Background. Candida glabrata is a human opportunistic pathogen that can cause life-threatening systemic infections. Although there are multiple effective vaccines against fungal infections and some ...of these vaccines are engaged in different stages of clinical trials, none of them have yet been approved by the FDA. Aim. Using immunoinformatics approach to predict the most conserved and immunogenic B- and T-cell epitopes from the fructose bisphosphate aldolase (Fba1) protein of C. glabrata. Material and Method. 13 C. glabrata fructose bisphosphate aldolase protein sequences (361 amino acids) were retrieved from NCBI and presented in several tools on the IEDB server for prediction of the most promising epitopes. Homology modeling and molecular docking were performed. Result. The promising B-cell epitopes were AYFKEH, VDKESLYTK, and HVDKESLYTK, while the promising peptides which have high affinity to MHC I binding were AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL, and YFKEHGEPL. Two peptides, LFSSHMLDL and YIRSIAPAY, were noted to have the highest affinity to MHC class II that interact with 9 alleles. The molecular docking revealed that the epitopes QTSNGGAAY and LFSSHMLDL have the lowest binding energy to MHC molecules. Conclusion. The epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines in that they are more specific, less time consuming, safe, less allergic, and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidate’s epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cell epitopes from the Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine against C. glabrata.
Abstract
Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the ...impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.
Dynamic wireless power transfer (DWPT) systems are becoming increasingly important for on-the-move electric vehicle (EV) charging solutions, to overcome range anxiety and compensate for the consumed ...energy while the EV is in motion. In this work, a DWPT EV charging system is proposed to be implemented on a straight road stretch such that it provides the moving EV with energy at a rate of 308 Wh/km. This rate is expected to compensate for the vehicle’s average energy consumption and allow for additional energy storage in the EV battery. The proposed charging system operates at an average power transfer efficiency that is higher than 90% and provides good lateral misalignment tolerance up to ±200 mm. Details of the proposed system’s design are presented in this paper, including EV specifications, inductive link and compensation network design and power electronic circuitry.
Neurologic disorders are common reasons for emergency consultations. Most neurologic disorders seen in the emergency department (ED) are life-threatening and require urgent treatment. The goal of ...this study is to investigate the pattern of neurological disorders among patients evaluated in the ED.
This is a cross-sectional study conducted in the ED of Mogadishu Somali Turkish Training and Research Hospital, from July 2021 to February 2022. The clinical and epidemiological characteristics of adult patients with neurologic manifestations in the ED were evaluated. Age, gender, distribution of neurological disease manifestations, neurological examination findings, and neurological diagnoses made by consultant neurologists were assessed.
During the study period, 321 patients were assessed (3.7 % of all ED admissions). The majority of the patients in the study were above 50 years of age (62.6% male). Hypertension was the most common comorbidity among these patients with 122 (38%) cases, followed by diabetes mellitus with 65 (20.2%), and heart diseases with 26 (8.1%) cases. The main reasons for neurology consultations were altered mental status with 141 (44%) cases, motor weakness with 102 (31.8%), seizures with 33 (10%), headache with 17 (5.3%), and vertigo with 9 (2.8%) cases. 196 (61%) had hemiplegia, 60 (18.7%) had consciousness impairment, and 38 (11.8%) had normal neurological examination. The most frequent neurological diagnoses were ischemic strokes with 125 (39%) cases, hemorrhagic strokes with 65 (20.2%), epileptic seizures with 28 (8.7%), and metabolic encephalopathies with 13 (4%) cases. The median duration of the neurology consultations was 20 minutes. 251 (78%) of the patients were admitted to the hospital, while 70 (22%) were discharged from the emergency department. After neurology consultation, the neurology department made the most admissions with 226 (90%) cases, while 25 (10%) were admitted by other departments. Of those admitted, 186 (74.2%) were admitted to the neurology ward, and 65 (25.8%) were admitted to the intensive care unit.
In our study, neurologic emergencies accounted for 3.7% of all emergency admissions. Stroke, epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases were the most common neurological disorders. The admission rate was very high following neurologic assessment by neurologists.
Helicobacter pylori (H. pylori) infects nearly half of the world's population with a variation in incidence among different geographic regions. Genetic variants in the promoter regions of the IL1B ...gene can affect cytokine expression and creates a condition of hypoacidity which favors the survival and colonization of H. pylori. Therefore, the aim of this study was to characterize the polymorphic sites in the 5'- region -687_ + 297 of IL1B in H. pylori infection using in silico tools.
A total of five nucleotide variations were detected in the 5'-regulatory region -687_ + 297 of IL1B which led to the addition or alteration of transcription factor binding sites (TFBSs) or composite regulatory elements (CEs). Genotyping of IL1B - 31 C > T revealed a significant association between -31 T and susceptibility to H. pylori infection in the studied population (P = 0.0363). Comparative analysis showed conservation rates of IL1B upstream -368_ + 10 region above 70% in chimpanzee, rhesus monkey, a domesticated dog, cow and rat.
