Utilizing sludge-based activated carbon for targeted leachate mitigation in wastewater treatment.

Activated carbon (AC) based adsorbents derived from waste sludge were utilized to remediate mixed contaminants in wastewater as an integrated waste-to-resource approach promoting a paradigm shift in management of refuse sludge and wastewater. This review specifically focuses on the remediation of constituents of landfill leachate by sludge-based activated carbon (SBAC). The adsorption effectiveness of SBAC for the exclusion of leachate characters including heavy metals, phenols, dyes, phosphates, and phosphorus were explored with regard to modifiers such as pH, temperature, properties of the adsorbent including functional groups, initial doses of absorbent and adsorbate, and duration of exposure to note the impact of each parameter on the efficiency of adsorption of the sludge adsorbent. Through the works of various researchers, it was noted that the properties of the adsorbent, pH and temperature impact the working of SBACs. The pH of the adsorbent by influencing the functional groups. Temperature was expected to have a paramount effect on the adsorption efficiency of the SBACs. The importance of the regeneration and recycling of the adsorbents as well as their leachability is highlighted. Sludge based activated carbon is recommended as a timely, resource-efficient, and sustainable approach for the remediation of wastewater.

A computational quest for identifying potential vaccine candidates against Moraxella lacunata: a multi-pronged approach.

Moraxella lacunata is an emerging gram-negative bacterium that is responsible for multiple nosocomial infections. The bacterium is evolving resistance to several antibiotics, and currently, no effective licensed vaccines are available, which warrants the search for new therapeutics. A multi-epitope-based vaccine has been designed for M. lacunata. The complete proteome of M. lacunata contains 10,110 core proteins. Subcellular localization analysis revealed the presence of five proteins in the extracellular matrix, while 19 proteins were predicted to be located in the outer membrane, and 21 proteins were predicted to be located in the periplasmic region. Only two proteins, the type VI secretion system tube protein (Hcp) and the transporter substrate-binding domain-containing protein, were selected for epitope prediction as they fulfilled all the criteria for being potential vaccine candidates. Shortlisted epitopes from the selected proteins were fused together using "GPGPG" linkers to overcome the limitations of single-epitope vaccines. Next, the cholera toxin-B adjuvant was attached to the peptide epitope using an EAAAK linker. Docking analysis was performed to examine the interaction between the vaccine and immune cell receptors, revealing robust intermolecular interactions and a stable binding conformation. Molecular dynamics simulation findings revealed no drastic changes in the binding conformation of complexes during the simulation period. The net binding free energy of vaccine-receptor complexes was estimated using the molecular mechanics energies combined with the Poisson-Boltzmann and surface area continuum solvation (MM-PBSA) method. The reported values were -586.38 kcal/mol, -283.74 kcal/mol, and -296.88 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. Furthermore, the molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) analysis predicted binding free energies of -596.69 kcal/mol, -287.39 kcal/mol, and -298.28 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. The theoretical vaccine design proposed in the study could potentially serve as a powerful therapeutic against targeted pathogens, subject to validation through experimental studies.Communicated by Ramaswamy H. Sarma.

A chemoinformatic-biophysics based approach to identify novel anti-virulent compounds against Pseudomonas aeruginosa disulfide-bond protein A1.

