Efficacy and Safety of Methotrexate in Articular and Cutaneous Manifestations of systemic Lupus Erythematosus

Aim:  A prospective open-label study comparing the efficacy and safety of methotrexate (MTX) and chloroquine (CQ) in articular and cutaneous manifestations of systemic lupus erythematosus (SLE). Methods:  Consecutive SLE patients were randomly assigned to either 10 mg MTX weekly or 150 mg CQ daily during 24 weeks. Outcome measures were: numbers of swollen and tender joints, duration of morning stiffness, visual analog scale (VAS) for articular pain, physician global assessment index, patient global assessment index, SLE Disease Activity Index (SLEDAI), disappearance of skin rash and erythrocyte sedimentation rate (ESR). Results:  Forty-one patients consented to participate, 15 were allocated in the MTX group and 26 in the CQ group. Two patients on MTX dropped out due to side-effects and two in the CQ group, one due to side-effects and one due to inefficacy. Baseline demographic, clinical and laboratory parameters of the two groups were nearly identical. In both groups the clinical and laboratory parameters improved significantly over 24 weeks, except the ESR in the MTX group. The results of the outcome measures at the end of the trial did not differ significantly between the two groups, except morning stiffness (P < 0.05 in favor of the MTX group) and ESR (P < 0.01 in favor of the CQ group). Rise of serum alanine aminotransferase was observed in two cases in the MTX group and in none in the CQ group. Conclusion:  Low-dose MTX appears to be as effective as CQ in patients with articular and cutaneous manifestations of SLE, having an acceptable toxicity profile. Results of this prospective study need to be confirmed in a larger study

Modeling and Control of pH Process for Weak Acid-Weak Base System

This paper studies the model and control of pH neutralization process of waste water system using different control schemes. An experimental investigation was conducted for the dynamic behavior of neutralization process of waste water in a continuous stirred tank reactor (CSTR). A dynamic model for pH neutralization process in a continuous stirred tank reactor (CSTR) is described by a first order plus dead time (FOPDT). The pH value is calculated by solving the charge balance of the mixture. Good agreement is obtained between the simulated and experimental responses. However, a small differences between the responses due to the error in the measurements. The conventional feedback control was studies in this work and the controller parameters was tuned by Ziegler-Nichols reaction curve method to find the best values of proportional gain (Kc), integral time (t I) and derivative time (t D). Artificial Neural Network Model Predictive Control (ANN MPC) was used as another strategy to compare with above strategy. The ANN controller was compared with conventional controller and it was found that ANN controller provides better control for the set point changes with low settling time and lower overshoot. Whereas the conventional controller provides sluggish behavior in set point change. Also it was found that the ANN controller provides better response to regulated change than the conventional controllers where the PI and PID controllers provide sluggish disturbance responses because the approximate FOPTD model has relatively small time delay. As non-linear process the conventional feedback controller was unable to control this system adequately

Knowledge Regarding Basic Facts of Stroke Among Final Year MBBS Students and House Officers: A Cross-Sectional Survey of 708 Respondents from Pakistan

Abstract Introduction

Knowledge Regarding Basic Facts of Stroke Among Final Year MBBS Students and House Officers: A Cross-Sectional Survey of 708 Respondents from Pakistan

Abstract Introduction

Workplace Violence Among Health Care Professionals in Public and Private Health Facilities in Bangladesh

Objectives: The main objectives of this study were to examine the prevalence of workplace violence (WPV), its associated factors and explore the experiences of healthcare workers. Methods: A hospital-based cross-sectional study design used a nationally representative sample of 1,081 healthcare workers covering eight administrative divisions of Bangladesh. Logistic regression analysis was employed to estimate the adjusted effect of independent factors on WPV among healthcare workers. Results: Of the participants, 43% (468) experienced some form of WPV. Of those, 84% reported experiencing nonphysical violence, and 16% experienced physical violence in the past year. About 65% of victims claimed no action was taken to investigate the incident, and 44% reported no consequence for perpetrators. Four factors: being married (AOR = 1.63; CI: 1.12–2.39); public sector healthcare worker (AOR = 2.74; CI:1.99–3.76); working in an emergency department (AOR = 2.30; CI:1.03–5.12); and undertaking shift work (AOR = 1.52; CI: 1.10–2.11) were found to be significantly associated with WPV. One-third of the participants were worried about violence in their workplace. Conclusion: WPV is highly prevalent among healthcare workers in Bangladesh. Formal guidelines for reporting and managing WPV are urgently needed at the individual, hospital, and national levels

