia and decreasing the incidence of aspiration pneumonia in acute ischemic stroke patients.
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Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/reabilitação , Transtornos de Deglutição/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Método Simples-Cego , Idoso , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Pneumonia/prevenção & controle , Pneumonia/complicações , Modalidades de FisioterapiaRESUMO
Introduction: Adaptive radiotherapy (ART) is an essential approach to account for anatomical and biological uncertainties. Adaptive radiotherapy is, however, time-consuming, and it is unclear which patients are eligible or when is the best time to start ART. Methods: This prospective study was conducted at Kasr El-Aini Center of Clinical Oncology and Nuclear Medicine, Cairo, Egypt from January 2019 to December 2020. Thirty patients with pathologically proven, limited-stage small cell or stage I-II non-small cell lung cancer who were either not fit for or refused surgery or had stage III disease were recruited and underwent treatment planning to receive 60 Gy on a conventional 3D conformal radiation schedule with platinum-based chemotherapy. All patients underwent computed tomography (CT) planning within 2 and 4 weeks of starting radiation therapy to assess the need for adaptation. Pulmonary function test and echocardiography findings were assessed at the end of treatment and at 3 and 6 months after treatment, and were compared to the baseline. Results: We found a significant reduction in mean value of the planning target volume (PTV) in the CT scans at the second (331 cm3) and fourth (257 cm3) weeks of treatment as compared to baseline (342 cm3) (p-value < 0.0001). Adaptation decreased the dose to the organ at risk with statistical significance and with improvement of the target coverage. At week 2 of radiotherapy, the need for adaptation was correlated to the conformity index (p = 0.0473), esophageal V35 (p = 0.0488), esophageal V50 (p = 0.0295), and its mean dose (p = 0.0087). At week 4 it was correlated to forced expiratory volume in 1 second (FEV1) (p = 0.0303), ratio between the forced expiratory volume in 1 second and the forced vital capacity (FEV1/FVC) (p = 0.0024), and echocardiography (p = 0.0183). Conclusions: Conformity index and esophageal dose constraints can predict the need for adaptation at week 2, whereas baseline pulmonary function parameters and echocardiography can predict the need for adaptation at week 4 of radiotherapy.
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Background: Effective communication is crucial for broad acceptance and applicability of alternative methods in 3R biomedical research and preclinical testing. 3D bioprinting is used to construct intricate biological structures towards functional liver models, specifically engineered for deployment as alternative models in drug screening, toxicological investigations, and tissue engineering. Despite a growing number of reviews in this emerging field, a comprehensive study, systematically assessing practices and reporting quality for bioprinted liver models is missing. Methods: In this systematic scoping review we systematically searched MEDLINE (Ovid), EMBASE (Ovid) and BioRxiv for studies published prior to June 2nd, 2022. We extracted data on methodological conduct, applied bioinks, the composition of the printed model, performed experiments and model applications. Records were screened for eligibility and data were extracted from included articles by two independent reviewers from a panel of seven domain experts specializing in bioprinting and liver biology. We used RAYYAN for the screening process and SyRF for data extraction. We used R for data analysis, and R and Graphpad PRISM for visualization. Results: Through our systematic database search we identified 1042 records, from which 63 met the eligibility criteria for inclusion in this systematic scoping review. Our findings revealed that extrusion-based printing, in conjunction with bioinks composed of natural components, emerged as the predominant printing technique in the bioprinting of liver models. Notably, the HepG2 hepatoma cell line was the most frequently employed liver cell type, despite acknowledged limitations. Furthermore, 51% of the printed models featured co-cultures with non-parenchymal cells to enhance their complexity. The included studies offered a variety of techniques for characterizing these liver models, with their primary application predominantly focused on toxicity testing. Among the frequently analyzed liver markers, albumin and urea stood out. Additionally, Cytochrome P450 (CYP) isoforms, primarily CYP3A and CYP1A, were assessed, and select studies employed nuclear receptor agonists to induce CYP activity. Conclusion: Our systematic scoping review offers an evidence-based overview and evaluation of the current state of research on bioprinted liver models, representing a promising and innovative technology for creating alternative organ models. We conducted a thorough examination of both the methodological and technical facets of model development and scrutinized the reporting quality within the realm of bioprinted liver models. This systematic scoping review can serve as a valuable template for systematically evaluating the progress of organ model development in various other domains. The transparently derived evidence presented here can provide essential support to the research community, facilitating the adaptation of technological advancements, the establishment of standards, and the enhancement of model robustness. This is particularly crucial as we work toward the long-term objective of establishing new approach methods as reliable alternatives to animal testing, with extensive and versatile applications.
