Activity

  • Galbraith Thygesen posted an update 1 week, 5 days ago

    The thioredoxin (Trx) system, a key antioxidant pathway, represents an attractive target for cancer therapy. This study investigated the chemotherapeutic and radiosensitising effects of a novel Trx reductase (TrxR) inhibitor, IQ10, on brain cancer cells and the underlying mechanisms of action. Five brain cancer cell lines and a normal cell type were used. TrxR activity and expression were assessed by insulin reduction assay and Western blotting, respectively. IQ10 cytotoxicity was evaluated using growth curve, resazurin reduction and clonogenic assays. Radiosensitivity was examined using clonogenic assay. Reactive oxygen species levels were examined by flow cytometry and DNA damage assessed by immunofluorescence. Epithelial-mesenchymal transition (EMT)-related gene expression was examined by RT-PCR array. IQ10 significantly inhibited TrxR activity but did not affect Trx system protein expression in brain cancer cells. see more The drug exhibited potent anti-proliferative and cytotoxic effects against brain cancer cells under both normoxic and hypoxic conditions in both 2D and 3D systems, with IC50s in the low micromolar range. It was up to ~ 1000-fold more potent than temozolomide. IQ10 substantially sensitised various brain cancer cells to radiation, with such effect being due, in part, to functional inhibition of TrxR, making cells less able to deal with oxidative stress and leading to increased oxidative DNA damage. IQ10 significantly downregulated EMT-associated gene expression suggesting potential anti-invasive and antimetastatic properties. This study suggests that IQ10 is a potent anticancer agent and could be used as either a single agent or combined with radiation, to treat brain cancers.Sternohyoid, sternothyroid, omohyoid and thyrohyoid muscles belong to a group of muscles called infrahyoid muscles. A few variations of these muscles and additional muscles in this area have been reported. We report an anomalous muscle in this area. The anomalous muscle took its origin from the posterior surface of the manubrium sterni and was inserted to the posterior surface of the clavicle. This muscle was 6 cm long and interestingly, it made a loop, which was clinging on to the inferior belly of omohyoid posteriorly, superiorly and anteriorly. The muscle was situated between the lower end of sternocleidomastoid and the carotid sheath. It was supplied by ansa cervicalis. Knowledge of this muscle could be useful in surgeries like removal of cervical rib, and cervical lymph node clearance. Hypertrophy of this muscle might compress the internal jugular vein.BACKGROUND AND OBJECTIVE Piperacillin is a broad-spectrum β-lactam antibiotic commonly prescribed in intensive care units. Many piperacillin population pharmacokinetic models have been published, but few underwent an external evaluation. External evaluation is an important process to determine a model’s capability of being generalized to other hospitals. We aimed to assess the predictive performance of these models with an external validation dataset.

    Six models were evaluated with a dataset consisting of 30 critically ill patients (35 samples) receiving piperacillin by continuous infusion. Models were subject to prediction-based (bias and imprecision) and simulation-based evaluations. When a model had an acceptable evaluation, it was used for dosing simulations to evaluate the probability of target attainment.

    Bias and imprecision ranged from -35.7 to 295% and from 22.7 to 295%, respectively. The models of Klastrup et al. and of Udy et al. were acceptable according to our criteria and were used for dosing simulations. Simulations showed that a loading dose of 4 g followed by a maintenance dose of 16g/24h of piperacillin infused continuously was necessary to remain above a pharmacokinetic-pharmacodynamic target set as a minimal inhibitory concentration of 16mg/L in 90% of patients, for a median patient with a creatinine clearance of 76mL/min.

    Despite the considerable variation in the predictive performance of the models with the external validation dataset, this study was able to validate two of these models and led to the elaboration of a dosing nomogram for piperacillin by continuous infusion that can be used by clinicians in intensive care units.

