Ethnicity and Response to Drug Therapy

Hypercholesterolemia is a complex disorder presenting in different forms, including the familial form (FH), with varying underlying aetiology, and contributing substantially to coronary artery disease. Particularly, the FH underlies monogenic changes in genes involved in cholesterol synthesis and transport, including the low density lipoprotein receptor, proprotein convertase sublitisin/kexin type 9 and apolipoprotein B. However, hyperlipidemia is largely a complex interaction of changes in multiple genes with environmental factors, such as diet, overweight and obesity that are controllable by adopting healthy eating habits and exercise, which may vary by ethnicity. Diet alone is often not adequate to achieve the desired lipid lowering effect in individuals harbouring very high cholesterol levels, necessitating the use of lipid lowering medication or other forms of therapy. Antilipidemic drugs fall into (a) bile acid sequestrants (b) cholesterol absorption inhibitors, (c) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, (d) fibric acid derivatives (e) proprotein convertase subtilisin/kexin type 9 inhibitors, (f) miscellaneous agents and (g) drug combinations. Mutations in their various metabolizing enzymes, particularly the cytochrome P450 family, often lead to partially/non-functional, or even rapid metabolizing phenotypes, triggering great variations in the way individuals respond to drug therapy, which in turn depends on ethnicity. This may produce unexpected outcomes such as therapeutic failure, adverse side effects and toxicity in individuals of different ethnic origin. Hence, in-depth information of the impact of ethnicity on these relationships has the huge potential of achieving optimal quality use of drugs as well as improving the efficacy and safety of antilipidemic therapeutic agents

Education in Light of the Sustainable Development Goals in the Kingdom of Bahrain

Quality education is one of the goals of sustainable development - ensuring quality, equitable and inclusive education for all and promoting lifelong learning opportunities for all, the Ministry of Education in the Kingdom of Bahrain has set a set of sub-goals to achieve this goal. Hence, the study aims to investigate the impact of sustainable development goals on education in Bahrain in order to identify the challenges and opportunities available to improve the quality of education, knowledge economy and develop human capital. This paper attempts to answer a major question: What is the impact of sustainable development on education in the Kingdom of Bahrain? To answer this question, the researchers will show quantitative data released by Bahrains local government institutions and international organizations. The study is based on the hypothesis that Bahrain is among the countries that pay great attention to education and sustainable development by investing in technical and vocational education and training, and encouraging innovation and creativity. In order to test the hypothesis, the researchers preferred to use the analytical descriptive approach, by describing the quantitative data that related to education and its relationship to sustainable development. The study sought to demonstrate the impact of sustainable development goals on education in the Kingdom of Bahrain, solve the problem from which it was launched, and answer its questions, by analyzing the basic elements of the impact of sustainable development on education. As it was proven to us through testing the hypothesis, its validity, which was based on the fact that Bahrain is among the countries that pay great attention to education and sustainable development through investing in technical and vocational education and training, and encouraging innovation and creativity. The Bahraini government has taken serious steps in this direction, by focusing on improving the quality of education, developing skills, enhancing job opportunities, and promoting technical and vocational education and e-training. Moreover, Bahrain seeks to achieve a knowledge economy, by transforming the economy into a knowledge economy, developing infrastructure and investing in scientific research and technological development