The conventional course of drug discovery is a lengthy, expensive and complex process and often experiences a high failure rate. This in-silico based study screened novel drug molecules against Pseudomonas aeruginosa disulfide-bond protein A1 (PaDsbA1; PDB ID of 4ZL7) using a variety of chemoinformatic and biophysics approaches. The structure-based virtual screening identified three antipseudomonal compounds (BDC_30129064, BDC_20699588 and BDC_25329008) that targeted PaDsbA1 enzyme with a binding energy score of -7.8 kcal/mol, -7.7 kcal/mol and -7.7 kcal/mol, respectively. The compounds revealed deep binding at the enzyme active pocket with close distance hydrogen bond interactions with Thr46, Pro55, Val58, Arg62, His88, and Asp180. The co-crystalized hexaethylene glycol revealed a binding energy of -6.02 kcal/mol. The docked compounds were further subjected to molecular dynamics simulation analysis in order to check the dynamic movements of docked complexes. The complexes reported no drastic changes during simulation time. In the simulation, stable compounds binding and docked conformation were accomplished. The docking and simulation results were validated using free binding energies calculation through molecular mechanics with generalized born surface area solvation and molecular mechanics Poisson Boltzmann surface area (MMGBSA/MMPBSA) approaches. The net binding energy estimated by MMGBSA for BDC_30129064, BDC_20699588 and BDC_25329008 was -75.07 kcal/mol, -77.87 kcal/mol and -59.1 kcal/mol, respectively while that of MMPBSA for the compounds was -72.47 kcal/mol, -78.99 kcal/mol and -60.991 kcal/mol, respectively. The physiochemical properties of the selected compounds indicated them to be physiochemically stable with good absorption, distribution, metabolism and elimination properties. From the above observations and predictions, the compounds can be recommended for further experimental validation in order to decipher their anti-virulence capacity in blocking disulfide bond formation in P. aeruginosa.Communicated by Ramaswamy H. Sarma.

Experimental Investigation of Engine Valve Train Friction Considering Effects of Operating Conditions and WPC Surface Treatment.

Reduction in friction ensures fuel economy, control on emissions and durability of components in internal combustion engines. A modern gasoline internal combustion engine was instrumented to determine the friction values at the cam-roller interface considering the effects of surface treatment and engine operating state. A series of tests under different operating speeds and lubricant inlet temperatures were undertaken using both an original surface roller and a Wonder Process Craft (WPC) surface-treated engine roller. The results clearly revealed a substantial reduction in friction magnitude for the WPC surface-treated engine roller in comparison to the original roller while operating under similar conditions, indicating their strong potential for employment in engines. An increase in friction with the rise in temperature was also observed for both types of rollers, whereas increased lubricant entraining velocity due to higher operating speed had the opposite impact. A considerable reduction in frictional drive torque ranging from 8% to 28% was observed by employing the WPC-treated roller in comparison to original/untreated roller at various operating conditions, which signifies the strong potential for employment of WPC surface treatment in the roller/follower valve train engines.

Green bonds issuance, innovation performance, and corporate value: Empirical evidence from China.

This study investigates the impact of green bond issuance on corporate performance and further checks the intermediate effect of corporate innovation performance on the primary relationship. This study uses the quarterly panel data of Chinese non-financial listed companies in 11 subdivided industry categories from January 1, 2016, to September 30, 2020. Using the difference-in-difference (DID) model and the parallel trend test, it is found that companies' issuance of green bonds has a significant positive effect on improving corporate innovation performance and corporate value. Furthermore, the improvement of innovation performance assists in enhancing the promotion effect of green bond issuance on corporate value. Despite data limitations, this study's findings can be very helpful for all relevant stakeholders, especially regulators, to introduce conducive policies to support the issuance of green bonds in Chinese. Our findings can be useful for other emerging markets that are dealing with the same green bond-based growth-sustainability conundrum.

Machine Learning Model for Assessment of Risk Factors and Postoperative Day for Superficial vs Deep/Organ-Space Surgical Site Infections.

Background. Deep and organ space surgical site infections (SSI) require more intensive treatment, may result in more severe clinical disease and may have different risk factors when compared to superficial SSIs. Machine learning (ML) algorithms provide the opportunity to analyze multiple factors to predict of the type and time of development of SSI. Therefore, we developed a ML model to predict type and postoperative week of SSI. Methodology. A case-control study was conducted among patients who developed a SSI after undergoing general surgery procedures at a tertiary care hospital between 2019 to 2020. Patients were followed for 30 days. Six ML algorithms were trained as predictors of type of infection (superficial vs deep/organ space) and time of infection, and tested using area under the receiver operating characteristic curve (AUC-ROC). Results. Data for 113 patients with SSIs was available. Of these 62 (54.8%) had superficial and 51 had (45.2%) deep/organ space infections. Compared with other ML algorithms, the XG boost univariate model had highest AUC-ROC (.84) for prediction of type of SSI and Stochastic gradient boosting univariate, logistic regression univariate, XG boost univariate, and random forest classification univariate model had the highest AUC-ROC (.74) for prediction of week of infection. Conclusions. ML models offer reasonable accuracy in prediction of superficial vs deep SSI and time of developing infection. Follow-up duration and allocation of treatment strategies can be informed by ML predictions.

