Deinduction of P‐glycoprotein resulting in delayed viral response during hepatitis C treatment

xloma.fota13 shared this article with you from Inoreader Deinduction of P‐glycoprotein resulting in delayed viral response during hepatitis C treatment Via Journal of Clinical Pharmacy and Therapeutics Drug‐drug interactions can involve induction of cell membrane transporters. Deinduction refers to the time course for enzymes or drug transporters to return to normal activity and can be delayed beyond the time required for clearance of the inducing agent. Clinicians should consider deinduction when starting and stopping medications involving strong inducers. Abstract What is known and objective Drug‐drug interactions can involve inhibition or induction of cell membrane transporters. Deinduction occurs after an inducing agent is stopped. Case summary This case describes suspected P‐glycoprotein (P‐gp) deinduction by carbamazepine resulting in a slow viral response during treatment of chronic hepatitis C virus (HCV) infection. Evidence of deinduction occurred beyond clearance of carbamazepine and resulted in extension of HCV treatment. What is new The understanding of the role P‐gp transport plays in drug elimination is relatively new and evidence of P‐gp deinduction is variable. Conclusion Clinicians should consider deinduction when starting and stopping medications involving strong inducers of P‐gp transport proteins. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Apotex Corp. Issues Voluntary Nationwide Recall of Enoxaparin Sodium Injection, USP Due to Mislabeling of Syringe Barrel Measurement Markings

xloma.fota13 shared this article with you from Inoreader Apotex Corp. Issues Voluntary Nationwide Recall of Enoxaparin Sodium Injection, USP Due to Mislabeling of Syringe Barrel Measurement Markings Via Drugs.com - FDA MedWatch Alerts Audience: Consumer, Patient, Health Professional, Pharmacy February 03, 2021 -- Apotex Corp is voluntarily recalling two (2) batches of Enoxaparin Sodium Injection, USP to consumer level due to a packaging error resulting in some syringes barrels... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Turbulence and turbulent flow structures in a ventricular assist device—A numerical study using the large‐eddy simulation

xloma.fota13 shared this article with you from Inoreader Turbulence and turbulent flow structures in a ventricular assist device—A numerical study using the large‐eddy simulation Via International Journal for Numerical Methods in Biomedical Engineering In this article the turbulence and turbulent flow structures in a ventricular assist device (VAD) are investigated in detail. First, the VAD flow is computed using the turbulence resolving large‐eddy simulation method. Then, the turbulent flow state within an axial VAD is globally quantified with a self‐developed evaluation method. Subsequently, local turbulent flow structures are investigated. The structures found are universal and can be expected in every axial blood pump. Finally, the relevance of these structures for the blood damage prediction will be highlighted. Abstract Numerical flow simulations that analyze the turbulent flow characteristics within a turbopump are important for optimizing the efficiency of such machines. In the case of ventricular assist devices (VADs), turbulent flow characteristics must be also examined in order to improve hemocompatibility. Turbulence increases the shear stresses in the VAD flow, which can lead to an increased damage to the transported blood components. Therefore, an understanding of the turbulent flow patterns and their significance for the numerical blood damage prediction is particularly important for flow optimizations in VADs in order to identify and thus minimize flow regions where blood could be damaged due to high turbulent stresses. Nevertheless, the turbulence occurring in VADs and the local turbulent structures that lead to increased turbulent stresses have not yet been analyzed in detail in these machines. Therefore, this study aims to investigate the turbulence in an axial VAD in a comprehensive and double tracked way. First, the flow in an axial VAD was computed using the large‐eddy simulation method, and it was verified that the majority of the turbulence was directly resolved by the simulation. Then, the turbulent flow state of the VAD was quantified globally. For this purpose, a self‐designed evaluation method, the power loss analysis, was used. Subsequently, local flow regions and flow structures were identified where significant turbulent stresses prevail. It will be shown that the identified regions are universal and will also occur in other axial blood pumps as well, for example, in the HeartMate II. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Coronary arterial geometry

