An Efficient Numerical Approach for Solving Nonlinear Coupled Hyperbolic Partial Differential Equations with Nonlocal Conditions

One of the most important advantages of collocation method is the possibility of dealing with nonlinear partial differential equations (PDEs) as well as PDEs with variable coefficients. A numerical solution based on a Jacobi collocation method is extended to solve nonlinear coupled hyperbolic PDEs with variable coefficients subject to initial-boundary nonlocal conservation conditions. This approach, based on Jacobi polynomials and Gauss-Lobatto quadrature integration, reduces solving the nonlinear coupled hyperbolic PDEs with variable coefficients to a system of nonlinear ordinary differential equation which is far easier to solve. In fact, we deal with initial-boundary coupled hyperbolic PDEs with variable coefficients as well as initial-nonlocal conditions. Using triangular, soliton, and exponential-triangular solutions as exact solutions, the obtained results show that the proposed numerical algorithm is efficient and very accurate

Knowledge about anesthesia and the role of anesthesiologists among Jeddah citizens

Background: The anesthesiologist has a vital role in the operating theatres. Awareness of the role of the anesthesiologist and the types of anesthesia is essential for every person. This study was made to estimate how much information the general population have about the anesthesiologist and the different types of anesthesia.Methods: This research was a cross sectional non-interventional study. The research team conducted a questionnaire in which each participant in the study was interviewed by the research team. The sample size was 159 participants.Results: From the participants,99 (62.2%) recognized the anesthesiologist as a specialized doctor who administers the anesthetics,62 (38.9%) know that the anesthesiologist has a role in resuscitating the patient with the team if crises occurred. However, 85 (53.4%) believe that the surgeon has the responsibility of postoperative pain management. Physicians were the source of knowledge for most participant’s information.Conclusions: A reasonable percentage of people appreciated the role of the anesthesiologist in administrating the anesthesia, however there is a lack of information about the role of the anesthesiologist intra and postoperatively. The need for more education for people about anesthesia is essential as the amount of information about anesthesia in general is rather low

Crystallization and X-ray diffraction analysis of the N-terminal domain of the Toll-like receptor signalling adaptor protein TRIF/TICAM-1

As part of the mammalian innate immune response, Toll-like receptors 3 and 4 can signal via the adaptor protein TRIF/TICAM-1 to elicit the production of type-I interferons and cytokines. Recent studies have suggested an auto-inhibitory role for the N-terminal domain (NTD) of TRIF. This domain has no significant sequence similarity to proteins of known structure. In this paper, the crystallization and X-ray diffraction analysis of TRIF-NTD and its selenomethionine-labelled mutant TRIF-NTDA66M/L113M are reported. Thin plate-like crystals of native TRIF-NTD obtained using polyethylene glycol 3350 as precipitant diffracted X-rays to 1.9 Å resolution. To facilitate phase determination, two additional methionines were incorporated into the protein at positions chosen based on the occurrence of methionines in TRIF homologues in different species. Crystals of the selenomethionine-labelled protein were obtained under conditions similar to the wild-type protein; these crystals diffracted X-rays to 2.5 Å resolution. The TRIF-NTD and TRIF-NTDA66M/L113M crystals have the symmetry of space groups P2 12121 and P1, and most likely contain two and four molecules in the asymmetric unit, respectively. These results provide a sound foundation for the future structure determination of this novel domain

Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of the TIR domain from the Brucella melitensis TIR-domain-containing protein TcpB

In mammals, Toll-like receptors (TLRs) recognize conserved microbial molecular signatures and induce an early innate immune response in the host. TLR signalling is mediated by interactions between the cytosolic TIR (Toll/interleukin-1 receptor) domains of the receptor and the adaptor proteins. Increasingly, it is apparent that pathogens target this interaction via pathogen-expressed TIR-domain-containing proteins to modulate immune responses. A TIR-domain-containing protein TcpB has been reported in the pathogenic bacterium Brucella melitensis. Studies have shown that TcpB interferes with the TLR2 and TLR4 signalling pathways to inhibit TLR-mediated inflammatory responses. Such interference may involve TIR-TIR-domain interactions between bacterial and mammalian proteins, but there is a lack of information about these interactions at the molecular level. In this study, the cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of the protein construct corresponding to the TIR domain of TcpB (residues 120-250) are reported. The crystals diffracted to 2.6 angstrom resolution, have the symmetry of the monoclinic space group P2(1) and are most likely to contain four molecules in the asymmetric unit. The structure should help in understanding the molecular basis of how TcpB affects the innate immunity of the host