Management of infected arteriovenous grafts for haemodialysis: Outcomes and strategies using a novel objective scoring system.

BACKGROUND: In haemodialysis patients with exhausted autogenous options, prosthetic arteriovenous grafts (AVGs) are frequently utilised as tertiary vascular access. However, the prosthetic nature of AVGs precipitates an increased risk of infection which may translate to excess morbidity and life-threatening complications. The current evidence remains divided on the optimal treatment strategy for arteriovenous graft infections (AVGi) with arguments for conservative management by antibiotics, salvaging with graft revision or total/subtotal excision. To address this gap, we assessed the outcomes of AVGi patients treated in our institution, developing an AVGi severity classification model and a proposed treatment algorithm to guide AVGi management. METHODS: We conducted a single centre retrospective review of outcomes of patients with AVGi managed either by sole antibiotics therapy, graft revision or surgical excision between June 2016 and May 2021. Outcomes of AVGi patients across differing treatment groups were compared, including 1-year mortality, 6-month and 1-year functional vascular access. We also analysed the outcomes of tunnelled haemodialysis lines (THL), which were used as a temporary vascular access in several AVGi patients in our study. RESULTS: A total of 34 AVGi patients were managed within that time frame and included in the study (5 conservatively management by antibiotics, 5 graft revisions and 24 surgical excision) with a mean age of 60.4 ± 14.4 years (67.6% males). Overall 1-year mortality was 14.7%. A 6-month functional vascular access status across the three groups stood at 60%, 60% and 10% while 1-year functional vascular access status was 60%, 75% and 42% respectively. CONCLUSIONS: When clinically appropriate, conservative management by antibiotics or salvage/graft revision can present as prudent AVGi treatment options. The adoption of our proposed severity classification system and treatment algorithm provides a more thorough objective assessment of the infection and helps guide the clinical decision-making process.

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis.

The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs. Infected animals also represent the major source of infection for humans. Development of safer and effective vaccines for brucellosis remains a priority to support disease control and eradication in animals and to prevent infection to humans. In this research study, we designed an in-silico multi-epitopes vaccine for B. melitensis using computational approaches. The pathogen core proteome was screened for good vaccine candidates using subtractive proteomics, reverse vaccinology and immunoinformatic tools. In total, 10 proteins: catalase; siderophore ABC transporter substrate-binding protein; pyridoxamine 5'-phosphate oxidase; superoxide dismutase; peptidylprolyl isomerase; superoxide dismutase family protein; septation protein A; hypothetical protein; binding-protein-dependent transport systems inner membrane component; and 4-hydroxy-2-oxoheptanedioate aldolase were selected for epitopes prediction. To induce cellular and antibody base immune responses, the vaccine must comprise both B and T-cells epitopes. The epitopes were next screened for antigenicity, allergic nature and water solubility and the probable antigenic, non-allergic, water-soluble and non-toxic nine epitopes were shortlisted for multi-epitopes vaccine construction. The designed vaccine construct comprises 274 amino acid long sequences having a molecular weight of 28.14 kDa and instability index of 27.62. The vaccine construct was further assessed for binding efficacy with immune cell receptors. Docking results revealed that the designed vaccine had good binding potency with selected immune cell receptors. Furthermore, vaccine-MHC-I, vaccine-MHC-II and vaccine-TLR-4 complexes were opted based on a least-binding energy score of -5.48 kcal/mol, 0.64 kcal/mol and -2.69 kcal/mol. Those selected were then energy refined and subjected to simulation studies to understand dynamic movements of the docked complexes. The docking results were further validated through MMPBSA and MMGBSA analyses. The MMPBSA calculated -235.18 kcal/mol, -206.79 kcal/mol, and -215.73 kcal/mol net binding free energy, while MMGBSA estimated -259.48 kcal/mol, -206.79 kcal/mol and -215.73 kcal/mol for TLR-4, MHC-I and MHC-II complexes, respectively. These findings were validated by water-swap and entropy calculations. Overall, the designed vaccine construct can evoke proper immune responses and the construct could be helpful for experimental researchers in formulation of a protective vaccine against the targeted pathogen for both animal and human use.

