Highly cross-conserved burkholderia T cell epitopes generate effector T cell responses in vitro

Burkholderia pseudomallei and Burkholderia mallei cause glanders and melioidosis, respectively. Both of them are classified as Category B biothreat agents due to their high infectivity and potential use as a bioweapon. The related species Burkholderia cepaciae causes fatal \u27cepacia syndrome\u27 in cystic fibrosis patients, which is characterized by rapid deterioration, bacteremia and necrotizing pneumonia. Clinical eradication of Burkholderia infection often fails due to antimicrobial resistance. Effective vaccination against Burkholderia infection is critically important to protect populations living in endemic areas worldwide and against bioterror threats. No vaccines or other prophylactics for these pathogens are available. Vaccines against Burkholderia should target cell-mediated immune response, which is believed to be essential to successfully clear Burkholderia infection. We hypothesize that a single vaccine comprising highly cross-conserved Burkholderia T cell epitopes might generate protective cell-mediated immune response against all the three species. Immunoinformatics tools were used to identify immunogenic consensus sequences (ICS) that are enriched for promiscuous and highly conserved CD4+ T cell epitopes in all three Burkholderia species. The ICS peptides were validated in peripheral blood mononuclear cells (PBMCs) derived from healthy donors [1]. All of the peptides (100%) bound to at least two HLA alleles, 98% bound to at least three HLA alleles, 98% bound to at least four HLA alleles and 92% bound to all seven HLA alleles. The overall predictive accuracy was 81% (both positive and negative) [2]. Significant IFNg response was induced by all peptides in at least one human donor as measured by IFNg ELISpot assay. 86% of the peptide-specific IFNg ELISpot responses were completely inhibited by antibody block of HLA-DR, indicating that these peptides are HLA-DR-restricted. Significant peptide-specific proliferation and Th1 cytokine production (IFNg, TNFa and IL-2) in CD4+ T cells from healthy donors were observed in flow cytometry analysis. Immunoinformatics predictions, coupled with in vitro validation, can accelerate the selection of highly conserved T cell epitopes from genome sequence databases. The approach can be used for rapid selection of vaccine candidates for a wide array of emerging infectious diseases and biodefense targets. References: 1. Wullner D, Zhou L, Bramhall E, Kuck A, Goletz TJ, Swanson S, Chirmule N and Jawa V. Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics. Clinical Immunology. 2010,137, 5-14. 2. De Groot AS, Ardito M, Moise L, Gustafson EA, Spero D, Tejada G and Martin W. Immunogenic Consensus Sequence T helper Epitopes for a Pan-Burkholderia Biodefense Vaccine. Immunome Res. 2011, 7(2). pii: e7

Enhanced combined assimilative and bound phosphorus uptake in concurrence with nitrate removal in pre-anoxic cyclic sequencing batch reactor

Needless to specify, controlling nitrogen and phosphorus discharge from wastewater treatment plants is synonymous with the prevention of eutrophication of surface waters, as one of the major issues related to water security. The present study investigates the performance of a pre-anoxic sequencing batch reactor (SBR) working on the basis of intermittent aeration, operated at varied carbon (bCOD) to nitrogen (C/N) ratio of 3, 7.5, and 10, and readily biodegradable (rbCOD) to slowly biodegradable (sbCOD) ratio of 0.1, 0.25, and 0.5. The findings revealed that an enhanced nitrogen removal was observed, together with higher C/N and rbCOD to sbCOD ratios. The results also show a consistent increase in total phosphorus removal with an increase in nitrogen removal. The phosphorus uptake of sludge varied from 0.02 – 0.045 mgP/mgVSS (avg. 0.031 ± 0.004), which resulted in enrichment levels of 0.88 – 1.68 times the stoichiometric value of 0.0267 mgP/mgVSS (avg. 1.45 ± 0.14). On an average basis, the assimilative total phosphate (TP) content was increased by 0.008 gTP/gNO -/3 -N removal rate. The excess phosphorus removal was due to the formation of poorly soluble polyvalent phosphate compounds, which was found based on dry analysis, which persisted as bound phosphate in the sludge

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Towards A Structural Judicial Approach in The Egyptian Administrative Courts: Proportionality as A Practical Solution

The lack of detailed and explicit law provisions governing human rights cases obliges judges to fill this legal gap by applying generic constitutional articles. Now that all human rights are interdependent and overlapping, they practically conflict with each other. Therefore, Egyptian judges are obliged to issue a decision in these cases despite such tensions, taking into consideration the lack of detailed and explicit law provisions regulating these disputes. The question here concerns the criteria that the administrative courts should adopt when overseeing administrative decisions to judge in a case when there are two or more disputing and conflicting interests organized by several constitutional articles with no plain or detailed legislation drawing their correlation and limitations. Realistically, the Egyptian administrative courts have applied various and disparate judicial approaches such as legitimacy, suitability, necessity, gross error in the assessment, and comparison between benefits and harms. The concern is that applying different methodologies may lead to different conclusions. This paper argues that using proportionality through its four degrees may unite the mechanism of judicial review, reconcile constitutional values to avoid a hierarchy amongst them, organize the mind of judges, and raise transparency within courts