xloma.fota13 shared this article with you from Inoreader Coronary arterial geometry: a comprehensive comparison of two imaging modalities Via International Journal for Numerical Methods in Biomedical Engineering Summary The characterization of vascular geometry is a fundamental step towards the correct interpretation of coronary artery disease. In this work, we report a comprehensive comparison of the geometry featured by coronary vessels as obtained from coronary computed tomography angiography (CCTA) and the combination of intravascular ultrasound (IVUS) with bi‐plane angiography (AX) modalities. We analyzed 34 vessels from 28 patients with coronary disease, which were deferred to CCTA and IVUS procedures. We discuss agreement and discrepancies between several geometric indexes extracted from vascular geometries. Such an analysis allows us to understand to which extent the coronary vascular geometry can be reliable in the interpretation of geometric risk factors, and as a surrogate to characterize coronary artery disease. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Spatial and Temporal Discretization in Cardiac Electrophysiology

xloma.fota13 shared this article with you from Inoreader A Numerical Study on the Effects of Spatial and Temporal Discretization in Cardiac Electrophysiology Via International Journal for Numerical Methods in Biomedical Engineering Summary Millions of degrees of freedom are often required to accurately represent the electrophysiology of the myocardium due to the presence of discretization effects. This study seeks to explore the influence of temporal and spatial discretization on the simulation of cardiac electrophysiology in conjunction with changes in modelling choices. Several finite element analyses are performed to examine how discretization affects solution time, conduction velocity and electrical excitation. Discretization effects are considered along with changes in the electrophysiology model and solution approach. Two action potentialmodels are considered: the Aliev‐Panfilovmodel and the ten Tusscher‐Noble‐Noble‐Panfilovmodel. The solution approaches consist of two time integration schemes and different treatments for solving the local system of ordinary differential equations. The efficiency and stability of the calculation approaches are demonstrated to be dependent on the action potential model. The dependency of the conduction velocity on the element size and time step is shown to be different for changes inmaterial parameters. Finally, the discrepancies between the wave propagation in coarse and fine meshes are analysed based on the temporal evolution of the transmembrane potential at a node and its neighbouring Gauss points. Insight obtained from this study can be used to suggest new methods to improve the efficiency of simulations in cardiac electrophysiology. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Modelling Human Liver Microphysiology on a Chip Through a Finite Element Based Design Approach

xloma.fota13 shared this article with you from Inoreader Modelling Human Liver Microphysiology on a Chip Through a Finite Element Based Design Approach Via International Journal for Numerical Methods in Biomedical Engineering Abstract Organ‐on‐a‐chip are microfluidic devices capable of growing living tissue and replicate the intricate microenvironments of human organs in vitro, being heralded as having the potential to revolutionize biological research and healthcare by enabling unprecedented control over fluid flow, relevant tissue to volume ratio, compatibility with high‐resolution content screening and a reduced footprint. Finite element modelling is proven to be an efficient approach to simulate the microenvironments of organ‐on‐a‐chip devices, and may be used to study the existing correlations between geometry and hydrodynamics, towards developing devices of greater accuracy. The present work aims to refine a steady‐state gradient generator for development of a more relevant human liver model. For this purpose, the finite element method was used to simulate the device and predict which design settings, expressed by individual parameters, would better replicate in vitro the oxy gen gradients found in vivo within the human liver acinus. To verify the model's predictive capabilities, two distinct examples were replicated from literature. Finite element analysis enabled obtaining an ideal solution, designated as liver gradient‐on‐a‐chip, characterized by a novel way to control gradient generation, from which it was possible to determine concentration values ranging between 3% and 12%, thus providing a precise correlation with in vivo oxygen zonation, comprised between 3 − 5% and 10 − 12% within respectively the perivenous and periportal zones of the human liver acinus. Shear stress was also determined to average the value of 0.037 Pa , and therefore meet the interval determined from literature to enhance liver tissue culture, comprised between 0.01 − 0.05 Pa . This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effectiveness and Tolerability of Treatment for Isolated Actinic Keratoses: A Retrospective Comparison Between Cryotherapy, CO2 laser and 5‐Fluorouracil 0.5% /Salicylic Acid 10%