In H. pylori-infected patients, three detected SNPs (- 338, - 155 and - 31) located in the IL1B promoter were predicted to alter TFBSs and CE, which might affect the gene expression. These in silico predictions provide insight for further experimental in vitro and in vivo studies of the regulation of IL1B expression and its relationship to H. pylori infection. However, the recognition of regulatory motifs by computer algorithms is fundamental for understanding gene expression patterns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Kidney injury from chemotherapy is one of the worsening problems associated with methotrexate (MTX) use. This work aims to examine the nephroprotective effects of empagliflozin (EMPA) and ...neohesperidin dihydrochalcone (NHD) provoked by MTX. A rat model was implemented by a single administration of MTX (20 mg/kg, i.p.). EMPA and NHD were administered in two doses (10 and 30 mg/kg, p.o.) and (40 and 80 mg/kg, p.o.), respectively for 14 consecutive days, using N-acetylcysteine (150 mg/kg, p.o.) as a reference standard. Pretreatment with EMPA and NHD showed significant attenuation in the renal function biomarkers, histopathological abrasions, and renal oxidative parameters. Also, EMPA and NHD pretreatment produced marked reductions in the expression of IL-6 and TNF-α level as proinflammatory biomarkers. Furthermore, EMPA and NHD pretreatment revealed marked decreases in the expression level of NF-ĸB, Keap1, HSP70, and caspase-3 and notable increases in Nrf2, PPARγ and HO-1 expression levels. EMPA and NHD can constrain oxidative stress liberation, inflammatory mediators proliferation, and apoptotic reactions in the renal tissue, which may be promising for further clinical applications to protect against MTX-induced renal injury or at least to reduce its adverse effects.
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•Empagliflozin and Neohesperidin mitigated methotrexate-induced increase of serum creatinine and urea.•Empagliflozin and Neohesperidin attenuated the renal histopathological injury.•Empagliflozin and Neohesperidin downregulated renal TNF-α and IL-6 expression.•Empagliflozin and Neohesperidin suppressed renal NF-ĸB/Keap1/HSP-70/caspase-3 expression.•Empagliflozin and Neohesperidin induced renal Nrf2/PPARγ/HO1 expression.
Recently, electric vehicles (EVs) have been introduced as an alternative method of transportation to help mitigate environmental issues, such as carbon emissions and fuel consumption, caused by ...conventional transportation systems. The implementation of effective EV charging systems is essential to motivate mass adoption of EVs. Accordingly, fast and reliable communications between the charging systems and the EVs are vital for efficient management of the charging process. Different radio access technologies (RATs) are discussed in the literature to enable communication between the highly mobile EVs and the charging subsystems, to collect and exchange information such as state of charge (SoC), users’ locations, and charging decisions between the different network entities. This information can be used to coordinate charging plans and select the optimal routes for moving vehicles. This paper presents a survey of existing literature on vehicular communications for EV charging coordination and management. The communication requirements and feasible communication technologies for vehicular communication are first discussed in details. A review of the physical layer security strategies is then presented and the role of the different RATs in EV charging coordination and management is described and studied.
Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to ...developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.
To address range anxiety concerns of current and potential EV drivers, on-the-move charging of electric vehicles (EV) is introduced through the development of roadway electrification solutions, i.e., ...wireless charging lanes (WCLs). These lanes allow EVs to recharge their batteries and compensate for the energy consumed during their motion. Nevertheless, the high deployment and operational costs of WCLs raise concerns about their expected utilization and returns on the investment. This calls for a detailed analysis of the potential locations for WCL implementation. This work proposes a two-staged multi-criteria decision making (MCDM) framework that integrates the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) with binary goal programming (BGP), to evaluate potential locations for WCL implementation according to geospatial, environmental, technical and economic criteria. In the first stage, the TOPSIS method is utilized to rank several alternative locations according to their geospatial, environmental and technical specifications. The alternatives with the highest ranking are then shortlisted and evaluated using a mathematical BGP model, to provide recommendations on the most optimal locations and the corresponding WCL lengths that meet budget constraints according to the economic evaluation criteria. The proposed integrated TOPSIS-BGP model offers a comprehensive decision-making approach by acknowledging diverse criteria that are otherwise difficult to integrate into a single combinatorial mathematical program. A case study of major UAE cities, namely Dubai and Sharjah, is presented to illustrate the implementation of the proposed framework.
Key Clinical Message
Bilateral thalamic infarction in paramedian artery territory may present with severe acute illness, confusion, coma and memory impairment. However, subtle clinical presentation ...as in our case should alert the clinician to consider such a diagnosis as it can be associated with good prognosis.
Bilateral thalamic infarct is a rare form of stroke. Mostly thalamic infarcts are unilateral. In most cases, bilateral thalamic infarction leads to cognitive dysfunction, opthalmoparesis, conscious impairment, behavioral disturbance, and corticospinal dysfunction. Here, we describe the case of a 75‐year‐old male patient who presented to the emergency department of our hospital with agitation and somnolence for one day. He had poorly controlled hypertension. There was no previous history of stroke, diabetes mellitus, hyperlipidemia, known cardiac disease, or smoking history. There was no seizure, recent headache, or visual disturbance. The patient was somnolent and not oriented to time, person, or place. Neurological examination did not show any focal weakness or vertical eye movement restrictions. Other systemic examinations, including those of the respiratory and cardiovascular systems, were unremarkable. Extensive laboratory investigations excluded potential metabolic, infectious, endocrine, or toxic etiologies. The patient did not have any recent history of drug misuse, including benzodiazepines. Brain MRI with diffusion‐weighted imaging showed an acute bilateral thalamic infarct. Cerebral angiography was unremarkable. The patient was treated with low molecular weight heparin 60 mg subcutaneously, aspirin 300 mg daily, and haloperidol 5 mg twice daily for agitation. After two weeks of intrahospital treatment, his condition improved (consciousness and orientation massively improved).
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