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Diabetes mellitus (DM) is a metabolic disorder with a notable increase in global incidence in recent years. Individuals diagnosed with diabetes are at an elevated risk of morbidity and mortality compared with the general population. For several years, the potential of phytochemicals as anti-inflammatory agents to improve the healing of diabetic wounds has been under investigation. Rutin, a flavonoid, is a particularly promising candidate for use in wound healing. Our study aims to investigate the potential impact of a topical application of rutin nanoformulation on wound healing in streptozotocin (STZ)-induced hyperglycemic rats controlled with metformin, with a focus on its anti-inflammatory and antioxidant properties. Rats are randomized into 3 groups. GI: diabetic control group; wound untreated. GII: diabetes and rutin-NP-treated wound. GIII: diabetic + ß-sitosterol-treated wound. The findings suggest that topical application of rutin-NPs has the potential to enhance the wound-healing process by attenuating oxidative stress, as evidenced by restoring GSH, CAT, and SOD antioxidants, and decreasing MDA production mediated by Nrf2 activation. Also, inflammation is suppressed, as indicated by the decreased CRP, IL-1ß, IL-6, and TNF-α levels. Molecular docking data confirm the biological data of rutin, where rutin is docked into the catalytic site of the X-ray crystallographic structures of CRP, Keap-1, IL-1ß, IL-6, and TNF-α via grid-based ligand docking. The binding affinity and binding energy of ligand-protein interactions demonstrate the affinity and binding to the specifically selected proteins.
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BACKGROUND: Many non-pharmacological interventions have been proposed for spasticity modulation in spastic stroke subjects. OBJECTIVE: To investigate the immediate effect of dry needling (DN), electrical stimulation (ES), and dry needling with intramuscular electrical stimulation (DN+IMES) on H-reflex in post-stroke spasticity. METHODS: Spastic subjects with stroke (N = 90) (55-85 years) were evaluated after 1 month of stroke onset using Modified Ashworth Scale (MAS) score ≥1. Subjects were randomly allocated to receive one session of DN - Soleus (N = 30), ES - posterior lateral side of the leg with 100 Hz and 250 µs pulse width (N = 30), or DN+IMES - Soleus (N = 30). MAS, H-reflex, maximum latency, H-amplitude, M-amplitude and H/M ratio, were recorded before and after one session of intervention. Relationships for each variable within group or the difference among groups were calculated by effect size. RESULTS: Significant decrease in H/M ratio in Gastrocnemius and Soleus at post-treatment within DN group (P = .024 and P = .029, respectively), large effect size (d = 0.07 and 0.62, respectively); and DN+IMES group (P = .042 and P = .001, respectively), large effect size (d = 0.69 and 0.71, respectively). No significant differences in all variables at pre-treatment and post-treatment was recorded among ES, DN, and DN+IMES groups. Significant decrease in MAS was recorded at post-treatment compared to pre-treatment within ES group (P = .002), DN group (P = .0001), and DN+IMES group (P = .0001), but not significant (P > .05) among three groups at pre-treatment (P = .194) and post-treatment (P = .485). CONCLUSIONS: Single session of DN, ES, and the DN+IMES can significantly modulate post-stroke spasticity by possible bottom-up regulation mechanisms.
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The AUC0-24 is the most accurate way to track the vancomycin level while the Cmin is not an accurate surrogate. Most hospitals in Saudi Arabia are under-practicing the AUC-guided vancomycin dosing and monitoring. No previous work has been conducted to evaluate such practice in the whole kingdom. The current study objective is to calculate the AUC0-24 using the Bayesian dosing software (PrecisePK), identify the probability of patients who receive the optimum dose of vancomycin, and evaluate the accuracy and precision of the Bayesian platform. This retrospective study was conducted at King Abdulaziz medical city, Jeddah. All adult patients treated with vancomycin were included. Pediatric patients, critically ill patients requiring ICU admission, patients with acute renal failure or undergoing dialysis, and febrile neutropenic patients were excluded. The AUC0-24 was predicted using the PrecisePK platform based on the Bayesian principle. The two-compartmental model by Rodvold et al. in this platform and patients' dose data were utilized to calculate the AUC0-24 and trough level. Among 342 patients included in the present study, the mean of the estimated vancomycin AUC0-24 by the posterior model of PrecisePK was 573 ± 199.6 mg, and the model had a bias of 16.8%, whereas the precision was 2.85 mg/L. The target AUC0-24 (400 to 600 mg·h/L) and measured trough (10 to 20 mg/L) were documented in 127 (37.1%) and 185 (54%), respectively. Furthermore, the result demonstrated an increase in odds of AUC0-24 > 600 mg·h/L among trough level 15-20 mg/L group (OR = 13.2, p < 0.05) as compared with trough level 10-14.9 mg/L group. In conclusion, the discordance in the AUC0-24 ratio and measured trough concentration may jeopardize patient safety, and implantation of the Bayesian approach as a workable alternative to the traditional trough method should be considered.