The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins

TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 angstrom resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-beta promoter, as well as NF-kappa B-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation

Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy

Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence

Incidence of hip fracture in Saudi Arabia and the development of a FRAX model

Summary A prospective hospital-based survey in representative regions of Saudi Arabia determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Saudi Arabia. Objective This paper describes the incidence of hip fracture in the Kingdom of Saudi Arabia that was used to characterize the current and future burden of hip fracture, to develop a country-specific FRAX® tool for fracture prediction and to compare fracture probabilities with neighbouring countries. Methods During a 2-year (2017/2018) prospective survey in 15 hospitals with a defined catchment population, hip fractures in Saudi citizens were prospectively identified from hospital registers. The number of hip fractures and future burden was determined from national demography. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Saudi Arabia. Fracture probabilities were compared with those from Kuwait and Abu Dhabi. Results The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 2,949 and is predicted to increase nearly sevenfold to 20,328 in 2050. Hip fracture rates were comparable with estimates from Abu Dhabi and Kuwait. By contrast, probabilities of a major osteoporotic fracture or hip fracture from the age of 70 years were much lower than those seen in Abu Dhabi and Kuwait due to higher mortality estimates for Saudi Arabia. Conclusion A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment

Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling

Impact of the Glycemic Control and Duration of Type 2 Diabetes on Vitamin D Level and Cardiovascular Disease Risk

Background and Aims. To investigate the impact of glycemic control and T2D duration on vitamin D status and cardiovascular disease (CVD) risk among Saudi patients. Methods. This case-control study was conducted in King Faisal Specialist Hospital, Saudi Arabia. A total of 25 nondiabetic controls and 92 patients with confirmed T2D, aged 20–60 years, were included. Patients with T2D were divided into the following groups based on disease duration (newly diagnosed: ≈6 months and long duration: ≥5 years) and glycemic control based on their glycated hemoglobin (HbA1C) level with a threshold of ≤0.053 mol/mol: newly diagnosed controlled (NC, n=25), newly diagnosed uncontrolled (NU, n=17), long duration controlled (LC, n=25), and long duration uncontrolled (LU, n=25). Blood levels of fasting blood glucose, HbA1C, lipid profile, and serum 25-hydroxyvitamin D (25(OH)D) were assessed and used to define the CVD risk score. Results. Our study showed that T2D duration was an independent predictor of vitamin D deficiency. The longer disease duration, the lower odds of being vitamin D deficient (odds ratio (OR) = 0.05, 95% CI: 0.01–0.29, p<0.05). No significant association was observed between vitamin D and HbA1C levels. In the NU group, CVD risk scores were directly correlated with serum 25(OH)D (r=0.53, p<0.05). On the contrary, 25(OH)D was moderately inversely correlated with CVD risk score in the LU group (r=−0.45, p<0.05). Conclusion. Duration of diabetes rather than glycemic control is associated with vitamin D deficiency. Glycemic uncontrol may augment vitamin D deficiency-associated CVD risk in both newly diagnosed and old patients with type 2 diabetes

A higher order frozen Jacobian iterative method for solving Hamilton-Jacobi equations

It is well-known that the solution of Hamilton-Jacobi equation may have singularity i.e., the solution is non-smooth or nearly non-smooth. We construct a frozen Jacobian multi-step iterative method for solving Hamilton-Jacobi equation under the assumption that the solution is nearly singular. The frozen Jacobian iterative methods are computationally very efficient because a single instance of the iterative method uses a single inversion (in the scene of LU factorization) of the frozen Jacobian. The multi-step part enhances the convergence order by solving lower and upper triangular systems. The convergence order of our proposed iterative method is 3(m-1) for m>=3. For attaining good numerical accuracy in the solution, we use Chebyshev pseudo-spectral collocation method. Some Hamilton-Jacobi equations are solved, and numerically obtained results show high accuracy.Peer ReviewedPostprint (published version