Modulation Peroxisome Proliferators Activated Receptor alpha (PPAR α) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) Gene expression by Fatty Acids in Foam cell

<p>Abstract</p> <p>Background</p> <p>One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. Fatty Acids are important ligands of PPARα and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells.</p> <p>Methods</p> <p>This study examined effects of c9, t11-Conjugated Linoleic Acid(c9, t11-CLA), Alpha Linolenic Acid (LA), Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells.</p> <p>Results</p> <p>Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular Total Cholesterol, Free Cholesterol, cellular and Estrified Cholesterol concentrations (<it>P </it>≤ 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (<it>P </it>= 0.003). Treatment with EPA increased PPARα mRNA levels (<it>P </it>≤ 0.001), although CLA, LA had no significant effect on PPARα mRNA expression.</p> <p>Conclusion</p> <p>In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.</p

Sleep disorders and its effect on community

The main aim of this paper is to analysis the effect of sleep disorders on the community. This study is quantitative. The questionnaire was designed and distributed among the student in school in the city of Riyadh high and intermediate school. The sample of this study consist 100 students. The researcher visited a school in the city of Riyadh high and intermediate school sections and that on December 10 to 11 to measure the impact of sleep disorders through a questionnaire that measures the effects of lack of sleep and then make them aware of the benefits of sleep and harm of lack of sleep from the physical and psychological effects, and it gave a lecture educate the students and then distribute them brochure contain the benefits and harmful effects of sleep. SPSS 21 was used to analysis that data. The results of the study indicated that lack of sleep limits a person's ability to think and solve the problem effectively, which means that people who wake up for a long time influence them to learn at an effective level. Lack of sleep affects the ability of thinking and can limit your ability to accurately interpret events, which can be difficult to respond correctly to situations in which effective decision-making is intelligent. The lack of sleep, even for one night can lead to swelling of the eyes and turn the skin into pale skin. Keywords: Sleep disorders, community

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran):a pragmatic, cluster-randomised trial

Background: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. Methods: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40�75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle�eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome�occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)�was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. Findings: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study�3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5) of 3421 participants in the polypill group were women, as were 1679 (49·1) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5 (IQR 48·5�92·2). During follow-up, 301 (8·8) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9) of 3421 participants in the polypill group (adjusted hazard ratio HR 0·66, 95% CI 0·55�0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49�0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51�1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33�0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up�ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. Interpretation: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. Funding: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou. © 2019 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved

Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: a randomized, double-blind, placebo-controlled trial

Objective The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). Methods Saudi adults with naïve T2DM (n=61; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5×109cfu/gram of Ecologic®Barrier (multi-strain probiotics; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. Results Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (-3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. Conclusion Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy

Paraneoplastic autoimmunity and small‐cell lung cancer: Neurological and serological accompaniments

Paraneoplastic neurological autoimmunity is often associated with small‐cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC‐predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti‐neuronal nuclear antibody‐type 1, voltage‐gated calcium channel (VGCC)‐N‐type, VGCC‐P/Q‐type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle‐AChR, and VGCC‐P/Q‐type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody‐positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited‐stage disease at diagnosis

Solving pickup and drop-off problem using hybrid pointer networks with deep reinforcement learning

In this study, we propose a general method for tackling the Pickup and Drop-off Problem (PDP) using Hybrid Pointer Networks (HPNs) and Deep Reinforcement Learning (DRL). Our aim is to reduce the overall tour length traveled by an agent while remaining within the truck’s capacity restrictions and adhering to the node-to-node relationship. In such instances, the agent does not allow any drop-off points to be serviced if the truck is empty; conversely, if the vehicle is full, the agent does not allow any products to be picked up from pickup points. In our approach, this challenge is solved using machine learning-based models. Using HPNs as our primary model allows us to gain insight and tackle more complicated node interactions, which simplified our objective to obtaining state-of-art outcomes. Our experimental results demonstrate the effectiveness of the proposed neural network, as we achieve the state-of-art results for this problem as compared with the existing models. We deal with two types of demand patterns in a single type commodity problem. In the first pattern, all demands are assumed to sum up to zero (i.e., we have an equal number of backup and drop-off items). In the second pattern, we have an unequal number of backup and drop-off items, which is close to practical application, such as bike sharing system rebalancing. Our data, models, and code are publicly available at Solving Pickup and Dropoff Problem Using Hybrid Pointer Networks with Deep Reinforcement Learning.</p