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The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0-24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½ß, and the first-order rate constant for the elimination process ß in FN compared to non-FN patients. Furthermore, AUC0-24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0-24, which may require specific consideration during the treatment initiation.
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Objective: To evaluate the efficacy of castor oil in initiation of labor in women who had one previous cesarean section. This study was conducted as a trial to increase the rate of vaginal birth after cesarean (VBAC) and decrease the rate of elective repeated cesarean section (ERCS).Methods: A double-blinded randomized controlled study was conducted in an Egyptian University Hospital from July 2019 to July 2020. The participants were 70 pregnant women who had one previous cesarean section, singleton pregnancy in cephalic presentation, with a Bishop score ≤6 attempting to perform a trial of labor. Sixty mL castor oil was administered to group A and 60 mL sunflower oil was administered to group B (as a placebo) for initiation of labor at the start of week 39. Primary outcomes were the percentage of women entering the active phase of labor within 24 h after receiving castor oil or placebo and the number of successful VBAC deliveries.Results: Labor started in 16 patients (45.7%) within 24 h in the castor oil group and in 3 patients in the placebo group (8.5%), while the rate of successful VBAC was 65.7% (23 patients) in the castor oil group and 48.5% (17 patients) in the placebo group.Conclusion: Castor oil appears to be an effective, low-cost, and non-harmful method for the initiation of labor in patients with a previous cesarean section.
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Prova de Trabalho de Parto , Nascimento Vaginal Após Cesárea , Feminino , Gravidez , Humanos , Cesárea , Óleo de Rícino , Resultado da Gravidez , Estudos Retrospectivos , RecesarianaRESUMO
Increasing success of adaptive cell therapy (ACT), such as genetically engineered T cells to express chimeric antigen receptors (CARs) proven to be highly significant technological advancements and impressive clinical outcomes in selected haematological malignancies, with promising efficacy. The evolution of CAR designs beyond the conventional structures is necessary to address some of the limitations of conventional CAR therapy and to expand the use of CAR T cells to a wider range of malignancies. There are various obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. Here we describe details of modular CAR structure with all the necessary domains and what is known about proximal CAR signalling in T cells. Furthermore, the global need for adoptive cell therapy is expanding very rapidly, and there is an urgent increasing demand for fully automated manufacturing methods that can produce large scale clinical grade high quality CAR engineered immune cells. Despite the advances in automation for the production of clinical grade CAR engineered cells, the manufacturing process is costly, consistent and involves multiple steps, including selection, activation, transduction, and Ex-Vivo expansion. Among these complex manufacturing phases, the choice of culture system to generate a high number of functional cells needs to be evaluated and optimized. Here we list the most advance fully automated to semi-automated bioreactor platforms can be used for the production of clinical grade CAR engineered cells for clinical trials but are far from being standardized. New processing options are available and a systematic effort seeking automation, standardization and the increase of production scale, would certainly help to bring the costs down and ultimately democratise this personalized therapy. In this review, we describe in detail different CAR engineered T cell platforms available and can be used in future for clinical-grade CAR engineered ATMP production.
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Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Linfócitos T , Terapia Baseada em Transplante de Células e Tecidos , Reatores BiológicosRESUMO
Lepidium sativum L. (Garden cress/Hab El Rashad) (Ls), family Brassicaceae, has considerable importance in traditional medicine worldwide because of its antioxidant and anti-inflammatory activities. Ls fruits were used in Ayurvedic medicines as a useful drug for injuries, skin, and eye diseases. The aim of this study was to examine the effectiveness of the total ethanol extract (TEE) and polysaccharide (Poly) of Ls seeds loaded on poly(vinyl alcohol) (PVA) nanofibers (NFs) as a wound healing dressing and to correlate the activity with the constituents of each. TEE and Poly were phytochemically analyzed qualitatively and quantitatively. Qualitative analysis proved the presence of phenolic acids, flavonoids, tannins, sterols, triterpenes, and mucilage. Meanwhile, quantitative determinations were carried out spectrophotometrically for total phenolic and total flavonoid contents. High-performance liquid chromatography (HPLC) for TEE identified 15 phenolic acids and flavonoid compounds, with gallic acid and catechin as the majors. Separation, purification, and identification of the major compounds were achieved through a Puriflash system, column Sephadex LH20, and spectroscopic data (1H, 13C NMR, and UV). Eight compounds (gallic acid, catechin, rutin, kaempferol-3-O-rutinoside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, quercetin, and kaempferol) were obtained. Gas-liquid chromatography (GLC) analysis for Poly identified 11 compounds, with galactose being the main. The antioxidant activity for both extracts was measured by three different methods based on different mechanisms: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). TEE has the highest effectiveness as an antioxidant agent with IC50 82.6 ± 8.35 µg/mL for DPPH and 772.47 and 758.92 µM Trolox equivalent/mg extract for FRAP and ABTS, respectively. The PVA nanofibers (NFs) for each sample were fabricated by electrospinning. The fabricated NFs were characterized by SEM and Fourier transform infrared spectroscopy (FTIR); the results revealed successful encapsulation of TEE and Poly in the prepared NFs. Moreover, the swelling index of TEE in the prepared NFs shows that it is the most appropriate for use as a wound dressing. Cytotoxicity studies indicated a high cell viability with IC50 216 µg/mL and 1750 µg/mL for TEE and Poly, respectively. Moreover, the results revealed that nanofibers possess higher cell viability compared to solutions with the same sample quantities: 9-folds for TEE and 4-folds for Poly of amount 400 µg. The in vitro wound healing test showed that the TEE nanofibers performed better than Poly nanofibers in accelerating wound healing, with 90% for TEE, more than that for the Poly extract (82%), after 48 h. These findings implied that the incorporation of TEE in PVA nanofibers was more efficient than incorporation of Poly in improving the biological activity in wound healing. In conclusion, the TEE and polysaccharides of L. sativum L seed are ideal candidates for nanofibrous wound dressings. Furthermore, the contents of phenolic acids and flavonoids in TEE, which have potential antioxidant activity, make the TEE of L. sativum more favorable for wound healing dressing.