Extracellular Vesicles Released by Human Induced-Pluripotent Stem Cell-Derived Cardiomyocytes Promote Angiogenesis

Although cell survival post-transplantation is very low, emerging evidence using stem cell therapy for myocardial repair points toward a primary role of paracrine signaling mechanisms as the basis for improved cardiac function, decreased fibrosis, and increased angiogenesis. Recent studies have demonstrated that extracellular vesicles (EVs) such as exosomes secreted by stem cells stimulate angiogenesis, provide cytoprotection, and modulate apoptosis. However, the angiogenic potential of EVs secreted from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), a terminally differentiated cell type, has not been elucidated yet. Therefore, the main objective of this study is to isolate, characterize, and evaluate the in vitro angiogenic potential of EVs collected from hiPSC-CM conditioned media. The hiPSC-CM were cultured for 2 weeks and EVs were isolated from cell culture medium. Isolated EVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis, and immunoblotting. Furthermore, the angiogenic potential of these EVs was evaluated by tube formation, wound-healing, and cell-proliferation assays in bovine aortic endothelial cells (BAEC). In addition, gene expression levels of growth factors was evaluated in hiPSC-derived endothelial cells (hiPSC-EC) treated with hiPSC-CM-derived EV (CM-EVs) to assess their role in promoting angiogenesis. TEM imaging of CM-EVs showed a presence of a double-membrane bound structure, which is a characteristic of EV. Nanoparticle tracking analysis further confirmed the size and shape of the secreted particles to be consistent with EVs. Furthermore, EV-specific markers (CD63 and HSP70) were enriched in these particles as illustrated by immunoblotting. Most importantly, BAEC treated with 100 μg/ml of CM-EVs showed significant increases in tube formation, wound closure, and cell proliferation as compared to control (no-EVs). Finally, treatment of hiPSC-EC with CM-EVs induced increased expression of pro-angiogenic growth factors by the endothelial cells. Overall, our results demonstrated that EVs isolated from hiPSC-CM enhance angiogenesis in endothelial cells. This acellular/cell-free approach constitutes a potential translational therapeutic to induce angiogenesis in patients with myocardial infarction

Development and validation of a weakly supervised deep learning framework to predict the status of molecular pathways and key mutations in colorectal cancer from routine histology images : a retrospective study

Background: Determining the status of molecular pathways and key mutations in colorectal cancer is crucial for optimal therapeutic decision making. We therefore aimed to develop a novel deep learning pipeline to predict the status of key molecular pathways and mutations from whole-slide images of haematoxylin and eosin-stained colorectal cancer slides as an alternative to current tests. Methods: In this retrospective study, we used 502 diagnostic slides of primary colorectal tumours from 499 patients in The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) cohort and developed a weakly supervised deep learning framework involving three separate convolutional neural network models. Whole-slide images were divided into equally sized tiles and model 1 (ResNet18) extracted tumour tiles from non-tumour tiles. These tumour tiles were inputted into model 2 (adapted ResNet34), trained by iterative draw and rank sampling to calculate a prediction score for each tile that represented the likelihood of a tile belonging to the molecular labels of high mutation density (vs low mutation density), microsatellite instability (vs microsatellite stability), chromosomal instability (vs genomic stability), CpG island methylator phenotype (CIMP)-high (vs CIMP-low), BRAFmut (vs BRAFWT), TP53mut (vs TP53WT), and KRASWT (vs KRASmut). These scores were used to identify the top-ranked titles from each slide, and model 3 (HoVer-Net) segmented and classified the different types of cell nuclei in these tiles. We calculated the area under the convex hull of the receiver operating characteristic curve (AUROC) as a model performance measure and compared our results with those of previously published methods. Findings: Our iterative draw and rank sampling method yielded mean AUROCs for the prediction of hypermutation (0·81 [SD 0·03] vs 0·71), microsatellite instability (0·86 [0·04] vs 0·74), chromosomal instability (0·83 [0·02] vs 0·73), BRAFmut (0·79 [0·01] vs 0·66), and TP53mut (0·73 [0·02] vs 0·64) in the TCGA-CRC-DX cohort that were higher than those from previously published methods, and an AUROC for KRASmut that was similar to previously reported methods (0·60 [SD 0·04] vs 0·60). Mean AUROC for predicting CIMP-high status was 0·79 (SD 0·05). We found high proportions of tumour-infiltrating lymphocytes and necrotic tumour cells to be associated with microsatellite instability, and high proportions of tumour-infiltrating lymphocytes and a low proportion of necrotic tumour cells to be associated with hypermutation. Interpretation: After large-scale validation, our proposed algorithm for predicting clinically important mutations and molecular pathways, such as microsatellite instability, in colorectal cancer could be used to stratify patients for targeted therapies with potentially lower costs and quicker turnaround times than sequencing-based or immunohistochemistry-based approaches. Funding: The UK Medical Research Council

