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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Sun Oct 31 2021
Journal Name
Research Journal Of Pharmacy And Technology
A Review on Film Forming Drug Delivery Systems
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Conventional dosage forms for topical and transdermal drug delivery have several disadvantages related mainly to its poor skin permeation and patient compliance. Many approaches have been developed to improve these dosage forms. Film forming drug delivery systems represents a recent advancement in this field. It provides improved patient compliance with enhanced skin permeation of drugs. In its simplest form, these consist of a polymeric solution, usually in a supersaturated state, in a suitable solvent. A plasticizer is usually added to improve the flexibility and enhance the tensile strength to the film. It is also possible to control and sustain the drug release from the films by controlling the polymeric content, concentration o

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Publication Date
Mon Jun 06 2022
Journal Name
International Journal Of Health Sciences
effect of a training curriculum for the development of some functional variables and the level of achievement in the effectiveness of air rifle shooting
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There are significant differences between the pre and post-tests in favor of the post-test in the tests) stroke volume (S.V), cardiac thrust (C.O.P), left ventricular volume, maximum oxygen consumption Vo2max), which indicates the effect of the proposed training approach.There are significant differences between the pre and post-tests in favor of the post-test in the achievement level test with air rifle shooting for young female shooters, which indicates the effect of the proposed training curriculum.There are no significant differences between the pre and post-tests in the tests (heart rate (HR) before exercise, heart rate (HR) after exercise, systolic blood pressure rate before exercise, systolic blood pressure rate after exercis

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Publication Date
Thu Jul 11 2024
Journal Name
Maaen Journal For Medical Sciences
Pharmacological Supplements Efficacy in Management of chronic pain associated with Sickle Cell Disease: A narrative review
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Sickle cell disease (SCD) is a hereditary ailment that can cause severe pain and suffering to people who are affected. However, with continued investment in research and treatment options, we can make progress towards improving the lives of those with SCD. Over 40% of patients experience painful vaso-occlusive crises (VOCs), so we must work towards finding solutions and providing support for those living with this condition, These episodes, a hallmark of SCD, significantly contribute to morbidity, mortality, and a diminished quality of life, while also incurring substantial healthcare costs. Chronic pain particularly affects older adolescents and adults with SCD, with over half reporting daily discomfort. Opioid-based analgesics, though sti

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Characterization of Alginate with Natural Polymers Combination for Drug Encapsulation
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Alginate is one of the natural biopolymers that is widely used for drug formulations, combination of alginate with other polymers, such as gum acacia, pectin, and carrageenan can increase mechanical strength, therefore, can reduce leakage of the encapsulated active pharmaceutical ingredient from the polymer matrix. Interaction of alginate and these polymers can occur via intermolecular hydrogen bonds causing synergism, which is determined from the viscosity of polymer mixture.

Alginate was combined with gum acacia/pectin/carrageenan in different blending ratios (100:0, 75:25, 50:50, 25:75, and 0:100) with and without addition of CaCl2. The synergism effect is obtained from the design of experimental (DoE), and calculati

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Publication Date
Wed Jan 01 2020
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees20
Capitalized effect of gamma radiation on blood thinning drug (Aspirin)
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n this work, the effect of gamma rays on blood thinning drugs was studied using the drug (Aspirin), where gamma rays were spread with the drug using a radioactive source (Co60), and 15,000 grams of Aspirin were placed in the device (gamma chamber 900). The drug was subjected to different irradiation doses (5 KGy, 10 KGy, 15 KGy) and the amount of absorption of the drug was observed in the gamma for different doses and the study of x-rays. After confirming the absorption of the drug to radiation, the effect of the drug on blood thinning was calculated using the rat model and compared with the same drug and the same dose but without exposing the drug to radiation and comparing all results with the control group. The way drugs absorbed radiati

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Publication Date
Wed Jan 01 2020
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees20
Capitalized effect of gamma radiation on blood thinning drug (Aspirin)
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Publication Date
Wed Jun 30 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
SYNTHESIS, CHARACTERIZATION, AND STUDY THE BIOLOGICAL ACTIVITY OF SOME SCHIFF'S BASES, AND 1,3 - OXAZEPINE COMPOUNDS DERIVED FROM SULFAMETHOXAZOLE DRUG: SYNTHESIS, CHARACTERIZATION, AND STUDY THE BIOLOGICAL ACTIVITY OF SOME SCHIFF'S BASES, AND 1,3 - OXAZEPINE COMPOUNDS DERIVED FROM SULFAMETHOXAZOLE DRUG
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This study including synthesis of some new Schiff bases compounds [16] from the reaction of Sulfamethoxazole drug with some aromatic aldehydes in classical Schiff base method then treatment Schiff  bases with succinic anhydride to get oxazepines rings [7-11]These derivatives were characterized by melting point, FTIR, 1H NMR and mass spectra. Some of synthesized compounds were evaluated in vitro for their antibacterial activities against three kinds of pathogenic strains Staphylococcus aureus, Escherichia coli

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Publication Date
Mon Jun 26 2023
Journal Name
Journal Of Contemporary Medical Sciences
Glyceryl Trinitrate, a Vasodilating Drug Acts as an Antibiofilm Agent in Serratia marcescens
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Objectives: Serratia marcescens is a gram-negative pathogen of many species. The ability of S. marcescens to form biofilms and its potent innate resistance to antimicrobials and cleaning solutions are both essential for its pathogenicity and survival. The present study was conducted to investigate the effect of glyceryl trinitrate (GTN) on the biofilm of S. marcescens, as an alternative for antibiotic therapy. Methods: Different specimens, including ear swabs, burns, mid-stream urine, wound swabs, and sputum, were collected from patients who were brought to Al-Ramadi Hospital, Iraq. All samples were cultured, and the colonies that were obtained were detected using the VITEK® 2 compact. The ability of biofilms to develop was e

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Publication Date
Sun Apr 30 2023
Journal Name
Al-kindy College Medical Journal
Pharmacist Intervention to Address Drug Related Problems in Patients with Decompensated Liver Cirrhosis
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Background: Patients with decompensated cirrhosis are often given therapeutic and prophylactic drugs. Polypharmacy raises both the likelihood of prescription errors and the complications associated with drugs. Clinical pharmacists are excellent at recognizing, addressing, and preventing clinically significant drug-related problems.

Objectives: Identification types of pharmacist interventions to address drug-related problems in patients with decompensated cirrhosis and assess the acceptance/implementation of these recommendations. And identify patient factors associated with accepting pharmacist recommend

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Publication Date
Tue Apr 24 2018
Journal Name
Journal Of The American Geriatrics Society
A Systems Approach to Identify Factors Influencing Adverse Drug Events in Nursing Homes
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The objectives of the study were to identify the incidence rate and characteristics of adverse drug events (ADEs) in nursing homes (NHs) using the ADE trigger tool and to evaluate the relationships between resident and facility work system factors and incidence of ADEs using the System Engineering Initiative for Patient Safety (SEIPS) model. The study used 2 observational quantitative methods, retrospective resident chart extraction, and surveys. The participating staff included Directors of nursing, registered nurses, certified nurse assistants (CNAs). Data were collected from fall 2016 to spring 2017 from 11 NHs in 9 cities in Iowa. Binary logistic regression with generalized estimated equations was used to measure the association

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