We first introduce the concept of b-metric-like space which generalizes the notions of partial metric space, metric-like space and b-metric space. Then we establish the existence and uniqueness of fixed points in a b-metric-like space as well as in a partially ordered b-metric-like space. As an application, we derive some new fixed point and coupled fixed point results in partial metric spaces, metric-like spaces and b-metric spaces. Moreover, some examples and an application to integral equations are provided to illustrate the usability of the obtained results. MSC: Primary 47H10; 54H25; 55M20
A protein undergoes many types of posttranslation modification. Citrullination is one of these modifications, where an arginine amino acid is converted to a citrulline amino acid. This process depends on catalytic enzymes such as peptidylarginine deiminase enzymes (PADs). This modification leads to a charge shift, which affects the protein structure, protein-protein interactions, and hydrogen bond formation, and it may cause protein denaturation. The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells. A defect in the clearance system either in terms of efficiency or capacity may occur due to massive cell death, which may result in the accumulation and leakage of PAD enzymes and the citrullinated peptide from the necrotized cell which could be recognized by the immune system, where the immunological tolerance will be avoided and the autoimmune disorders will be subsequently triggered. The induction of autoimmune responses, autoantibody production, and cytokines involved in the major autoimmune diseases will be discussed.
Drug shortages are a multifaceted problem that has been recurring in Saudi Arabia over the past decade with its significant negative impact on patient care. However, there is a dearth of evidence about possible domestic reasons, if any, behind this recurring problem. Recently, the Pharmacy Education Unit at King Saud University College of Pharmacy has called for a meeting with multiple stakeholders from academia, pharmaceutical care, pharmaceutical industry, purchasing and planning, and regulatory bodies to unveil the root domestic causes of the drug shortages in the Kingdom. Four major topics were used to guide the discussion in this meeting, including: current situation of drug shortages in Saudi Arabia, major factors contributing to drug shortages, challenges and obstacles to improve drug supply, and stakeholders’ recommendations to manage drug shortages. The meeting was audio-recorded and transcribed into verbatim by five authors. The text was then reviewed and analyzed to identify different themes by the first and third authors. Multiple causes were identified and several recommendations were proposed. The main domestic causes of drug shortages that were explored in this study included poor medication supply chain management, lack of government regulation that mandates early notification of drug shortages, a government procurement policy that does not keep pace with the changes in the pharmaceutical market, low profit margins of some essential drugs, weak and ineffective law-violation penalties against pharmaceutical companies and licensed drug importers and distributors, and overdependence on drug imports. The participants have also proposed multiple recommendations to address drug shortages. Policy makers should consider these factors that contribute to drug shortages in Saudi Arabia as well as the recommendations when designing future initiatives and interventions to prevent drug shortages.
In this paper, we develop a Jacobi-Gauss-Lobatto collocation method for solving the nonlinear fractional Langevin equation with three-point boundary conditions. The fractional derivative is described in the Caputo sense. The shifted Jacobi-Gauss-Lobatto points are used as collocation nodes. The main characteristic behind the Jacobi-Gauss-Lobatto collocation approach is that it reduces such a problem to those of solving a system of algebraic equations. This system is written in a compact matrix form. Through several numerical examples, we evaluate the accuracy and performance of the proposed method. The method is easy to implement and yields very accurate results.
Lepidium sativum seed (LSS) (family: Cruciferae) has been used in traditional medicine for the treatment of jaundice, liver problems, spleen diseases and gastrointestinal disorders. It was also reported to possess antihypertensive, diuretic, anti-asthmatic, antioxidant, and anti-inflammatory activities. Attempt has been made to study hepatoprotective potential of LSS available in Saudi Arabian Market. The aim of the present study was to determine the hepatoprotective effect of ethanolic extracts of LSS against carbon tetrachloride (CCl4) induced acute liver injury in rats. The bioactive compounds responsible for this activity have been analyzed by GCMS.To evaluate the hepatoprotective activity, six groups (n = 6) of rats were taken. First group was control, second was toxic and other groups received oral test solutions: 100 mg/kg silymarin, or LSS (100, 200, and 400 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver tissues were collected for biochemical, antioxidant and microscopic analyses. The bioactive constituents present in the extract were analyzed by GCMS. Results showed that pretreatment with LSS and silymarin significantly reduced the level of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin (BIL), which was increased significantly in toxic group treated with only CCl4. Histological analysis of liver tissues in groups pretreated with LSS and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the toxic group. GCMS analysis of LSS showed the presence of twelve major fatty acids including alpha-linolenic acid as a major constituent. These results indicated that LSS exerts enhance hepatoprotective activity that could be attributed towards its antioxidant activity, coupled together with the presence of anti-inflammatory compounds in LSS extract.
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