Association of Blood Lead (Pb) and Plasma Homocysteine: A Cross Sectional Survey in Karachi, Pakistan

Background: High blood lead (Pb) and hyperhomocysteinemia have been found to be associated with cardiovascular disease (CVD). Mean blood Pb and mean plasma homocysteine levels have been reported to be high in Pakistani population. The objective of the present study was to assess the relationship of blood Pb to the risk of hyperhomocysteinemia in a low income urban population of Karachi, Pakistan. Methodology/Principal Findings: In a cross sectional survey, 872 healthy adults (355 males, 517 females, age 18-60 years) were recruited from a low income urban population of Karachi. Fasting venous blood was obtained and assessed for blood Pb and plasma/serum homocysteine, folate, pyridoxal phosphate (PLP, a coenzymic form of vitamin B6) and vitamin B12. The study population had median (IQR) blood Pb of 10.82 microg/dL (8.29-13.60). Prevalence of high blood Pb (levels\u3e10 microg/dL) was higher in males compared to females (62.5% males vs 56% females, p value=0.05). Mean+/-SD/median (IQR) value of plasma homocysteine was significantly higher in the highest quartile of blood Pb compared to the lowest quartile 16.13+/-11.2 micromol/L vs 13.28+/-9.7micromol/L/13.15 (10.33-17.81) micromol/L vs 11.09 (8.65 14.31) micromol/L (p valu

Levocarnitine Improves AlCl3-Induced Spatial Working Memory Impairment in Swiss albino Mice

Background: Aluminum, a neurotoxic substance, causes oxidative stress induced-neurodegenerative diseases. Several lines of evidence suggest that levocarnitine has an antioxidant effect and also plays an important role in beta-oxidation of fatty acids. However, the role of levocarnitine in aluminum-induced neurotoxicity has not been well documented. Here we aimed to investigate the effect of levocarnitine on aluminum chloride (AlCl3)-induced oxidative stress and memory dysfunction.Methods: Male Swiss albino mice (n = 30) were treated with either control (saline) or AlCl3 or AlCl3 plus levocarnitine or levocarnitine or astaxanthin plus AlCl3 or astaxanthin alone. The spatial working memory was determined by radial arm maze (RAM). In addition, we measured the lipid peroxidation (MDA), glutathione (GSH), advanced oxidation of protein products (AOPP), nitric oxide (NO) and activity of superoxide dismutase (SOD) in the various brain regions including prefrontal cortex (PFC), striatum (ST), parietal cortex (PC), hippocampus (HIP) hypothalamus (HT) and cerebellum (CB). We used astaxanthin as a standard antioxidant to compare the antioxidant activity of levocarnitine.Results: The RAM data showed that AlCl3 treatment (50 mg/kg) for 2 weeks resulted in a significant deficit in spatial learning in mice. Moreover, aluminum exposure significantly (p &lt; 0.05) increased the level of oxidative stress markers such as MDA, GSH, AOPP and NO in the various brain regions compared to the controls. In addition, combined administration of levocarnitine and AlCl3 significantly (p &lt; 0.05) lowered the MDA, AOPP, GSH and NO levels in mice.Conclusion: Our results demonstrate that levocarnitine could serve as a potential therapeutic agent in the treatment of oxidative stress associated diseases as well as in memory impairment