xloma.fota13 shared this article with you from Inoreader Effectiveness and Tolerability of Treatment for Isolated Actinic Keratoses: A Retrospective Comparison Between Cryotherapy, CO2 laser and 5‐Fluorouracil 0.5% /Salicylic Acid 10% Via Dermatologic Therapy Abstract Background Actinic keratoses (AK) have been described as either intraepithelial keratinocytic dysplasia that can evolve into invasive squamous cell carcinoma (SCC) or as in situ SCC that can progress into an invasive form. Materials and Methods A retrospective study was conducted to compare outcomes of three different topical therapies for patients with single AK (<4): cryotherapy, CO2 laser and 5‐fluorouracil 0.5% /salicylic acid 10%. We included 72 patients who presented at the Dermatology Clinic of Maggiore Hospital of Trieste between November 1st 2019 and January 31st 2020 for the treatment of AKs. Results All treatments led to a significant reduction in the average diameter of AK. Pain felt by patients was significantly lower after 5‐FU 0.5%/SA 10%. Side effects appeared similarly distributed among the three groups, with erythema and crusts being the most frequent. Aesthetic outcomes were highest in the 5‐FU 5%/SA 10% group, as evaluated by both the patient and the operator. Conclusion Cryotherapy, CO2 laser and 5‐FU 5%/SA 10% were all effective, with no significant efficacy differences among them. Additionally, 5‐FU 5%/SA 10% was proved to have the best aesthetic result and to cause the least pain, while necessitating long‐term administration. This should be taken into account for patients with low pain tolerance and low treatment adherence. Cryotherapy and CO2 laser have the advantage of requiring a single session, which might be more suitable for uncooperative patients. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

COVID‐19 related masks increase severity of both acne (Maskne) and rosacea (Mask rosacea): Multi‐center, real‐life, telemedical, observational prospective study

xloma.fota13 shared this article with you from Inoreader COVID‐19 related masks increase severity of both acne (Maskne) and rosacea (Mask rosacea): Multi‐center, real‐life, telemedical, observational prospective study Via Dermatologic Therapy ABSTRACT Background Masks are essential for COVID‐19 prevention, but recently they were suggested to modify cutaneous facial microenvironment and trigger facial dermatoses. Objective To evaluate mask‐ related rosacea and acne (maskne) in untreated patients during lockdown Methods In this multi‐center, real‐life, observational prospective study, we enrolled stable, untreated acne and rosacea patients that wore masks during lockdown at least 6h/day. They underwent two teledermatological consultations, at the baseline and after 6 weeks. Clinical, pharmacological and psychological data were recorded. Results A total 66 patients, 30 (median age: 34.0 [30.25‐29.75] yoa) with acne and 36 patients (median age: 48 [43‐54] years) with rosacea, were enrolled in this study. After 6 weeks of mask and quarantine, patients with acne displayed an increased Global Acne Grading Scale (GAGS) score in mask‐related areas (P<0.0001). Likewise, after 6 weeks of mask and quarantine, patients with rosacea displayed a worsen in both physican (P<0.0001) and patient (P<0.0001) reported outcomes. Remarkably, patients reported also a statistically significant decrease in their quality of life (P<0.0001). Conclusions Masks appear to trigger both acne and rosacea flares. Additional studies are needed to generate evidence and inform clinical decision‐making. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Demographic data, comorbidities, quality of life, and survival probability of biologic therapy associated with sex‐specific differences in psoriasis in the Czech Republic

xloma.fota13 shared this article with you from Inoreader Demographic data, comorbidities, quality of life, and survival probability of biologic therapy associated with sex‐specific differences in psoriasis in the Czech Republic Via Dermatologic Therapy ABSTRACT BIOREP is a Czech registry of patients with psoriasis undergoing biological treatment. The objective of the study was to compare differences in demographic data, previous therapy, comorbidities, severity of psoriasis, quality of life, drug survival rates, and reasons for discontinuation between men and women. We analyzed a cohort of patients from the registry treated between May 2005 and January 2020. The total study population of 2,472 patients (4,051 treatment series) included 913 females and 1,559 males. Women were significantly older than men at the onset of the biological treatment (47.8 vs. 45.4 years, p < 0.0012) and the mean durations of psoriasis and that from its diagnosis until initiation of biological therapy, were longer in women (29.6 vs. 27.2 years and 23.2 vs. 20.6 years, p < 0.0012). Women as compared with men were also more often diagnosed with psoriatic arthritis (43.5% vs. 33.0%, p < 0.0012). The prevalence rate of comorbidities was equival ent for both sexes except for that of depression (11.4% females vs. 3.7% males, p < 0.0012). Both the DLQI and PASI scores were significantly different at baseline (DLQI = 16.0 and PASI = 19.5 for men vs. DLQI 17.6 = and PASI = 17.7 for women, p < 0.0012). The survival probability with biological therapy was significantly lower in women for both biologically naïve and non‐naïve patients, and there was more evidence of adverse effects in women. Our research demonstrates significant differences relative to multiple factors associated with psoriasis between men and women. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The role of topical timolol in wound healing and the treatment of vascular lesions; a narrative review