Management equity incentives and corporate tax avoidance: Moderating role of the internal control.

Introduction: Under the modern enterprise system, the principal-agent relationship can cause a conflict of interest between the two power counterparts, thus affecting the degree of corporate tax avoidance. As a tool to align the interests of management and owners, management equity incentives can alleviate the conflict of interests brought about by the separation of powers and, therefore, may influence corporate tax avoidance. Objectives and methods: We examine the relationship between management equity incentives and corporate tax avoidance from both theoretical and empirical perspectives by using data from Chinese A-share listed companies from 2016 to 2020. Firstly, the effect of management equity incentives on tax avoidance is theoretically and normatively analyzed. Secondly, examine the effectiveness of moderating the effect of internal control and distinguishing the ownership of enterprises' nature through regression analysis. Results: (1) There is a positive relationship between management equity incentives and corporate tax avoidance which means, more the stock incentive offered to executives, the more likely corporations are to pursue tax avoidance strategies aggressively. (2) Internal control deficiencies enhance the positive relationship between equity incentives and enterprise tax avoidance behavior. Therefore, in Chinese enterprises, the lack of an internal control system and the failure of internal control measures are prevalent, and such loopholes can intensify the tax avoidance behavior that arises when executives are subject to equity incentives. (3) The influence of management equity incentives on enterprise tax avoidance behavior is greater in state-owned (SOE) than private enterprises. State-owned enterprises are more likely to increase enterprise tax avoidance behavior when management is subject to equity incentives for reasons such as strict performance requirements, lower regulatory oversight, and less interference from negative information. Finally, our findings have significant implications for policymakers/regulators, public companies, investors, standard setters, managerial labor markets, and the welfare of the overall economy.

Municipal solid waste treatment for bioenergy and resource production: Potential technologies, techno-economic-environmental aspects and implications of membrane-based recovery.

World estimated municipal solid waste generating at an alarming rate and its disposal is a severe concern of today's world. It is equivalent to 0.79 kg/d per person footprint and causing climate change; health hazards and other environmental issues which need attention on an urgent basis. Waste to energy (WTE) considers as an alternative renewable energy potential to recover energy from waste and reduce the global waste problems. WTE reduced the burden on fossil fuels for energy generation, waste volumes, environmental, and greenhouse gases emissions. This critical review aims to evaluate the source of solid waste generation and the possible routes of waste management such as biological landfill and thermal treatment (Incineration, pyrolysis, and gasification). Moreover, a comparative evaluation of different technologies was reviewed in terms of economic and environmental aspects along with their limitations and advantages. Critical literature revealed that gasification seemed to be the efficient route and environmentally sustainable. In addition, a framework for the gasification process, gasifier types, and selection of gasifiers for MSW was presented. The country-wise solutions recommendation was proposed for solid waste management with the least impact on the environment. Furthermore, key issues and potential perspectives that require urgent attention to facilitate global penetration are highlighted. Finally, practical implications of membrane and comparison membrane-based separation technology with other conventional technologies to recover bioenergy and resources were discussed. It is expected that this study will lead towards practical solution for future advancement in terms of economic and environmental concerns, and also provide economic feasibility and practical implications for global penetration.

The management of dialysis access thrombosis during the COVID-19 pandemic.

BACKGROUND: Maintaining patent access is essential for haemodialysis dependent end stage renal failure patients. The COVID-19 pandemic has significantly affected surgical and interventional radiology services worldwide. We aimed to review the impact COVID-19 has caused to the management of acute dialysis access thrombosis. METHODS: We conducted a single centre retrospective review of outcomes of patients with arteriovenous fistula and arteriovenous graft thrombosis between March and May 2020, which coincided with the first peak of the COVID-19 pandemic in London, and a similar period in the previous year, March-May 2019. Outcomes in both cohorts of patients were compared, including attempts at salvage, salvage success, 1-month patency rates after salvage and subsequent surgery on the same access. We also analysed the use of tunnelled haemodialysis lines (THL), either due to failed salvage attempts or when salvage was not attempted. RESULTS: There was a similar incidence of access thrombosis in both periods (26 cases in 2019, 38 in 2020). There were 601 patients dialysing via an arteriovenous fistula or graft in 2019, and 568 patients in 2020. Access salvage, when attempted, had similar success rates and 1-month patency (salvage success 74% vs 80%, p = 0.39; 1-month patency 55% vs 62%, p = 0.69). The proportion of patients where access salvage was not attempted and a THL inserted was significantly higher in 2020 compared to 2019 (32% vs 4%, p = 0.007). There were more patients who subsequently had surgery to salvage or revise the same access in 2019 compared to 2020 (62% vs 13%, p < 0.001). CONCLUSIONS: During the peak of the COVID-19 pandemic, there were fewer attempts at access salvage. This was a conscious decision due to increased pressure on the healthcare system, access to emergency interventional radiology or operative theatres and the perceived risk/benefit ratio of access salvage. The long-term effects of this change in practice remain unknown.