    Despite the considerable variation in the predictive performance of the models with the external validation dataset, this study was able to validate two of these models and led to the elaboration of a dosing nomogram for piperacillin by continuous infusion that can be used by clinicians in intensive care units.Bio-inspired design (BID) means the concept of transferring functional principles from biology to technology. The core idea driving BID-related work is that evolution has shaped functional attributes, which are termed “adaptations” in biology, to a high functional performance by relentless selective pressure. For current methods and tools, such as data bases, it is implicitly supposed that the considered biological models are adaptations and their functions already clarified. Often, however, the identification of adaptations and their functional features is a difficult task which is not yet accomplished for numerous biological structures, as happens to be the case also for various organismic features from which successful BID developments were derived. This appears to question the relevance of the much stressed importance of evolution for BID. While it is obviously possible to derive an attractive technical principle from an observed biological effect without knowing its original functionality, this kind of BID (“analog BID”) has no further ties to biology. In contrast, a BID based on an adaptation and its function (“homolog BID”) is deeply embedded in biology. It is suggested that a serious and honest clarification of the functional background of a biological structure is an essential first step in devising a BID project, to recognize possible problems and pitfalls as well as to evaluate the need for further biological analysis.This study aims to compare the concentrations of circulating levels of iron, zinc, and copper in blood samples of rheumatoid arthritis (RA) patients which determine the correlations with inflammation and disease activity. A total of 102 RA patients and 66 healthy controls were enrolled. Circulation of iron, zinc, and copper levels in whole blood were assessed. Hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anticyclic citrullinated peptide antibody (anti-CCP) levels were collected. A meta-analysis was performed to validate our findings. Single and multiple variate generalized linear regression were applied to identify the correlation between trace elements and clinical characteristics. Blood copper level was significantly higher in RA patients (P  less then  0.001), while iron and zinc levels were decreased (P  less then  0.001 and P = 0.02, respectively). Meta-analysis confirmed our findings for zinc (SMD =  - 1.17, P  less then  0.001) and copper (SMD = 1.24, P  less then  0.001). Copper level was positively correlated with DAS28-CRP (r = 0.35, P  less then  0.01), CRP (r = 0.45, P  less then  0.01) and ESR (r = 0.58, P  less then  0.01). Iron level was negatively correlated with DAS28-CRP (r =  - 0.37, P  less then  0.01), CRP (r =  - 0.46, P  less then  0.01) and ESR (r =  - 0.55, P  less then  0.01). Circulating blood copper was significantly higher and positively correlated with DAS28-CRP and inflammatory markers, while circulating blood iron was decreased and negatively correlated with DAS28-CRP and inflammatory markers in RA patients.

    Theoretical advantages of Turnbull-Cutait pull-through delayed coloanal anastomosis (DCAA) are a reduced risk of anastomotic leak and therefore avoidance of stoma. Gradually abandoned in favor of immediate coloanal anastomosis (ICAA) with diverting stoma, DCAA has regained popularity in recent years in reconstructive surgery for low RC, especially when combined with minimally invasive surgery (MIS). The aim of this study was to perform the first meta-analysis, exploring the safety and outcomes of DCAA compared to ICAA with protective stoma.

    A systematic search of MEDLINE, EMBASE, and CENTRAL and Google Scholar databases was performed for studies published from January 2000 until December 2020. The systematic review and meta-analysis were performed according to the Cochrane Handbook for Systematic Review on Interventions recommendations and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines.

    Out of 2626 studies screened, 9 were included in the systematic review and 4 stfocusing on oncologic and functional outcomes are needed.

    Data are scarce regarding the prevalence and predictors of perinatal mood and anxiety disorders (PMADs) among Black women. The purpose of this study was to examine the prevalence and predictors of symptoms of PMADS among Black women.

    Black women completed a paper survey between August 2019 and October 2019. Binomial logistic regression was employed to examine predictors of PMAD symptoms.

    The prevalence of symptoms of PMADs was 56%. A higher proportion of women with PMADs had experienced depression (16% vs. 32%, p = 0.006); physical (18% vs. 31%, p = 0.030), emotional (35% vs. 61%, p = 0.000), or sexual abuse (12% vs. 29%, p = 0.002); and symptoms of depression or anxiety before pregnancy (18% vs. 46%, p = 0.000). After adjusting for socio-demographics in multivariate analysis, experiencing symptoms of depression or anxiety before pregnancy (adjusted odds ratio [aOR] = 3.445, p = 0.001) was positively associated with experiencing symptoms of PMADs, whereas higher levels of self-esteem (aOR = 0.837, p = 0.000) were negatively associated with experiencing symptoms of perinatal mood and anxiety disorders.

    The prevalence of PMAD symptoms among this sample of Black women was alarmingly high. Women who experienced PMADs were more likely to report adverse childhood experiences (e.g., physical, emotional, and/or sexual abuse). By understanding the prevalence of PMADs and the factors associated with these disorders, healthcare professionals can improve diagnosis and treatment rates among this understudied and underserved population.

    The prevalence of PMAD symptoms among this sample of Black women was alarmingly high. Women who experienced PMADs were more likely to report adverse childhood experiences (e.g., physical, emotional, and/or sexual abuse). By understanding the prevalence of PMADs and the factors associated with these disorders, healthcare professionals can improve diagnosis and treatment rates among this understudied and underserved population.In this work, GAC@Ni/Fe particle electrodes were prepared and employed for the degradation of sulfamethylthiadiazole (SMT) by three-dimensional electrocatalytic technology. The effects of particle electrode bi-metal loading ratio, cell voltage, particle electrode dosage, electrode plate spacing, and SMT initial concentration on SMT removal were studied. In addition, GAC@Ni/Fe particle electrode was analyzed by the scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), X-ray photoelectron spectrometer (XPS), and Fourier transform infrared spectrometer (FTIR) to characterize which indicated that a significant amount of iron-nickel oxide was formed on the surface of GAC@Ni/Fe particle electrode. The results indicated that when the nickel-iron loading ratio is 11, the SMT removal effect is the best, and the removal rate can reach 90.89% within 30 min. Compared with the granular activated carbon without bimetal, the removal efficiency is increased by 37.58%. The degradation of SMT in the GAC@Ni/Fe particle three-dimensional electrode reactor is the joint result of both direct oxidation and indirect oxidation.