Sustainable Development in light of the Bahraini National Action Charter

The objectives of the National Action Charter of Bahrain include improving the quality of life, encouraging investment in the green economy, providing job opportunities, developing skills, promoting environmental management, protecting the environment and biodiversity, developing civil society, and encouraging womens participation in economic and political life. The National Action Charter has achieved great success in achieving the goals of sustainable development in Bahrain, as it contributed to improving the quality of life, providing job opportunities, protecting the environment, and raising awareness of the importance of sustainable development. In order to sustain this success, the National Action Charter requires a commitment to promoting economic diversification, improving environmental management, supporting civil society, and encouraging womens participation in economic and political life. Despite Bahrains challenges, it is committed to achieving sustainable development goals and strengthening its position as a model for sustainable development in the world. The study also raises a major question, which is what is the role of the Bahrain National Charter in achieving the goals of sustainable development? In order to answer the study question and test the hypothesis, the researchers will review previous studies in the field of sustainable development, and study the basic concepts of sustainable development and its role in comprehensive development. As well as studying the history and work of the Bahraini National Charter and how to apply it on the ground, and analyzing the challenges Bahrain faces in achieving sustainable development and how to overcome them. In addition to studying the sustainability practices adopted in Bahrain. : It was proven to us that the hypothesis from which the study was based was correct, which was based on the fact that the Bahraini National Charter includes a number of procedures and policies that aim to achieve sustainable development in Bahrain. It has become clear to us that the National Charter plays a vital role in directing efforts towards achieving the goals of sustainable development, and it is one of the main tools used by Bahrain in achieving these goals, by encouraging innovation and green technology, the transition to a low-carbon economy, and improving the quality of air, water and soil. Protecting the environment and promoting biodiversity. The Bahrain National Charter also works to promote the sustainability of economic growth, the environment and society. In order for this success to continue, the Bahraini National Charter requires commitment to promoting economic diversification, improving environmental management, supporting civil society, and encouraging womens participation in economic and political life. Despite the challenges facing Bahrain, it is committed to achieving the goals of sustainable development and strengthening its position as a model for sustainable development in the world

Major depression and disease activity among systemic lupus erythematosus Egyptian females

AbstractAim of the workThe aim of this study was to identify the relationship between disease activity in SLE Egyptian females and the presence, severity and pattern of major depression in these patients.Patients and methodsThe study sample included 100 female patients; fifty SLE patients and fifty healthy adults with matching age serving as control. Patients were assessed using Beck Inventory Score for the presence of major depression, SLEDAI to determine disease activity, SLICC/ACR damage index and HAQ score for functional disability.ResultsThe majority of patients had symptoms of major depression 32/50 (64%) based on Beck Inventory Score while in controls only 16/50 (36%) had major depression. The most common depressive symptoms in SLE patients were: Guilty feeling (92%), Self-dislike (91.6%), Self-criticalness (90.4%), Crying spells (87.5%), Loss of pleasure (83.3%), Change in appetite (83.3%), Agitation (82.8%) and Pessimism (82%). Patients with major depression presented a trend toward having greater severity of SLE disease activity compared with those without major depression (p=0.04). The presence of major depression was significantly associated with functional disability measured by HAQ score (p=0.01). The patients with major depression did not differ significantly from patients without major depression regarding their steroid dosage (p=0.55), SLICC/ACR damage score (p=0.16) and disease duration (p=0.69) but differed significantly as regards Beck Hopelessness Scale (p<0.0001) and suicidal ideation score (p=0.009).ConclusionMajor depression was highly presented in Egyptian SLE patients (64%); its severity was associated with disease activity, but not with steroid administration, cumulative damage or disease duration

Major depression and disease activity among systemic lupus erythematosus Egyptian females

AbstractAim of the workThe aim of this study was to identify the relationship between disease activity in SLE Egyptian females and the presence, severity and pattern of major depression in these patients.Patients and methodsThe study sample included 100 female patients; fifty SLE patients and fifty healthy adults with matching age serving as control. Patients were assessed using Beck Inventory Score for the presence of major depression, SLEDAI to determine disease activity, SLICC/ACR damage index and HAQ score for functional disability.ResultsThe majority of patients had symptoms of major depression 32/50 (64%) based on Beck Inventory Score while in controls only 16/50 (36%) had major depression. The most common depressive symptoms in SLE patients were: Guilty feeling (92%), Self-dislike (91.6%), Self-criticalness (90.4%), Crying spells (87.5%), Loss of pleasure (83.3%), Change in appetite (83.3%), Agitation (82.8%) and Pessimism (82%). Patients with major depression presented a trend toward having greater severity of SLE disease activity compared with those without major depression (p=0.04). The presence of major depression was significantly associated with functional disability measured by HAQ score (p=0.01). The patients with major depression did not differ significantly from patients without major depression regarding their steroid dosage (p=0.55), SLICC/ACR damage score (p=0.16) and disease duration (p=0.69) but differed significantly as regards Beck Hopelessness Scale (p<0.0001) and suicidal ideation score (p=0.009).ConclusionMajor depression was highly presented in Egyptian SLE patients (64%); its severity was associated with disease activity, but not with steroid administration, cumulative damage or disease duration