RESUMO
A Promising nanocomposite from ß-Cyclodextrin/Alginate (ß-CD/Alg) composite impregnated with nickel oxide nanoparticles (NiO) has been synthesized and characterized using diverse techniques like FT-IR, XRD, TGA, and SEM. The new nanocomposite has been investigated for the efficient remediation of 51Cr and 56Mn radionuclides from simulated contaminated radioactive water. All the controlling experimental parameters such as solution pH, contact time, initial radionuclides concentration and adsorbent mass have been investigated and optimized. The distribution coefficient values Kd (mL/g) for 51Cr and/or 56Mn radionuclides have been calculated for all factors it was found that the optimum pH values were at 5 and 6 with Kd 5300, and 4500, for 51Cr and/or 56Mn, respectively and the equilibrium was at 90 and 100 (min) with Kd values 5600 and 4800 for 51Cr and/or 56Mn, respectively.
Assuntos
Recuperação e Remediação Ambiental , Poluentes Radioativos , beta-Ciclodextrinas , Adsorção , Alginatos , Concentração de Íons de Hidrogênio , Cinética , Níquel , Radioisótopos , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise , beta-Ciclodextrinas/químicaRESUMO
BACKGROUND: one of the major annoying disorders occurring in people with multiple sclerosis is lower urinary tract disorders (LUT). Urgency is considered the main one seriously influencing the quality of life. Neurogenic detrusor over activity (DOAB) is characterized by a hyperreflexic, overactive detrusor that responds quickly to low-intensity sensory input from general visceral afferent fibers. Overactivity has been claimed to induce random, uncontrolled contractions of the detrusor muscle, leading to intravesicular pressure rise, producing urgency, frequency, and consequently incontinence AIM: To demonstrate the therapeutic efficacy for posterior tibial nerve stimulation (PTNS) in neurogenic over active bladder (NOAB) in people with multiple sclerosis METHODS: The current trial is a prospective, randomized controlled study. Forty remitting relapsing males with MS with moderate NOAB symptoms were randomly assigned into two equal groups; control group (C) treated by selected therapeutic exercises program for strengthening pelvic floor muscles and an intervention group (ES) receiving an additional posterior tibial nerve electrical stimulation. Each session ranged from 45- 50 minutes, three days weekly for a month. Outcome measures were recorded before starting the treatment and after termination of the study intervention and included over active bladder symptoms score (OVBS) score, urodynamic parameters (uroflow, filling and voiding cystometry), and post voiding residual volume by abdominal ultrasound RESULTS: There was a significant improvement of all voiding parameters compared to baseline and the group C except frequency of urgency incontinence. A significant decrease was detected in post-treatment mean episodes number of nighttime frequency, urgency, urgency incontinence (1.65 ± 0.93, 1.2 ± 0.52 and 1.5 ± 0.76) respectively of the ES group compared to that of group C (3.05 ± 1.09, 2.25 ± 0.71 and 2.25 ± 1.06) (P < 0.01). There was a significant decrease in median post-treatment OVBS score 3 (3-3) compared to group C median score 5 (6-4). A statistically significant improvement was observed of all urodynamic parameters (bladder capacity and compliance, Detrusor overactivity (DO), maximum flow rate and post voidal residual volume in the ES group compared to the group C CONCLUSION: PTNS is a promising and potentially beneficial treatment option for NOAB symptoms in males with MS and superior to pelvic floor muscle training alone.