The importance of site selection for road transportation management and emergency services has been underscored, particularly in the wake of the global Covid-19 pandemic in addition to road accident ...injuries, which emphasized the need for swift patient, injured and wounded peoples transfer to hospitals. As a result, comprehensive road transportation management is essential during crises to ensure the safety and convenience of road users. To achieve effective road network management, a robust database is imperative. The aim of this study is to employ multi-criteria decision analysis with the aid of Geographical Information System (GIS) technology and remote sensing for the optimization of site selection for traffic signals, fire stations, and emergency services in Kafr El-Sheikh city, Egypt. The methodology incorporates two different methods which are Fuzzy Analytical Hierarchy Process (F-AHP) and the spline transformation method. The integration of Fuzzy set theory with AHP principles has given rise to a variant of AHP known as F-AHP. F-AHP combines qualitative and quantitative approaches. Fuzzy logic handles situations that are vague or poorly defined by assigning numerical values. Through the F-AHP approach, criteria that decision-makers unanimously deem “absolutely not important” in comparison to others are eliminated, allowing them to focus on the most significant criteria. As a case study, an Egyptian city was selected to apply these techniques. The results revealed multiple sites that were identified and selected through the applied analytical methods. These selected sites were also marked on the city map and verified in reality.
Intravenous recombinant tissue-plasminogen-activator (rtPA) and mechanical-thrombectomy (MT) are currently the only approved treatments for acute ischemic stroke. Their effectiveness was demonstrated ...in several clinical trials, and is therefore standard of care. Pregnant women were not included in these studies and consequently the effectiveness and safety in this group are unclear. We present a rare case of a patient in the third-trimester of pregnancy that underwent MT. A 29-year-old woman of 39 weeks’ gestation presented with left facial-paresis, hemiparesis, and neglect. Her CT-Angiogram showed a large occlusive thrombus within the right M1-M2 segments. During pregnancy she had developed thrombocytopenia. There was initial treatment decision dilemma. In view of her history of thrombocytopenia, there was concern about administering rtPA due to the risk of bleeding. As the thrombus was large, rtPA may also be ineffective. MT was proposed by the Stroke Physician as the preferred treatment option. A concern from the Interventional-Radiologist was the risk of exposure to radiation and contrast agents. As the patient had a disabling stroke at a young age, decision was made to proceed with MT which started 141 minutes after symptom onset. The clot was aspirated without complications. Final check angiogram showed complete resolution of flow within the right middle cerebral artery territory. The patient underwent elective uncomplicated Caesarean-section 5 days later delivering a healthy new born. Severe stroke in pregnancy is rare, but has grave consequences for both mother and infant. Timely decision-making is crucial. Our case demonstrates that MT can be provided safely and effectively in the third trimester of pregnancy.
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. Studies on in vitro mutagenized AID as well as ...its mutations in human patients with hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact. The C-terminal mutants of AID were speculated to exert the dominant negative effect on wild-type (WT) AID whereas its mechanism remains unknown. We generated the JP41 (R190X) mutation in one allele and a null mutation on the other allele in a mouse B cell line (CH12F3-2A) using CRISPR/Cas9 genome-editing tools and studied the effect of JP41 expression on the function of exogenously introduced WT AID fused with estrogen receptor (AIDER) in AIDJP41/∆/AIDER CH12F3-2A cells. We found that JP41 expression strongly suppressed not only CSR but also Igh/c-Myc chromosomal translocations by AIDER. We showed that the dominant negative effect is not evident at the DNA cleavage step but obvious at both deletional and inversional recombination steps. We also confirmed the dominant negative effect of other C-terminal mutants, JP8Bdel (R183X) and P20 (34-aa insertion at residue 182) in AID-deficient spleen B cells. Finally, we showed that the expression of JP41 reduced the binding of AIDER with its cofactors (hnRNP L, SERBP1 and hnRNP U). Together, these data indicate that dominant negative effect of JP41 on CSR is likely due to the depletion of the CSR-specific RNA-binding proteins from WT AID.
Diabetes mellitus is a common disease which is prevalent globally, presenting with chronic complications and constitutes a major risk to the patient. Diabetic foot ulcers are the single biggest risk ...factor for non-traumatic lower limb amputations in persons with diabetes. We aimed to screen for the chronic vascular diabetic complications in patients with diabetic foot ulcers (DFUs) and to assess the association of diabetic foot ulcers with these complications in the study group.