Incorporation of the Multi-Layer Plastic Packaging in the Asphalt Binders: Physical, Thermal, Rheological, and Storage Properties Evaluation

The amount of residual Multi-layer Plastic Packaging (MPP) in Canada has greatly increased in the last two decades, which has economic and environmental consequences. MPP is primarily made up of two or more layers of Polyethylene (PE), Polyester (PET), Nylon (NY), and Metalized Polyester (METPET). While MPP has not been used as an asphalt modifier, some of the materials commonly found in MPP, such as PE and PET, have also been successfully used as asphalt modifiers. Nevertheless, a few recent studies have demonstrated the potential for reusing MPP as an asphalt modifier to improve asphalt pavement performance. Recycling post-industrial MPP instead of using raw polymers could lead to economic and environmental benefits. However, a comprehensive study to evaluate MPP as a viable asphalt additive is lacking. The main objective of this study is to evaluate the feasibility of using MPP as an asphalt modifier via the wet method, considering the physical, thermal, rheological, and storage properties of the MPP-modified binder at different MPP concentrations (2%, 4%, and 8%) in asphalt cement (PG 58–28). MPP-modified binders were evaluated using the following instruments: Differential Scanning Calorimeter (DSC), Thermogravimetric Analysis (TGA), Superpave Dynamic Shear Rheometer (DSR), Rotational Viscosity (RV), and Environmental Scanning Electron Microscopy (ESEM). Test results indicated that the incorporation of MPP has a strong potential to improve permanent deformation resistance at high temperatures. In addition, MPP shows a moderate impact on fatigue cracking performance at intermediate temperatures. Overall, in low-temperature climates, using less than 4% of MPP additives would offer higher fatigue damage resistance along with adequate permanent deformation. In high-temperature climates, higher concentrations of additives may be preferable to resist permanent deformation. Finally, MPP is a challenge for existing recycling systems, and its incorporation into asphalt applications may develop more sustainable materials that would contribute to circular economy principles

Phenol Biodegradation and Bioelectricity Generation by a Native Bacterial Consortium Isolated from Petroleum Refinery Wastewater

Phenolic compounds are highly toxic, along with being one of the most persistent substances in petroleum refinery effluents. The most potent solution is through phenol bioremediation to produce demi-water and bioenergy, which are two effective outcomes for a single process. Fifteen genetically identified native bacterial strains were isolated from the effluents of the petrochemical industry plant (AMOC, Egypt) and were investigated for potential phenol biodegradation activity and energy bioproduction individually and as a consortium in a batch culture. Successful and safe phenol biodegradation was achieved (99.63%) using a native bacterial consortium after statistical optimization (multifactorial central composite design) with bioelectricity generation that reached 3.13 × 10−6 mW/cm3. In conclusion, the native consortium was highly potent in the bioremediation process of petroleum refinery wastewater, protecting the environment from potential phenol pollution with the ability to generate an electrical current through the bioremediation process

Phenol Biodegradation and Bioelectricity Generation by a Native Bacterial Consortium Isolated from Petroleum Refinery Wastewater

Phenolic compounds are highly toxic, along with being one of the most persistent substances in petroleum refinery effluents. The most potent solution is through phenol bioremediation to produce demi-water and bioenergy, which are two effective outcomes for a single process. Fifteen genetically identified native bacterial strains were isolated from the effluents of the petrochemical industry plant (AMOC, Egypt) and were investigated for potential phenol biodegradation activity and energy bioproduction individually and as a consortium in a batch culture. Successful and safe phenol biodegradation was achieved (99.63%) using a native bacterial consortium after statistical optimization (multifactorial central composite design) with bioelectricity generation that reached 3.13 × 10−6 mW/cm3. In conclusion, the native consortium was highly potent in the bioremediation process of petroleum refinery wastewater, protecting the environment from potential phenol pollution with the ability to generate an electrical current through the bioremediation process

Multimodality annotated hepatocellular carcinoma data set including pre- and post-TACE with imaging segmentation

Measurement(s) Image Segmentation • hepatocellular carcinoma Technology Type(s) Neural Network • Multiphasic Computed Tomography of the Abdomen Sample Characteristic - Organism multiphasic CT of the abdomen Sample Characteristic - Location contiguous United States of Americ