Solving traveling salesman problem with time windows using hybrid pointer networks with time features

This paper introduces a time efficient deep learning-based solution to the traveling salesman problem with time window (TSPTW). Our goal is to reduce the total tour length traveled by -*the agent without violating any time limitations. This will aid in decreasing the time required to supply any type of service, as well as lowering the emissions produced by automobiles, allowing our planet to recover from air pollution emissions. The proposed model is a variation of the pointer networks that has a better ability to encode the TSPTW problems. The model proposed in this paper is inspired from our previous work that introduces a hybrid context encoder and a multi attention decoder. The hybrid encoder primarily comprises the transformer encoder and the graph encoder; these encoders encode the feature vector before passing it to the attention decoder layer. The decoder consists of transformer context and graph context as well. The output attentions from the two decoders are aggregated and used to select the following step in the trip. To the best of our knowledge, our network is the first neural model that will be able to solve medium-size TSPTW problems. Moreover, we conducted sensitivity analysis to explore how the model performance changes as the time window width in the training and testing data changes. The experimental work shows that our proposed model outperforms the state-of-the-art model for TSPTW of sizes 20, 50 and 100 nodes/cities. We expect that our model will become state-of-the-art methodology for solving the TSPTW problems.</p

Sustained release of CIP from TiO₂‐PVDF/starch nanocomposite mats with potential application in wound dressing

Abstract Electrospinning is an economical and alluring method to fabricate wound dressing mats from a variety of natural and synthetic materials. In this study, polyvinylidene fluoride (PVDF) and starch composite mats containing ciprofloxacin (CIP) loaded on titanium dioxide nanoparticles (TiO₂) were prepared. Fourier Transform Infrared spectra of CIP, synthesized TiO₂ NPs, TiO₂/CIP, and PVDF/starch composite mats are analyzed. Scanning electron microscopy images revealed that the fiber diameter of PVDF nanofibers thickens by increasing starch, which varies between 180 nm and 550 nm. Strain at break of PVDF, starch, PVDF/starch (2:1 w:w; P2S1), PVDF/starch (1:1 w:w; P1S1), PVDF/starch (1:2 w:w; P1S2), and nanofibers were 103 ± 11, 3 ± 0.6, 27 ± 4, 52 ± 5.2, 7.7 ± 1%, respectively. Based on strain at break and young modulus, P2S1 was selected as a suitable candidate for wound dressing to which load TiO₂/CIP as a bioactive agent. The release rate of CIP showed that about 40% of the drug is released in the first 2 days. Furthermore, the antibacterial activity of dressings was investigated using Escherichia coli and Staphylococcus aureus microorganisms and zones of clearance were obvious around the specimen on the agar plate

Vitamin D Supplementation Modestly Reduces Serum Iron Indices of Healthy Arab Adolescents

Vitamin D deficiency has been shown to affect iron status via decreased calcitriol production, translating to decreased erythropoiesis. The present study aimed to determine for the first time whether vitamin D supplementation can affect iron levels among Arab adolescents. A total of 125 out of the initial 200 Saudi adolescents with vitamin D deficiency (serum 25(OH)D &lt; 50 nmol/L) were selected from the Vitamin D-School Project of King Saud University in Riyadh, Saudi Arabia. Cluster randomization was done in schools, and students received either vitamin D tablets (1000 IU/day) (N = 53, mean age 14.1 &#177; 1.0 years) or vitamin D-fortified milk (40IU/200mL) (N = 72, mean age 14.8 &#177; 1.4 years). Both groups received nutritional counseling. Anthropometrics, glucose, lipids, iron indices, and 25(OH)D were measured at baseline and after six months. Within group analysis showed that post-intervention, serum 25(OH)D significantly increased by as much as 50%, and a parallel decrease of &#8722;42% (p-values &lt;0.001 and 0.002, respectively) was observed in serum iron in the tablet group. These changes were not observed in the control group. Between-group analysis showed a clinically significant increase in serum 25(OH)D (p = 0.001) and decrease in iron (p &lt; 0.001) in the tablet group. The present findings suggest a possible inhibitory role of vitamin D supplementation in the iron indices of healthy adolescents whose 25(OH)D levels are sub-optimal but not severely deficient, implying that the causal relationship between both micronutrients may be dependent on the severity of deficiency, type of iron disorder, and other vascular conditions that are known to affect hematologic indices. Well-designed, randomized trials are needed to confirm the present findings