This cross-sectional study included 180 type 2 diabetic patients (aged 30–70 years) with diabetic foot ulcers who attended the Outpatient Clinic of Diabetes in Alexandria Main University Hospital. Full diabetic foot examination was done to all study subjects. DFUs were assessed using University of Texas Diabetic Wound Classification System. HbA1c, LDL-C, serum creatinine, and urinary albumin creatinine ratio (ACR) were measured for all study subjects. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Fundus examination was done for all study subjects.
The prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) was 86.1% and 90% respectively among the study group. 86.7% of patients had neuropathic DFUs, 11.1% of them had ischemic DFUs and 2.2% had neuro-ischemic DFUs. Regarding diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) as risk factors for developing DFU, the prevalence of both of them respectively was 82% and 20% among the study group. There was statistically significant association between both DKD, DR and peripheral neuropathy. There was also statistically significant association between both DKD, DR and peripheral arterial disease (PAD).
Chronic vascular diabetic complications are common among type 2 diabetic patients with diabetic foot ulcers. There is statistically significant association between these complications and diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD).
Background
Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms ...and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited.
Objectives
This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling.
Methods
A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists.
Results
A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria.
Conclusions
Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk–benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.
The change in the adsorbed amounts of four cyanine dyes as a function of time and alkyl chain length onto Na+-MMT. Display omitted
► The adsorption of cyanine dyes from aqueous solution onto ...Na+-montmorillonite was investigated. ► The kinetics and adsorption isotherms were studied. ► The equilibrium amount of the dye adsorbed depends largely on the alkyl chain length. ► The adsorption of the dye is affected by the conditions controlling the clay/dye interaction. ► The adsorption process is physical, endothermic, and non-spontaneous.
Adsorption of cyanine dyes from aqueous solution onto the surface of Na+-montmorillonite (Na+-MMT) was investigated spectrophotometrically. A set of four linear alkyl chain cyanine dyes (D-C5, D-C7, D-C10, and D-C18), were used in this work to evaluate the effect of carbon chain length on the efficiency of dye adsorption. The loading of the dye onto Na+-MMT surface was increased with increasing the length of alkyl chain. The effect of the contact time, initial concentration of the dye, pH of solution and temperature on the adsorption process were studied. Adsorption isotherms were established and found to correlate well with the Freundlich, Langmuir, and Dubinin–Radushkevich adsorption models. Values of the constants Kf and 1/n determined from the Freundlich isotherm decreased with the increase in the tail length of the dye (D-C5→D-C18). The same trend was observed for the Langmuir adsorption constant, KL. The E values calculated from Dubinin–Radushkevich isotherm increased with increasing the alkyl chain length of the cyanine dyes but still less than 16kJmol−1, suggesting physical adsorption process. Further, the thermodynamic parameters (the enthalpy, ΔH, Gibb’s free energy, ΔG, and entropy, ΔS) characteristics of Na+-MMT/dye interaction were evaluated. The adsorption of cyanine dyes onto Na+-MMT was not spontaneous and endothermic. The magnitudes of ΔH and ΔS have dropped on going from D-C5 to D-C18. In contrast, as the size of the alkyl tail on the dye increased, Gibb’s free energy ΔG was decreased. As far as the adsorption kinetics is concerned, the present adsorption regime followed pseudo-second-order kinetic model rather than pseudo-first-order model. The intraparticle diffusion model resulted in the existence of both the bulk and intraparticle diffusions of the dye molecules into the interior pore surface of Na+-MMT particles.
The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory ...actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC
50
values of 0.09-0.14 µM) with significant 15-LOX inhibitory activities (IC
50
s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.
Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active ...inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation. Although international guidelines and recommendations have been published for clinical and technical aspects of AHSCT in MS, there has been no detailed appraisal of the rehabilitation needed following treatment nor any specific guidelines as to how this is best delivered by hospital and community-based therapists and wider multidisciplinary teams in order to maximize functional recovery and quality of life. These expert consensus guidelines aim to address this unmet need by summarizing the evidence-base for AHSCT in MS and providing recommendations for current rehabilitation practice along with identifying areas for future research and development.