Rapid Testing System for Rice Quality Control through Comprehensive Feature and Kernel-Type Detection.

The assessment of food quality is of significant importance as it allows control over important features, such as ensuring adherence to food standards, longer shelf life, and consistency and quality of taste. Rice is the predominant dietary source of half the world's population, and Pakistan contributes around 80% of the rice trade worldwide and is among the top three of the largest exporters. Hitherto, the rice industry has depended on antiquated methods of rice quality assessment through manual inspection, which is time consuming and prone to errors. In this study, an efficient desktop-application-based rice quality evaluation system, 'National Grain Tech', based on computer vision and machine learning, is presented. The analysis is based on seven main features, including grain length, width, weight, yellowness, broken, chalky, and/or damaged kernels for six different types of rice: IRRI-6, PK386, 1121 white and Selah, Super kernel basmati brown, and white rice. The system was tested in rice factories for 3 months and demonstrated 99% accuracy in determining the size, weight, color, and chalkiness of rice kernels. An accuracy of 98.8% was achieved for the classification of damaged and undamaged kernels, 98% for determining broken kernels, and 100% for paddy kernels. The results are significant because the developed system improves the local rice quality testing capacity through a faster, more accurate, and less expensive mechanism in comparison to previous research studies, which only evaluated four features of the singular rice type, rather than the seven features achieved in this study for six rice types.

Pan-Genome Analysis of Oral Bacterial Pathogens to Predict a Potential Novel Multi-Epitopes Vaccine Candidate.

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium, mainly present in the oral cavity and causes periodontal infections. Currently, no licensed vaccine is available against P. gingivalis and other oral bacterial pathogens. To develop a vaccine against P. gingivalis, herein, we applied a bacterial pan-genome analysis (BPGA) on the bacterial genomes that retrieved a total number of 4908 core proteins, which were further utilized for the identification of good vaccine candidates. After several vaccine candidacy analyses, three proteins, namely lytic transglycosylase domain-containing protein, FKBP-type peptidyl-propyl cis-trans isomerase and superoxide dismutase, were shortlisted for epitopes prediction. In the epitopes prediction phase, different types of B and T-cell epitopes were predicted and only those with an antigenic, immunogenic, non-allergenic, and non-toxic profile were selected. Moreover, all the predicted epitopes were joined with each other to make a multi-epitopes vaccine construct, which was linked further to the cholera toxin B-subunit to enhance the antigenicity of the vaccine. For downward analysis, a three dimensional structure of the designed vaccine was modeled. The modeled structure was checked for binding potency with major histocompatibility complex I (MHC-I), major histocompatibility complex II (MHC-II), and Toll-like receptor 4 (TLR-4) immune cell receptors which revealed that the designed vaccine performed proper binding with respect to immune cell receptors. Additionally, the binding efficacy of the vaccine was validated through a molecular dynamic simulation that interpreted strong intermolecular vaccine-receptor binding and confirmed the exposed situation of vaccine epitopes to the host immune system. In conclusion, the study suggested that the model vaccine construct has the potency to generate protective host immune responses and that it might be a good vaccine candidate for experimental in vivo and in vitro studies.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Recent advancement challenges with synthesis of biocompatible hemodialysis membranes.