xloma.fota13 shared this article with you from Inoreader The role of topical timolol in wound healing and the treatment of vascular lesions; a narrative review Via Dermatologic Therapy Abstract Beta‐2 adrenergic receptors are the only subgroup of beta‐adrenergic receptors expressed in the membrane of large cells, including skin keratinocytes, fibroblasts, and melanocytes. Alterations in the function or concentration of β2 adrenoreceptors related to keratinocytes are associated with some skin conditions. Some findings suggest the role of β2 adrenoreceptors in maintaining the function and integrity of the epidermis. Beta‐receptor antagonists can be systemically and topically effective in healing hemangioma, paronychia, vasculitis ulcer, tufted angioma, acute and chronic wounds. Most studies with a strong design on this subject deal with the systemic form, but recently, numerous case and group reports and smaller studies have focused on topical forms, especially topical timolol. The present comprehensive review study surveys the role of topical timolol in acute and chronic wound healing in the field of dermatology. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO‐mediated MZF1/c‐Myc axis

xloma.fota13 shared this article with you from Inoreader Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO‐mediated MZF1/c‐Myc axis Via Journal of Cellular and Molecula... Abstract Colorectal carcinoma (CRC) poses heavy burden to human health and has an increasing incidence. Currently, the existing biomarkers for CRC bring about restrained clinical benefits. GSK3β is reported to be a novel therapeutic target for this disease but with undefined molecular mechanisms. Thus, we aimed to investigate the regulatory effect of GSK3β on CRC progression via FTO/MZF1/c‐Myc axis. Firstly, the expression patterns of GSK3β, FTO, MZF1 and c‐Myc were determined after sample collection. Lowly expressed GSK3β but highly expressed FTO, MZF1 and c‐Myc were found in CRC. After transfection of different overexpressed and interference plasmids, the underlying mechanisms concerning GSK3β in CRC cell functions were analysed. Additionally, the effect of GSK3β on FTO protein stability was assessed followed by detection of MZF1 m6A modification and MZF1‐FTO interaction. Mechanistically, GSK3β mediated ubiquitination of demethylase FTO to reduce FTO expression. Besides, G SK3β inhibited MZF1 expression by mediating FTO‐regulated m6A modification of MZF1 and then decreased the proto‐oncogene c‐Myc expression, thus hampering CRC cell proliferation. We also carried out in vivo experiment to verify the regulatory effect of GSK3β on CRC via FTO‐mediated MZF1/c‐Myc axis. It was found that GSK3β inhibited CRC growth in vivo which was reversed by overexpressing c‐Myc. Taken together, our findings indicate that GSK3β suppresses the progression of CRC through FTO‐regulated MZF1/c‐Myc axis, shedding light onto a new possible pathway by which GSK3β regulates CRC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Paeonol attenuates inflammation by confining HMGB1 to the nucleus

xloma.fota13 shared this article with you from Inoreader Paeonol attenuates inflammation by confining HMGB1 to the nucleus Via Journal of Cellular and Molecula... Abstract Inflammation is a biological process that exists in a large number of diseases. If the magnitude or duration of inflammation becomes uncontrolled, inflammation may cause pathological damage to the host. HMGB1 and NF‐κB have been shown to play pivotal roles in inflammation‐related diseases. New drugs aimed at inhibiting HMGB1 expression have become a key research focus. In the present study, we showed that paeonol (Pae), the main active component of Paeonia suffruticosa, decreases the expression of inflammatory cytokines and inhibits the translocation of HMGB1 induced by lipopolysaccharide (LPS). By constructing HMGB1‐overexpressing (HMGB1+) and HMGB1‐mutant (HMGB1m) RAW264.7 cells, we found that the nuclear HMGB1 could induce an LPS‐tolerant state in RAW264.7 cells and that paeonol had no influence on the expression of inflammatory cytokines in HMGB1m RAW264.7 cells. In addition, the anti‐inflammatory property of paeonol was los t in HMGB1 conditional knockout mice, indicating that HMGB1 is a target of paeonol and a mediator through which paeonol exerts its anti‐inflammatory function. Additionally, we also found that HMGB1 and P50 competitively bound with P65, thus inactivating the NF‐κB pathway. Our research confirmed the anti‐inflammation property of paeonol and suggests that inhibiting the translocation of HMGB1 could be a new strategy for treating inflammation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.