Appraisal survey of the knowledge, attitudes, and behaviors of Jordanian society toward diet and nutrition during COVID-19 era

Introduction: This study aimed to evaluate the knowledge, attitudes, and behavior (KAB) of the Jordanian society toward nutrition and diet during the COVID-19 era. Design and methods: This study is an observational, cross-sectional study using a structured, validated, reproducible, self-administered online Arabic questionnaire. KAB of the study participants was assessed via a web-based, structured, validated, reproducible Arabic questionnaire. The tool for the assessment of the KAB was composed of 33-closed-ended multi-answer questions. Results: A total of 672 people were surveyed, 70.2% were between 18 and 34, and 69.5% were females. Participants have paid little attention to the healthfulness of their diet in the last year. The majority of participant’s attitudes towards using different approaches to manage weight in the next year were: eating smaller portions for weight management, tracking to maximize the amount of time of physical activity, and substituting lower-calorie foods for full-calorie alternatives. Only tenth of participants utilize the time to perform physical activity. The majority made changes to their diet and exercise, and strictly follow commitment in connection with planning for the following year. Conclusions: Educators, legislative, food manufacturers, household heads, and policymakers are called upon to improve Jordanians’ KAB on nutrition and diet. Furthermore, Jordanian nutrition and diet behavior can be invested to improve the dietary interventions designed by nutrition and dietetics professionals

Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4⁺PD-1⁺ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma

PURPOSE: Immune dysregulation is described in multiple myeloma(MM). While preclinical models suggest a role for altered T cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterise marrow infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first line therapy. EXPERIMENTAL DESIGN: We undertook detailed characterisation of T cells from bone marrow(BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression free survival. RESULTS: We found that patients with MM had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared to healthy donors. Patients with a higher frequencies of Tregs (Treghi) had shorter PFS, and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared to Treglopatients. Analysis of CD4 and CD8 effectors revealed that low CD4effector:Treg ratio, and increased frequency of PD-1 expressing CD4effcells were independent predictors of early relapse over and above conventional risk factors such as genetic risk and depth of response. Ex-vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. CONCLUSIONS: BM infiltrating T cell subsets, specifically Treg and PD-1 expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies

Increased Immune-Regulatory Receptor Expression on Effector T Cells as Early Indicators of Relapse Following Autologous Stem Cell Transplantation for Multiple Myeloma

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios. Compared to paired pre-treatment marrow, both CD4 and CD8 compartments showed a reduction in naïve, and increase in effector memory subsets, suggestive of a more differentiated phenotype. This was supported by increased levels of several immune-regulatory and activation proteins (ICOS, PD-1, LAG-3, CTLA-4 and GzmB) when compared with HD. Unsupervised analysis identified a patient subgroup with shorter PFS (p=0.031) whose BM contained increased Tregs, and higher immune-regulatory markers (ICOS, PD-1, LAG-3) on effector T cells. Using single feature analysis, higher frequencies of marrow PD-1+ on CD4+FoxP3- cells and Ki67+ on CD8 cells were independently associated with early relapse. Finally, studying paired pre-treatment and post-ASCT BM (n=5), we note reduced abundance of TCR sequences at day+100, with a greater proportion of expanded sequences indicating a more focused persistent TCR repertoire. Our findings indicate that, following induction chemotherapy and ASCT, marrow T cells demonstrate increased activation and differentiation, with TCR repertoire focusing. Pending confirmation in larger series, higher levels of immune-regulatory proteins on T cell effectors at day+100 may indicate early relapse

Geographical distribution of hepatitis C virus genotypes in blood donors:an international collaborative survey

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.link_to_subscribed_fulltex