The focus of this study is to enhance the protein fouling resistance, hydrophilicity, biocompatibility, hemocompatibility and ability of the membranes and to reduce health complications like chronic pulmonary disease, peripheral vascular disease, cerebrovascular disease, and cardiovascular disease after dialysis, which are the great challenges in HD applications. In the current study, the PSF-based dialysis membranes are studied broadly. Significant consideration has also been provided to membrane characteristics (e.g., flowrate coefficient, solute clearance characteristic) and also on commercially available polysulfone HD membranes. PSF has gained a significant share in the development of HD membranes, and continuous improvements are being made in the process to make high flux PSF-based dialysis membranes with enhanced biocompatibility and improved protein resistance ability as the major issue in the development of membranes for HD application is biocompatibility. There has been a great increase in the demand for novel biocompatible membranes that offer the best performances during HD therapy, for example, low oxidative stress and low change ability of blood pressure.

Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii.

Antibiotic resistance (AR) is the result of microbes' natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, ß-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinformatics, proteomics, and biophysical analyses to identify potential vaccine antigens against A. baumannii. By doing so, four outer membrane proteins were prioritized: TonB-dependent siderphore receptor, OmpA family protein, type IV pilus biogenesis stability protein, and OprD family outer membrane porin. Immuoinformatics predicted B-cell and T-cell epitopes from all four proteins. The antigenic epitopes were linked to design a multi-epitopes vaccine construct using GPGPG linkers and adjuvant cholera toxin B subunit to boost the immune responses. A 3D model of the vaccine construct was built, loop refined, and considered for extensive error examination. Disulfide engineering was performed for the stability of the vaccine construct. Blind docking of the vaccine was conducted with host MHC-I, MHC-II, and toll-like receptors 4 (TLR-4) molecules. Molecular dynamic simulation was carried out to understand the vaccine-receptors dynamics and binding stability, as well as to evaluate the presentation of epitopes to the host immune system. Binding energies estimation was achieved to understand intermolecular interaction energies and validate docking and simulation studies. The results suggested that the designed vaccine construct has high potential to induce protective host immune responses and can be a good vaccine candidate for experimental in vivo and in vitro studies.

Prevalence and Biochemical Associations of Fever in Adults With Reverse Transcription Polymerase Chain Reaction Proven Coronavirus Disease Presenting at Tertiary Care Hospitals in Rawalpindi.

Background Clinically most apparent symptoms of COVID-19 include fever and cough, which in some patients show a worsening trend but are completely non-apparent in patients who present with an asymptomatic course of the disease. The aim of this study was to identify clinical and biochemical differences among polymerase chain reaction (PCR) positive patients who are either febrile or afebrile. Methods This study was conducted in Rawalpindi Medical University and Allied Hospitals between September and December 2020. All patients who tested positive for reverse transcription polymerase chain reaction (RT-PCR) COVID-19 were included in the study. After evaluation of 146 patients, 100 were selected, and with a response rate of 97%, a total of 97 patients were included in the final analysis. Depending on the presence of fever, the participants were divided into two groups. Both groups were then compared for baselines vitals and laboratory investigations. Data was entered and analyzed in SPSS v23.0 (IBM Inc., Armonk, New York). Results Among the 97 patients, 66 (68%) of the participants were male, and 31 (32%) were females. The mean age of the study participants was 45.23±18.08 years. Fever was present in 39 (40.2%) of the participants. When compared with patients with no fever, the patients with fever had greater severity of disease (p<0.001), higher heart rate (p<0.001), decreased oxygen saturation (p<0.001). Among the laboratory investigations, the fever group had a greater tendency of having deranged alanine aminotransferase (ALT) (70.82±29.23 vs. 32.83±16.22, p=0.010), Lymphocytes (1.56±0.54 vs. 2.12±0.94, p=0.003) and serum total bilirubin (1.06±0.36 vs. 0.55±0.21, p=0.009). Based on multiple regression analysis, the presence of fever is a predictor of derangement in ALT (OR=1.034, CI=1.001-1.068 p=0.025) and total bilirubin (OR=4.38, CI=2.14-6.78, p=0.021). Conclusion Fever may not be present among all patients presenting with COVID-19 infection, but those who have a fever have a greater risk of having deranged liver function tests. Hence, it is important to monitor liver function tests (LFTs) in COVID-19 patients presenting with fever.

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach.

Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler's diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.